Comparative studies of the cross-linked regions of elastin from bovine ligamentum nuchae and bovine, porcine and human aorta. 1. The preparative Edman degradation of desmosine-containing peptides permitted the isolation of peptides C-terminal to the desmosine cross-links in bovine, porcine and human aortic elastin as well as bovine ligamentum nuchae elastin. This identifies the lysines in the tropoelastin which give rise to the desmosine cross-links. 2. The sequences from bovine aortic elastin were identical with those obtained from bovine ligamentum nuchae elastin but differed from those obtained from the other species. The most striking difference involves the occurrence of phenylalanine in bovine elastin and tyrosine in porcine and human elastin C-terminal to the desmosine cross-links. 3. The sequences of the C-terminal peptides were found to fall into two distinct classes, one starting with hydrophobic residues, the other starting with alanine. It is proposed that thehydrophobic residue prevents the enzymic oxidative deamination of the adjacent lysine e-amino group and this then contributes the nitrogen to the pyridinium ring of the cross-links.


Teaching the doctor-patient relation to medical students. Learning experience in a behaviour therapy clinic. The results of a 2-year trial of teaching medical students in a phobia clinic are described. This has been found a useful experience by the students, particularly as an introduction to the doctor-patient relation. The success rate and attitude of patients justified this experiment, and there might be an indication for extension to other teaching and possibly regional hospitals. The long-term benefits to the medical student are discussed.


Structural requirements for the action of steroids as quenchers of albumin fluorescence. 1. Androgens, corticoids, gestagens, estrogens and related steroids are effective quenchers of the intrinsic fluorescence of bovine serum albumin. The quenching effect involves the formation of a steroid albumin complex which formation constant (Kf) and free energy of formation (delta G 0) can be determined by fluorescence titration. The fluorimetrically determined delta G 0 values range from -6.5 to -7.5 kcal/mol. 2. 5 alpha-Androstane and 5 alpha-pregnane are effective quenchers of albumin fluorescence, in accord with the essentially hydrophobic nature of the steroid-albumin interaction. Introduction of hydroxy or oxo groups in 5 alpha-androstane decreases the fluorescence quenching action, but the effect of each group declines when other polar groups are present in the steroid molecule. Similar effects occur with 5 alpha-pregnane except that 20-hydroxy (or oxo) duo-polar derivatives are more effective than the parent hydrocarbon. 3. Comparison of delta G 0 values for steroids differing in a single grouping shows that the steroid-albumin interaction is increased by (a) the benzenoid A-ring; (b) sulfate or carboxylate ions in the vicinity of C-3; (c) the 3-oxo group in place of the 3 alpha-hydroxyl (with 5 beta-pregnane derivatives; not with 5 alpha-androstane derivatives); (d) 17 beta-acetyl or 17 beta-hydroxyethyl residues; (e) acetylated or propionated 17 beta-hydroxy groups; (f) acetylated or methylated hydroxy groups at the C-3 of estrogens; (g) delta 5 and delta 6 double bonds; and (h) the 19 beta-methyl group. The maximal variation of delta G 0 determined by affinity-enhancing groups is -0.8 kcal/mol. Conversely, the steroid-albumin interaction is decreased by introduction of (i) oxygen atoms at C-3, C-6, C-11, C-16, and C-17; (j) 17 alpha-ethynyl and 17 alpha-acetoxyl residues; (k) benzoylated or hexahydro-benzoylated beta-hydroxy groups at C-17; (l) acetylated and benzoylated hydroxy groups at C-3; and delta 1 (conjugated) double bond. Oxo groups at C-3, C-6, C-16 and the 16 alpha, 17 alpha-epoxy group are more effective than the corresponding alpha-hydroxyl in decreasing affinity, while at C-11 and C-17, the alpha-hydroxyl is more effective than the beta-hydroxyl and the oxo group. The effect of substituents is influenced by the whole molecular structure, particularly, by the stereostructure at the A/B juncture, and the presence of an oxo group at C-17. 4. The stereospecific effect of substituents at different positions in the steroid molecule suggests that with non-aromatic, A/B trans (planar) steroids, binding to albumin primarily involves the (alpha) rear surface of the B-, C- and D-ring, and possibly, the 17 beta-side chain. With estrogens and A/B cis (dihedral) steroids, the benzenoid A-ring and electron attracting groups at C-3, respectively, may participate in binding.


Kinetic mechanism of formininotransferase from porcine liver. Formiminotransferase (EC 2.1.2.5) and cyclodeaminase (EC 4.3.1.4) constitute an enzyme complex that catalyses two sequential metabolic reactions. The activity of native formiminotransferase can be measured without interference from cyclodeaminase, and its kinetic mechanism has been investigated. Although initial velocity plots yield families of parallel lines suggesting that the transferase utilizes a ping-pong mechanism, product inhibition and alternate substrate studies with tetrahydropteroic acid clearly show the mechanism to be sequential. Of the possible mechanisms compatible with these observations, several could be ruled out through the effects of various dead-end inhibitors. The data indicate that the transferase mechanism is rapid equilibrium random with formation of a dead-end complex enzyme-tetrahydrofolate-glutamate.


Guine pig liver L-asparaginase. Separation, purification, and intracellular localisation of two distinct enzymatic activities. Two distinct L-asparaginase (EC 3.5.1.1) activities were detected in guinea pig liver: Asparaginase 1 and Asparaginase 2. Asparaginase 1 has been purified 272 fold from the crude homogenate; its molecular weight was evaluated by gel filtration to be about 150 000. The purified preparation was shown to be homogeneous by cellulose acetate strip and polyacrylamide disc-gel electrophoresis. Asparaginase 2 has been purified 63.5 fold from the crude homogenate. Its molecular weight was evaluated by gel filtration to be about 21 500. Cellulose acetate strip electrophoresis demonstrated two bands, one of which corresponded to Asparaginase 1 and the other to Asparaginase 2. Cellular fractionation in the ultracentrifuge, showed Asparaginase 1 to be present only in the cytosol fraction. Asparaginase 2 which was unstable at 105 000 X g seemed mostly localized in the mitochondria and secondarily in the cytoplasmic fraction.


