Management of idiopathic thrombocytopenic purpura during pregnancy. Management of idiopathic thrombocytopenic purpura (ITP) during pregnancy requires concern for both fetal and maternal morbidity and death.  A review of 14 pregnancies revealed significant maternal morbidity but no maternal deaths.  The perinatal mortally was21 per cent.  Current recommendations for management include: (1) corticosteroids, (2) splenectomy if response is unsatisfactory with (1), (3) liberal use of platelet transfusion if surgical intervention is required in the face of significant thrombocytopenia, and (4) careful observation of the newborn infant and treatment with corticosteroids and/or platelets if thrombacytopenia is severe.


Hysteroscopy: a useful diagnostic adjunct in gynecology. Advancements in instrumentation and the introduction of new media for uterine distention have enhanced the potential of hysteroscopy as a diagnostic technique.  In a10 month period at the University of Minnesota, hysteroscopy was preformed in 110 patients with suspected urine pathology.  Paracervical block ansthesia was used in 70 ambulatory patients and the remainder were investigated under general anesthesia because ofconcomitant laparoscopy or planned surgical intervention.  Both dextran 30 per cent and5 per cent dextrose in water were used for uterine distention.  Hysteroscopic abnormalities were found in 70 per cent of the patients ezamined.  These findings included endometrial polyps (32 patients), 12 intrauterine foreign bodies, submucous myomas (10 patients),developmental anomalies and cesarean section scar defects (7 patients), and 16 patients with miscellaneous pathologic conditions, including one patient with adenocarcinoma of theendometrium.  In 33 patients the hysteroscopic findings were normal.  In severalpatients intrauterine devices were removed under hysteroscopic control.  There were no complications related directly to hysteroscopic abservation.


Current status of artificial insemination with donor semen. As male infertility secondary to oligospermia and azoospermia reamins refractory to treatment, donor insemination has gained greater acceptance.  Wives of azoospermic and severely oligospermic men were evaluated for donor insemination.  One hundred and thirty-four patients were found to be ovulating normally and to be free from pelvic pathology.Sixty-five accepted donor insemination.  Fifty-one conceptions accurred in 41 patients, resulting in 43 live births and 8 miscarriages.  The mean number of inseminations was 4.2 (range 1 to 13).  Eighty-three patients were found to have endocrinopathies or pelvic pathology interfering with fertility; 58 were considered candidates for corrective  therapy to be followed by donor insemination.  Conception rates approached those observed in the average population; however, there was a greater incidence of abortion and ectopic gestation.  Careful consideration of the patient prior to donor inseminationensures greater success and avoids unnecessary procedures when the patient is not considered a candidate for corrective therapy.


Changes in the transfer of nutrients across the placenta during normal gestation in the rat. Transfer of labeled glucose and alpha-amino isobutyric acid from the maternal circulation into the fetus was studied in the rat at various times during gestation and the results were correlated with placental and fetal growth. It was found that the rate of transfer of both substances per gram of placental tissue increase markedly near term in coincidence with a simultaneous fetal growth spurt. The data suggest a bimodal sequence of growth of the conceptus with a first phase of rapid placental growth and reduced placental transfer and a second phase of slow placental growth, increased transfer, and rapid fetal growth.


Variations in the level of uterine norepinephrine during pregnancy in the guinea pig. The uterine smooth musculature is innervated by short adrenergic neurons which are unique in that their transmitter content varies during pregnancy and under the influence of exogenous sex hormones. Uterine norepinephrine was measured fluorometrically at 25 stages throughout pregnancy in the guinea pig, which was chosen because one of the pregnant uterine horns often is devoid of fetuses and hence not subject to mechanical tension. During the initial 10 days of pregnancy, the total organ content of norepinephrine was almost doubled whether the horn contained conceptuses or not. In the horn with conceptuses, norepinephrine was subsequently reduced in the course of the remaining gestation time to reach near-zero levels at term (about 65 days post coitus). In the empty horn, the amine level was constantly elevated until the last two weeks, during which it fell to the same low values as in the contralateral horn. Cervical norepinephrine exhibited the same variations during pregnancy as the empty horn. It is suggested that the characteristic variations in uterine norepinephrine reflect a hormonal influence on the system of short adrenergic neurons, with the addition of mechanical factors in that horn containing fetuses.


Renal lithium reabsorption in man: physiologic and pharmacologic determinants. In order to evaluate the premise that renal lithium reabsorption may reflect proximal tubular sodium reabsorption, the fractional excretion of lithium (FELi) was measured, during a variety of experimental maneuvers known to affect renal cation reabsorption, in normal volunteers who had been pre-loaded with lithium. Furosemide increased FELi, as well as sodium, calcium, and magnesium excretion, during the first hour following diuretic administration. Subsequently, sodium, calcium, and magnesium excretion continued to remain elevated after furosemide, despite progressive volume depletion, but FELi values usually declined at least to pretreatment levels. Oral glucose  ingestion increased lithium, calcium, and magnesium excretion while sodium and potassium excretion decreased concomitantly. Increases in FELi during volume expansion with saline were correlated with changes in fractional flow (V/GFR) in natriuretic subjects. Parathyroid extract (PTE) increased both FELi and fractional phosphate excretion (FEphos). FELi and FEphos were correlated significantly in the studies with furosemide and PTE, but not after saline volume expansion. In persons who previously had undergone unilateral nephrectomy, FELi was not increased over values in normal subjects. These results indicate that changes in lithium reabsorption may be dissociated from the reabsorption of other cations. They are consistent with the hypothesis that FELi may reflect proximal tubular sodium rejection, but do not exclude other more distal sites of lithium reabsorption.


Retinal hemorrhage associated with thrombasthenia. A healthy 20-year-old man presented with a spontaneous unilateral retinal hemorrhage. Because of a history of easy bruisability, we obtained hematologic studies and diagnosed thrombasthenia, a hereditary hemorrhagic disorder. The association of retinal hemorrhage and thrombasthenia is rare. Thrombasthenia and other platelet functional disorders are becoming better defined as tests for these abnormalities become more reliable and available. Patients with apparent spontaneous retinal hemorrhages of unknown origin should be questioned about hemorrhagic tendencies, and the various tests for hemorrhagic disorders should be obtained. The hematologic survey should include the more sophisticated tests of platelet function. Patients with thrombasthenia should avoid aspirin intake.


Pathologic findings and laboratory data in a new strain of obese hypertensive rats. A new strain of rat characterized by genetic obesity, endogenous hyperlipidemia, and hypertension was obtained in this laboratory.  The abnormal phenotype is inherited as a homozygous recessive trait.  The animals exhibit marked hypertriglyceridemia, moderate hypercholesterolemia, and an electrophoretic pattern resembling that of human Type IV hyperlipoproteinemia.  The average life-span is less than 1 year, due largely to the development of premature renal and vascular disease.  The kidney lesion has both glomerulonephritic and nephrosclerotic components and is accompanied by marked proteinuria.  About 12% of animals develop urinary tract calculi.  The vascular disease consists of fibrous and fatty-fibrous intimal plaques, and polyarteritis.  The obese animal offers a useful model for investigating abnormal lipid metabolism and the etiology and pathogenesis of atherosclerosis.


Evolutionary dental changes.

Evolutionary dental changes. In the evolution of primates there has been a tendency towards reduction in jaw length and prognathism, mandibular canine size and first molar cusp number, and third molar presence. These oral structures were contrasted, and compared with cranial size, body height and weight, and finger length in 118 males and 102 females of the Burlington Growth Centre. Body weight was significantly related to canine width and to jaw length and prognathism. These relationships were stronger in the males than in the females. The evolutionary reduction in these dental dimensions may result from an evolutionary reduction in genetically determined body size. In the males the number of molar cusps was related to finger length and cranial height. Agenesis of third molars was related to the length of the maxilla in both sexes. In the females, canine width was related to the number of cusps of the first molars, agenesis of third molars, and length of a finger. Simultaneous reductions in dental structures were more frequent in the females.


Effect of amygaloid lesions on gonadal maturation in male and female ferrets. Two experiments were performed to determine whether the amygdala is involved in theregulation of gonadal maturation in the ferret.  In an experiment with prepuberal males it was found that testicular and epididymal wieghts, seminiferous tubule diameters, Leydid cell number, and ratings of spermatogenic development were the samein animals autopsied 4 wk after either the placement of a platinum-elctrode lesion in the amygdala or a sham operation.  Testosterone concentrations both in testis and in blood tended to be lower, and body growth was significantly retarded in males with amygdaloid lesions.  In a second experiment with prepuberal females it was found that the first estrus occurred significantly earlier in ferrets that had received amygdaloidlesions than in sham-operated controls.  Neither body growth nor fertility of femaleswas affected.  These findings suggest that the amygdala exerts an inhibitory influence on the hypothalamic mechanism which controls the secretion of gonadotropins required for initial estrus in female ferrets, but not for the initail masturation of the testes in males.


Critique of a hypothesis of dominance and sexual behavior. The author critically evaluates the article "Dominance and Sexual Behavior: A Hypothesis," which appeared in this journal last year and hypothesized that "male dominance facilitates male-female copulatory behavior while female dominance inhibits it." He concludes that such unitary-cause hypotheses of complex behaviors may be reductionistic and therefore less helpful than intended.


The first reported case from Panamá of acute gastroenteritis caused by Vibrio parahaemolyticus. The first confirmed case of Vibrio parahaemolyticus gastroenteritis in Panama is reported. This marine organism, causing food poisoning in some countries and isolated only recently from seawater in Panama, was recovered from the stools of a patient with acute gastroenteritis, as well as from fresh shrimp used in preparing seafood dishes. This person and 39 other individuals became acutely ill a few hours after eating shrimp at the same restaurant.


Phocanema-type larval nematode coughed up by a boy in California. A 13-year-old Palo Alto boy coughed up an immature Phocanema-type larva about 4 days after having eaten "ceviche" made of raw red snapper marinated in lime juice.


Evaluation of the brachial artery to brachial vein bovine heterograft arteriovenous fistula for hemodialysis. The use of the bovine heterograft in the severely ill patient is reviewed. From personal experience and a review of the literature we believe the preferred site of placement is between the brachial artery and brachial vein in the arm.


