[Treatment of extreme obesity in a case of Prader-Willi-Labhart-syndrome (author's transl)]. A boy 14 years of age, weighing 93,45 kg and 143 cm in height was refered to our clinic with hyperphagia and pain in the joints. The patient showed the Prader-Labhart-Willi-syndrome. Through maximal diet therapy, 2 admittances in our ward and through intensive psychological outpatient care, we have seen a weight loss of 26 kg in 18 months and clear improvement in the patient's health. We would like to draw attention to the fact that a weight reduction diet is a cooperative family effort. To satiate uncontrollable hunger an intermittent dose of Fenfluramine (0,5 mg/kg) is recommended.


[Investigation of the frequency of heterozygotes for galactose-1-phosphate-uridyl-transferase-deficiency(galactosemia) in the Vienna area. Comparison with the frequency of homozygotes found by newborn screening (author's transl)]. By routine newborn screening for galactose blood level elevations a great difference in the frequency of Galactosemia by transferase deficiency was observed between Eastern- and Western-Austria. This made enzymatic heterozygousity determinations desirable. At the same time it should be examined whether the frequency of homozygotes found by screening correlates with the frequency derived from the heterozygousity frequency. In a first step the region of Vienna was studied. 377 unselected blood samples were examined following BEUTLER-BALUDA's method. As technical control samples of 9 homozygotes and 12 heterozygotes as found by screening were examined but not included in the frequency study. Arranged following age groups a slight but significant decrease of enzym activity with increasing age could be confirmed (23,89 versus 21,99 U/g Hb). This, increasing the overlapping between normals and heterozygotes of different ages possibly should be kept in mind in individual heterzygousity determinations. The enzymatically determined frequency of heterozygotes was found to be twice as high as the frequency calculated from the frequency of biochemically detected but enzymatically proven homozygotes (1:53 versus 1:99). A comparison of the heterozygousity frequencies found in literature with the results of the most efficient (technically most reliable) screening programs shows that this discrepancy is great and general. Bases on heterozygousity frequencies the frequency of homozygotes found by screening programs seems to be at least 50% too low. Analysis of theoretical possibilities for loss of homozygotes by screening programs makes this explanation highly improbable. It seems more probable that the enzymatically determined heterozygotes frequency is too high by including still undefined allels or allel combinations which result in about half normal activity but not in disturbances resembling classical Galactosemia.


[A simple thin-layer chromatographic assay of urocanic acid in the stratum corneum for evaluation of skin histidase activity (author's transl)]. A simple and rapid urocanic acid estimation by mean of TLC as an indirect assay for skin histidase activity is described. Very small amounts of stratum corneum (about 1 mg) are eluated in concentrated NH3, 5 mul of the eluate were chromatographied and stained with Pauly's reagent. Investigations were done in 76 healthy persons, 17 heterocygotes and 24 children with histidinemia. In 18 histidinemic children urocanic acid was found not at all, in 5 as a trace and in 1 - at the age of 24-28 months. - as a nearly normal concentration. In 11 children with histidinemia and 3 controls the results of our method are compared with these of direct enzyme activity essay and a good correlation could be shown. Identification of heterocygous is not possible.


[Routine screening for inborn errors using urine filterpaper specimens at age 4-5 weeks (author's transl)]. Since 1972 we have been using a urine screening for the detection of inborn errors of amino acid metabolism, which cannot be revealed in newborn-blood-screening with Guthrie's bacterial inhibition assay. It is performed at an age of 4-6 weeks by means of thin layer chromatography of urine specimens collected on filter paper using a method adapted by us for mass-screening. We tested 70,400 newborns and found 59 cases of incomplete Cystinuria, 9 of Prolinuria, 3 of Histidinaemia and one each of Hartnup disease, Alkaptonuria, Glycinuria and Hydroxyprolinuria. The problems of the disorders found are discussed. Comparison with newborn-blood-screening that 3 cases of Histidinaemia, proven by enzyme assay were missed by newborn-blood-screening because of their (still low) low blood levels. On the other hand we did not find additional cases of phenylalanine-metabolic disorders. These cases were probably all already detected by newborn-blood-screening. Homocystinuria, Maple syrup urine disease and Arginino-succinicaciduria which are rare diseases were neither found in the urine or blood tests. As disorders, detectable by means of urine screening exclusively and curable, are rare urine screening has to be reevaluated for its usefulness.


[Wilson-Mikity-syndrome in twins (author's transl)]. The course of a Wilson-Mikity-syndrome in biovular twins born 19 weeks prematurely is reported. The disease started in the second week of life, reached its peak in the ninth week and it was complicated by a bronchopneumonia as well as a spastic bronchitis resulting in cardiac failure in both infants. On infant suffered spontaneous fracture of the ribs. Both patients were stationary for 26 weeks and 31 weeks respectively. A routine-examination at the age of 1 year revealed still distinct lung abnormalities, but nevertheless showing a tendency of improvement. Signs of right ventricular hypertrophy were found in the ECG of both children but more distinctly in the girl. The neurological development of the infants were found to be normal.


[New aspects of the feeding of the newborn and young infant (author's transl)]. A classification of formulas with defined compositions of their nutritive substances into 3 groups has been made in the Federal Republic of Germany with the objective to achieve a standardization. It is differentiated between adapted, partially adapted, and non-adapted formulas. As defined, the composition of adapted formulas is closest to human milk. Since adapted formulas are thought to be of physiological value, one is surprised by the fact, that shortly after discharge from the maternity hospital partially adapted or nonadapted formulas are favoured by a high percentage (of mothers). The reasons for this are analyzed. By the end of the third month of life the premature infant is depending on the administration of iron. At this time signs of a more or less latent iron deficiency are developing. In the full term infant this condition will be reached approximately by the age of six months. Since iron-salts may interfere with the vitamin E supply in the premature infant, one should either administer a water soluble vitamin E preparation or the necessary iron prophylaxis should be started in these children only in the third month of life.


[On "gespür" (author's transl)].

[On "gespür" (author's transl)]. The term "Gespür" frequently used by H. ASPERGER is analyzed by the author. Predispositions for perceptual abilities and formal interpretation of expression and behavior, their ontogenetic and phylogenetic background are examined as well as defects (lack of sensitivity for expression), and their consequences for subjects involved. The questions of trainability and differentiation to parapsychological phenomena are also discussed.


[Training and further education in pediatrics: experience and models in Austria (author's transl)]. A new legal standard was destined for the postgraduate medical training in Austria in 1973. Details and the practical application of this regulation concerning the pediatric specialty are discussed. Special emphasis is given to the need for better integration of the didactic technics in the teaching methods of university hospitals. A special board examination is still point at issue, but should be established in the near future.


[The mother and her sick newborn (author's transl)]. The care of the mother during the pre- and postnatal period is of great importance not only for the act of birth but also for the establishment of the mother child relationship. There are indications that the quality of mothering during later childhood is determined by the way the mother child relations are established during the first days of life. It is important to realise the needs of the mother to see and to touch her child and to enable her to do so as often as possible even if this child is under special care. In cases of neonatal illness the mother especially needs the psychological help of her doctor and the nurses. The professional persons can provide this help better if they are aware of the normal reactions of the mother to neonatal illness or even death of her child.


[Long-term-follow-up-study after measles-vaccination (author's transl)]. Following a first field trial in the year 1966 a second field trial was carried out in the Pediatric Clinic of the University of Vienna in the years 1967 und 1968, in which 420 children were vaccinated against measles by various methods. Apart from the observations of the clinical reactions the chief purpose of the examination was to establish the height of the antibodies achieved, how long they persisted and whether the primary vaccination with split-vaccine had any influence on the level and persistance of antibodies. The results following the combined vaccination were compared with those following with Schwarz-strain alone, whereby no significant differences appeared. The serological follow-up examinations were made after a month, a year, after 3 and finally after 7 years. Whilst in the first year the combined vaccinated children showed an average higher titre, the average antibody titre following single live vaccination were somewhat higher after 7 years and showed a lesser degree of scatter. The values of antibody titres are impart so high that one has to assume a silent booster effect since none of the examined children were taken ill with measles. The single live vaccination by means of Schwarz-vaccine has thus been proved outstanding, is to be regarded as the general method of choice and should be applied as widely as possible since the morbidity risk of measles is considerably high and vaccination is not dangereous. The use of split-vaccine is indicated only with chronically ill children for instance with leukaemia, mucoviscidosis etc. and in infants in the first year of life, if one wants to protect them against measles. If we reach our aim of through-vaccination of the population against measles, infants will no longer be in danger and a prevaccination in the first year of life will not be indicated.


[The disseminated intravascular coagulation (dic) from a pediatric point of view (author's transl]. A review of our knowledge of causes and consequences of disseminated intravascular coagulation (DIC) on hemostatic functions and clinical manifestations is given, based on experiences in a children's hospital in collaboration with a central laboratory for blood coagulation. The problems of early diagnosis, starting and guidance of therapy are especially stressed.


[Smallpox vaccination in a country district (author's transl]. This survey deals with the matter of smallpox vaccination (serum, complications, age, degree of immunity, compulsory vaccination) also with the percentage of first vaccinations, booster vaccinations of children with birth years from 1962 to 1974, as well as the vaccination coverage of 2000 adults within a district. The survey showed a high degree of first vaccination coverage and a satisfactory percentage of booster vaccinations. Of the 2000 adults interviewed 19% had never been vaccinated, 54% ten or more years ago, 17% between the last 3 to 10 years, and only 10% had been vaccinated within the past three years. As a minimum safety measure it is requested that persons who could be exposed to smallpox (public servants, medical officers, flight personnel) be satisfactorily immunized against the disease.


Developmental characteristics of pulmonary superoxide dismutase: relationship to idiopathic respiratory distress syndrome. Pulmonary superoxide dismutase (SOD) acitivity was determined for various groups of human fetuses, infants, and adults. Enzyme activity was found to increase with age from a low of 17 +/- 1 units/mg DNA in fetal lung to 49 +/- 6 units/mg DNA in infant lung and finally to 110.2 +/- 14.8 units/mg DNA in adult lung (P less than 0.05). No difference in lung SOD activity was demonstrated between normal infants and those with idiopathic respiratory distress/hyaline membrane disease (IRDS/HMD). No significant differences in SOD activity were found among all the samples of infant blood. Adult blood samples, however, contained significantly greater SOD activity both in terms of heme concentration and volume of whole blood (P less than 0.05). SOD activity in lung tissue from both rats and rabbits were also found to increase with age from a low value in fetal animals to a maximum activity in adults (P less than 0.05). Exposure of New Zealand White rabbits, prematurely delivered by caesarian section, to 80% oxygen for 24 hr resulted in a 42% increase in lung SOD activity. Similarly, 7-day-old Sprague-Dawley rats exposed to 85% oxygen for 24 hr showed a 43% increase in pulmonary SOD activity. No increase in pulmonary SOD was observed when adult rats were exposed to 85% oxygen for 24 hr. The effect of hyperoxia on SOD activity in excised lung was investigated. Rat lung, incubated in either heparinized whole blood or in plasma and exposed to 100% oxygen, showed a 30% increase in SOD activity after 2 hr. This capacity of lung tissue to respond to hyperoxia in vitro with increased SOD activity was age dependent. The maximum increase in SOD activity was seen with lungs from 10-12-day-old rats. The oxygen-stimulated increase in lung SOD activity disappeared at about 19-20 days of age.