Effect of calcium ions on pyruvate carboxylase from pigeon liver. Pigeon liver pyruvate carboxylase (pyruvate: CO2 ligase (ADP forming), EC 6.4.1.1) shows allosteric properties similar to those of chicken or rat liver enzyme. Kinetic methods have been used to determine the effect of Ca2+ on this enzyme. The Ca2+ activation effect is absolutely dependent on the Mg2+ concentration; in the absence of Mg2+, pyruvate carboxylase has no catalytic activity. Furthermore, Ca2+ cannot replace Mg2+ and also shows a paradoxical effect on the liver enzyme activity. It is an activator at low pyruvate or Mg2+ concentrations; at increased pyruvate concentrations, however, it becomes an inhibitor. At low levels of ATP a pronounced activation of pigeon liver pyruvate carboxylase by Ca2+ has been demonstrated. The results of this communication demonstrate pigeon liver pyruvate carboxylase to be different from pyruvate carboxylase from other sources.


On the specificity of porcine elastase.

On the specificity of porcine elastase. The specificity of porcine elastase (EC 3.4.4.7) has been studied. Ethyl esters derived from benzoyl amino acids with straight side chains are better substrates than those with branched side chains; the best substrate is norvaline ester. In the series of benzoylalanine alkyl esters the alcohol moiety markedly affects the susceptibility. The benzyl ester was found to be the best nonactivated substrate derived from monomeric amino acid. With elastase acylation is rate limiting, in contrast to chymotrypsin and trypsin where deacylation is generally the rate determining step with specific ester substrates.


Different effects of polylysine and polyarginine on the transition to a condensed state of DNA in polyethyleneglycol/salt solution. Circular dichroism spectroscopy has been used to investigate the influence of polylysine and polyarginine on the transition to a condensed state of DNA brought about by high concentrations of polyethyleneglycol and salt. From the dependence on DNA concentration of the CD signals, the anomalous CD of free DNA in polyethyleneglycol/salt solution was attributed to the intermolecular association of DNA molecules. The CD spectral changes in polyethyleneglycol/salt solution of the DNA - polylysine complex were indistinguishable from those of free DNA while the DNA-polyarginine complex suffered much smaller spectral changes as compared with free DNA, at low DNA concentrations where time-independent CD spectra were observed in polyethyleneglycol/salt solution for both the complexed and free DNA. The repression of the spectral change by the latter complex was more remarkable at higher ratios of polyarginine to DNA. The facts indicate that, whereas polylysine binding has little influence on the intermolecular structural transition of double-stranded DNA into a compact molecular configuration in polyethyleneglycol/salt solution, polyarginine binding has an effect of inhibiting the transition.


[Vitamin B6 fluorescence in cells].

[Vitamin B6 fluorescence in cells]. The band of cell fluorescence with the maximum of 395-400 nm is registered. This band is exposed on the phone of the tryptophane by wavelength excitation lambdaex=250-260 nm, and in pure scape by lambdaex=310-326 nm. Pyridoxin - substrate of vitamin B6 has identical parameters of spectra excitation and emission of neutral (pH 7) and acid (pH 2) solutions. After temperature damage of cells the intensity of this band increases.


[Model of bifunctional binding of rotenone and piericidin with mitochondrial NADH-dehydrogenase]. Based on authors' and literature data on the effect of inhibitors of mitochondrial NADH-dehydrogenase a scheme concerning bifunctional binding of specific inhibitors--piericidin A and rotenone with the enzyme is suggested. Analysis on the models, made in correspondence with the requirements of this scheme, permitted to propose conformations in which rotenoides interact with the enzyme.


Gestational stress: effects on open-field behaviour and heart rate reactivity in rat offspring. Home-cage heart rate (HR) and open-field defecation, ambulation, rearing and HR, were recorded in the offspring of mothers who had been exposed to stress during gestation. Compared with controls, experimental animals showed no significant differences in ambulation and rearing, while defecation was significantly lower. The only significant finding on HR was an increase from home-cage level to open-field level in the experimental group. The results confirmed previous findings that illumination level is a useful independent variable in gestational stress studies, and suggested that different types of HR measure yield a similar picture of the HR/defecation relationship, which appears to be a negative function. These conclusions were discussed in the light of other findings in this area, and traditional assumptions about the emotionality construct were questioned.


[Primary structure of cytoplasmic aspartate aminotransferase from pit heart muscle. Amino acid sequence of thermolytic peptides]. Amino acid sequences of 128 thermolytic peptides from carboxymethylated aspartate aminotransferase were determined. These peptides contain a total of 515 amino acid residues and account for a sequence of 384 amino acid residues in the aspartate aminotransferase.


[Activation of prothrombin, modified by maleic anhydride, some properties of N-maleyl-thrombin with free alpha-amino groups]. Conditions for the acylation of bovine prothrombin by maleic anhydride are worked out. The reaction is shown to modify not more than 95% of amino groups. The changes in hydrodynamic and electrophoretic properties testify about structural changes of prothrombin as a result of the modification of free amino groups. The activation of maleyl-prothrombin to maleyl-thrombin took place in 25% sodium citrate only in the presence of thrombin and the Xa factor.  The increase of modified amino groups in prothrombin resulted in the decrease of the activity of generated maleyi-thrombin. The main fraction of maleyl-thrombin with free alpha-amino groups had a sedimentation coefficient of 2.1 S and possessed a residual esterase activity.