16alpha-hydroxy-progesterone as a sex hormone antagonist: effect on venous diameters in the female mouse. Pellets of progesterone plus 1% 16alpha-hydroxy-progesterone (16alpha-OH), testosterone plus 1% 16alpha-OH, and estradiol-17beta plus 1% 16alpha-OH were implanted in the right uterine fat mass in ovariectomized (O) and ovariectomized-hysterectomized (OH) mice. Three weeks later they were killed and the diameters of the ovarian, uterine, and femoral veins and the inferior vena cava were measured and averaged. The averages were compared with averages for O and OH mice bearing pellets of glass and of progesterone, testosterone, and estradiol-17beta without 16alpha-OH. It is concluded that in castrate mice the size of ovarian and uterine veins is influenced not by the presence or absence of the uterus but by sex steroids, that progesterone usually causes decreases while testosterone and estradiol-17beta cause increases in vein diameter, and that both the presence of the uterus and the administration of 1% 16alpha-OH are associated with partial inhibition of increases in vein size induced by steroids. Uterine hypertrophy and urinary bladder distention resulting from the administration of testosterone and estradiol-17beta were not prevented by the addition of 1% 16alpha-OH.


Ultrastructure of the oocytes of the Egyptian sping mouse (Acomys cahirinus). The oocytes of types 2, 3, 4 and 5 follicles from the normal spiny mouse were examined withe the electron microsome. Multiple juxtanuclear Golgi bodies, mitochondria associated with flattened granular endoplasmic reticulum, and large nucleus are the main features of the type 2 follicle oocyte. The numbers of mitochondria and Golgi apparati increase significantly at later stages. Small mitochondrial aggregates lacking "intermitochondrial cement" are seen in the ooplasm of types 3, 4 and 5 follicles. "Lamellar complexes" comprising two to six elongate flattened rough ER cisternae and intercisternal filaments begin to appear in the occyte of the type 3 follicle. The intercisternal filaments may be observed as punctate-, dashed-, and solid-lines in cross sections. In tangential sections the filaments display a paracrystalline structure. In the type 4 follicle oocytes, the "lamellar complex" becomes more extensive; polysomes and ribosomal fibrils are juxtaposed to the "lamellar complexes." Bundles of ribosomal fibrils are abundant in the ooplasm of the type 5 follicle. The origin of ribosomal filaments and the functional significance of "lamellar complexes" are discussed.


Effects of testosterone on the behaviour of the domestic chick. I. Effects present in males but not in females. In male chicks, specific facilitation of male copulatory movements occurs at a lower dosage of testosterone oenanthate than does facilitation of approach to the test object, or of attack. The latter effects can be dissociated in other ways from the first; they may depend upon a single central change in visual responsiveness or persistence. Females show none of these changes, although they are capable of the behaviour patterns involved, and do show other behavioural effects of testosterone. On day 3 normal males copulate and attack more, and flee less than do females.


Effects of testosterone on the behaviour of the domestic chick. II. Effects present in both sexes. In female chicks, testosterone increases both binocular fixation of the thrusting hand and avoidance of direct gaze. The hand is thus treated as though it had become more conspicuous. Males show signs of such changes, which are obscured by a progressive locking of attention on the hand, along with which develop head shaking and pecking. These latter three effects, together with later full attacks, may be a consequence of increased persistence in males due to testosterone. In both sexes testosterone facilitates waltzing and three characteristic calls, probably by specific effects. Latencies and dosage dependency are similar in both sexes. Ten changes in behaviour due to testosterone can be explained by as few as five basic effects, both general and specific.


Mouse-killing in the rat: effects of sensory deficits on attack behaviour and stereotyped biting. Sensory transections were performed in rats that killed mice after food-deprivation and subsequent satiation. Following partial maxillary or combined maxillary and optic deafferentation, but not after optic lesions alone, the number of mouse-kills declined sharply. This decline was accounted for by approximately a 50 per cent decrease in the number of mouse-presentations in which attack-behaviour took place and in the occurrence of attack-behaviour that did not always lead to a kill because rats frequently failed to bite. Furthermore, examination of killed mice revealed a shift in the distribution of body-bites away from the rostral regions normally seized by rats to more caudal areas of the mouse's body. Results indicate that certain stimulus-characteristics of mice mediated by the maxillary and optic nerves are important determinants of attack-behaviour and stereotyped biting in the rat.


Comparative studies of the aggressive behaviour of two gymnotid electric fish (Gymnotus carapo and Hypopomus artedi). Electrical and motor behaviour was studied during aggressive interactions in two species of electric fish (Gymnotus carapo and Hypopomus artedi). Paired comparison methods were used to obtain the data, and analysis of the results was undertaken at three different levels: (1) The repertoire of behaviour (motor and electrical); (2) The changes in relative frequency of components with increasing exposure to conspecifics; (3) Sequential analysis of patterns of behaviour occuring both within and between individuals. The results of the three analyses showed: (1) A great similarity in repertoire although a much higher rate of interaction for Gymnotus. The relative importance of the "off" and "burst" signals was reversed for the two species. A prolonged orientation component in Hypopomus was found to be related to the occurrence of discharge synchrony. (2) Habituation of intense components in favour of electrical signalling in both species. (3) Important differences in both the length and structure of sequences.


Dairy calf mortality rate: influence of meteorologic factors on calf mortality rate in Tulare County, California. Monthly calf mortality data for a period of 5.5 years in Tulare County, California, were compared with monthly summarized weather data for that county, using multivariate statistical techniques. In winter, increases in the calf mortality rate (CMR) were significantly associated with cold, wet, windy weather; in summer, greater death losses were associated with hot, dry weather. In general, the calf losses in winter seemed more closely related to weather phenomenon than those in summer. The CMR during a 6-month period (July to December, 1973) were predicted, using equations containing data on the more important weather variables. The predicted CMR significantly differed from the observed death rate during July through September. During October through December, the predicted and observed CMR did not significantly differ. An increase in mortality rate was not predicted for winter, mainly because of low rainfall, and none occurred.


Control of estrus with prostaglandin F2alpha in mares: minimal effective dose and stage of estrous cycle. To determine the minimal effective dose of prostagiandin (PGF2alpha; tromethamine salt) given subcutaneously (SC), mares of mixed breeding (400 kg av body weight) were given 2-, 3-, 5-, and 10-mg doses from 7 to 9 days after ovulation. In some but not all mares given doses of 2 and 3 mg of PGF2alpha, luteolysis occurred, but doses of 5 or 10 mg of PGF2alpha were luteolytic in all mares. The 10-mg dose of PGF2alpha did not cause luteolysis in mares 1 day after ovulation, and caused luteolysis in only 2 of 5 mares on day 3 after ovulation. The same dose of PGF2alpha, however, caused luteolysis in all mares on days 5 or 7 after ovulation. The results indicate that the minimal effective luteolytic dose of PGF2alpha (free-acid equivalent) is about 9 mug/kg, and that PGF2alpha is effective fromday 5 after ovulation.


Influence of the anthelmintic mebendazole on microtubules and intracellular organelle movement in nematode intestinal cells. The ultrastructural changes in the intestines of Ascaris suum and Syngamus trachea, induced by in vivo treatment of the hosts with the anthelmintic mebendazole, are reported. The primary site of drug action seemed to be the organelles involved in the secretory mechanism of the intestinal cells. The block in the transport of secretory granules and in the movement of other subcellular organelles coincided clearly with the disappearance of cytoplasmic microtubules. On the other hand, the microtubular system of the host cells was unaffected by the treatment. Degenerative changes in the intestinal cells of the parasites observed afterwards were correlated with the primary deteriorative effect of the drug on cytoplasmic microtubules.


Plasma corticoid changes during diarrhea in neonatal calves. An acute, and usually fatal, diarrhea was induced in 11 healthy neonatal dairy calves by oral administration of an enteropathogenic viral inoculum. Fluid and electrolyte therapy was administered to several affected calves. Plasma corticoid values were determined by radio-immunoassay and competitive protein-binding assay, after purification of the plasma by paper chromatography. Statistical comparisons between control and diarrheic groups of calves were made on 5 corresponding experimental days. Plasma aldosterone values of 2 groups of diarrheic calves which died with and without treatment were greater (P less than 0.01) just before death than those of controls and diarrheic calves which recovered. Plasma hydrocortisone and progesterone values in the calves not treated were higher (P less than 0.05) on the day preceding death than in the controls. Plasma corticosterone concentration was increased (P less than 0.05) throughout the disease in both groups of calves that recoverd. These results indicate that the adrenal cortex of the neonatal calf can respond to the severe stressor influences and fluid-electrolyte losses of diarrhea.


Hyperprolactinemia in sarcoidosis: incidence and utility in predicting hypothalamic involvement. Patients with sarcoidosis have been reported frequently to have elevated concentrations of serum prolactin.  On this basis, it was suggested that the hypothalamus might be a common site of involvement by sarcoidosis and that measurement of serum prolactin concentrations might serve as a sensitive indicator of hypothalamic disease.  We measured serum prolactin concentrations in a group of 61 patients with sarcoidosis.  Hyperprolactinemia was detected in only 2 of the entire group and was not observed in any of the 9 patients with central nervous system involvement.  Because radioimmunoassayable prolactin concentrations are infrequently elevated in patients with disseminated sarcoidosis, even when pitutitary hypofunction is apparent, it is concluded that the measurement  of serum prolactin is not a reliable method for screening these patients for pituitary or hypothalamic disease.


Differential potentiation by nystatin of the effect of antibiotics on yeast and mammalian cells. The effect of the polyene antibiotic nystatin, used in combination with several other antibiotics, on the membranes of Candida albicans SC#8169 (yeast) cells and of Chinese hamster ovary and 3T3 (mammalian) cells was investigated. It was concluded from determinations of the viability of the yeast cells and from measurements of deoxyribonucleic acid synthesis by the mammalian cells that nystatin acts synergistically with several antibiotics on yeast cells, but not on CHO and 3T3 cells. This selective action of nystatin may prove useful in chemotherapy.


Comparison of the survival and metabolic activity of psychrophilic and mesophilic yeasts subjected to freeze-thaw stress. A mesophilic yeast, Candida utilis, and a psychrophilic yeast, Leucosporidium stokesii, were subjected to freeze-thaw cycling over the range 25 to -60 C. Viability after freeze-thaw stress was directly correlated with the rate of cooling and the physiological age of the cultures. Rates of glucose fermentation and oxidation could be directly correlated with viability. The optimal cooling rate for both yeast strains was 4.5 to 6.5 C/min; however, their levels of survival obtained at this optimal cooling rate varied considerably. In addition, the psychrophile was less resistant to freeze-thaw stress than was the mesophile.