Conditioning as sensitization.

Conditioning as sensitization. The concept of sensitization has a long history in psychology, and on both empirical and logical grounds it has been argued that sensitization and conditioning denote different neurophysiological processes. Investigators have devised elaborate control procedures that purport to differentiate sensitized and conditioned responses. But, mainly on logical grounds, it is argued that there is no valid basis for considering sensitization and conditioning as separate processes. A theory of learning is proposed in which sensitization is the basic construct.


Utilization of dietary amino acids for energy production in neonatal rat liver. The 3-day-old rat has a high basal level of phosphoenolpyruvate carboxykinase (PEPCK), the activity of which is not increased upon starvation. The lower basal activity of the enzyme in 19-day-old rat liver can, however, be stimulated by starvation. Serum glucose levels increased from 3 days to 19 days of age, with a decrease to adult levels. Liver glycogen concentration increased from 3 days to 19 days of age, with no additional increase observed at 3 months. There was a decrease with age in the specific activity of liver glycogen (from [14C]alanine and [14C]leucine). In fed rats given [14C]alanine, 14CO2 expiration tended to decrease with age. The 14CO2 production from [14C]leucine was less than that from alanine, and also decreased with age. Three-day-old rats showed no change in serum glucose when starved for 4 hr. On the other hand, 19-day-old rats responded with a decrease in serum glucose; although the adult animal's basal level of serum glucose was less than that of the 19-day-old rats, starvation for 15 hr also caused a significant decrease. There was no statistically significant difference in liver glycogen concentration between the fed and starved 3-day-old animals. Liver glycogen concentration in the 19-day-old adult rats was affected, however, by starvation. The 3-day-or glycogen during starvation. Starvation resulted in a tremendous increase in the specific activity of hepatic glycogen in the 19-day-old and adult rats. Starvation decreased the percentage of labeled amino acid expired as 14CO2. The proportion expired also decreased with age. Urinary nitrogen concentration increased significantly between 3 and 19 days of age. Starvation produced differential effects in the animals, with no change being observed in either the 3-day or adult rats; a decrease was observed in the 19-day-old animals. Urinary nitrogen concentration was measured in adult carbohydrate-deprived rats and was significantly higher than control values. These rats had a high gluconeogenic rate, reflected in the increased urinary nitrogen concentration. The young rat is at the mercy of a continuous supply of substrate in that it has a limited capacity for directing substrat


The behavioral specificity of stimulation: a systems approach to procedural distinctions of classical and instrumental conditioning. This paper presents a new methodological approach to classical Pavlovian investigations. Using a yoked group for stimulus pairing trial pacing, behavioral occurrence frequencies, sequential behavior patterns, and behavioral change dynamics are analyzed for rats in both a non-discriminative and a general setting discrimination paradigm. Theoretical issues addressed by a variety of new dependent measures are discussed, and a special emphasis is placed on comparing instrumental and classical procedures as viewed from the behavioral perspective of the subject.


Umbilical cord cutting triggers hypertriiodothyroninemia and nonshivering thermogenesis in the newborn lamb. The present studies in the newborn sheep were undertaken to further clarify the mechanism or mechanisms for the early increases in serum thyroid hormone concentrations in the newborn as well as the significance of these changes to newborn nonshivering thermogenesis.  Six groups of animals were studied to determine the influence of neonatal cooling, cord cutting, and the effects of thyrotropin-releasing hormone (TRH) and triiodothyronine (T3) injections.  Group I newborns were delivered into room air with immediate cord cutting.  Group II animals were delivered into room air and cord cutting was delayed 60 min.  Group II animals were delivered into a 39 degrees water bath and maintained for 60 min with the umbilical cord intact; the cord was cut at the time of removal from the water bath...


Absence of a serum factor in patients with cystic fibrosis. A serum factor was demonstrated in normal individuals which (1) enhances the incorporation of L-[3H]fucose into cultured human skin fibroblasts, (2) is nondialyzable, (3) is heat labile at 50 degrees, (4) is present in the noneuglobulin fraction, and (5) appears to be deficient in serum from patients with cystic fibrosis. The specific activity of L-[3H]fucose incorporated into skin fibroblasts from normal individuals in the presence of serum from 12 control subjects was 3,337 +/- 168 cpm/mg protein in contrast to 2,294 +/- 172, the activity obtained either in the presence of serum from 10 age-matched patients with cystic fibrosis or in the absence of serum. These differences were significant at P less than 0.001. In comparison, no significant difference was detected in the amount of L-[3H]fucose incorporated into skin fibroblasts derived from normal individuals and patients with cystic fibrosis. The plasma membrane of cultured skin fibroblasts derived from patients with cystic fibrosis appears to be grossly unaltered in its protein and L-fucose labeling pattern.


The Pavlovian analysis of instrumental conditioning. An account was given of the development within the Russian literature of a uniprocess formulation of classical and instrumental conditioning, known as the bidirectional conditioning hypothesis. The hypothesis purports to offer a single set of Pavlovian principles to account for both paradigms, based upon a neural model which assumes that bidirectional (forward and backward) connections are formed in both calssical and instrumental conditioning situations. In instrumental conditioning, the bidirectional connections are hypothesized to be simply more complex than those in classical conditioning, and any differences in empirical functions are presumed to lie not in difference in mechanism, but in the strength of the forward and backward connections. Although bidirectional connections are assumed to develop in instrumental conditioning, the experimental investigation of the bidirectional conditioning hypothesis has been essentially restricted to the classical conditioning operations of pairing two CSs (sensory preconditioning training), a US followed by a CS (backward conditioning training) and two USs. However, the paradigm involving the pairing of two USs, because of theoretical and analytical considerations, is the one most commonly employed by Russian investigators. The results of an initial experiment involving the pairing of two USs, and reference to the results of a more extensive investigation, leads us to tentatively question the validity of the bidirectional conditioning account of instrumental conditioning.


Insulin, a possible regulator of ketosis in newborn and suckling rats. A possible regulatory role of insulin in the development of ketosis in newborn and suckling rats was investigated. The average plasma concentration of total ketone bodies measured at birth was 0.414 +/- 0.037 mumol/ml. Within 24 hr after birth the level of ketones had increased to 4 times its initial value. The 3- to 4-fold increase in plasma ketones was maintained during the first 5 days of life but started to decline thereafter. Plasma insulin of newborn rats at birth (62 +/- 8 muU/ml) was comparable to that of fed adult rats (85 +/- 10 muU/ml). The levels decreased to 28 muU/ml on the first day of life and stayed low throughout the suckling period despite a tendency to increase at the time close to weaning. The capacities for ketone production in liver homogenates of suckling rats was inversely related to the levels of insulin. Administration of insulin (0.125 mU/g body weight, im) and glucose (1.75 mg/g body weight, ip) both suppressed plasma ketone bodies in suckling rats. Insulin administration increased plasma insulin but failed to decrease plasma glucose. Injection of glucose increased plasma insulin and glucose. Neither insulin nor glucose treatment changed the plasma levels of free fatty acids. These data suggest that a limited availability of insulin permits a high rate of ketogenesis and hence induced ketosis in newborn and suckling rats.


A study of the renal handling of water in lipoid nephrosis. Children with lipoid nephrosis were studies during clinical relapse and after complete remission. As expected, the calculated serum oncotic pressure was reduced severely from the remission value of 28.6 +/- 0.9 mm Hg to 15.4 +/- 1.1 (P less than 0.005) during relapse. Although no apparent change in plasma volume was noted using the volume of distribution of labeled human albumin, calculated plasma volume was reduced 13 +/- 8% during relapse when estimated from changes in hematocrit. After a water load, the ability to excrete water was markedly blunted during relapse. The clearance of solute-free water (CH2O) was 0.9 +/- 0.8 ml/min during relapse, compared with 3.6 +/- 0.6 ml/min during remission (P less than 0.005). In addition, there was a reduced maximal urinary concentrating ability during relapse in four of the six patients examined. Mean urine osmolality for the group during relapse was 778 +/- 82 mOsm/kgH2O and 991 +/- 71 during remission (P less than 0.05). The demonstrated alteration in nephron function during relapse of nephrotic syndrome could result from either (1) a decrease in the amount of sodium delivered to the ascending limb of the loop of Henle because of increased proximal reabsorption or (2) a change in the intrinsic characteristics for sodium reabsorption in that segment. Although this observation does not prove that proximal reabsorption is increased, it suggests a common underlying mechanism for altered nephron function in all of the major edema-forming conditions.


Osteomyelitis: early scintigraphic detection in children. The value of scintigraphy in the early detection of osteomyelitis is demonstrated in children who had signs and symptoms suggestive of bone infection. Nine patients between 2 and 13 years of age were evaluated with technetium Tc 99m diphosphonate bone scintigrams and roentgenograms. Blood cultures were performed in all patients, and bone biopsy or drainage was obtained in six patients. The diagnosis of osteomyelitis was made in seven patients; one patient had a subperiosteal abscess surrounded by osteomyelitis, and one patient had cellulitis. The seven children with osteomyelitis had focal increase of radiopharmaceutical uptake in the bone. The child with the subperiosteal abscess had an area of decreased uptake in the center of the abscess surrounded by a zone of increased uptake of the radioactive bone-seeker. The patient with cellulitis had soft tissue changes by X-ray and a normal bone scintigram. In the seven patients with osteomyelitis, the bone scintigram was performed during the early phase of the disease and no bony changes were present on the roentgenogram. In one patient with subacute osteomyelitis, soft tissue changes were seen radiologically. Only three of the seven children with osteomyelitis developed radiological bony changes. Since bone scintigraphy can detect early local bone derangement, it is recommended in the initial evaluation of children in whom osteomyelitis is suspected.