[Substrate specificity of cysteine lyase]. Substrate specificity is studied of cysteine lyase, a phosphopyridoxal-dependent enzyme belonging to the subgroup of beta-replacing lyases. This enzyme has a narrow specificity for the amino substrate; its only primary substrate is L-cysteine. Cysteine lyase has a broad specificity for the cosubstrate (replacing agent), catalysing the synthesis of L-cysteic acid from L-cysteine and sulfite ion or cystein thioesters (in the presence of some thiols). Enzyme is incapable to use alpha-phenyl- and alpha-methylcysteine as substrates. It is found that enzyme catalyses the exchange of alpha-H atoms of the aminoacid substrate cysteine with 3H2O. It does not catalyse alpha-hydrogenexchange in close structural analogues of substrate: L-alanine, D-serine, treonine, allo-threonine and 3-phosphoserine. L-Serine inhibited the synthesis of S-hydroxyethylcystein from cysteine and beta-mercaptoethanol (Ki of L-serine is 0,8-10(-2) M), participating at the first stage of reaction: the formation of a pyridoxylidenic derivative, which does not undergo the further alpha,beta-elimination of beta-replacement reactions.


[Thyroid pigments in Gunn rats].

[Thyroid pigments in Gunn rats]. The structural and histochemical characteristics of the thyroid pigment in homozygous Gunn rats were examined. The pigment occurs in the form of numerous yellow granules in the cytoplasm of the follicular cells. The focal depositions of the pigment were also seen in the central part of the luminal colloid. However, the pigment granules were not present in the light or parafollicular cells. The main histochemical properties of the pigment are that it is basophilic, PAS-positive, acid-fast and reducing toward alcaline silver nitrate and ferricyanide. Besides, it was easily bleached with oxidizing agents. It was deduced that the pigment was a lipofuscine. Ultrastructurally, pigment bodies are characterised by an electron dense content, and a smooth surface single limiting membrane. They resembled lysosomes or peroxisomes. It was concluded that the pigment granules visible at the light microscopic level resulted frim the accumulation of the pigment substance in the preexisting lysosomes.


[Multiplication of the different varieties of cells of the mouse pubic symphysis during growth and early gestation: radioautographic study with the use of tritiated thymidine]. 1) A radioautographic study was undertaken after injection of tritiated thymidine during post-natal growth. The mitotic activity was localized in the three constituents of the mouse pubic symphysis: - in the osteogenic cartilage, labelled nuclei are numerous throughout animal growth; - in the articular cartilage, labelled nuclei are seldom encountered; - in the medial region, the chondroblasts, elongated dorso-ventrally, and the fibroblasts of the dorsal ligament show numerous labelled nuclei. 2. During the first pregnancy, the mitotic activity of the three constituents were examined separately: - in the osteogenic cartilage, the number of labelled cells increases at the beginning of the first pregnancy : the tibia epiphyseal cartilage apparently simultaneously shows revival of mitotic activity. After the 15th day of pregnancy, the osteogenic cartilage disappears by endochondral ossification; - in the articular cartilage and fibrocartilage, no mitotic activity is detectable as long as their typical characteristics are conserved. However, mititic activity becomes evident again when these cartilaginous cells cease to be surrounded by the typical chondroid matrix and become incorporated into the ligament. Cell multiplication therefore participated in symphyseal ligament dilatation.


[New data on the "critical period" of the luteinizing action of estradiol benzoate in female rats]. The luteinizing action of oestradiol benzoate (OB) has been studied in 4-day cyclic female Wistar rats submitted to a dose of 10 mug on the morning of dioestrus I at 10-11 a.m. In a first experimental series a blockage of luteinization was observed in females injected with pentobarbital (PB) either on dioestrus I at 11 a.m. and 5 p.m. respectively or on dioestrus II at 1:30 p.m. In the second series the blockage of luteinization only occured in females injected with PB on dioestrus II at 1:30 p.m. Early mating during the night following dioestrus II overcame this action of PB. The luteinizing effects of OB were therefore concluded to be dependent on the activation on the afternoon of dioestrus II, of the nervous hypothalamic structures. They were also shown to depend on the sensitivity to PB and/or to OB, on the day of dioestrus I, of the hypothalamo-pituitary system.


Inhibition by apomorphine of the metoclopramide-induced catalepsy and increase in striatal homovanillic acid content. 1 The mechanism of the cataleptic effect of metoclopramide was analyzed by using drugs which alter the activity of dopaminergic or cholinergic neurones or the content of  psi-aminobutyric acid in the central nervous system of rats. 2 The cataleptic effect of metoclopramide (20 mg/kg) was antagonized by apomorphine (10 mg/kg) and by atropine (50 mg/kg). Aminoxyacete acid (AOAA, 25-50 mg/kg) potentiated the catalepsy induced by metoclopramide (5 mg/kg). 3 Metoclopramide alone did not alter the rectal temperature of rats. It did not alter the AOAA-induced hypothermia, but it partially antagonized apomorphine-induced hypothermia. 4 Metoclopramide induced a six-fold increase in striatal homovanillic acid (HVA) concentration, but it did not change the dopamine or noradrenaline content in the brain of rats. Apomorphine decreased the striatal HVA concentration in control and in metoclopramide-treated rats. Atropine and AOAA did not alter the metoclopramide-induced increase in striatal HVA concentration. 5 The results suggest that metoclopramide produces catalepsy by blocking striatal dopamine receptors.


Identification of talc on surgeons' gloves and in tissue from starch granulomas. Particles of talc have been identified on the route surface of surgeons' rubber gloves and in sections of tissue classified as 'starch' or 'foreign body' granulomas. This analytical study indicates that under certain circumstances these granulomas could have been caused by talc contamination.