Comparative inhibitory effects of antigen and antibody in the staphylococcal enterotoxin solid-phase radioimmunoassay system. A solid-phase radioimmunoassay employing 125I-labeled enterotoxins and polystyrene tubes coated with specific antibody has been developed for assaying the relative concentrations of antibodies to staphylococcal enterotoxins A and B. Competitive binding occurs between tube-bound antibody and free antibody for binding sites on 125I-labeled enterotoxin. The sensitivity of the system is affected by the amount of antibody on the walls of the tubes, the concentration of 125I-labeled enterotoxin added to the system, and probably by the relative binding affinities of the bound and unbound antibodies. Antibody, 0.01 to 0.07 mug/ml, inhibited the uptake of 125I-labeled enterotoxin by 20%. Both the antibody and antigen solid-phase radioimmunoassay inhibition systems can be appropriately represented by either of the following two models: Loge (Y/1 - Y) = alpha0 + alpha1 LogeX and LogeY = beta0 + beta1 LogeX, where Y is bound activity, X is antigen or antibody concentration for inhibition, and alpha0, alpha1, beta0, and beta1 are regression coefficients. Estimates from the first model were slightly more precise for the antibody system, whereas the reverse was true for the antigen system.


[Chemical study of "Penicillium" and "Trichoderma" pigments (author's transl)]. The green pigments from the fungi of the genera Trichoderma and Penicillium were partially extracted with formic acid. After two acid and one alkaline hydrolysis, the pigments of Trichoderma viride and Trichoderma koningii were sufficiently purified to undertake the chemical studies. The elemental and functional analyses, the U. V. and visible spectra and the chromatographic observations showed that these pigments are polyphenolic in nature. Gel filtration on Sephadex G50 suggested, on the one hand, the homogeneity of the pigment of T. viride and, on the other, the heterogeneity of the pigment of T. koningii.


Production of aflatoxin on soybeans.

Production of aflatoxin on soybeans. Probable factors influencing resistance to aflatoxin synthesis in soybeans have been investigated by using cultures of Aspergillus parasiticus NRRL 3240. Soybeans contain a small amount of zinc (0.01 mug/g) bound to phytic acid. Autoclaving soybeans at 15 pounds (6803.88 g) for 15 min increases the aflatoxin production, probably by making zinc available. Addition of zinc to both autoclaved and nonautoclaved soybeans promotes aflatoxin production. However, addition of varying levels of phytic acid at a constant concentration of zinc depresses aflatoxin synthesis with an increase in the added phytic acid. In a synthetic medium known to give good yields of aflatoxin, the addition of phytic acid (10 mM) decreases aflatoxin synthesis.


Ultrastructure of cell envelopes of bacteria of the bovine rumen. Most of the bacteria found in rumen fluid samples taken from cows fed hay, or a concentrate diet, had cell walls of the gram-negative type. Most were intact, with only a small proportion of lysed cells, and many of the cells contained electron-translucent cytoplasmic deposits similar to the carbohydrate reserve material described in pure cultures of rumen organisms. All of the bacteria observed in these samples had an external "coat" layer outside the outer membrane when fixed in glutaraldehyde and osmium, stained with uranyl acetate and lead citrate, and examined as sectioned material. These coat layers varied from thin (ca. 8 nm) structures to very extensive fibrous systems, sometimes including concentric arrangements and radial fibers extending up to 1,200 nm from the cell. The thin-coat layers sometimes exhibited a rough periodicity. In all, 10 different types of coat layers were distinguishable on a morphological basis. It is proposed that these external coat layers have protective and adherence functions for the rumen bacteria in the environment.


Isolation and identification of a genus, Chromobacterium, not previously found on processed poultry. An organism identified as Chromobacterium lividum was isolated from processed poultry in Georgia.


[Purification of a protein characteristic of pathogenic strains of "Beauveria tenella" (author's transl)]. Purification of the protein which in immunoelectrophoresis is responsible for the precipitation are characteristic of the pathogenic strains, can easily be obtained by isoelectrofocalisation: two protein fractions are isolated. These differ in their isoelectric points and in their relative electrophoretic migration coefficients in polyacrylamide gel, but exhibit the same antigenic specificity.


The experimental chemotherapy of leishmaniasis. I: Techniques for the study of drug action in tissue culture. Three lines of Leishmania have been grown successfully in tissue culture. L. mexicana mexicana, L.tropica major and L. donovani develop readily as amastigotes in dog sarcoma cells, and in a hamster peritoneal exudate cell line. The procedures used for cultivating both host cells and parasites are described, as are the methods employed for studying the senitivity of the parasites and hosts to drugs. It is concluded that the use of a tissue culture system is a valid way of determining the baseline sensitivity of a Leishmania to chemotherapy and the limitations of the technique are discussed. Illustrative data are presented of the response of two Leishmania species to amphotericin B and to a quinine analogue. L. mexicana mexicana is highly sensitive to amphotericin B and the response is shown to be consistent in duplicate experiments. L. mexicana mexicana and L. donovani are shown to have a different innate sensitivity to the quinine analogue.


Albumin binding of thioridazine and some of its metabolites. The binding of thioridazine, northioridazine, mesoridazine and sulforidazine to bovine serum albumin is studied by means of equilibrium dialysis. For these four substances the percent binding in function of the albumin concentration is determined, as well as the apparent binding constant in the concentration range studied. The importance of the hydrophobic character and the chemical structure for the albumin binding is discussed.


Sensitivity changes to morphine and other drugs induced by cholinergic blockade. Mice were given several atropine injections at a high dosage level. After 2 to 5 days of cessation of treatment the effects of morphine, arecoline, amphetamine, pentylenetetrazol, reserpine, and hexobarbital were determined and compared with those found in saline injected controls. The influence of atropine treatment on tolerance development to morphine was also studied. After withdrawal of atropine a reduction of the analgesic responses to morphine and arecoline was observed. A decrease in hexobarbital sleeping time was also found. There was no significant influence on the analgesic effect of amphetamine, on the depressant action of reserpine, and on the convulsant effect of pentylenetetrazol. The influence of the administration and further withdrawal of atropine on tolerance development to morphine was masked by the concomitant reduction of morphine analgesia. It was impossible to observe a supersensitivity to the pharmacological agents studied.


Pharmacological analysis of a new anorexic substance: 5-hydroxy-5(4'-chlorophenyl)-2, 3-dihydro-5H-imidazo-(2, 1-a) isoindole (Mazindol). 5-Hydroxy-5-(4'-chlorophenyl-2, 3-dihydro-5H-imidazo (2, 1-a)isoindole (mazindol), a novel tricyclic compound, has been shown to suppress food consumption in rats at doses causing weak central stimulation and little effects on blood pressure or heart rate. The substance produces dose-related decreases in the consumption of orange juice in cebus monkeys trained on an operant behavior schedule. The compound did not alter cardiac or pulmonary hemodynamics in the anesthetized dog but provided potentiation of norepinephrine pressor responses. Mazindol also demonstrated potent but incomplete antagonism of reserpine-induced hypothermia in mice, antagonism of tetrabenazine catalepsy in rats, and suppression of mouse-killing behavior of rats. Suppression of mouse-killing was reduced by lesions placed in the septal area of the brain. Brain monoamine oxidase or catechol-o-methyl-transferase activities were not altered, although preliminary experiments showed that mazindol reduced uptake of norepinephrine in brain tissue.


Effects of some cholinergic drugs on the actions of morphine on the ileum of the guinea-pig in vitro. The sensitivity of the isolated, electrically stimulated guinea-pig ileum to acetylcholine aan physostigmein was found not to be reduced during 'dependence' or 'withdrawal' responses to morphine. There was no evidence that exaggerated release of acetylcholine occurred following withdrawal of high concentrations of morphine from 'dependent' longitudinal muscle strips incubated with 14C-choline. These data cast doubt on the hypothesis put forward by Paton in 1963to explain the development of 'tolerance' and 'dependence' to morphine in the ileum. The potency of morphine in producing responses of the ileum was reduced in the presence of raised concentrations of calcium, indicating that the effect of morphine may be mediated via a calcium-sensitive step.


Growth of the haploid phase of the myxomycete Physarum flavicomum in defined minimal medium. The haploid phase (myxamoebae-swarm cells) of the myxomycete Physarum flavicomum grew readily in chemical defined liquid media. The minimal medium contained salts, glucose, biotin, thiamine, hematin, glycine, L-arginine and L-methionine. Cell yields of 1.4 times 10(7) cells/ml were obtained in this medium in aerobic shake culture. These cells consumed about 35 muliters of oxygen/mg protein-hr in the minimal medium. The morphology of cells maintained in this medium appeared to be "normal". L-valine replaced either glycine or L-methionine in the minimal medium but the growth rates and cell yields were reduced. Growth rates increased in media containing four, seven, or fourteen amino acids.


Chemical analysis of cell wall regeneration and reversion of protoplasts from Schizophyllum commune. In the presence of MgSo4 as osmotic stabilizer, nucleated protoplasts of Schizophyllum commune developed a large vacuole and could be isolated on the basis of their low buoyant density. All these protoplasts were capable of wall regeneration and about 50 percent reverted to the hyphal mode of growth in liquid medium. The kinetics of the formation of three main cell-wall components, S-glucan (alpha-1,3-glucan), R-glucan (beta-1,3, beta-1,6-glucan) and chitin were studied from the onset of regeneration. S-glucan and chitin accumulation as well as RNA and protein synthesis started simultaneously after a short lag, but R-glucan formation was delayed. The reversion of hyphal tubes only began after several hours of rapid R-glucan synthesis. Cycloheximide (0.5 mug/ml), inhibiting protein synthesis by 98% inhibited the formation of R-glucan and the reversion to hyphal growth but the formation of chitin and S-glucan did start and continued seemingly unimpaired for several hours. This indicates that the enzymes responsible for the synthesis of S-glucan and chitin remained intact during protoplast preparation. Polyoxin D inhibited both the synthesis of chitin and R-glucan and also the reversion to hyphal growth. However, the synthesis of S-glucan was not suppressed. These inhibitor studies as well as the kinetics of R-glucan formation during normal regeneration suggest that the synthesis of R-glucan is required for the initiation of hyphal morphogenesis.


The effect of alfalfa saponins on growth and lysis of Physarum polycephalum. The prelytic events associated with the interaction of saponins with Physarum polycephalum membrane components were studied. It was found that alfalfa saponins form interaction products with membranal sterols, proteins and phospholipids. The interaction of saponins with proteins affect also certain membranal enzymic activities such as NADH oxidase and Malate dehydrogenase. It is suggested that although the interaction of the saponin with sterols is much more specific than with other membranal components, the lysis of plasmodia of P. polycephalum should be attributed to a concerted attack on the various membrane constituents. In continuation of these interactions, the changes of permeability of plasmodia membrane were expressed by increment of inorganic sodium ions and water influx, traced by lysis, while no efflux of ions was observed.