Effective pulmonary blood flow in preterm and light-for-date infants. Using a method employing low concentrations (3%) of nitrous oxide, we measured effective pulmonary capillary blood flow (Qpc eff) in 23 preterm infants, 26 light-for-date infants, and 15 infants who were both preterm and light-for-date. All infants studied had no clinical or laboratory evidence of idiopathic respiratory distress syndrome (IRDS) and were studied before the age of 48 hours. The mean Qpc eff of 175 ml/kg/min in preterm infants (a group at high risk of developing IRDS), although significantly less than the mean of 214 ml/kg/min found in light-for-date infants (a group with a low risk of developing IRDS), was similar to that reported in normal term infants. The mean result for preterm, light-for-date infants was 189 ml/kg/min. No evidence was found that preterm infants were predisposed to IRDS as a consequence of preexisting pulmonary hypoperfusion.


Respiratory illness in preschool children with different forms of day care. The incidence of respiratory tract disease was investigated in three groups of Swedish children: those in 14 day-care centers with 18 to 68 children each; those in home care (usually no siblings); and those in family day-care homes (average, four children). In family day-care homes a mother cared for her own and one to four other children during the day. A preliminary nine month study of 41 preschool children attending a day-care center and 41 comparable children in home care showed that children under 2 years of age in the center had more days with respiratory symptoms and more febrile illnesses (four per child) than those in home care (one per child). In a subsequent eight-month study of children under 2 years of age, children in day-care centers and home care were compared with children in family day-care homes. The 108 children in centers had more febrile illness (five per child) than the 57 children in home care (two per child), but the 42 children in family day-care homes had as many illnesses as those in day-care centers. The data suggest that increasing the number of contacts of an infant in day care beyond four to six children does not increase remarkably the incidence of respiratory tract disease.


Developmental effects of seizures: role of malnutrition. Eighty-eight rats were paired at birth according to sex and weight. One member of each pair received two electroconvulsive seizures a day during the neonatal period (days 2 to 11). Access of its control littermate to the mother was restricted so that the body weights of any two paired rats never diverged by more than 2 gm on any day of life, and were usually within one half gram of each other. This guaranteed that the nutritional status of seizure-treated and control animals was similar throughout development. On day 30 of life, seizure-treated rats had smaller brains (-56 mg, P less than .05) and reduced numbers of brain cells (-13.10(6), P less than .05) compared to their control littermates. It was concluded that the reduction of brain DNA brought about by neonatal seizures was not simply caused by malnutrition of seizure-treated animals.


Carbohydrate malabsorption in necrotizing enterocolitis. A prospective investigation was conducted to determine if infants with necrotizing enterocolitis had evidence of carbohydrate intolerance prior to the onset of clinical symptoms of advanced disease. Stool specimens were examined for fecal reducing substances with Clintest tablets from well, full-term infants and sick premature infants. Only two of 45 (4.4%) formula-fed, full-term infants demonstrated higher than 2+ fecal reducing substances. Ten of 14 (71%) formula-fed premature infants who developed necrotizing enterocolitis had higher than 2+ reducing substances detected in their stools. Daily measurement of fecal reducing substances can be a useful adjunct in the management of sick premature infants.


Pseudomonas cepacia in an intensive care nursery. A small epidemic of Pseudomonas cepacia infection in an intensive care nursery was associated with contaminated, distilled water. This appeared to have occurred because of a leak in the distiller, contaminating its effluent. The distilled water was not subsequently sterilized, nor were the bottles used to distribute it. The epidemic was promptly terminated by substitution of sterile, distilled water distributed in sterile containers. Both professional and nonprofessional hospital personnel failed to oversee the appropriateness of handling of patient care materials.


Continuous monitoring of arterial oxygen tension using a catheter-tip polarographic electrode in infants. An oxygen electrode mounted in the tip of an umbilical artery catheter was used in 36 newborn infants with severe respiratory illnesses, 28 of whom survived. Thirty-seven electrodes were used. The median age at insertion was 4 hours (range, 30 minutes to 122 hours). Three electrodes failed to work and they were removed or replaced, and two could not be properly evaluated. Thirty-two electrodes functioned satisfactorily for 10 to 190 hours (mean, 75 hours) after a one-point calibration against blood sampled through the catheter. Twenty-two did not need recalibrating before they were removed after 10 to 190 hours (mean, 88 hours. Four of the remaining ten electrodes were recalibrated once after 33 to 97 hours and then functioned until removed 15 to 55 hours later. The other six electrodes failed after 32 to 105 hours (mean, 49 hours). Complications were few. A total of 356 arterial blood samples, obtained after the initial calibration and before any recalibration was necessary, gave a correlation coefficient of 0.93 (P less than .0001) against an independent system for measuring arterial oxygen tension (Pao2) (Radiometer Type E.5046 oxygen electrode). We conclude that the catheter-tip electrode is a safe and reliable instrument for continuously recording Pao2 in newborn infants which much simplifies the management of serious respiratory illnesses.


Carrier detection in classical hemophilia. Rabbit antibody to purified human factor VIII was prepared and absorbed until it formed only one precipitin line against normal and hemophilic plasmas and no line against severe von Willebrand's disease plasma. The plasma protein which combines with this rabbit antibody to factor VIII is referred to as factor VIII antigen. The ratio of percent factor VIII activity (by coagulation assay) to percent factor VIII antigen was used for carrier detection. Thirty-seven normal women, 33 obligate carriers, 12 probable carriers, and 39 possible carriers, were studied by this technique. Using the ratio of 0.84 as the division between normals and carriers, 31 of the 33 carriers (91%) were classified carriers. Twenty of the 39 possible carriers were classified as carriers (51%) and ten of the 12 probable carriers were positively identified. The results of discriminate analysis of all three variables (VIII activity, VIII antigen, and the ratio of VIII activity to VIII antigen indicated that the discrimination power of the ratio alone could not be improved by introducing the other variables on this set of data. These findings confirm the usefulness of the VIII activity to VIII antigen ratio in the detection of carriers of classical hemophilia.


Acute myositis associated with influenza B infection. An epidemic of acute myositis affecting children occurred in association with influenza B infections. The myositis followed the initial influenza-like episode, and almost exclusively involved the gastrocnemius and soleus muscles. Patients improved without specific treatment and made a complete recovery in four to five days. Laboratory studies characteristically showed elevated CPK, SGOT values, and a low peripheral white blood cell count. Influenza B virus was isolated from 11 of the 17 patients studied. This influenza-associated acute myositis of childhood is a recognized syndrome that should not be confused with dermatomyositis.


Multiple gastrointestinal atresias, with intraluminal calcifications and cystic dilatation of bile ducts: a newly recognized entity resemblin "a string of pearls". The siblings reported here represent a new and complex congential anomaly. A genetic basis is strongly suggested. The natural preparation of closed loop duodenal obstruction and cystic dilatation of the bile ducts is a unique finding. The hallmark of this new entity--intraluminal calcifications strung out through small and large intestine like pearls--is a striking radiographic feature and, in the proper clinical setting, pathognomonic. This entity has been uniformly lethal. Once the diagnosis is confirmed, no known therapy is useful.


Bordetella bronchiseptica isolations from the nasal cavity of pigs in relation to atrophic rhinitis. The occurrence of Bordetella bronchiseptica and atrophic rhinitis was studied during a one-year period in four Danish sow herds. In three of the heards, the epidemiological studies revealed a relation between the occurrence of B. bronchiseptica in 3--10-week-old pigs and the presence and severity of atrophic rhinitis at slaughter. In the fourth herd no such relation was found.


The effect of grassmeal and alfalfa meal on daily gain, thickness of backfat and on the esophagogastric region in bacon pigs. In pigs dietary factors often are involved as causes of lesions in pars esophagea of the stomach. In experiments the primary purpose of which was to clarify the effect of grassmeal or alfalfa meal on growth, feed efficiency and carcass quality in bacon pigs, an influence of these feedstuffs on the growth rate and degree of esophagogastric lesions was detected. Pigs with these lesions had as an average a lower daily gain and less backfat than pigs without lesions.


Herd incidence of bovine mastitis in four danish dairy districts. III. Relation between frequency of mastitis and cell counts on bulk molk samples. The correlations between monthly bulk milk cell counts and the actual frequency of mastitis was investigated in 399 Danish dairy farms with a total of about 7000 cows. The correlation coefficients varied from 0.3 to 0.5. Correlations were improved by using more than one cell count, but not further improved by using more than two cell counts. The correlations were higher for large than for small herds. It was not possible by combining cell counts in different ways, as indicated in (Table IV, to point out every heavily mastitis-affected herd without also pointing out some not so heavily affected ones. Table IV shows what infection levels can be expected when different criteria based on bulk milk cell counts are applied. The figures cannot be transferred directly from Danish conditions to conditions in other countries, but similar tendencies can probably be found anywhere.


[The formaldehyde content in fish in relation to anemia in mink (author's transl)]. The fish-induced anemia in mink is an alimentary disease produced by feeding high amounts of some raw marine fishes. The anemiogenic properties of the fish has been related mainly to its content of the iron binding agent-trimethylaminoxide. The aim of the present investigation was to examine how far formaldehyde could also play a part as an anemiogenic factor. The content of formaldehyde has been analysed in all species of raw, cold stored fish known to be used in mink food and in a few samples of ready made food (Table II). The content of formaldehyde varied within wide limits from 12 to 105 ppm, but none of the measured contents reached the high values obtained by Costly (1970). The mean values of formaldehyde in gutted coalfish, fillet waste of coal fish, cod and haddock prepared for the feeding experiments, were all close to 50 ppm. 175 female mink and 632 mits were tested during the whole of the breeding period from 15.2-30.6, 80 per cent of the diet (page 1) was fish products with and without supplements of formaldehyde. Amounts from 200 to 50 ppm were tried (Table I). The supplement of 200 ppm formaldehyde had an appetite-decreasing and anemiogenic effect, but the supplement of 50 ppm, i.e. a formaldehyde content up to the highest value observed in fillet waste, had no effect on appetite or hemoglobin synthesis neither in females nor in kits. This content of formaldehyde did not counteract the anti-anemiogenic effect of iron glutamate. The fish-induced anemia occurred in mink thus appears unaffected by the quantities of formaldehyde found in fish diets to fur bearing animals. Triox must be regarded as the dominant anemiogenic factor in raw fish diets.