The effect of isoprenaline and propranolol on rat myocardial ornithine decarboxylase. The intraperitoneal injection of isoprenaline in rats caused an increase in myocardial ornithine decarboxylase activity which reached a maximum of about four times the control value one hour after the injection. The intraperitoneal injection of dl-propranolol had no effect on myocardial ornithine decarboxylase activity. The  injection of dl-propranolol 30 min before the injection of isoprenaline almost completely prevented the effect of isoprenaline.


[Splenectomy by ethylpalmitate in Wistar rats]. Necrosis of the spleen resulting from previous storage of the substance within the cells was produced by intravenous injections of 500 mg and 800 mg, respectively, of ethylpalmitate in 30 male Wistar [VELAZ] rats weighting, on average, 200 g. A certain inhomogeneity of the results indicates differences in tissue susceptibility obviously related to the actual functinal state at the spleen. Ethylpalmitate storage was observed to a lesser degree in the Kupffer cells of the liver and in the cells of pulmonary alveoli and septa. This, however, was unassociated with marked necrosis. Other organs [lymph nodes, bone marrow, thymus, kidney, myocardium] did not display significant changes.


Studies on lysophospholipases, V. The action of lysolecithin-hydrolyzing enzymes on lecithins and 1-acyl lysolecithins with varying fatty acid chain-length. The activity of two purified lysolecithin-hydrolyzing enzymes on homologous series of synthetic lecithins containing two identical fatty acyl chains and of 1-acyl-lysolecithins has been measured as a function of substrate concentration. In general, enzymatic activity toward lecithins decreased with increasing chain length. Maximal hydrolysis rates for the lysolecithin series were measured with 1-dodecanoyllysolecithin. In this series increased affinities for substrates with increasing acyl-chain length was noticed. In the substrate concentration versus enzymatic velocity curves no breaks were observed at the critical micelle concentration of the various substrates. The initial site of attack during hydrolysis of short-chain lecithins was determined using 1-octanoyl-2pentanoyl-lecithin, 1-hexanoyl-2-hexyllecithin and 1 -hexyl-2-hexanoyllecithin. Both enzymes exhibited a pronounced preference for hydrolysis of the acyl ester bond at the 1-position. Especially the enzyme from beef pancreas seems to be suitable for the enzymatic preparation of 2-acyl lysolecithins from the corresponding short-chain lecithins.


Permeability and integrity properties of lecithin-sphingomyelin liposomes. The properties of multibilayered liposomes formed from mixtures of sphingomyelin and phosphatidylcholine in varying mole ratio (all containing one mole dicetylphosphate per 10 moles of phospholipids) have been studied. The principal findings are: (1) Over the range 0 to 1 mole fraction sphingomyelin the liposomes exhibit multibilayer structure as visualized by electron microscopy using negative staining. (2) The two phospholipids differ in their interaction with dicetylphosphate in a bilayer structure. In mixtures of the two the effect of sphingomyelin is dominant. (3) The ability of sphingomyelin to form osmotically active liposomes depends on its fatty acid's composition. (4) Liposomes of all mole fractions of sphingomyelin are osmotically active if the C24: 1 fatty acid content of sphingomyelin exceeds 10% of the total acyl residues. The degree of osmotic activity, however, depends upon the molar ratio between the two phospholipids. The highest initial rate of water permeability was found for lecithin liposomes. The maximal change of volume by osmotic gradients was obtained for liposomes composed of 1:1 lecithin to sphingomyelin (mole ratio). (5) Permeability to glucose increased with increasing lecithin mole fraction. (6) Liposomes composed of 1:1 lecithin to sphingomyelin have the largest aqueous volume per mole of phospholipid as measured by glucose trapping. (7) The osmotic fragility of liposomes made of sphingomyelin is higher than for those made of lecithin but the highest osmotic fragility was obtained for liposomes containing lecithin and sphingomyelin in 1:1 molar ratio. (8) When the temperature is abruptly lowered to about 2 degrees C, lipsomes formed from phosphatidylcholine release about 20% of trapped glucose during a transient increase in permeability. Liposomes containing 0.5 mole fraction sphingomyelin release about 30% of the trapped glucose under these conditions. Liposomes composed of sphingomyelin alone do not exhibit this phenomenon.


Fetal loss and familial chromosome 1 translocations. A structural abnormality of chromosome No. 1 was found in two families who had a history of repeated abortions. The propositus in Family H was a low birth weight, malformed infant who had a partial trisomy of 1g. His mother and a sibling were balanced carriers of a t(1;4) (q25;135). In family B, the 29-year-old phenotypically normal propositus and his mother were found to be balanced carriers of a t(1;12) (p12;q24). It is suggested that the fetal wastage in both families was related to the abnormal karyotypes of the parents. These two families also provide an opportunity to further understand the effect of an abnormality of chromosome number 1 on phenotype.


Variable expression of Marfan syndrome in monozygotic twins. A pair of monzygotic twins with the Marfan syndrome with variable expression is presented. One of the twins, in addition to more severe musculoskeletal and ocular manifestations, had coarctation of the aorta as the cardiovascular manifestation of this symdrome. Analysis of red cell antigens, serum proteins and dermatoglyphic examination suggests a high probability of monozygosity. Accordingly, the variation in expression of this autosomal dominant disorder between the twins is most likely due to the modifying influences of environmental factors. Also noteworthy is the fact that the resected coarctation tissue demonstrated the histopathologic changes characteristic of cystic medial necrosis, and thus served as an additional piece of evidence supporting the diagnosis of the Marfan syndrome. This was of particular importance in view of the absence of any family history of this syndrome and the absence of ectopia lentis or the more typical cardiovascular manifestations in either twin.