Germination and mitochondrial damage in spores of Dictyostelium discoideum following supraoptimal heating. Spores of Dictyostelium discoideum may be quantitatively activated with a heat treatment of 45 degrees C for 30 min. Heat activation at either higher temperatures of for longer duration at 45 degrees C resulted in damaged spores. The spores showed an increased postactivation lag time at 23 degrees C and an increased inability to respond to deactivation with 0.2 M sucrose. As the severity of supraoptimal heating increased, a greater percentage of the spores appeared to contain phase dark lesions and to lose viability. Oxygen uptake began to decrease during and after the appearance of the lesions. Using electron microscopy, the phase dark lesions were found to be mitochondria with disrupted cristae.


Protoplasts of Trichoderma viride: formation and regeneration. High yields of protoplasts from the 18-hr old mycelium of Trichoderma viride were obtained by using the lytic system, produced by Streptomyces venezuelae RA and Micromonospora chalcea grown on a synthetic medium containing laminarin and chitin, when 0.7 M MgSO4 or (NH4)2SO4 were used as osmotic stabilizers. Regeneration of these protoplasts occurred through the production of an abortive tube and direct germination of the protoplasts. Regeneration could also take place in the medium used to produce protoplasts, but the process was different in many details.


Role of glycosidases in the membranlytic, antifungal action of Saponins. In studies on the membranlytic action of various saponins on mycelium of Botrytis cinerea and Rhizoctonia solani digitonin, alpha-hederin and tomatin caused considerable leakage of free amino acids, while aescin and theasaponin were less effective. Cyclamin significantly damaged cell membranes of R. solani, but did not change the selective permeability of B. cinerea. Cell membrane disruption was accompanied by an enzymatic conversion of saponins into their corresponding aglycones in cell membrane vicinity, an effect which was significantly inhibited by aldonolactones, known inhibitors of beta-glycosidases. These results lead to the conclusion that the hardly water soluble aglycones are the active part of the saponin molecules, the saponins themselves being only water soluble transport forms. It follows, that the presence of appropriate glycosidases in cell membranes, capable of converting saponins into their aglycones, is a prerequisite for the membranlytic action of saponins. The similarity of the membranlytic effects of saponins towards fungi and erythrocytes is descussed.


[The importance of chorionic gonadotropin excretion in diagnosis and therapy of testicular tumours (author's transl)]. Systematic investigations of the chorionic gonadotropin excretion were performed in 79 patients with testicular tumours. The influence of the hormonal activity in diagnosis and prognosis of metastatic testicular tumours was investigated. It was discovered, that the part of hormonal active testicular tumours is relatively small and that the evidence of the chorionic gonadotropin excretion is only possible in a few cases before the clinical and radiological evidence of metastases. The hormonal activity of testicular tumours is without influence on the survival time of tumour carriers.


Dumbbell neuroblastomas in children.

Dumbbell neuroblastomas in children. A "dumbbell" neuroblastoma is a malignant neoplasm usually primary in the mediastinum or retroperitoneum with posterior extension through an intervertebral foramen to additional tumor within the spinal canal. Neurologic deficits are found in almost all cases. Nineteen patients with such tumors were reviewed with respect to diagnosis, management, and results. Treatment consisted of prompt laminectomy with total or subtotal excision of the extradural tumor. The primary tumor in the mediastinum or retroperitoneal area was removed at a second stage. All patients received postoperative radiation therapy. Eleven of the 17 patients observed more than two years are free of disease, a cure rate much higher than the overall experience with neuroblastoma. Substantial recovery of neurologic function occurred in most, but kyphoscoliotic deformities were a disturbingly frequent late complication.


Human parathyroid autotransplantation: proved function by radioimmunoassay of plasma parathyroid hormone. The possibility of transplanting parathyroid gland fragments into accessible muscle as functioning autografts in the human being has been supported but unproved. During operations in the thyrocervical area, the parathyroid glands frequently are removed, either intentionally or inadvertently. We have had occasion to transplant slices of parathyroid glands in five instances; four parathyroid glands were proved to be normal, and a benign adenoma appeared in the fifth. The parathyroid gland was positioned in a muscular bed in the patient's forearm. Plasma parathyroid hormone (PTH) measurements by radioimmunoassay were made from the implant venous effluent. The venous outflow from the contralateral arm was used for control. We have concluded that parathyroid tissue can be transplanted, does function, and might be capable of providing calcium homeostasis.


[Development of the nephrons of the mesonephros of chicken embryo]. The number of nephron populations in the postinduction period was established in 6- and 8-days chicken embryos and the development of an individual nephron and its parts was studied. The investigation by microdissection method has shownand the number of nephrons is different along the length  of the kidney. Only two layers ofthe nephrons were found in the cranial portion, while in the caudal direction their number increased up to 4-6 populations which distinguished from one another by the glomerule position, the length of the nephron and its segments. All the populations of the ventral nephrons enter immediately into the mesonephritic (Wolffian) duct, while the dorsal nephrons have a system ofcollecting tubes by which they are connected with the mesonephric duct. The development of mesonephros was accompained by the increase of the absolute length of the nephrons of all populationsand their segments. Laboratory of Individual Development, Institute of Physiology, Czechoslovakian Academy of Sciences, Prague, and Laboratory of the Evolution of the Kidney and Water-Salt Exchange, Sechenov Institue of Evolutionary Physiologyand Biochemistry, Leningrad.


[Disorders in the development of the crystalline lens in chick embryos following exposure to insulin]. Inection of insulin into the chicken egg-white in dosage of 4 i. u. during the 1st - 14th days of incubation results in degenerative changes in the lens. Injection of insulin during the 1st day of incubation (before the beginning of eye differentiation) fails to prevent development of the eye vesicle and determination of the lens. The morphogenesis of the lens goes normally up to the 10-13th days of incubation. From this moment abrupt degenerative alterations make their appearance as well as destruction of the lens fibres. When the lens is affected by insulin the destruction is observed on the following day. The mechanism of insulin effects upon the lens seems to be as follows: Exogeneous insulin remains in the embryo tissues for along time. When the tissues are preparing to accept endogeneous insulin and become susceptible to it (the 10th-11th days of incubation) exogeneous insulin begins its pathological influence on the lens fibres. After the 13th-14th days of incubation endogeneous insulin comes into the blood. Against the background of exogeneous insulin it results in excessive increase of concentration of insulin in the embryo tissues and great degenerative changes in the lens.


Visual fields and electroretinography following extensive photocoagulation. Twenty-four patients with proliferative or preproliferative diabetic retinopathy underwent extensive argon laser photocoagulation in one eye. Detailed central and peripheral visual-field examinations and electroretinography were performed before treatment, and at intervals after treatment. Visual field changes were as follows: (1) eight patients had only mild to moderate constriction of all isopters, (2) 11 had discrete scotomata in addition, (3) two had prominent nerve-fiber-bundle defects, (4) three had severe constriction of all isopters, save (in two) that to the largest peripheral test object. Electroretinographic b-wave amplitudes were reduced an average of 40% to white test flashes. Blue test flashes showed an even larger reduction of the rod response. This suggests the receptors in approximately 40% of the retinal area are destroyed by such extensive photocoagulation, covering predominantly that part of the retina that has the highest concentration of rods.


Cardiopulmonary Effects of Combined Exercise and +Gz Acceleration. Acceleration (+Gz) handicaps gas exchange in man by creating a ventilation/perfusion (VA/Q) mismatch in the lung. At 1 G, leg exercise makes VA/Q more nearly homogeneous, primarily because peripheral pumping reduces venous pooling and improves pulmonary capillary filling. Four men were studied at rest and pedaling 0, 300 and 600 kpm/min at +1, 2, and 3 Gz. Acceleration raised the resting Vo2, VE, VE/Vo2 and HR but lowered O2 pulse and PetCO2. Since acceleration increased the cost of moving the legs (unloaded pedaling), all work data were considered as a function of VO2. Low levels of exercise returned all variables toward their control (1 G) values. At higher workloads, the combination of G with exercise caused divergence from control measurements, probably also reducing maximal work capacity. Cardiogenic oscillation amplitude increased with G and decreased with work, evidence that exercise improved VA/Q homogeneity at all G-levels. Where man must undergo prolonged exposure to moderate acceleration, use of the peripheral pump might offer some advantages over the conventional anti-G suit.


Deoxyribonucleic acid poymerase of BHK-21/C13 cells. Heterogeneity, molecular asymmetry and subcellular distribution of the enzymes. Nuclear and cytoplasmic fractions were prepared from exponentially-growing BHK-21/C13 cells; DNA polymerase was extracted from them and analysed by gel filtration and sucrose-density-gradient centrifugation. DNA polymerase I is heterogeneous comprising species covering a considerable range of molecular weights. These have been tentatively identified as four subspecies of apparent molecular weights 900000-1000000 (IA), 460000-560000 (IB), 270000-320000 (IC) and 140000-200000 (ID), as assessed by gel filtration through Sepharose 6B. DNA polymerase II has a mol.wt. of 46000 +/- 4000 as assessed by gel filtration on Sepharose 6B, and 48000 +/- 2000 as assessed by gel filtration on Sephadex G-100. Sedimentation analyses on sucrose density gradients showed that the DNA polymerase I species had sedimentation coefficients predominantly in the range 6-8 S. DNA polymerase II had predominantly a sedimentation coefficient of 3.2 S although a component with lower sedimentation coefficient was found. The lack of correlation between the molecular weights derived from gel filtration and the sedimentation coefficients is attributed to molecular asymmetry. DNA polymerase I was found to be associated predominantly with the cytoplasm although certain types of nuclear preparation contained large amounts of it. DNA polymerase II was found to be mostly if not exclusively in nuclear preparations.


Dexyribonucleic acid polymerases of BHK-21/C13cells. Relationship to the physiological state of the cells, and to synchronous indution of synthesis of deoxyribonuleic acid. BHK-21/C13 cells were grown in culture under conditions that provided exponentially growing cells and quiescent cells, by modifying the concentration of serum in the growth medium. The high-molecular-weight DNA polymerase (DNA polymerase I) from exponentially growing cells accounted for 90% of the total polymerase activity; the low-molecular-weight DNA polymerase (DNA polymerase II) accounted for the remaining 10%. In quiescent cells, DNA polymerase I contributed only 39% of the total polymerase activity and DNA polymerase II 61%. The total amount of DNA polymerase I in exponentially growing cells was 11.3-fold greater than that in quiescent cells, whereas the amount of DNA polymerase II appeared to be relatively independent of the physiological state of the cells. In an extension of these experiments, cells in a quiescent state (Go cells) were stimulated by the 'serum-step-up' method of Burk (1970) to grow and to enter a synchronous wave of DNA synthesis (S-phase cells), 87% of the cells synthesizing DNA at 20 h after the 'serum-step-up'. During the synchrony experiment, the total cytoplasmic and total nuclear DNA polymerase activities each increased about 4-fold in parallel with the increase in the rate of DNA synthesis. Cytoplasmic polymerase activity was always greater than nuclear polymerase activity. The increases observed were maximal at 20 h after 'serum step-up'. By 26 h, there was a decrease in enzyme activity (8% for cytoplasmic polymerase and 16% for nuclear polymerase, both relative to the maximum at 20 h), but the rate of DNA synthesis had declined by 37% relative to the maximum at 20 h. In Go cells, DNA polymerase II (mol.wt. 46000 +/- 4000) was the predominant species, there being twice as much of it as of the total DNA polymerase I. In these cells there was little DNA polymerase IC and ID; the amounts of IA (mol.wt. 900 times 10(3)-1100 times 10(3)) and IB (mol.wt. 460 times 10(3)-560 times 10(3)) were about equal but small.