Streptoccal infections in pigs. 2. Serological and biochemical examinations. A total of 2,275 strains of haemolytic streptococci (HS) from 1,338 post mortem examined sucking pigs were studied. The serological examination revealed that 43.9 per cent of the strains belonged to group-C and 33.7 per cent belonged to group-L (Table I). Other serogroups amounted to 8.0 per cent and 13.8 per cent of the strains were non-typable. The distribution of serogroups in relation to different organs is presented in Table II. The fermentation pattern of 115 group-C strains against trehalose, sorbitol and lactose was determined (Table III). All but one of the strains appeared to be S. equisimilis. The ability of 127 group-L strains to ferment lactose, hippurate, sorbitol and glycerol is shown in Table IV. Eleven different fermentation patterns were encountered. An antimicrobial resistance pattern was determined for 69 strains (Table V). All the strains, except one, were sensitive to penicillin and chloramphenicol. Only two strains were sensitive to streptomycin. None of the isolated serogroups or biochemical types could be related to a particular pathological lesion or to a particular herd or group of sows within the herd. By comparing the fermentation patterns of the group-L strains isolated from pigs dead with HS infection with those of previously group-L strains from healthy swine, different predominant patterns were found. Possibilities of using these differences in biochemical reactions in separating pathogenic and saprophytic strains are discussed.


Preferential protection of the minor groove of non-operator DNA by lac repressor against methylation by dimethyl sulphate. The binding of lactose repressor to non-operator DNA was studied by the modification of several DNA's, including glycosylated DNA, with dimethyl sulphate, which affects the minor and major grooves of DNA and single stranded DNA regions. The non-specific binding of the repressor to DNA protected the minor groove but apparently not the major groove of the DNA double helix against methylation and did not increase the content of single stranded DNA regions. This suggests that the repressor on binding to non-operator DNA makes contacts mainly in the minor groove of DNA and does not uncoil the DNA double helix. This is different from the interaction of the repressor with lactose operator DNA which occurs, as shown by Gilbert et al. (1), along both the major and the minor groove.


Chemical evidence that chromatin DNA exists as 160 base pair beads interspersed with 40 base pair bridges. Digestion of rat liver nuclei by an endogenous endonuclease generates double-stranded DNA fragments which are initially about 205 base pairs long, as reported previously by Hewish and Burgoyne. As digestion proceeds, the average size of these fragments is reduced to about 160 base pairs. Electrophoresis under denaturing conditions shows that these DNA fragments contain single strand nicks at ten base intervals. Fifteen bands, 10-150 bases, are clearly resolvable. DNA Fragments of 160 to 200 nucleotides are not resolved as distinct species. The results suggest that the chromosomal subunit contains both a 160 base-pair DNA segment, in a conformation susceptible to single strand nicking at ten base intervals, and a forty base-pair DNA segment in a conformation more uniformly susceptible to endogenous endonuclease activity. This chemical evidence agrees with morphological observations suggesting that chromatin has a "bead and bridge" structure.


Cooperative binding of fluorescein-labeled clupeine by DNA. The alpha-amino group of clupeine fraction Z from herring sperm was coupled with fluorescein. Binding of the labeled protamine by DNA is accompanied by significant fluorescence quenching up to 80%. This allowed the convenient determination of the binding behavior of protamine and DNA. Binding was found to be strongly cooperative and not be significantly affected by the size of DNA. The ionic strength dependence in the range up to 0.3 M NaCl was rather small. Binding parameters were derived according to classical unique-site treatment and to a concept which includes vagrant multi-site binding.


Studies on the low molecular weight RNA associated with 28S ribosomal RNA from Crotalus durissus terrificus liver. A low molecular weight RNA was released from the purified rattlesnake 28 S RNA by brief heat treatment as well as by treatment with 80% dimethylsulfoxide or formamide. The sedimentation coeficient of this low molecular weight RNA was found to be 5.5 S, corresponding to a nucleotide number of 140 and a molecular weight of 46 000. It was also observed that 5.5S RNA is present in equimolar ratio to 5 S rRNA. Heat treatment of the purified 60 S ribosomal subunit also released the 5.5 S RNA. The possibility that this low molecular weight RNA is located on the surface of the large ribosomal subunit is discussed.


The use of a dipolar ion-exchanger for the fractionation of transfer ribonucleic acid. Transfer ribonucleic acid is well fractionated on columns of arginine-agarose, whose properties appear in general to be similar to those of DEAE-Sephadex. However, the amino acid acceptor species are separated into sharper peaks and in several instances, notably for methionine, glycine, serine, leucine and aspartate accepting tRNAs from Escherichia coli, isoaccepting species are well resolved. In the case of methionine accepting tRNA from E. coli the tRNA Met-m species is eluted before the tRNA Met-f species and since it is also eluted prior to the bulk of the tRNA it is obtained in a high degree of purity. By comparing the properties of columns of arginine-agarose and its methyl ester in which the carboxylate anion is blocked, it is seen that the carboxylate ion plays a role in the fractionation of the tRNA Met species.


Conformational changes of nucleic acids and poly (d(A-T)-d(A-T)) caused by photoaddition of furocoumarins. DNA's of various AT content, poly[d(A-T)-d(A-T)], and double-stranded RNA were irradiated with UV light at 365 nm in the presence of linear (xanthotoxin) or angular (angelicin) furocoumarins. The covalent photobinding is strongly dependent on the spatial arrangement of furocoumarin molecules at the polymer conformation. CD measurements demonstrate that the bifunctional photochemical binding of xanthotoxin with double-stranded DNA's and poly[d(A-T)-d(A-T)] is accompanied by conformational changes which involve probably decreasing helical twisting of the double helix. This effect is greatly enhanced with increasing AT content. The formation of A-like structures is very unlikely since the B leads to A transition induced by ethanol addition was found to be strongly suppressed in xanthotoxin photoreacted DNA. The B-type helix appears to be the most sensitive conformation with minor restriction to produce photochemically induced cross-links.


Protonated polynucleotide structures. 18. Interaction of oligocytidylates with poly (G). The faculty for and degree of oligo(C)-poly(G) interaction is described as an essentially chain length - sensitive phenomenon. At neutral pH under suitable experimental conditions, oligocytidylates of chain length greater than four associate with poly(G) to form double-stranded structures, as does poly(C). The extent of complex formation increases with degree of polymerization. The complex at acid pH is shown to be triple-stranded, of stoicheometry 2C/1G. The observation of a 2G/1C artifact is discussed.


Thermostable polynucleotide phosphorylases from Bacillus stearothermophilus and Thermus aquaticus. Polynucleotide phosphorylase from Bacillus stearothermophilus has been purified to homogeneity. Polyacrylamide gel electrophoresis run under denaturing conditions indicates that the enzyme is a tetramer with subunits of apparent molecular weight 51,000 daltons. A partial purification of polynucleotide phosphorylase from Thermus aquaticus has also been effected. The two enzymes show similar catalytic properties, which differ little from those of mesophilic polynucleotide phosphorylases. The use of thermostable polynucleotide phosphorylases for in vitro nucleic acid synthesis is discussed.


A new synthesis of inosine from 5-amino-1-beta-D-ribofuranosyl-4-imidazole-carboxamide. Inosine was prepared (15% yield) by treatment of 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (AICA-riboside) with chloroform in the presence of sodium methoxide. This ring closure can be reasonably explained by assuming the formation of dichlorocarbene from chloroform and alkali. Carbon tetrachloride or hexachloroethane as a carbene source was more effective for the ring closure of AICA-riboside, giving inosine in 48% and 51% yields respectively.


Synthesis of guanosine and its derivatives from 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide. III. Formation of a novel cycloimidazole nucleoside and its cleavage reactions. A new cycloimidazole nucleoside, 5-(1 inch -benzamido-1 inch-hydroxymethylene) amino-2', 1 inch-anhydro-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (III) was synthesized by reaction of 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (AICA-riboside) with benzoyl isothiocyanate followed by methylation with methyl iodide. The structure of III was elucidated on the basis of its nmr spectra and chemical reactions. Of special interest are reactions of III with various nucleophiles. For example, guanosine (IX) was obtained by amination of III wtih ammonia in 72% yield. Analogous reactions of III with methylamine and dimethylamine gave N2-methylguanosine (X) and N2-dimethylguanosine (XI), respectively. Refluxing of III in alkaline solution afforded xanthosine (VII). The probable mechanism of formation and facile ring-opening of III is also discussed.


Synthesis of guanosine and its derivatives from 5-amino-1-beta-D-ribofuranosyl-e-imidazolecarboxamide. IV. A new route to guanosine via cyanamide derivative. 4-Cyanamido-5-imidazolecarboxamide (IV) was prepared by brief treatment of 5-(S-methylisothiocarbamoyl) amino-4-imidazolecarboxamide (V) with alkali. Compound VI was converted in an alkaline solution to either guanine (VII) or isoguanine (VIII), depending on the concentration of alkali. This procedure was applied to the synthesis of 2',3'-0-isopropylideneguanosine (XVI) from the riboside of 5-(N'-benzoyl-S-methylthiocarbamoyl) amino-4-imidazolecarboxamide (IX), PROviding a new route to XVI.


Induced formation of covalent bonds between nucleoprotein components. V. UV or bisulfite induced polynucleotide-protein crosslinkage in bacteriophage MS2. UV (lambda = 254 nm) irradiation of bacteriophage MS2 or its treatment with bisulfite induce covalent crosslinkage of the RNA to the coat protein. epilsonN-(2-oxopyrimidyl-4)-lysine was found in the phage hydrolysates after either type of treatment. An equimolar mixture of 0-methylhydroxylamine and bisulfite causes complete disappearance of the cross-links. This led to the conclusion that one of the factors responsible for the UV-induced polynucleotide-protein crosslinkage and the main factor in treatment with bisulfite is substitution of the exocyclic amino group of the activated cytosine nucleus by the lysine residue epilson-amino group of the protein.


The presence of terminal deoxynucleotidyl transferase in the N-methyl-N-nitrosourea induced leukaemia in BDF1 mice and its effect on the accuracy of the DNA polymerases. DNA polymerases have been prepared from leukaemic and normal spleens and their fidelity in copying a polyd AT).polyd(AT) template assessed. The leukaemic cytoplasmic DNA polymerases were less accurate than the controls whereas no difference in accuracy was observed in the nuclear DNA polymerases. The preparations of leukaemic cytoplasmic DNA polymerase also contained the enzyme terminal deoxynucleotidyl transferase. When this enzyme was removed by further purification the accuracy of the cytoplasmic DNA polymerases increased to that of the controls.


An improved method for the separation and quantitation of the modified nucleosides of transfer RNA. A method is described which allows a very efficient determination of the modified nucleosides of tRNA. The technique involves enzymatic degradation of the tRNA to nucleosides at pH 7.6 and their separation by two-dimensional thin-layer chromatography on cellulose-coated aluminum foils. Based on the analysis of two mammalian tRNAs it is shown that the technique is suitable for the determination of chemically unstable nucleosides as well as the ribose-methylated compounds. At least 36 of the 45 known modified nucleosides can be separated and quantitatively determined by the method described. This procedure is especially suitable for the estimation of the nucleoside composition of unlabeled tRNAs as well as for studying the post-transcriptional modifications of tRNA.