Cellular immune response to acetylcholine receptor-rich fraction, in patients with myasthenia gravis. Lymphocytes from patients with myasthenia gravis were stimulated when cultured in vitro with an electric eel extract enriched in acetylcholine receptor. No stimulation was observed with other antigens from nerve or muscle origin. Lymphocytes from non-myasthenic patients showed no response to any of these antigens. These findings suggest that an in vivo sensitization of lymphocytes to self acetylcholine receptor may occur in myasthenia gravis. The presence of sensitized lymphocytes, probably resulting from an autoimmune mechanism, might be an important factor in the pathogenesis of the neuromuscular block in this disease.


Immunoconglutinins and C3 in human saliva. High titres of immunoconglutinin activity (antibody to bound complement components) have been found in the parotid, sublingual and submandibular saliva of most healthy subjects. The immunoconglutinin (IK) titre in mixed saliva was substantially lower than in the other samples of saliva. C3 was detectable in only three of 164 samples of parotid, submandibular and sublingual saliva but was present in forty-seven of 117 mixed saliva samples. It is suggested that crevicular fluid is the major source of C3 in mixed saliva. A negative correlation was found in mixed saliva between the C3 concentration and the IK titre, and this suggested that C3 was the inhibitor of IK in mixed saliva. Binding of C3 to IK has been demonstrated in mixed saliva by using highly purified salivary IK and C3. Purified C3, C3i, C3c and C3d inhibited the activity of purified IK. It is suggested that salivary IK represents the secretion of a B-lymphocyte population which has evaded the mechanism responsible for inducing B-cell tolerance to autologous serum proteins. The reason for its persistence in the salivary glands, however, is not known at present.


[Production and splenic storage of platelets in autoimmune thrombocytopenia (author's transl)]. Platelet kinectics (using 51Cr labelling) was measured in 66 tests on 59 patients with autoimmune thrombocytopenia (the majority with chronic Werlhof's disease plus cases of acute Werlhof's disease, Evans' syndrome and visceral lupus), measuring platelet survival time, platelet production, and splenic storage rate of platelets. Dependent on the severity of the disease, the elimination curve showed an abnormal course during the initial phase which - in comparison with the normal - indicated approximately a difference of the spleen-dependent part of the disappearance rate from the antibody-dependent destruction. Accordingly, platelet storage in the spleen was slightly supernormal in the studied diseases. On average, platelet destruction was increased to more than twice normal. In 36% of cases platelet production remained within normal range. On average, the least increase in platelet production occurred in the acute form of Werlhof's disease. Maximal storage capacity, which can be six times normal and above, was reached in only a few cases.


Regulation of pineal rhythms in chickens: effects of blinding, constant light, constant dark, and superior cervical ganglionectomy. Pineal serotonin N-acetyltransferase activity and melatonin content exhibit marked daily changes in chickens; peak values occur during the period of low locomotor activity which coincides with dark in a 24-hour light-dark cycle. The photic and neural regulation of these daily changes were studied by measuring pineal serotonin N-acetyl-transferase activity, hydroxyindole-O-methyltransferase (HIOMT) activity, and melatonin content in experiments in which chickens were subjected to light-dark cycles, constant light, and constant dark and were surgically blinded or superior cervical ganglionectomized. It was found that: 1) The daily changes in N-acetyltransferase activity and melatonin content appear to persist in constant dark, and they disappear in constant light. 2) The eyes are not necessary for photic control of the daily changes, and the effect of constant light on N-acetyltransferase activity and melatonin content may be non-visual, that is, the eyes not being necessary. 3) The occurrence of the daily change in N-acetyltransferase activity and melatonin content does not require the superior cervical ganglia; the persistence of the changes in constant dark, however, may require the ganglia. 4) HIOMT activity was lower in constant light than in light-dark cycles and lower still in constant dark than in constant light. Neither the presence of the eyes nor the superior cervical ganglia affected HIOMT activity, as previously reported.


Loss of uterine luminal fluid in the rat: relative importance of changing peripheral levels of estrogen and progesterone. Experiments were conducted to determine the relative importance of the decline in circulating estrogen levels, as opposed to the increase in progesterone levels, in the hormonal control of the loss of luminal fluid from the uterus of the rat, an event which usually occurs early on the morning of estrus. Silastic capsules containing crystalline estradiol-17beta (E2) were implanted subcutaneously in ovariectomized immature rats. Approximately 64 h later, the capsules were either removed (E2 withdrawal) to mimic the fall in peripheral estrogen levels occurring at proestrus, or left in place (continuous E2), and, at the same time, progesterone or oil was administered. Fifteen hours later, irrespective of whether E2 was withdrawn or not, 2 mg progesterone reduced uterine luminal fluid accumulation to levels usually seen in intact animals on the morning of estrus; however, the loss of fluid occurred slightly sooner if E2 was withdrawn when progesterone was administered. By itself, E2 withdrawal resulted in only a small decrease in uterine luminal fluid by 15 h, even though serum E2 levels had fallen to less than 1.5 pg/ml by this time. This loss was brought about by escape of the fluid through the cervix rather than by its reabsorption from the lumen. The dose-response relationships between progesterone and uterine luminal fluid accumulation indicated that when E2 was withdrawn, a smaller amount of progesterone brought about the loss of uterine luminal fluid accumulation than when E2 was continuous. These results suggest that increased progesterone secretion on the afternoon of proestrus is essential for the loss of uterine luminal fluid, and that the decline in estrogen secretion at this time may be of importance by allowing the progesterone to be more effective.