The amino acid sequence of rabbit muscle triose phosphate isomerase. The amino acid sequence of rabbit muscle triose phosphate isomerase was deduced by characterizing peptides that overlap the tryptic peptides. Thiol groups were modified by oxidation, carboxymethylation or aminoen. About 50 peptides that provided information about overlaps were isolated; the peptides were mostly characterized by their compositions and N-terminal residues. The peptide chains contain 248 amino acid residues, and no evidence for dissimilarity of the two subunits that comprise the native enzyme was found. The sequence of the rabbit muscle enzyme may be compared with that of the coelacanth enzyme (Kolb et al., 1974): 84% of the residues are in identical positions. Similarly, comparison of the sequence with that inferred for the chicken enzyme (Furth et al., 1974) shows that 87% of the residues are in identical positions. Limited though these comparisons are, they suggest that triose phosphate isomerase has one of the lowest rates of evolutionary change. An extended version of the present paper has been deposited as Supplementary Publication SUP 50040 (42 pages) at the British Library (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1975) 145, 5.


Active-sitve titration of pig plasma benzylamine oxidase with phenylhydrazine. Pig plasma benzylamine oxidase is a protein containing cupric copper and pyridoxal phosphate. The pyridoxal phosphate is stably linked to the enzyme. Discrepancies in the numbers of active sites per molecule of enzyme are reported in the literature. This paper shows that the fully active pure enzyme contains 3 mol of pyridoxal phosphate per mol, whereas enzymes with a lower specific activity are shown by titration with phenylhydrazine to have a lower pyrdoxal phosphate content.


[Arteriopathia calcificans infantum].

[Arteriopathia calcificans infantum]. A report is given on all 11-weeek-old male child who, after normal development, suddenly became critically ill and died within 8 hours. The autopsy revealed a rare aetiologically and in its pathogenesis unclarified, always lethal clinical picture of so-called "Arteriopathia calcificans infantum" (ACI). An analysis of 90 published cases revealed an average age of the diseased children of 150.9 days and a mean duration of the disease of 32.8 days; in the large majority of the cases (64.7%), death occurred at the latest within 3 days of the first symptoms. A statistical familial concentration of the disease could neither be shown nor excluded. No indication of an exogenous cause of the disease could be found in the reports on previous parental disease, in the history of the pregnancy, in the placenta findings, the case history of the children themselves or in the clinical data. The pathological-anatomical substrate of ACI comprised a calcification, predominantly of the muscular arteries, and located at the boundary between the intima and the media, within the course of the internal elastic lamina. Depending upon the stage of the disease, we first see a fragmentation of the elastic fibres, calcific dust deposits, calcific plaques and the complete replacement of the media by concentric, in part coarsely distingrating, calcific rings. As a result of proliferation of the intima a marked constriction of the lumen occurs in the diseased arteries. Most frequently involved at 90% are the coronary arteries. The genesis of this disease has a considerable similarity to experimental calciphylactic arteriopathy, but no sensitizer mechanism can be demonstrated for ACI. Morphological similarities also exist to generalised elastorrhexis, which is also very rare. There is probably a causal relationship between the two diseases. In a hypothesis on the aetiology of the ACI, it is suggested that this disease may be triggered by a congenital enzyme defect localised in the myointimal cells of the vascular wall. These cells produce incorrectly structured mucopolysaccharides, collagen and elastic material with pathologically increased calcipexy.


Purification and some characteristics of the coagulation factor IX from human plasma. Non-activated coagulation factor IX was purified approx. 10,000-fold from human plasma. The final product was electrophoretically homogeneous and comprised a tingle polypeptide chain with a molecular weight of about 70,000 and a pI of 4.3-4.45. The N-terminal amino acid was glycine. The amino acid and the carbohydrate contents were analysed and a monospecific antiserum to the factor was raised in rabbits.


Isolation and characterization of a variant of ovomucoid. A simple procedure, which can be used on a preparative scale, for the isolation and purification of a major variant of ovomucoid from egg white is described. Ovomucoid was precipitated by salt, and further fractionated by chromatography on sulphoethyl-Sephadex. It showed size homogeneity as revealed by gel chromatography and sodium dodecyl sulphate-polyacrylamide-gel electrophoresis where the mobility was consistent with a molecular weight of 28 300+/-2300. The inhibitor showed full antiryptic but no antichymotryptic activity. The u.v.-absorption and fluorescence characteristics indicated the absence of tryptophan. Polyacrylamide-gel electrophoresis in the presence of 9M-urea demonstrated absence of charge heterogeneity. The intrinsic viscosity of ovomucoid was 5.36ml/g which yielded an equivalent hydrodynamic radius (2.9nm), axial ratio (6.0) and frictional ratio (1.31) of the molecule. The Stokes radius (3.5nm), diffusion coefficient (7.8 times 10(-7 cm2/s) and frictional ratio (1.35) were calculated from gel-filtration data. These results suggest that ovomucoid exists in non-globular conformation under native conditions and that the deviation from the behaviour of a typical globular protein seems to be due both to asymmetry and hydration.


The composition and proposed subunit structure of egg-white beta-ovomucin. The isolation of an unreduced soluble ovomucin. 1. New preparations of reduced carboxymethylated beta-ovomucin (S-carboxymethyl-beta-ovomucin) were homogeneous by sedimentation analysis, analytical sedimentation to equilibrium in CsCl gradients, and disc electrophoresis in sodium dodecyl sulphate. 2. Degradation of S-carboxymethyl-beta-ovomucin with either CNBr or trypsin indicated the presence of a subunit (approx. mol. wt. 112300). 3. Electron microscopy showed that S-carboxymethyl-beta-ovomucin consisted of chains of globular units (approx. mol. wt. 103 000). IN 6M-guanidinium chloride S-carboxymethyl-beta-ovomucin existed mainly as an aggregate (mol. wt. 720 000). 4. S-Carboxymethyl-beta-ovomucin contained ester sulphate (4.24%, W/W) and carbohydrate (60%, W/W), which consisted of large amounts of galactose (22%, W/W), galactosamine (8.9%, W/W) and sialic acid (10.6%, W/W). 5. An unreduced soluble fibrous component (component SGH) extracted from crude ovomucin precipitate with 5M-guanidinium chloride contained beta-ovomucin (approx. 70%, W/W). By using the Scheraga-Mandelkern equation the molecular weight of component SGH was calculated to be 11.5 times 10(6).


The specificity and metabolic implications of the inhibition of pyruvate transport in isolated mitochondria and intact tissue preparations by alpha-Cyano-4-hydroxycinnamate and related compounds. 1. Effects of alpha-cyano-4-hydroxycinnamate and alpha-cyanocinnamate on a number of enzymes involved in pyruvate metabolism have been investigated. Little or no inhibition was observed of any enzyme at concentrations that inhibit completely mitochondrial pyruvate transport. At much higher concentrations (1 mM) some inhibition of pyruvate carboxylase was apparent. 2. Alpha-Cyano-4-hydroxycinnamate (1-100 muM) specifically inhibited pyruvate oxidation by mitochondria isolated from rat heart, brain, kidney and from blowfly flight muscle; oxidation of other substrates in the presence or absence of ADP was not affected. Similar concentrations of the compound also inhibited the carboxylation of pyruvate by rat liver mitochondria and the activation by pyruvate of pyruvate dehydrogenase in fat-cell mitochondria. These findings imply that pyruvate dehydrogenase, pyruvate dehydrogenase kinase and pyruvate carboxylase are exposed to mitochondrial matrix concentrations of pyruvate rather than to cytoplasmic concentrations. 3. Studies with whole-cell preparations incubated in vitro indicate that alpha-cyano-4-hydroxycinnamate or alpha-cyanocinnamate (at concentrations below 200 muM) can be used to specifically inhibit mitochondrial pyruvate transport within cells and thus alter the metabolic emphasis of the preparation. In epididymal fat-pads, fatty acid synthesis from glucose and fructose, but not from acetate, was markedly inhibited. No changes in tissue ATP concentrations were observed. The effects on fatty acid synthesis were reversible. In kidney-cortex slices, gluconeogenesis from pyruvate and lactate but not from succinate was inhibited. In the rat heart perfused with medium containing glucose and insulin, addition of alpha-cyanocinnamate (200 muM) greatly increased the output and tissue concentrations of lactate plus pyruvate but decreased the lactate/pyruvate ratio. 4. The inhibition by cyanocinnamate derivatives of pyruvate transport across the cell membrane of human erythrocytes requires much higher concentrations of the derivatives than the inhibition of transport across the mitochondrial membrane. Alpha-Cyano-4-hydroxycinnamate appears to enter erythrocytes on the cell-membrane pyruvate carrier. Entry is not observed in the presence of albumin, which may explain the small effects when these compounds are injected into whole animals.


Rates of accumulation of glycosidase activities during growth and differentiation of Dictyostelium discoideum. 1. The rates of accumulation (enzyme units/h per 10(8) cells) of a number of glycosidase activities were studied in Dictyostelium discoideum cells during the growth and differentiation phases of this organism's life cycle. 2. The rates of accumulation of the enzymes beta-N-acetylglucosaminidase, alpha-glucosidase and beta-galactosidase remain unchanged during the growth and early differentiation phases. 3. The considerable changes in specific activity of the enzymes which occur in the early differentiation phase are due to the massive loss of total cellular protein which occurs at this time. 4. Significant alterations can occur in the rates of accumulation of alpha-mannosidase during both the growth and differentiation phases, and since, on the onset of differentiation, beta-glucosidase activity is excreted and degraded, the rate of accumulation of this enzyme differs in the growth and differentiation phases. 5. The characteristic rates of accumulation of all these glycosidases change markedly with changes in the growth conditions of the myxamoebae, and thus these rates of synthesis must be regulated independently; however, addition of cyclic AMP to the growth medium has no effect on them.