Thermal denaturation of DNA from bromodeoxyuridine substituted cells. The thermal denaturation of DNA from cell lines extensively substituted with bromodeoxyuridine has been examined spectrophotometrically over a wide range in ionic strength and by thermal elution from hydroxyapatite columns. BrdU substitution stabliizes DNA at all ionic strengths between 7.5 mM and 1350 mM potassium ion concentration, although a plot of log ionic strength vs Tm deviates from linearity above 150 mM. This nonlinearity is most pronounced with BrdU-substituted DNAs, resulting in a lowered delta Tm between unsubstituted and substituted DNA with increasing ionic strength. DMSO is shown to decrease the Tm of both unsubstituted and BrdU-substituted DNA equally, at a rate of .5 degrees C per 1% DMSO.


Spectroscopic properties of various 2'(3')-O-aminoacyldinucleoside phosphates analogous to the 3' terminus of AA-tRNA. Hypochromicity and circular dichroism data are reported for the 2' and 3'-0-aminiacyldinucleoside phosphates cytidylyl-(3'-5')-2'(3')-0-L-phenylalanyl-adenosine, cytidylyl-(3'-5')-2'-deoxy-3'-0-L-phenylalanyladenosine, cytidylyl-(3'-5')-2'-deoxy-3'-0-glycyladenosine, and cytidylyl-(3'-5')-3'-deoxy-2'-0-L-phenylalanyladenosine, all of which can act as analogs of the 3' terminus of AA-tRNA in various partial reactions of protein biosynthesis. Although all these systems have a 2'-OH group in the furanose of the 3'-residue, differences exist in the extent and/or mode of base-base overlap for most of them, except for cytidylyl-(3'-5')-2'(3')-0-L-phenylalanyladenosine and cytidylyl-(3'-5')-3'-deoxy-2'-0-L-phenylalanyladenosine. It is concluded that the biological activity of the above analogs is affected both by the position of the aminoacyl group and the stacking properties of the bases.


Chromatin model calculations: Arrays of spherical nu bodies. Chromatin fibers consists of globular nucleohistone particles (designated nu bodies) along the length of the chromatin DNA with approximately 6-to7-fold compaction of the DNA within the nu bodies. We have calculated theoretical small-angle x-ray scattering curves and have compared these with experimental data in the literature. Several models predict maxima at the correct angles. The first maximum (approximately 110 degrees A) results from interparticle interference, while both the spatial arrangement and the structure factor the nu bodies can contribute to the additional small-angle maxima. These calculations suggest models which can account for the electron microscopic observation that chromatin is seen as either approximately 100-or approximately 200-to 250 degrees A-diameter fibers, depending on the solvent conditions. They also account for the limited orientability of the x-ray pattern from pulled chromatin fibers.


New Jersey's coordinated CME system.

New Jersey's coordinated CME system. After six years of collaboration between professional associations and academic institutions, a coordinated system of continuing medical education has been developed in New Jersey. The functions of institutional accreditation, program review, and educational development have been clarified and then assumed by appropriate organizations. Delegation of these functions at the state level has in turn fostered the development of accredited CME programs in more than half of New Jersey's community hospitals.


Growing pains: fact or fiction?

Growing pains: fact or fiction? Growing pains are recurrent limb pains peculiar to children. Brief episodes of leg pains occurring intermittently at night are typical, but the clinical spectrum is variable. A diagnosis of growing pains can be made with certainty only after other possible conditions have been ruled out by appropriate studies and after the child has been observed carefully for a period of months. The two diseases most often confused with this syndrome are rheumatic fever and juvenile rheumatoid arthritis. Aspirin and supportive measures are beneficial.


Pathologic hypofunction of the renin-angiotensin-aldosterone system. The literature now contains reports of many cases of aldosterone deficiency. Usually, the presenting features are persistent hyperkalemia and tendencies to serious urinary sodium loss and hypotension. A classification of defects leading to pathologic hypofunction of the renin-angiotensin-aldosterone system (RAAS hypofunction) is presented, with emphasis on idiopathic hyporeninemia (probably the most common). Criteria for diagnosis are (1) normal adrenal glucocorticoid function, (2) low aldosterone excretion under basal and stimulated conditions, and (3) renal tubular responsiveness to exogenous mineralocorticoid. The condition is effectively managed with mineralocorticoid replacement therapy and should be considered in the presence of unexplained persistent hyperkalemia, hyponatremia, or postural hypotension.


Evaluating peripheral arterial occlusive disease. The clinical history and physical examination remain the most important factors in determining the presence, anatomic location, and physiologic extent of arterial occlusive disease and the need for operation. The physician should refrain from ordering arteriography to confirm the diagnosis of arterial disease unless operation is warranted. If peripheral arterial occlusive disease is diagnosed clinically, its anatomic and physiologic extent can be determined qualitatively and quantitatively by Doppler ultrasonic studies. These studies are also useful in following the natural history of or the influence of therapy on the course of arterial occlusive disease. Ultrasonic studies coupled with careful clinical assessment and with arteriographic evaluation prior to planned operation provide an optimal armamentarium for the diagnosis and management of peripheral arterial occlusive disease.


Myocardial responses to acetylstrophanthidin during veratrum alkaloid refractoriness. Studies were undertaken in the isolated blood perfused dog heart to determine the nature of the myocardial refractoriness induced by veratrum alkaloids. The initial intracoronary injection of cryptenamine acetates (Unitensin) was always associated with an increase in myocardial contractility and a loss of myocardial potassium. Subsequent doses produced refractoriness with respect to both the contractile and potassium responses. Acetylstrophanthidin still produced an inotropic and potassium losing effect duct of the glycoside was potentiated whereas the contractile response was not.


Effect of bone marrow suppression on granulocyte opsonin levels. Levels of serum opsonin for neutrophilic granulocytes were measured in dogs made neutropenic by cyclophosphamide administration. Heat-labile opsonin became elevated within 24 hr following cyclophosphamide (P less than 0.005) and remained elevated over the 4-5 day period of observation (P less than 0.005). In contrast, heat stable opsonin was not significantly effected. Bone marrow suppression by X-ray and busulfan also caused serum opsonin levels to increase. Changes in the levels of IgG, C3, and total hemolytic complement during the course of bone marrow suppression did not correlate with the granulocyte opsonin levels. These findings suggest that serum granulocyte opsonin levels respond to bone marrow suppression and may provide an improved environment for the function of transfused granulocytes.


Evidence of calcitonin-induced inhibition of calcitonin secretion in porcine thyroid slices. In the present study, the possibility of calcitonin-induced self-inhibition in porcine thyroid slices was examined. Replacing the incubation medium at 5-min intervals during incubation and increasing the volume of incubation from 2 to 15 ml were observed to enhance calcium-stimulated calcitonin secretion in vitro.


Effects of masking H-2 and Ir gene products on the in vitro responses of cells from immunized and naive mice. Mouse spleen cells from immunized and naive animals were cultured for 3 days with SRBC and antisera to H-2K, H-2D, Ia, or aggregated IgG. Direct and indirect antibody responses were impaired by each of these agents only when the responding cells had been obtained from unimmunized mice. It was found that as lymphoid cells reacted to the antigen and progressed toward a fully matured antibody response, they first became resistant to inhibition by anti-H-2K and H-2D sera and somewhat later they lost their vulnerability to agents that reacted with Ia antigens.


Passive immunity to murine plasmacytoma by rabbit antiidiotypic antibody to myeloma protein. Antiidiotypic antisera to LPC-1 and MOPC-300 plasmacytoma globulins were produced in rabbits by immunization with the corresponding antigen and exhaustive immunoabsorption with normal BALB/c plasma and other myeloma globulins. IgG fractions of these antisera when given intraperitoneally on three consecutive days after tumor implantation, protected the animal specifically from the grafting of the corresponding plasmacytoma or induced regression of the tumors after their initial grafting and growth. In vitro cytotoxicity of the antisera to plasmacytoma cells was not demonstrated. Plasma of the antisera-treated normal BALB/c mice, though containing antiidiotypic antibody in high titers (320-640), was not cytotoxic to tumor cells. The inhibitory effect on tumor growth can be considered the result of passive immunization against plasmacytoma with xenogeneic humoral antibody.


Influence of volume expansion on sodium excretion during parabiotic dialysis. Dialysis of a saline-infused against a noninfused dog was associated with a significant increase in Na excretion in both animals without a significant change in creatinine clearance or filtered Na. This indicates that there was movement by diffusion of a humoral agent between the two animals. The observed increase in Na excretion in the noninfused animal resulted from gain of a natriuretic hormone, since in a second series of experiments a natriuretic rather than antinatriuretic hormone appeared to be involved.


Dengue virus replication enhancement in peripheral blood leukocytes from immune human beings. Dengue 2 virus replication in peripheral blood leukocyte cultures from 10 of 13 Asian or Polynesian subjects with actively acquired dengue immunity and two of three infants with passively acquired dengue antibody. Only 2 of 11 cultures from nonimmune infants or children supported viral replication. This study establishes a parallel in the biological behavior of human and simian PBL with respect to the immunological dependence of dengue virus replication in vitro. Elucidation of the mechanism (or mechamisms) regulating growth of dengue virus in leukocytes from immune hosts may contribute to an understanding of the role that virus-leukocyte interactions play in the pathogenesis of human dengue illness.


A rapid radioimmunoassay method of growth hormone in dog plasma. A rapid and sensitive homologous radioimmunoassay (RIA) system is described for the measurement of growth hormone (GH) in dog plasma. The method requires only 40 hr and is able to detect concentrations of GH as low as 1.0 ng/ml of dog plasma. Antiserum to canine growth hormone (cGH) prepared in monkeys, exhibited a complete cross-reactivity with porcine GH, suggesting that the latter can substitute cGH in a heterologous radioimmunoassay for cGH. Studies on GH regulation performed with this RIA in the unanesthetized dog showed that this species resembles the primate more than the rat or the rabbit.


Protein metabolism in weanling rats with hypothalamic obesity. Our findings indicate that protein synthesis is enhanced in weanling rats with hypothalamic obesity, that this enhancement is not dependent on increased amino acid transport into cells, and that muscle protein breakdown is also enhanced in these rats. The mechanisms of these changes are yet to be discovered. Finally, muscle protein has been demonstrated to be a probable source of the amino acids required to support enhanced gluconeogenesis in these rats.