Nyctohemeral and sex-related variations in plasma thyrotropin, thyroxine and triiodothyronine. TSH, T4, and T3 were measured by radioimmunoassay in plasma samples obtained from 77 young adult male and 114 female rats fed a Purina high-iodine diet and maintained in an isolated room, 2-4/cage, at 24 +/- 1 C with light from 0600-1800 h. In one experiment, 7 male and 7 female rats were decapitated every 3 h for 30 consecutive h and trunk blood was collected. There was a clear nyctohemeral rhythm of plasma TSH in both sexes characterized by a zenith at 1200 h and a nadir between 1800 and 2100 h. The plasma TSH cycle was approximately 180 degrees out of phase and negatively correlated (P less than .05) with that of plasma corticosterone (B) in both sexes. Although glucocorticoids have been reported to suppress TSH secretion, there was no causal relationship between plasma B and TSH in our experiments since the TSH cycles were normal in chronically adrenalectomized rats. Normal TSH cyclicity was not observed in severely iodine-deficient rats with extremely high plasma TSH levels although the nyctohemeral B rhythm was normal. Plasma TSH was approximately twice as high in males as in females (overall mean +/- SE: M = 149 +/- 11, F = 81 +/- 7 muU/ml, p less than 0.001). There was no significant difference (P greater than 0.05) in plasma TSH at different stages of the estrous cycle. Plasma T4 was slightly, but significantly, higher in males than females (overall mean +/- SE: M = 6.4 +/- 0.1, F = 6.0 +/- 0.1 mug/100 ml; P less than 0.001), while T3 was higher in females than in males (overall mean +/- SE: M = 69.5 +/- 1.7, F = 80.3 +/- 2.1 ng/100 ml; P less than 0.001). No significant nyctohemeral rhythm was observed in plasma T4 or T3 in either sex. These observations indicate that: 1) There is a nyctohemeral rhythm of plasma TSH which is independent of plasma B fluctuations and not associated with proportional changes in plasma thyroid hormones. 2) A sustained high rate of TSH secretion abolishes the normal nyctohemeral plasma TSH rhythm. 3) There are significant differences in plasma concentrations of TSH, T4, and T3 between male and female rats.


The effects of estrogens on sodium and potassium metabolism in rats. Male Wistar rats, housed in individual metabolism cages and fed standard rat chow, received, after a two-week acclimation period, daily intramuscular injections of 17beta-estradiol (0.17 mug/gram body weight) in peanut oil or 0.1 ml peanut oil alone for four days. Water and food intake were measured daily, as were urinary volume and electrolytes. 17beta-estradiol administration resulted in significant decreases in food and sodium and potassium intake and in urinary sodium and potassium excretion. In a second series of experiments, male rats treated with 17beta-estradiol or peanut oil as above had access to sodium-free food, water, and saline. In this group of animals, 17beta-estradiol administration resulted in a significant decrease in food intake but no significant changes in sodium intake or excretion. Potassium intake and excretion decreased as above. In a third experiment, sodium intake and output in female rats on standard rat chow correlated with the phase of the estrous cycle, being lowest during proestrus and estrous and highest during metestrus and diestrus. The data indicate that 17beta-estradiol reduces the renal excretion of sodium and potassium primarily as a consequence of a reduction in food intake and exerts no specific effect on either sodium or potassium metabolism.


Taxonomic difficulties in red tide and paralytic shellfish poison studies: the "tamarensis complex" of Gonyaulax. The type illustrations of the dinoflagellate Gonyaulax tamarensis contain an apparent reversal of the epithecal plates. Furthermore a culture from the type locality has been found not to be toxigenic. These two features have led a recent author to doubt the appropriateness of the allocation of toxic populations in the North Atlantic to this species or a variety of it (var. excavata Braarud). The latter has been raised to the status of a distinct species but the wrong name has been applied to it (G. excavata) as, according to the rules of priority, it should be G. phoneus (Woloszynska & Conrad) nov. comb. A history of this confused situation is provided. The criteria by which other similar species are recognised are summarised. The necessity for further study on the specific distinction of these taxa is stressed. G. conjuncta has been so inadequately described or rejected. Variability in the plate pattern of a culture of G. tamarensis var. excavata from British Columbia is illustrated and its bearing on the taxonomy of the group discussed. The presence of this toxic variety on the west coast of N. America is a new record for the Pacific Ocean.


Land drainage as a factor in "red tide" development. Although the exact mechanisms and factors of red tides are not fully understood, red tides are essentially a coastal phenomenon. The role of land drainage in the modification of coastal waters is discussed. The role of other factors (salinity, biologically active substances, etc.) that are altered by the process of land drainage is analyzed and correlated to experimental evidence derived from laboratory-grown dinoflagellate cultures.


Implications of dinoflagellate life cycles on initiation of Gymnodinium breve red tides. Florida Gymnodinium breve red tides are initiated in off-shore (approx. 18 to 74 km) coastal waters primarily in late summer-fall months. Past culture studies by W. B. Wilson suggested that this species could have a sexual cycle, inferring the possibility of an alternation of cytological and/or morphological generations. This possibility is further supported by numerous recent advances in dinoflagellate life cycle work which are reviewed in detail. If G. breve has a benthic resting stage (hypnozygote), as is suggested, then seed populations or seed "beds" can possibly be pinpointed and mapped.


The 1971 red tide and its impact on certain reef communities in the mid-eastern Gulf of Mexico. Effects of the 1971 spring-summer red tide upon mid-eastern Gulf of Mexico patch reef communities are discussed. In situ (SCUBA) observations at widely scattered reef localities between 13-30 m off Sarasota, Florida, both before and after the red tide support the following: 1) under the appropriate environmental conditions, red tides may result in near-complete extirpations of shallow-water (less than 40 m) reef biotas from extensive areas on the inner central-West Florida Shelf), 2) recolonization by certain biotic groups is relatively rapid (e.g., benthic algae and fishes) while that of others (e.g., alcyonarian corals, scleractinian corals, and echinoderms) is slow and may require several years, and 3) seasonal progression as well as true ecological succession following certain red tides may temporarily result in floral and faunal assemblages qualitatively and quantitatively distinctive from those prior to the red tide. It is therefore suggested that certain red tides, particularly those generated beneath pronounced thermoclines, may be previously underestimated phenomena regulating the composition, abundance, and distribution of shallow-water reef biotas in the mid-eastern Gulf of Mexico. It is surmised that the periodic occurrence of these red tides may prevent the evolution of a climax or equilibrium reef community.