Rates of degradation and synthesis of glycosidases de novo during growth and differentiation of Dictyostelium discoideum. 1. Injection of a purified preparation of beta-N-acetylglucosaminidase from the spent growth medium of myxamoebae of Dictyostelium discoideum into rabbits gave rise to an antibody preparation containing both anti-alpha-glucosidase and anti-beta-acetylglucosaminidase activities. 2. These two activities were shown to reside in different immunoglobulin molecules and it was concluded that the beta-N-acetylglucosaminidase preparation contained trace amounts of highly antigenic alpha-glucosidase. 3. A single precipitin band having beta-N-acetylglucosaminidase activity was formed in Ouchterlony plates when this antibody preparation was tested against extracts obtained from differentiated cells or from myxamoebae grown either axenically or on bacteria. 4. The antibody preparation was used to show that both beta-N-acetylglucosaminidase and alpha-glucosidase molecules are synthesized de novo from isotopically labelled amino acids during both the growth and differentiation phases of the life cycle and to show that neither of these proteins is significantly degraded during the growth phase or during the first 9h of differentiation. 5. The rates of accumulation of these assayable enzyme activities are thus equal to their rates of synthesis during growth and early differentiation. 6. The factors regulating cellular enzyme activity during the life cycle of D. discoideum are discussed.


Measurement of peak rates of left ventricular wall movement in man. Comparison of echocardiography with angiography. Estimates of peak systolic and diastolic rates of left ventricular wall movement were made in 23 patients by echocardiography and angiocardiography. Echocardiographic measurements were calculated as the rate of change of the transverse left ventricular dimension, derived continuously throughout the cardiac cycle. These were compared with similar plots of transverse left ventricular diameter, in the same patients, derived from digitized cineangiograms taken within 10 minutes of echocardiograms. The results indicate close correlation between the two methods, and suggest that either can be used to measure peak rates of left ventricular wall movements in patients with heart disease.


Echocardiographic mitral systolic motion in left ventricular aneurysm. An abnormal, convex systolic anterior motion of the mitral valve, somewhat similar to that seen in idiopathic hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy) and occasionally in atrial septal defect, was found on the echocardiogram in 8 out of 9 patients with angiographically (7 patients) and/or clinically (2 patients) diagnosed left ventricular aneurysm secondary to myocardial infarction. The only patient whose echocardiogram failed to demonstrate convex systolic anterior motion was the only patient who had an inferior wall aneurysm; the rest of the group had anterior and/or apical aneurysms. In contrast to patients with typical idiopathic hypertrophic subaortic stenosis, the convex systolic anterior motion of the mitral valve observed in our patients tended to 'peak' rather  than 'plateau'. Through the basis for this abnormal septal motion in our patients is uncertain, alterations in left vantricular configuration, plus a relatively vigorously contracting posterior left ventricular wall in the presence of abnormal interventricular septal motion, are probable contributory factors. Though non specific, in the proper clinical and echocardiographic setting convex systolic anterior motion of the mitral valve may be another sign of left ventricular aneurysm.


Neoplastic fibroblasts sensitive to the growth inhibition by homologous cells but insensitive to inhibition by parent normal cells. 3H-thymidine labelling and autoradiography were used to compare density dependent inhibition of growth in the cultures of two transformed lines of hamster fibroblasts and in primary cultures of their parent normal cells. Similar manifestations of density dependent inhibition were found in the isolated cultures of normal and neoplastic cells: at saturation densities these cultures had low labelling indices; these indices considerably increased when the cells migrated into the wound from the dense sheet, prelabelled cells seeded on the dense sheets of unlabelled homologous cells did not proliferate. However, proliferation of neoplastic cells was not inhibited when they were seeded on the dense sheet of normal fibroblasts. Thus, neoplastic hamster fibroblasts of both lines retained sensitivity to the inhibiting effect of homologous neoplastic cells but completely lost sensitivity to the inhibiting effect of normal fibroblasts. The possible significance of this selective loss of the sensitivity to normal cells is discussed briefly.


Determination of benzene and toluene in blood by means of a syringe-equilibration method using a small amount of blood. A gas chromatographic determination of benzene and toluene in blood with a small amount of blood sample, 0.02 or 0.1 ml, is described. In the method an aliquot of the blood sample in a sealed hypodermic syringe of 2 ml capacity is equilibrated at 37 degrees C in a thermo-regulated water-bath. After establishing equilibrium 1 ml of overlying air is submitted to gas chromatographic analysis. The value of this method was verified by experiments in which men, rabbits, and rats were exposed to benzene and toluene mixtures of various concentrations.


RNA synthesis in Chinese hamster cells. III. Non-coordinate increases during interphase in synthesis rates for informosomal, polysomal and heterogeneous nuclear RNAs. Cultured Chinese hamster ovary cells were synchronized by mitotic selection. Relative synthesis rates for informosomal messenger-like RNA (mlRNA), polysomal messenger RNA (mRNA), and heterogeneous nuclear RNA (HnRNA) were estimated from the amount of labeled adenosine or uridine incorporated into these species in early and late interphase. The amounts of uridine incorporated into HnRNA, mRNA, and mlRNA during a pulse administered 9.75-10.75 h post-mitosis were 3.48 4.64, and 2.82 times the amounts incorporated 1.5-2.5 h post-mitosis. Adenosine incorporation values 9.5-11.0 h post-mitosis were 1.64 (HnRNA), 2.49 (mRNA), and 1.18 (mlRNA) times the 1.5-3.0 h values. The realitive incorporation into MRNA of large polysomes corresponded to incorporation into mRNA of smell polysomes. Thus, the synthesis rates of mRNA, mlRNA, and HnRNA increase during interphase in a noncoordinate fashion.


Studies of the mitochondria from Eimeria tenella and inhibition of the electron transport by quinolone coccidiostats. Intact but fragile mitochondria were isolated from unsporulated oocysts of Eimeria tenella. The mitochondria respired in response to succinate, malate plus pyruvate, and L-ascorbate at rates of 1.00, 0.40, and 0.25 mu1 O2/min/mg protein, respectively. Spectrophotometric analyses of the cytochromes in mitochondria and whole oocysts revealed b-type and o-type cytochromes, at roughly similar levels, but no cytochrome c could be detected. The mitochondrial respiration was inhibited by cyanide, azide, carbon monoxide, antimycin A, and 2-heptyl-4-hydroxyquinoline-N-oxide, but was relatively resistant to rotenone and amytal. The quinolone coccidiostats buquinolate, amquinate, methyl benzoquate, and decoquinate were identified as very powerful inhibitiors of succinate and malate plus pyruvate supported respiration in E. tenella mitochondria. None of these four drugs exhibited any inhibitory effect on chicken liver mitochondria. Only 3 pmol of the quinolones per mg mitochondrial protein was needed to achieve 50% inhibition. The inhibition could not be reversed by coenzymes Q6 or Q10. Since the quinolones did not affect L-ascorbate-supported respiration or the activities of submitochondrial succinate dehydrogenase and NADH dehydrogenase, the site of action of the quinolone coccidiostats was tentatively identified as probably near cytochrome b in E. tenella mitochondria. Mitochondria isolated from an E. tenella amquinate-resistant mutant were much less susceptible to quinolone coccidiostats; 50% inhibition was attained by 300 pmol of the drugs/mg mitochondrial protein. The results suggest that the mechanisms of action of quinolone coccidiostats is by inhibiting the cytochrome-mediated electron transport in the mitochondria of coccidia. 2-Hydroxynaphthoquinone coccidiostats were identified as inhibitors of mitochondrial respiration of both E. tenella and chicken liver. They inhibited submitochondrial succinate dehydrogenase and NADH dehydrogenase of E. tenella, and remained equally active against the mitochondrial function of E. tenella amquinolate-resistant mutant.


Studies on the mechanism of the lipase reaction. II. Comparative studies on the adsorption of lipases and various proteins at the air-water interface. Adsorption of lipases (EC 3.1.1.3) and various proteins at the air-water interface has been investigated in relation to the mechanism of lipase reaction. Aqueous solutions of lipases and denaturated proteins show surface activity as strong as that of synthetic detergents. However, ths surface activity of esterases and various other proteins is little or none. By foam fractionation it was shown that lipases were adsorbed at the air-water interface and the adsorption followed the equation of Langmuir's adsorption isotherm. The properties of lipase at the interface are discussed in relation to the mechanism of lipase reaction and the differences from the esterase reaction.


Studies of the interaction of the fluorophores harmine and harmaline with calf thymus DNA. The binding to calf thymus DNA of the hallucinogen harmine and one of its analogues harmaline was studied by absorption spectrophotometry and fluorescence quenching analysis. Viscosity measurements were also carried out. For both molecules, quenched and unquenched sites on DNA are present. For each type of binding site, the value of the product of the number of sites times the association constant was determined. Harmine is more strongly bound than harmaline. Viscosity measurements indicate intercalation in the case of harmine only.


Properties and synthesis of ribosomal RNA in the free-living nematode Panagrellus silusiae. The normal S values of ribosomes and ribosomal subunits extracted from the free-living nematode. Panagrellus silusiae are similar to those of other eukaryotic organisms. Upon heating (70 degrees C, 15 min) a 5.5-S RNA is released from the larger ribosomal RNA (27 S; 1.40-10(6) daltons). Unlike other protostomes, however, the 27-S rRNA does not dissociate in an orderly manner to yield 18-S components. The electrophoretic mobility of the small ribosomal RNA species (18 S; 0.72-10(6) daltons) is unaltered by heat treatment. The base composition of both Panagrellus rRNA species has a 51% G+C content. Labelling worms with either [Me-3H] methionine or [14C] uridine at various stages of postembryonic development and subsequent analysis of the extracted RNA revealed eight radioactive fractions, two of which were the mature ribosomal RNAs. From both the time sequence of appearance of the eight RNA species and the relative degree of methylation of the various RNA fractions two maturation pathways for ribosomal RNA processing were deduced. A 37-S (3.6-10(6) daltons) RNA is the precursor to both 27-S and 18-S RNA. During processing about two-fifths of the original transcriptional unit is lost. In this organism the "transcribed spacer" regions may be methylated although alternate interpretations have not been precluded.