Abnormal levels of urinary catecholamines in dystrophic mice and hamsters. Twenty-four-hour urine was collected from normal and dystrophic mice and hamsters for catecholamine determinations. A new method of analysis was used whereby 3,4-dihydroxyphenylalanine (DOPA), dopamine (DA), norepinephrine (NE), and epinephrine (E) were measured simultaneously. The procedure is based on a combination of liquid-solid extraction, cation exchange chromatography, and controlled potential electrochemistry. The results of these experiments indicated that while DA levels were similar in both normal and pathological animal urine, DOPA levels decreased slightly in the dystrophic mouse but not the hamster, and NE and E levels in dystrophic groups were two and four times greater than normal in both species. The data supports the concept of biochemical alterations in tissue other than muscle. While not necessarily supportive to catecholamine abnormality as the primary cause of muscular dystrophy, the present data cast doubt that this disease is a primary muscle disease.


Des-Asp-1-angiotensin II. possible role in mediating the renin--angiotensin response in the rat. Angiotensin II and its heptapeptide fragment, Des-Asp-1-angiotensin II, produced a striking increase in aldosterone secretion in rats pretreated with dexamethasone and morphine to reduce ACTH release. 1-Sar-8-Ala-angiotensin II (10 mug/kg min-1) given simultaneously with angiotensin II (1 mug/min) blocked the aldosterone response to angiotensin II in rats pretreated to reduce ACTH release. In contrast, 1-Sar-8-Ala-angiotensin II at the same dose failed to block the steroid response to Des-Asp-1-angiotensin II (1 mug/min) but a larger dose of 50 mug/kg min-1 of the angiotensin II antagonist blocked completely both the aldosterone and the corticosterone responses to 1 mug/min of Des-Asp-1-angiotensin II. From these data it is suggested that the heptapeptide has a higher affinity for zona glomerulosa receptors than the octapeptide and that Des-Asp-1-angiotensin II mediates, at least in part, the steroidogenic response to the renin-angiotensin system in the rat. The pressor response to Des-Asp-1-angiotensin II was approximately 50% of that produced by the octapeptide in the rat, and 1-Sar-8-Ala-angiotensin II was as effective in partially blocking the pressor response to the octapeptide as in inhibiting the heptapeptide. The present observations indicate a dissociation of adrenal cortex and peripheral arteriolar receptors in their affinity for angiotensin.


Improvement and initial in vivo application of the radioimmunoassay of rat thyrocalcitonin. Previously we reported a homologous radioimmunoassy for rat thyrocalcitonin (TCT) which was sensitive enough (2--3 ng/ml serum) to measure TCT in thyroid venous blood or thyroid gland extracts but could not detect TCT in peripheral blood even after provocative challenge with iv calcium. In the present study chicken antisera to rat TCT were developed which were sufficiently sensitive (120--240 pg/ml serum) to permit initial evaluation of changes in TCT in rat peripheral blood. The following results were observed: (1) Basal serum TCT in young male Holtzman rats was undetectable, being less than 120--240 pg/ml; (2) induction of marked hypercalcemia by iv calcium increased TCT to approximately 1000--3000 pg/ml within 5 min; (3) thyroid cautery increased TCT to approximately 1000 pg/ml in 5--15 min; (4) calcium gavage (12.2 mg Ca/100 g) produced modest hypercalcemia in 30--60 min and increased serum TCT to approximately 500 pg/ml; (5) injection of isoproterenol raised serum TCT detectably; (6) injection of large doses of gastrin or pentagastrin did not produce detectable increases in TCT 5 or 30 min later. The results show that suitable antisera to rat TCT can be developed in chickens and applied to the measurement, by radioimmunoassay, of elevated circulating levels of TCT in the rat.


Plasma prostaglandin F2alpha and 15-keto-F2alpha concentrations during splanchnic artery occlusion shock. Arterial plasma concentrations of PGF2alpha and 15-keto-PGF2alpha were determined in sham shock and splanchnic artery occlusion shock dogs. Arterial PGF2alpha concentrations (expressed as percentage of control) increased significantly in the SAO group when compared to the sham group during postrelease sampling periods. Similarly, 15-keto-PGF2alpha, a major metabolite of PGF2alpha also increased significantly in arterial blood in SAO shock. Comparison of 15-keto-PGF2alpha and PGF2alpha at each sampling period suggest that the efficiency of 15-hydroxyprostaglandin dehydrogenase is not impaired during SAO shock in the dog. However, the ability of the kidney and other organs to remove 15-keto-PGF2alpha from the circulation during SAO shock does appear to be significantly reduced. Although the changes in circulating concentrations of PGF2alpha are significant, the role of the increased prostaglandin is not clearly understood. We found no basis for any toxic effect of the PGF2alpha nor of any beneficial action. Others, however, have found exogenous PGF2alpha to improve survival in circulatory shock.


Effects of acute administration of taurocholic and taurochenodeoxycholic acid on biliary lipid excretion in the rat. Comparison of the effects of biliary lipid excretion produced by infusion of taurochenodeoxycholate and taurocholate showed no significant difference when the bile acids were infused for a relatively short period of time. Cholesterol excretion rates measured during depletion of the bile acid pool were significantly higher than cholesterol excretion rates measured during infusion of bile acids at various rates. These data indicate that there is some mechanism in addition to bile acid excretion that is responsible for biliary excretion of cholesterol when the enterohepatic circulation is intact.


Angiotensin II stimulation of 5'-adenylic acid deaminase. Angiotensin II has been found to stimulate 5'-adenylic acid deaminase from rabbit skeletal muscle. Stimulation was discernible around 10(-9) M and peak stimulation of about threefold was seen at 10(-7) M, concentrations approximating those required for stimulation of vascular smooth muscle or adrenal glomerulosa cells. Higher concentrations produced less stimulation. Adenosine triphosphate stimulated to the same degree, but a concentration of 10(-5) M was required for maximum stimulation, while maximum stimulation with sodium or potassium required 0.5 M and 0.75 M, respectively. Although the physiologic significance of these observations has not been established, these data suggest an intracellular role for angiotensin II.


Contractile responses to angiotensin I and angiotensin II in hamster uterine smooth muscle. Angiotensin I (A-I) and angiotensin II (A-II) produced dose-dependent increases in isometric tension in isolated strips of uterine smooth muscle prepared from ovariectomized golden hamsters treated with estrogen. Responses to A-II were consistent with receptor--occupancy theory of agonist--receptor interactions. Inhibition of angiotensin-converting enzyme virtually abolished responses to A-I but not those to A-II. Blockade of A-II receptors inhibited responses to both A-I and A-II. Cholinergic or alpha-adrenergic blockade did not alter uterine responses to either A-I or A-II. These findings suggest that contractile responses elicited in the isolated uterus of the hamster are due to its local conversion to A-II and subsequent interactions with specific A-II receptors. Such conversion occurs at least to the extent of 14 to 27 %.


Effect of thyroidectomy on rhythmic gonadotropin release. Nonstress blood samples were obtained from intact and thyroidectomized (TE) male rats at 3-hr intervals over a 24-hr period via rapid decapitation. The animals were thyroidectomized when 40 days old and used 6 weeks later. Intact animals showed periodicity in serum LH (P less than 0.01) and prolactin (P less than 0.01). Both gonadotropins began increasing after 8 PM and peak levels occurred at 11 PM. In contrast, 24-hr periodicity was not observed in serum FSH. Corticosterone levels in these same serum samples showed the expected circadian periodicity. After TE, the 24-hr pattern in all gonadotropins was altered significantly. Serum LH increased (P less than 0.01) and circadian periodicity appeared to be absent. FSH and prolactin levels were increased and decreased, respectively (P less than 0.01), with serum prolactin showing a 9-hr phase shift. Prolactin began increasing at 2 AM and reached a peak at 8 AM. Corticosterone in TE animals showed a 24-hr rhythm similar to that of intact rats. These findings confirm our previous observations that nonstress serum LH and prolactin levels fluctuate with a 24-hr periodicity and suggest that the level of, and the phase angle betweeen, these rhythms is markedly influenced by pituitary-thyroid activity.


The serial cultivation of suspended BHK-21/13 cells in serum-free Waymouth medium. A simple medium system was developed to obtain growth of BHK-21 cells in shaker cultures in the absence of serum. These cells have now undergone over 80 serial passages in serum-free Waymouth medium and have been recovered from the frozen state after storage for over 1 month in medium containing 10% dimethyl sulfoxide (DMSO) and 1% bovine serum albumin (BSA). Various amounts of exogenous lipid in the form of sodium oleate were added to cultures of cells growing in serum-free Waymouth medium. Concentrations of 10-50 mug of sodium oleate/ml had no detrimental effects on the cells as measured by trypan blue uptake. Furthermore, the cells were serially passed ten times in the presence of 10 mug sodium oleate/ml. Depletion of calf serum from the growth medium and addition of known quantities of lipids to the system provides a means of revealing subtle changes in lipid synthesis and lipid turnover during cellular growth.


A comparison of the enzyme levels and the in vitro utilization of various substrates for lipogenesis in pair-fed lean and obese pigs. In this study of spontaneous obesity of pigs, specific metabolic shifts were observed, which explain an increase in fat deposition. Liver tissue utilization of pyruvate and glucose for oxidation and lipogenesis showed no significant difference between lean and obese pigs. Adipose tissue utilization of glucose, acetate and glycerol for triglyceride and fatty acid synthesis was greater in obese pigs than lean pigs (P less than 0.01). No significant difference in leucine incorporation into lipid fractions was found. Of the substrates utilized, glucose supplied 86 and 94% of the glyceride-glycerol synthesized in lean and obese pigs, respectively. Glycerol was not a major contributor to glyceride-glycerol synthesis (3.5 to 5.5%), in spite of the presence of adipose tissue glycerokinase. An increase (P less than 0.05) in alanine incorporation into glucose was observed in liver tissue from obese pigs. In general, the levels of enzymes activities associated with gluconeogenesis, glycolysis, and lipogenesis supported the findings of in vitro utilization of these substrates.


Serotonin deficiency and prolonged bleeding in beige mice. Beige mice have been observed to bleed excessively from small wounds. Platelets obtained from these mice were deficient in adenine nucleotides and serotonin and in vivo uptake of labeled serotonin was impaired. Heterozygotes of beige and C57BL/6 mice have adenine nucleotide and serotonin levels comparable to control and do not manifest a bleeding tendency, consistent with the recessive mode of inheritance of the beige mouse syndrome. Morphologic confirmation of the observed biochemical defects was obtained by the demonstration that serotonin storage organelles were not observed in electron photomicrographs of beige mouse platelets. The demonstration that small doses of serotonin were effective in reversing the bleeding tendency in beige mice suggested a causal role for defective storage and release of endogenous serotonin as the basis for the bleeding tendency, acting either independently or synergistically with impaired release of adenine nucleotides.