Effect of anaerobic conditions in bottom waters on the occurrence of red tides at omura bay. The field observation that the occurrence of red tides at Omura Bay may have a close connection with the development of anoxic conditions in bottom waters was tested by bioassays of seawater collected during summer 1971. The stimulating effect of anaerobically-decomposed products of bottom mud on the growth of Gymnodinium type-'65 was examined. The results suggest that the development of oxygen deficiency in the bottom waters of Omura Bay makes the environment favourable for the growth of red tide organisms, both by the supply of inorganic nutrients and of some unidentified stimulants.


Further remarks on red tide models.

Further remarks on red tide models. Vertical migration as an accumulation mechanism in the formation of red tide models is discussed with reference to extant mathematical models. Its relationship to other biological and physical factors such as population density changes, tidal rhythms, nutrient limitation and light intensity is evaluated in terms of its possible causal role in red tides.


Catalysis of the photochemical dismutation of N-methylacridinium cation to N-methylacridone and N-methyl-9, 10-dihydroacridine by hydrophobic sites of horse-liver alcohol dehydrogenase and human serum albumin. The N-methylacridinium cation is bound to hydrophobic sites of horse liver alcohol dehydrogenase and human serum albumin with an observed stoichiometry of one molecule N-methyl-acridinium chloride per subunit of alcohol dehydrogenase and 2.5 molecules of the dye per molecule human serum albumin; the dissociation constants are 3.6 X 10(-5) M and 1.7 X 10(-5) M, respectively. In light, the proteins catalyze the dismutation of N-methylacridinium chloride to N-methylacridone and N-methyl-9,10-dihydroacridine. The presence or absence of oxygen has no effect upon the observed reaction rate. If horse liver alcohol dehydrogenase is used as catalyst, the reaction is inhibited by adenosine diphosphoribose and by 1,1'-dimethyl-4,4'-bipyridylium dichloride. It is concluded that the N-methylacridinium cation is bound within the catalytic site of the enzyme interacting with the binding sites of the nicotinium ring and/or the binding site of the lipophilic part of the substrate. The anaerobic photodismutation of N-methylacridinium chloride to N-methyl-9,10-dihydroacridine and N-methylacridone can be explained by several alternative patways (see Appendix by S. Hünig), the overall reaction being 2[N-Methylacridinium]+ + H2Ohw leads to N-Methyl-9,10-dihydroacridine + N-methylacridone + 2H+. The prerequisite, a high rate of proton transfer from the reaction site, seems to be common property of the hydrophobic binding regions for the N-methylacridinium cation in both horse liver alcohol dehydrogenase and human serum albumin.


Cellular RNA and influenza-virion RNA are synthesized from different pyrimidine-nucleoside-triphosphate pools in chick-embryo cells. Chick embryo cells infected with an influenza A (fowl plague) virus have been labelled with (3H)-uridine for different lengths of time. Virion RNA and cellular RNA have been separated by specific hybridization with a surplus of unlabelled viral complementary RNA and RNase digestion. The ratio of the specific radioacticity in the UMP and CMP moieties of both types of RNA has been determined. Since the rate of approach to equilibrium of CMP to UMP labelling of both types of RNA is completely different it is concluded that cellular and virion RNA are synthesized using different pyrimidine nucleoside triphosphate pools.


Intermolecular renaturation of hairpin loops leads to stable and specific aggregates of 28-S rRNA and precursor rRNAs from Xenopus laevis. Under certain extraction conditions, 28-S rRNA of Xenopus laevis can form specific dimers by intermolecular renaturation of a particular hairpin loop near the B end of the molecules. This was demonstrated by electron microscopy of isolated aggregates under conditions where rRNA shows a reproducible pattern of secondary structure. In 50% formamide, 15 mM sodium chloride, 1.5 mM trisodium citrate, pH 7.0, the aggregates dissociate into their monomers at a temperature (61 degrees C) at which the most stable hairpin loops of the 28-S rRNA are melting. Precursor rRNAs containing the 28-S rRNA region also form aggregates with 28-S rRNA by the same linkage mechanism. Since such artificial aggregates yield molecular weights higher than expected for true precursors of Xenopus rRNA, they may interfere in precursor rRNA studies. Analysis of whole-cell RNA pulse-labeled with (Me-3H)methionine, or nucleolar RNA pulse-labeled with (3H)uridine in the presence of tubercidin (inhibitor of rRNA processing), as well as electron microscopy of high-molecular-weight RNA fractions confirm that the 40-S precursor rRNA (2.8 X 10(6)) is the primary transcript of the ribosomal genes in Xenopus laevis.


The effect of hunger on free fatty acid and corticosterone plasma levels in rats. The time function of free fatty acids and of corticosterone in plasma in fed and fasted rats was investigated. Also a study of the influence of hypoxia on the concentration of plasma free fatty acids was carried out. Whereas fasting does not seem to stimulate lipolysis markedly before 12 h, 2 h of hypoxia elevate the free fatty acid level to its maximum. In the fasted condition, all values are significantly higher than corticosterone in the fed animal.


Circadian rhythm of bile secretion in the rat. In rats the bile flow and the estimated bile acid independant flow (BAIF) were significantly lower at 17.00 h than at 08.00 and 24.00 h. The decrease in BAIF paralleled the decrease in liver weight. Bile acid excretion was not different.