Different binding of poly(A)-containing and poly(A)-free fractions of nuclear ribonucleic acid to ribosomes from rat liver. Total nuclear RNA extracted from nuclei of rat liver cells by phenol/chloroform in the presence of sodium dodecyl sulphate was separated by combined gel filtration on Sepharose 4 B and affinity chromatography on poly(U) Sepharose into fractions differing in their molecular weights and contents of poly(A) sequences. The poly(A)-containing 45-S RNA became labelled most rapidly if rats were administered [3H] orotic acid. This fraction showed a high template activity when added to postmitochondrial supernatants of the Krebs ascites tumour. Fractions of nRNA, free of poly(A) sequences, had no stimulating effect on protein synthesis in this system. The 45-S RNA-containing poly(A) was readily bound to crude polyribosomes from rat liver at 0 degrees C and both ATP and GTP were necessary for this reaction. Sucrose gradient analyses provided evidence that this RNA species is bound predominantly to 80-S ribosomes. No binding was obtained with polyribosomes washed with 0.5 M KCl. The binding ability of washed polyribosomes was restored by the addition of the ribosomal wash fraction or rat liver cytosol. Crude polyribosomes bound significantly lower quantities of nRNA species free of poly(A) when compared with poly(A)-45-S RNA. The label was scattered through the whole ribosomal sedimentation pattern with no predominant peaks and the binding reaction required neither soluble factors nor nucleotide cofactors. The labelling kinetics and high template activity of poly(A)-45-S nRNA indicate that this fraction contains precursors of cytoplasmic mRNA. Requirements for soluble factors and nucleotide cofactors in the binding of this RNA species to 80-S ribosomes suggest that this binding, unlike that of other nRNA species, has a specific mechanism resembling that of mRNA binding during peptide initiation.


Electrocorticographic distrubances after portacaval shunt in the rat: a quantitative evaluation. Electrocorticographic recordings were analyzed in two groups of Wistar rats with end-to-side portacaval shunt and sham portacaval shunt. The main electrical abnormalities observed in the shunted rats concerned slow wave sleep. Quantitative evaluation of these disturbances was made by measuring the duration of spindles normally present in this phase of sleep. Longer duration of the spindles appears to be a reliable index of electrocorticographic disorders after portacaval shunt in the rat.


Carbohydrate metabolism in pregnancy. Part I. Diurnal plasma glucose profile in normal and diabetic women. Diurnal plasma glucose profiles and oral glucose tolerance during pregnancy were studied in normal women, chemical diabetics, and insulin-requiring diabetics. In normal women the mean diurnal plasma glucose rose by only 0.22 mmol/1 (4 mg/100 m1) during pregnancy. Mild chemical diabetes resulted in an increase in both the mean diurnal glucose concentration and the fluctuation of plasma glucose levels during the day. Fluctuation in glucose concentration in insulin-dependent diabetics was about three times that found in non-diabetic women of similar gestation, with relative hyperglycaemia during the day and hypoglycaemia at night. In non-diabetic women and those with chemical diabetes the mean dirunal glucose correlated closely with the total area under the three-hour oral glucose tolerance curve and significantly, but less closely, with the two-hour glucose tolerance test value.


Carbohydrate metabolism in pregnancy. Part II. Relation between maternal glucose tolerance and glucose metabolism in the newborn. The objective of clinical management of the pregnant diabetic woman is to prevent the serious adverse effects of an abnormal glucose environment on the fetus. Neonatal glucose assimilation and insulin release over the first two hours of life were correlated with various indices of maternal carbohydrate metabolism in the third trimester. Of the 31 mothers studied 21 were defined as normal and 10 as having chemical diabetes. Neontal glucose assimilation during the first two hours of life correlated strongly with functions of both maternal glucose tolerance and mean diurnal glucose level, the strongest correlation being with the area under the three-hour oral glucose tolerance curve (P less than 0.001), Two-hour neonatal plasma glucose values of under 1.7 mmol/1 (30 mg/100 ml) were found only in the newborn of women whose glucose tolerance area measured over 41.6 area units (750 traditional units); thus, even in the borderline diabetic range glucose tolerance testing during the last trimester of pregnancy may be valuable in predicting likelihood of neonatal hypoglycaemia. The findings also shed light on the possible sensitizing role of mild maternal hyperglycaemia on fetal insulin production and secretion.


Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Eight mug of 6-hydroxydopamine (6-OHDA) injected bilaterally into the nucleus accumbens septi (NAS) or the caudate nucleus of the rat resulted in 79% and 50% depletion of endogenous dopamine (DA) at these respective sites. Fourteen days after the injection a low dose of amphetamine failed to induce the characteristic locomotor response in the NAS-lesioned rats but did so in the caudate-lesioned animals. By contrast the caudate lesion, but not the NAS lesions, abolished intense forms of stereotyped behaviour induced by higher doses of amphetamine. Both lesioned groups exhibited supersensitivity to the dopamine agonist, apomorphine; the NAS group showed enhanced locomotor activity and the caudate group enhanced stereotyped behaviour. The block of amphetamine locomotion and the enhanced response to apomorphine were maximal around 14 days after the operation and gradually attenuated up to 90 days. Theer is evidence that remaining DA levels in the NAS are greater at 90 than at 14 days postoperatively. Thus recovery of behavioural effects correlated with an increase in the remaining levels of DA in the NAS.


Behavioral effects in rats following intrastriatal microinjection of manganese. We have demonstrated that injection of manganese into one caudate nucleus in rats results in a predominant ipsilateral turning behavior, accompanied at higher doses by an intermittent, alternating and dose-related incidence of contralateral turning and stereotypies. Although the pharmacological evidence produced (effect of alpha-MT, L-DOPA, pargyline) indicates a definite participation of the dopaminergic system in the latter two phenomena, it is probable that ipsilateral turning is the result of involvement of other transmitter systems as well. Tegmental serotoninergic and intrastriatal cholinergic pathways appear to be involved in the production of the basic postural asymmetry resulting in turning. The amount of interference with the nigrostriatal and mesolimbic dopaminergic pathways may determine the speed of circling, and the concurrent inhibition of locomotion. This is more evident with bilateral injections. Manganese appears to act at presynaptic levels within the striatum by blocking release of the transmitter, thus creating a localized, relative deficit in caudate function. The end result is the release of the dominant "ipsilateral syndrome-inducing system' from its inhibitory control. Repeated or chronic administration of this metal in man or animals is known to result in a brain dopamine and/or serotonin deficit commensurate with the clinical manifestations of bradykinesia and dystonia. Our results are compatible with the anatomical findings of Poirier and collaborators and tend to support the dual ipsilateral and contralateral syndrome-inducing systems in the caudate postulated by Cools, and the complementary roles of dopamine, serotonin and acetylcholine within that nucleus. No one transmitter is involved alone in the experimental production of the manganese syndrome, or of its component symptoms.


Testosterone metabolism in benign and malignant breast lesions. Tissues from a variety of breast lesions were incubated with 14C-testosterone (17beta-hydroxy-4-androsten-3-one). Conversion to 14C-5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and 14C-androstenedione (4-androsten-3,17-dione) was measured. Normal breast tissue showed formation of 14C-androstenedione but no formation of 14C-5alpha-dihydrotestosterone. Fibroadenomas showed a high degree of testosterone metabolism forming both 14C-androstenedione and 14C-5alpha-dihydrotestosterone. The adenocarcinomas of the breast, contrary to a previous report in the literature, showed no conversion to 14C-5alpha-dihydrotestosterone. The data suggest that formation of 5alpha-dihydrotestosterone is a predominant metabolic pathway in fibroadenoma.


Ph1-positive megakaryoblastic leukemia.

Ph1-positive megakaryoblastic leukemia. A case of megakaryoblastic leukemia is presented. Megakaryoblastosis and erythrocytic hyperplasia of the bone marrow, thrombocythemia, and hepatosplenomegaly were the essential features; 100% of the marrow-derived metaphases were found to be Ph1-positive. Cytologic and chromosomal findings are compatible with the assumption that all three marrow systems were involved in the leukemic process.


External beam radiation therapy of primary carcinoma of the prostate. During the past 10 years, some 15 publications have appeared in the English literature on the definitive radiotherapy of prostatic cancer. The long-term followup required for rational assessment of the treatment of prostatic cancer is not yet available for most of these studies. However, in the Stanford series, the direct disease-free survival at 5 years for patients with disease localized to the prostate is 70%; at 10 years, 42%. The direct disease-free survival at 5 years for patients with extracapsular extension in 36%, and at 10 years, 29%. Recently, mapping of potential lymph node metastases has been studies by several authors.Early results of extended-field irradiation required for regional treatment are presented.


Immunosuppression in primary liver and colon tumor induction with N-hydroxy-N-2-fluorenylacetamide and azoxymethane. The question was examined as to whether immunosuppression in a rat model system would affect the carcinogenic processes leading to tumors in the liver and the large bowel. The protocols were designed to detect an increased incidence or a shorter latent period stemming from a change in immune status. Groups of rats were given injections prior to initiation of the carcinogen regimen and continuously thereafter with a purified gamma fraction of antilymphocytic serum (ALG). Appropriate controls received the gamma fraction of normal rabbit serum or 0.9% NaCl solution. Permanence of skin allografts showed that ALG was an effective immunosuppressive treatment. For liver cancer induction, rats were fed 120 ppm N-hydroxy-N-2-fluorenylacetamide in the diet for 16 weeks, then were continued on control diet. The animals given ALG developed liver tumors at a rate similar to that of controls. For cancer of the large bowel, rats received a single s.c. dose of 7.5 mg azoxymethane per kg per week for 16 weeks and were then held on control diet. With an identical ALG treatment, there were fewer intestinal tumors in the early part of the treatment, because of the important early development of liver angiosarcoma, not seen in control rats given injections of 0.9% NaCl solution. At a later time, the incidence of intestinal cancer was similar in rats on ALG or on 0.9% NaCl solution. Thus, immunosuppression had little effect on the rate of liver tumor formation with a liver carcinogen. Also, ALG led to the precocious development of liver angiosarcomas, but failed to affect intestinal cancer induction in animals given azoxymethane.


The amino acid sequence of thymopoietin II. The amino acid sequence of bovine thymopoietin II is presented. This T cell differentiating hormone of the thymus is a single 49 amino acid polypeptide chain of 5562 daltons. There is microheterogeneity at the C terminus with approximately two thirds of the molecules lacking the C terminal arginine found on the remaining molecules. Determination of the primary structure of thymopoietin II was facilitated by a long automated sequenator run on thymopoietin II coupled to 2-isothiocyanonaphthalene-4,8-disulfonic acid (NITC), tryptic cleavage of maleated thymopoietin II to yield the overlapping C terminal peptide, and efficient manual sequencing of this peptide using benzene extractions to minimize extractive losses of peptide.