Isoenzyme composition of human plasma monoamine oxidase in normal subjects and in fibrotic liver disease. Hydroxyapatite column chromatography elution profile reveals characteristic differences between monoamine oxidase (MAO) isolated from normal human plasma and from patients with hemochromatosis having hepatic fibrosis. In normal plasma, the alpha form constitutes about 84% of the enzyme, with the remainder in the beta and gamma forms. By contrast, in hemochromatosis there is less alpha form (less than 40%), an additional alpha1 form (about 20%) which was eluted immediately after alpha form, increased beta form (more than 25%), and no significant difference in gamma form. When calculated on the basis of total amount per liter, hemochromatosis is characterized by elevation of beta form (3- to 10-fold) and the presence of alpha1. These results also appear to indicate that the multiple forms separated by hydroxyapatite column chromatography represent true multiplicity of human plasma MAO in vivo.


Stimulation of prolactin release in rats by GABA. Infusion of GABA into the lateral ventricle of intact female rats on the morning of proestrus and in ovariectomized rats significantly stimulated PRL release. This response apparently is not mediated through a direct action on the pituitary since injection of GABA into hypophysectomized rats with a pituitary transplant under the kindney capsule did not alter serum prolactin levels. These observations suggest that GABA may have a role in regulating prolactin secretion.


The effect of age and norepinephrine on renin release by rat kidney slices in vitro. Basal renin release by rat kidney slices decreases with age in rats of SHR and Sprague-Dawley strains. In contrast, Kyoto-Wistar rats (from which SHR are derived) demonstrate no decrease in renin release with age. The decline in basal renin release observed in SHR occurs at a time when the animal develops hypertension. However, the ability of renin release to respond to stimuli, such as norepinephrine, is enhanced at the time of declining basal renin release and developing hypertension.


Distribution of kidney kininogenases.

Distribution of kidney kininogenases. The distribution of kininogenase activity in the dog kidney was studied. It was found that kininogenase decreased from the outer to the inner cortex and that the medulla and papilla have very little kininogenase activity. Kininogenase activity was also measured in isolated glomeruli devoid of juxtaglomerular apparatus and in the total cortex of rat kidney. In the isolated glomeruli, the kininogenase activity per milligram of protein was only 15% of that found in the total cortex. It was concluded that the main localization of these enzymes is not in the glomeruli, but somewhere else in the cortical segment of the nephron.


A study of the amino acids and proteins of some human T-mycoplasma membranes. Purified membranes were prepared from seven human T-mycoplasmas. Their amino acid composition was determined and was similar to that of other biological membranes. Their proteins were examined by isoelectric focusing and 7 to 10 protein bands were detected mostly in the pH 4 to 7 range of the gel. T-mycoplasma T-McA also had one distinctive band at pH 3 while T-mycoplasma T-213 had a prominent basic band at pH 9. The proteins were denatured by storage at -25 degrees. Five to seven Periodic Schiff-positive bands also were observed but were not identified.


The utilization of senescent red cell and hemolysate iron for erythropoiesis. We report experiments to determine the availability for new hemoglobin production of radioiron from nonviable red cells at various times after deposition in the reticulo-endothelial system and to determine the relative availability of radioiron derived from hemolysates versus that derived from nonviable red cells. When heated nonviable red cells labeled with 59Fe are injected into polycythemic mice the iron is deposited in the reticulo-endothelial system, and less than 1% of it is reutilized for hemoglobin synthesis. If the polycythemic mice are given nonviable red cells 48 hours after exposure to hypoxia, when hemoglobin synthesis is maximal, 25% of the iron is reutilized. When the cells are given 36 hr after exposure to hypoxia, iron reutilization declines to 16%, and when exposure to hypoxia is further delayed, reutilization of the iron falls to a plateau level of 11%. Radioiron from hemolysates, primarily deposited in parenchymal cells of the liver, is less available for new hemoglobin synthesis than is radioiron from nonviable red cells, which is primarily deposited in Kupffer cells of the liver. When transferrin-bound iron is given to polycythemic mice, this iron is also deposited in parenchymal cells of the liver and is also less available for new hemoglobin synthesis. Thus, in relation to an erythropoietic stimulus, the site and time of deposition of iron influence its accessibility for erythropoiesis.


Blood endotoxin inactivation after trauma and endotoxicosis. In contrast to the inability to demonstrate endotoxin detoxifying activity in either control rat blood, blood cells, plasma, or serum, the induction of mild endotoxemia or trauma resulted in a prompt and marked detoxifying activity in blood plasma or serum, but not in the cellular elements. The functional significance of the blood anti-endotoxin system was demonstrated by a capability for passive transfer and by its loss during severe traumatic shock. A role for the RES in elaboration of the blood anti-endotoxin system is postulated.


Pyrogen from mouse macrophages causes fever in mice. Mouse peritoneal macrophages, after phagocytosis, release an endogenous (leucocyte) pyrogen. Intravenous injection of stimulated cell culture supernatant produces a prompt, monophasic fever in mice maintained in a 35 degree environment. The pyrogen is distinct from endotoxin, and resembles cell pyrogens of other species in heat-lability and pronase sensitivity. Human leucocyte pyrogen produces identical responses in mice. Measurement of fever in mice appears to provide a sensitive biological assay for endogenous pyrogens.


Treponeme outer envelope: chemical analysis. The chemical composition of the outer envelope (OE) of Treponema phagedenis biovar Kazan 5 was investigated. After cultivation in a lipid-defined medium, the OE was removed from the cells with 0.7 mM sodium dodecyl sulfate. The solubilized OE was reaggregated by dialysis against 20 mM MgCl2, washed, lyophilized, and subjected to chemical analysis. The average yield of OE was 14.6% of the whole cell (WC) dry weight. The magnesium content was 0.683 mug/mg OE. Peptidoglycan components such as muramic acid and ornithine were detected in the WC but not in the OE, and diaminopimelic acid was absent in both WC and OE. The OE contained protein (60-73%), carbohydrate (1-2%), and lipid (4-5%), primarily polar lipid. The major polar lipids were monogalactosyldiglyceride (43%) and phospholipid (57%), of which phosphatidylcholine was the main phospholipid component, with phosphatidylethanolamine present in lesser amounts.


Effect of quality and quantity of dietary fat and dimethylhydrazine in colon carcinogenesis in rats. The effect, quality, and quantity of dietary fat on colon tumor induction by DMH were studied in rats exposed to a given regimen for two generations prior to treatment with DMH. Animals fed a 20% corn oil or 20% lard and treated with DMH had a higher incidence of colonic tumors than did rats fed a 5% corn oil, 5% lard or Purina lab chow and treated similarly. The quality of fat had no major difference on the incidence of colonic tumors.


Influence of serum albumin on the fertilizing ability in vitro of rat spermatozoa. Under defined conditions, in the presence of 10 mg/ml of bovine serum albumin, cauda epididymal rat spermatozoa displayed vigorous motility, and a high proportion (81%) of eggs were fertilized. In contrast, no fertilization was observed after omission of albumin, or replacement of the protein by 10 mg/ml of cytochrome c, beta-globulin, gamma-globulin, hemoglobin, lysozyme, and polyvinylpyrrolidone, and 5 mg/ml of ribonuclease. However, high motility occurred in suspensions containing 3 x 10(6) spermatozoa/0.1 ml of medium with cytochrome c, beta-globulin, or gamma-globulin. In medium with 1 mg/ml of ovalbumin, 7% (2/29) eggs were fertilized. Use of defatted albumin resulted in a higher rate of fertilization than unmodified albumin (87 vs 70%), and this difference approached statistical significance. No fertilization was obtained in the presence of albumin presaturated with cholesterol. These results suggest that: (a) rat sperm cells failed to capacitate in the absence of albumin; (b) the protein exerted more than a nonspecific macromolecular effect; and (c) lipids associated with albumin may modify its ability to promote sperm capacitation.


Species-specific hypoglycemic activity of triphenylphosphoranylideneacetophenones. The species-specific hypoglycemic activity of two 2-triphenylphosphoranylideneacetophenones is described. 2-Triphenylphosphoranylideneacetophenone (SK&F 45359) and 2-triphenylphosphoranylidene-m-trifluoromethyl-acetophenone (SK&F 62775) were hypoglycemic in various rat models, but failed to exhibit hypoglycemic activity in other species.


Fibrin clot retraction by human skin fibroblasts: effects of ADP and thrombin. Thrombin stimulated human skin fibroblasts to retract fibrin clots. When Bothrops marajoensis thrombinlike enzyme was substituted for thrombin, no retraction occurred. Fibroblasts were found to contain 12 nmole of ATP and 3.6 nmole of ADP/mg of protein, a value closely resembling that of nonmetabolic adenine nucleotides in platelets. Thrombin caused neither release of adenine nucleotides from the suspension of fibroblasts harvested enzymatically nor did addition of ADP stimulate fibroblasts to retract fibrin clots.


Effect of paraquat-induced lung damage on permeability of rat lung to drugs. To investigate the effect of paraquat-induced lung damage on pulmonary absorption of drugs, rats were given a single oral dose of paraquat (250 mg/kg), and rates of drug absorption from damaged and control lungs were compared after various times. To measure absorption rates of drugs, 0.1 ml of 10 mM drug solution was administered through a tracheal cannula to anesthetized animals and, after various times, lungs were assayed for unabsorbed compound. Drugs investigated were procaine amide ethobromide, p-aminohippuric acid, and procaine amide. Rates of drug absorption increased 1.4-2.8-fold at 3.5 days after paraquat administration and returned to near control values by the 15th day. The results suggest that paraquat-induced lung damage increases the porosity of the pulmonary epithelium.


In vivo inhibition of cholesterol uptake in rabbit aortas by 7-ketocholesterol. The iv injection of 7-ketocholesterol into rabbits, made soluble by combining with bile salts, inhibited cholesterol uptake by the aorta. However, the inhibition was not as marked or as uniform as previously demonstrated in in vitro experiments. This difference may have been the result of lower plasma concentrations of 7-ketocholesterol in the injected animals. Gastric feeding of 7-ketocholesterol failed to inhibit aortic cholesterol uptake, probably because of inadequate plasma concentrations of the inhibitory steroid. The results suggest that the mechanism of 7-ketocholesterol on aortic cholesterol uptake is through competitive inhibition.


Interferon and neutralizing antibody in sera of exercised mice with coxsackievirus B-3 myocarditis. Weanling ICR albino Swiss mice were inoculated ip with 1.9 x 10(4) PFU of coxsackievirus B-3 (Nancy) and subsequently forced to swim vigorously daily in a preheated pool (33 degrees). Viremias and virus in hearts of exercised mice were respectively 75 x 1000 x greater than in infected, but not exercised mice. At 24 hr after inoculation, pooled serum from mice that had been swum had no circulating interferon, while infected but not swum mice had interferon activity at a dilution of 1:10. At 72 hr after infection, circulating interferon disappeared from infected (not swum) mice, but continued to be present in high titers through the sixth day in sucklings forced to swim. Interferon was first detected in the hearts of both groups at 48 hr. Quantities in both infected groups were generally similar. Neutralizing antibodies were found in these baby mice on the 13th day of infection and were 16 x greater in nurslings that were not exercised. Measures of corticosterone taken at 4 PM daily were similar in infected, infected-swum, and uninfected mice.


Comparative cardiovascular effects of propranolol and practolol in puppies. The present results indicate that in 3-4-weeks-old puppies propranolol induces a significant depression of cardiovascular function expressed by a decrease in heart rate, myocardial contractility, and cardiac output, and an increase in systemic vascular resistance, in doses beyond beta-blocking levels. In contrast, practolol, in the same dose range, did not induce further cardio-circulatory depression, as shown by levels of heart rate, myocardial contractility, and cardiac output similar to the values obtained with beta-blocking doses of this agent. The cardio-depressant activity observed in puppies with doses of propranolol beyond blocking levels is thought to be due to direct negative inotropic and chronotropic effects of this agent, not related to influences on beta receptor sites. Such effect not observed with practolol at doses well beyond beta-blocking levels suggests that this drug exerts a more selective influence on cardiac sympathetic beta receptors.


Plasma concentrations of connective tissue compounds: I. the effect of uterine involution. The information obtained in a prospective study of plasma concentrations of connective tissue components during the third trimester of pregnancy, 4 days, and again at 6 weeks postpartum, suggests that the increased concentrations of plasma protein-hydroxyproline (hypro-protein), free proline, and GAG are associated with increased rate of hydrolysis of extraskeletal connective tissue components.


Effect of low calorie diet on the hyperlipidemia, hypertension, and life span of genetically obese rats. A new strain of genetically obese rat recently obtained in our laboratory exhibits endogenous hyperlipidemia (marked hypertriglyceridemia and moderate hypercholesterolemia) and spontaneous hypertension. The animals die prematurely from kidney failure or from the complications of atherosclerosis. A low calorie diet proved to be highly beneficial to these rats. Body weight declined, obesity diminished, the hypertriglyceridemia was almost eliminated, and the hypercholesterolemia was reduced. However, the hypertensive state was not alleviated. Since the life span of the rats was greatly prolonged by a low calorie diet, the latter undoubtedly served to prevent or arrest the development of renal and vascular disease in these obese animals.


Effects of glucagon on gluconeogenesis from lactate and propionate in the perfused rat liver. Quinolinic acid (Q.A.) which inhibits gluconeogenesis at the site of phosphoenolpyruvate (PEP) synthesis, reduced the content of PEP while elevating that of aspartate and malate in rat livers perfused with a medium containing 10 mM L-lactate. Glucagon at 10(-9) M did not affect Q.A. inhibition of lactate gluconeogenesis nor the depression of PEP level, but further elevated malate and aspartate accumulation. Exogenous butyrate had the same effect as glucagon on these parameters. Butylmalonate (BM), an inhibitor of mitochondrial malate transport, inhibited lactate and propionate gluconeogenesis to similar extents. The addition of 10(-9) M glucagon had no effect on BM inhibition of lactate gluconeogenesis, but almost completely reversed BM inhibition of propionate gluconeogenesis. These results suggest that glucagon may act on at least two sites, resulting in elevated hepatic gluconeogenesis. First, it may stimulate dicarboxylic acid synthesis (malate and oxaloacetate, specifically) through activation of pyruvate carboxylation. Secondly, it may stimulate synthesis of other dicarboxylic acids (fumarate, for example) by activating certain steps of the tricarboxylic acid cycle. The stimulatory effect of glucagon on gluconeogenesis in the perfused rat liver is well documented (1, 2). Exton et al., who earlier located the site of stimulation between pyruvate and PEP synthesis (3), proposed that glucagon stimulated PEP synthesis in the perfused rat liver (4), while reports from Williamson et al. (5) suggested the pyruvate-carboxylase reaction as the site of glucagon action. Stimulation at sites above PEP formation and of portions of the tricarboxylic acid cycle (4) by glucagon have also been suggested (6). In the present experiments, we have used substrates entering at different parts of the gluconeogenic pathway, and specific inhibitors to further resolve the action of glucagon.


Effects of synthetic single- and multistranded polynucleotides on human monocyte IgG receptor activity in vitro. Human peripheral monocytes demonstrated a higher IgG receptor activity in vitro after incubation with multistranded polynucleotides (poly(I:C) and poly(I:C:U)) after 6-hr cultivation periods. These changes were most pronounced using SRBC coated with low anti-Forssman antibody concentrations (EA, 1:1600 and 1:6400). Polyinosinic and polycytidylic acids failed to show changes in receptor activity. These findings suggest monocyte activation in vitro by multistranded polynucleotides and may in part explain their antitumor activity.


Plasma zinc levels in nephrectomized and ureteral ligated rats. The effect of nephrectomy and ureteral ligation on the plasma zinc levels of zinc-supplemented and unsupplemented rats was studied. Bilateral nephrectomy, and to a greater extent bilateral ureteral ligation, resulted in a significant lowering of plasma zinc in the unsupplemented rats. Sham operation caused a  lesser but significant lowering of plasma zinc which was not different from the effect of unilateral nephrectomy or unilateral ureteral ligation. Adding zinc to the drinking fluid of the bilateral nephrectomized rats raised their plasma zinc levels to that of sham-operated controls, but had no effect on the plasma zinc levels of the bilateral ureteral-ligated rats.


Blood pressure of rats as affected by diet and concentration of NaCl in drinking water. In the first experiment, weanling rats were fed a grain ration or one of three semipurified diets high in fat, sucrose, or cornstarch. Rats in each dietary group were divided into two subgroups, one of which drank distilled deionized water whereas the other group drank 2% NaCl solution. Blood pressure and sodium intake were individually measured for each rat at weekly intervals for a 10-week period. Rats receiving the salt solution had higher mean blood pressures (127-178 mmHg) than rats offered distilled water (108-127 mmHg). When drinking solutions were the same, more severe rises in blood pressure occurred in rats fed the semipurified diets than in those rats fed grain. In a second experiment, rats were fed one of the four diets used in the first experiment; however, they received a 1% NaCl drinking solution for 9 weeks followed by a 1.5% NaCl solution for an additional 9 weeks. At Week 18, pressures among these groups of rats ranged from 136-140 mmHg, regardless of diet.


Segregation of histone fractions from purified rat pancreas nuclei by isoelectric focusing. The present report describes the purification of nuclei from rat pancreas and the use of isoelectric focusing for the segregation of histone fractions, a heterogeneous mixture with respect to charge. This procedure employs gels of 5% polyacrylamide as support matrices, in 6.25 M urea, and spans a pH range of 7.5-10.8. It was, therefore, found adequate for study of the microheterogeneity of histones. The banding pattern of histone fractions in pancreas development using electrofocusing is presented.


Chain elongation and desaturation of palmitic acid in liver microsomes of rats subjected to hyperbaric exposure. The enzyme activities associated with chain elongation and desaturation of fatty acid in hepatic microsomes from rats held at 1 ATA of air, 1 ATA of He-O2, and 20 ATA of He-O2 were studied. It was found that both the microsomal chain elongation and desaturation of fatty acids were depressed in rats held at 1 ATA of He-O2 as compared to animals held at 1 ATA of air. When animals were exposed to an environment of 20 ATA of He-O2, the chain elongation of fatty acid was about the same as for rats held at 1 ATA of air and was two times greater than for the rats held at 1 ATA of He-O2. The desaturase activity was depressed as compared to the two groups of control animals held at 1 ATA of air and 1 ATA of He-O2.


Ovarian dehydrogenase activities: suggested adrenal involvement in luteolysis. Immature rat ovarian dehydrogenase activity was studied during corpus luteum regression following withdrawal of prior pregnant mare serum gonadotrophin. Glucose-6-phosphate dehydrogenase activity declined to nontreatment levels whereas 6-phosphogluconate, malate, and isocitrate dehydrogenase dehydrogenases exhibited a partial return to normal. Adrenalectomy prior to PMS withdrawal enhanced the decline in MAD while sharply elevating G6PD and 20alpha-hydroxysteroid dehydrogenase. Corticosterone and progesterone prevented the G6PD changes induced by adrenalectomy and moderated the rise in 20alpha-OHSD. Adrenalectomy appears to enhance the process of luteolysis.


Free gracilis muscle transplantation, with microneurovascular anastomoses for the treatment of facial paralysis. A preliminary report. A clinical operative technique for free muscle transplantation by microneurovascular anastomoses is presented. Two cases of free transfer of the gracilis muscle for dynamic reconstruction of facial paralysis are described, including a follow-up study with electromyography, light microscopy, and electron microscopy. We feel this new technique will have a wide range of application in reconstructive surgery.


Retrospective cephalometric analysis of mandibular bone absorption under silicone rubber chin implants. A longitudinal study was conducted on 85 patients who received silicone rubber implants to the chin. Over half of these patients were found to have some absorption of the bone beneath the implants, and much other information was obtained. There were no concomitant changes in the soft tissue profile in the patients who demonstrated bone absorption under their implants. It appeared that the bone absorption was less when the implant was placed over the hard bone of the lower part of the mandible, rather than higher or over alveolar bone.


Reconstruction of the breast after mastectomy for cancer. Seventeen women who had had a mastectomy for cancer of the breast underwent reconstructions. Alloplastic implants were used in all. Preservation of the nipple and areola was possible in some of these patients. The normal (or uninvolved) breast sometimes required reduction in size or reshaping, to match as nearly as possible the reconstructed breast. The conditions suitable and unsuitable for mammary reconstruction, after mastectomy for cancer, are discussed.


The use of soluble steroids within inflatable breast prostheses. A cortisone derivative (Solumedrol, Upjohn) has been added to the saline used to fill inflatable breast prostheses. In the experimental laboratory this drug passed slowly through the silicone rubber bag into a surrounding solvent. Clinically, this use has been evaluated in 100 cases of augmentation mammaplasty, with no evidence of wound complications attributable to the steroid. The influence of significant capsule formation (or "hardness") was less than 5 percent in this series.