Structural organization of the genome of the cellular slime mold Dictyostelium discoideum: interspersion of repetitive and single-copy DNA sequences. The length and interspersion of reiterated and single-copy DNA sequences in Dictyostelium have been examined. The results indicate that approximately 50-60% of the single-copy sequences in DNA fragments 1500 nucleotides long and 75% of the single-copy sequences in fragments 3000 nucleotides long are linked to short interspersed repeat DNA sequences. The average length of these single-copy sequences is 1500 nucleotides. The length of the reiterated DNA has also been analyzed and shows a bimodal distribution. One half is present in sequences greater than 2000 nucleotides long, while the remainder is present as short fragments 250-450 nucleotides long. These shorter fragments are interspersed with the bulk of the single-copy DNA.


Simultaneous operative correction of aortic valve stenosis and idiopathic hypertrophic subaortic stenosis. Idiopathic hypertrophic subaortic stenosis (IHSS) may coexist with aortic valve stenosis (AVS). This combination of lesions is uncommon and may not be identified by the usual preoperative clinical evaluation and laboratory studies including cardiac catheterization. Surgical relief of AVS without concomitant septal myectomy to relieve unrecognized underlying IHSS may be followed by a low cardiac output, evidence of residual outflow tract obstruction, and death. Echocardiography (ECHO) will accurately identify IHSS and should be performed in all patients suspected of having AVS. This report describes the first three patients in whom the preoperative diagnosis of both AVS and IHSS was made and who subsequently had both lesions corrected at the same operation. All patients survived operation. The outflow tract gradient was abolished in two patients and significantly reduced in the third. All patients with this combination of lesions should be offered operation for the same indication as isolated aortic valve stenosis. The operation should include a septal myectomy as well as relief of the aortic valve stenosis.


Behaviour of doxycycline in the tissues. Little is known about the behaviour of antibiotics in the tissues. To investigate this problem, rats were sacrificed in groups of six, 1, 2, 4, 6, 8, 12 and 18 h after an intraperitoneal injection of 10 mg doxycycline/kg body weight. The antibiotic levels were determined in the nine major organs and in the serum by a microbiological method. One hour after injection, the doxycycline concentrations in all the tissues were already higher than the serum concentrations. After 4 h, the concentration exceeded 2.5 mug/ml in the lungs, muscles, testes and heart, and were much greater in the excretory organs: 11.4 +/- 4.1 mug/ml in the liver, 10.2 +/- 1.6 in the renal medulla and 27.8 +/- 7.0 in the renal cortex. Throughout the experiment, the lung and muscle concentrations were about double the serum concentrations, and this occurred with great regularity. Doxycycline is thus capable of penetrating extremely rapidly and intensely into tissues, while still retaining a great degree of freedom of movement between plasma and tissues.


[Diagnostic criteria of idiopathic hypertrophic subaortic stenosis in the echocardiogram(author's transl)]. Idiopathic hypertrophic subaortic stenosis (IHSS) is morphologically characterized by ventricular septal hypertrophy. It is asymmetrical because there is no corresponding hypertrophy of the posterior wall of the ventricle. The proportion between septal thickness and posterior wall thickness is more than 1.2. In addition, the anterior mitral leaflet moves towards the ventricular septum during the ventricular systole. Finally, the aortic cusps may close prematurely, even during ventricular systole, if there is a marked outflow-tract obstruction. The thickness of the septum and posterior wall, as well as the movement of the mitral and the aortic valves, can be easily registered by the echocardiograph. IHSS is, therefore, more easily diagnosed by this non-invasive method than by any other method. The echocardiogram demonstrates (1) asymmetrical septal hypertrophy, (2) anterior movement of the anterior and frequently also the posterior mitral leaflet in midsystole, (3) partial or complete closure of the aortic valve in mid-systole, (4) relatively small end-diastolic and systolic diameters of the left ventricle, (5) delayed early-systolic closure movement of the anterior mitral leaflet in the sense of a functional mitral stenosis, (6) decreased systolic septal movement.


[Platelet dysfunction as a result of inhibition of ADP release (aspirin-like defect) in two identical twins(author's transl)]. An abnormal release of platelet adenosine diphosphate (ADP), as seen after intake of acetylsalicylic acid, was demonstrated to be the cause of a clotting disorder in two identical female twins. The signs of bleeding occurred at the age of 26 and consisted of an increased frequency of haematomas, hypermenorrhoea not explained on gynaecological grounds, and prolonged bleeding after minor injuries. Increased bleeding time, abnormal aggregation after stimulation with collagen and absence of the second aggregation phase after addition of ADP were the abnormal findings of this clearly hereditary form of platelet dysfunction. The platelets were slightly larger than normal ones and there were changes in ultrastructure.


Relationship of steroid structure to induction of chymotrypsinogen in embryonic chick pancreas in vitro. The effect of steroid structure on induction of chymotrypsinogen in embryonic chick pancreas was examined in vitro. In order of decreasing potency cortisol, corticosterone, and 21-deoxycortisol are classified as optimal inducers, whereas 11beta-hydroxyprogesterone, 11-deoxycortisol, cortisone, 11-deoxycorticosterone and 17-alpha-hydroxyprogesterone are classified as suboptimal inducers. Progesterone was inactive. It is concluded that the relative importance of the steroid hydroxyl groups for activity is 11beta greater than 21 greater than 17 alpha, and that their effect is cumulative.


[Spontaneous infection of Hymenolepis nana in hamsters (author's transl)]. Hymenolepis nana (von Siebold, 1852), the dwarf tapeworm causing hymenolepiasis, has been reported to be the common intestinal cestode of rodents and man throughout the world. The authors found spontaneously occurred hymenolepiasis in conventional laboratory hamsters with mass and heavy infections. Some individuals were infected with as many as 188 to 290 worms and in addition, numerous cysticercoids were found in the intestinal villi from the same hamsters. According to the early investigations it is said that there are two ways of infection to rodents. In this study the authors considered a natural autoinfection is to be the case because cysticercoids and immature worms were abundant in the intestines of hamsters. The infection rate of the hamsters was 15% as 6 hamsters were found infected out of 40. All the cases of the heavily infected hamsters showed showed loss of weight and some of them died. Particular damage of the intestinal mucosa was not seen by post-mortem examinations, however, chronic inflammation and destruction of intestinal mucosa caused by the worms observed microscopically (the given pictures). Heavy infection of Hymenolepis nana occurred spontaneously in hamsters has rarely been found in Japan. The case reported here seems to be very peculiar one.


[The effect of nasal obstruction on the susceptibility of mice to noxious gases (author's transl)]. The effect of nasal obstruction on mice--the maice were forced to breathe through the mouth--was studied when the animals were exposed to noxious gases. It was noted that the forced mouth breathing made the mice less vulnerable to hydrogen sulfide, carbon monoxide and toluen vapor when expressed by the time interval before they lost righting reflex or showed respiratory arrest. The levels of the gases which could induce these sings within 5-10 minutes were significantly elevated with the "mouth breathing" mice. Possible mechanisms for this phenomenon and its application for men were discussed.


[Normal prenatal growth of the golden hamster (author's transl)]. In the golden hamster (Mesocricetus auratus) the gestation period and the loculus size of the gravid uterus from day 6 to day 15.5 (parturition) of gestation as well as the weight, width (umbilcus-black) and lenght (crown-rump) of the embryos from day 9 to the parturition were measured. The results obtained were as follows: 1. The gestation period of the golden hamster was 15 days and 15 +/- 3 hours post coitum. 2. The average values of the length (in the direction of uterine long axis) and width (mesome-trial-antimesometrial axis) in the loculus of the gravid uterus were 0.39 cm and 0.56 cm at 6 days, and 2.42 cm and 1.74 cm at 15.5 days (partiurition), respectively. 3. The average values of the crown-rump measurements, width (umblicus-back) and weight in the hamster embryos were 0.42 cm, 0.24 cm and 0.026 g at 9 days, and 2.40 cm, 1.39 cm and 2.272 g at 15.5 days (parturition), respectively. 4. The loculus size of the gravid uterus, the crown-rump measurements and width (umblicus-back) of the embryos in the period from day 13 to day 14 of gestation were markedly increased in comparison with any other period, and the weight increase of the embryos occurred rapidly from day 13 of gestation. 5. The shape of the loculus during the gestation was ovoid (mesometrial-antimesometrial axis) until the end of 10 days converged to the spherical form and thereafter changed gradually to the ovoid from in the direction of uterine long axis contraly to the previous days.


[Present status of experimental animals in Japan (author's transl)]. The movement for modernization of experimental animals in Japan started around 1950. Since that time, a quarter of a century has passed. This article outlines the present status of experimental animals in Japan and makes comparisons with various other countries. Number of animals used: According to three surveys performed in the past (1956, 1960 and 1970), the numbers used of many species are increasing (Table 1). However, it can not be said simply that the numbers are increasing every year. Taking the United States where surveys are performed every year as an example (Table 3), it is evident that the peaks for use of some species are past (the same tendencies were seen in India and Sweden which have conducted more than four surveys in the past (Table 4). The same tendencies would probably also be seen in Japan if surveys were conducted annually. Quality of animals: It is easy to procure genetically and microbiologically controlled rats and mice. However, investigations into the establishment, production and supply of other species of such high quality are insufficient. This situation is almost the same as that in European countries. Miscellaneous: The present status of other items related to experimental animals is as follows: Facilities and equipment: Higher level facilities were first provided in companies, followed by testing and research institutes. At present, medical universities are providing such facilities. Feed: Pellet type diets are widely used for the various species. Care and management: In April, 1974, "The Law for the Protection and Control of Animals" came into force. This law includes regulations concerning animal experimentation but investigations concerning these standards have just begun. Training of technicians and specialists: The Japan Experimental Animal Research Association provides a correspondence course, tests and recognition for technicians. About 10 veterinary colleges have undergraduate or postgraduate courses for the training of specialists but these are elective except in two or three cases.


Trehalose of Culex pipiens fatigans.

Trehalose of Culex pipiens fatigans. Trehalose was found to occur in the mosquito, Culex pipiens fatigans, to the extent of 23 to 49% of total free sugars in different developmental stages of the insect. Induction of stress to the insects led to significant reduction in the trehalose of larvae and glucose of adults. The label from alpha,alpha'-U-14C-trehalose readily incorporated into lipids of the adults in which triglycerides seemed to undergo rapid turnover.


A preliminary report on the fine structure of Tripneustes esculentus eggs. The fine structure of Tripneustes esculentus eggs was studied with the aid of an electron microscope. Cells obtained from this West Indies sea urchin showed cortical granules, mitochondria forming a rosette around lipid granules, endoplasmic reticula, Golgi apparatus and annulated lamellae. These structures appear identical to those seen in eggs of the Atlantic sea urchin: Arbacia punctulata.