The effects of chronic alcohol ingestion in mice on contractile properties of cardiac and skeletal muscle: a comparison with normal and dehydrated-malnourished controls. In vitro isometric contractile tension was measured in heart and skeletal muscle in 3 groups of mice: 1. a control group, 2. a group maintained for 27 weeks on 20% alcohol, and 3. a group whose fluid intake was restricted to the extent equaling that which occurred in the alcohol treated animals. Results showed a reduction in cardiac twitch tension in both the alcohol and fluid restricted group, as compared to normal controls. We therefore consider that dehydration per se may play an important role in the etiology of alcoholic cardiomyopathy.


Further evidence for the genetic control of immune responsiveness to (T,G)-A--L by the B system in chickens. The association of the higher immune response to (T,G)-A--L with B1 allele was confirmed in F2 generation birds of the cross between the high responding CB and low responding IC chicken inbred lines. No influence of the C and I blood group systems on the anti-(T,G)-A--L antibody production was observed.


Radioimmunological determination of human C-peptide in serum. A routing radioimmunoassay for human C-peptide in serum is described. Antibodies against human C-peptide were raised by immunizing guinea pigs with human b-component. Nine out of 12 animals produced useful antibodies within 6 months. Insulin antibodies coupled to Sepharose were used to bind human proinsulin and insulin in the serum and after centrifugation C-peptide was determined in the supernatant. The detection limit of the assay (calculated as 2 SD from zero) was about 0.003 pmole of C-peptide (in 100 mul). The main sources of error were: (1) Normal and diabetic sera devoid of C-peptide gave a displacement of 125I-Tyr-C-peptide varying from 0 to 0.16 nM (6 different antisera). Only one antiserum (M 1181) showed no displacement, and the values of C-peptide determined with this antiserum in normal and diabetic sera were lower than the values determined with another antiserum, which gave a value of 0.07 nM in the sera free of C-peptide. It is suggested that displacement found with most antisera is due to substances in serum that are not related to C-peptide or proinsulin. (2) Serial dilutions of pancreatic extracts and sera may yield dilution curves slightly different to those of the synthetic standard. Possible explanations are discussed. These sources of error can be eliminated or reduced by the proper selection of antisera. Fasting sera from 15 normals, 8 maturity-onset diabetics and 10 insulin-requiring diabetics showed the following concentrations of C-peptide: (M 1181) 0.35 +/- 0.09, 0.74 +/- 0.51 and 0.21 +/- 0.14 (nM, mean +/- SD). One hour after 1.75 g/kg oral glucose the values increased to 2.24 +/- 0.71, 2.34 +/- 0.24 nM.


The influence of protein restriction imposed at various stages of pregnancy on fetal and placental development. The effect of protein restriction on fetal and placental growth was investigated. Pregnant rats were maintained on an isocaloric diet containing either 23% or 5% protein. The diet was imposed either from days 1-21 of gestation or from days 7-21 of gestation. Fetal body development was assessed. Fetal brain and placental growth were determined by both analysis of organ DNA, RNA and protein and differential radiochemical labelling procedures. Maternal protein restriction inhibited fetal growth. Brain weight was reduced due to a significant decrease in cellular content. Brain cell size was significantly increased and may have accounted for the reduction in cell concentration. Placental growth was similarly impaired. These data demonstrate impaired fetal and placental growth following decreased maternal dietary protein intake. Severity of growth retardation increased with the duration of malnutrition. The results also suggest that malnutrition may affect the rate of development, causing premature cessation of cell division and early cell differentiation.


Lysosomes in the cultivated mushroom (Psalliota bispora quel.). Fungine lysosomes are difficult to identify because some vesicular structures are present in hyphae, such as provacuoles, lomasome precursor, peroxisomes and spherosomes. Moreover, many Hymenomycetes, as the common cultivated mushroom (Psalliota bispora Quel.), lack tipical Golgi apparatuses, making ontogenesis of lysosomes a matter of difficult interpretation. As shown before (Scannerini, 1969) the hyphae of this fungus contain vesicles that reveal acid glycerophosphatase activity, thus we studied these organelles with morphological, cytochemical and biochemical criteria.


[Salmonella serotypes isolated at the Ospedale Maggiore at Novara during the years 1966-1973 in sporadic cases of enteropathy]. In 12.858 sporadic cases of enteric diseases examined from 1966 to 1973 at the Hospital Laboratory of Novara 380 strains of Salmonella were isolated. 19 different serotypes were identified. A large number of serotypes (SS. panama, agona, muenster, hato, manhattan, israel, anatum, stanleyville, coeln, sandiego, indiana, paratyphi A, urbana, vejle, thompson, goettingen) were encountered for the first time in this region.


Propagation of infantile gastroenteritis virus (orbi-group) in conventional and germfree piglets. Infantile gastroenteritis virus (orbi-group) recovered from stools of infants with acute nonbacterial gastroenteritis was administered per os to germfree and conventional piglets. Virus was found subsequently in stools and in the mucosal epithelial cells of the small intestine of these animals. Some animals developed diarrhea. Added proof of orbivirus replication was obtained through the use of tritiated uridine injections and the recovery of labeled virus in gut contents at the time of autopsy. Serological conversion was demonstrated in infected germfree piglets.


Subretinal fibrous membrane following argon laser photocoagulation of presumed histoplasmic maculopathy. Following an initial improvement after argon laser slit-lamp photocoagulation of histoplasmic choroiditis, progressive visual loss occurred. Histopathological examination showed a dense fibrous membrane between Bruch's membrane and the sensory retina. There was no recurrence of hemorrhage or subretinal fluid. This case report provides an explanation for visual loss in the absence of recurrent inflammation or vascular leakage.


Early photocoagulation treatment of active histoplasmic maculopathy. Photocoagulation has proved to be an effective means of treating active presumed histoplasmic maculopathy. Xenon arc and argon laser light sources have proved equally effective when moderately intense, confluent burns are produced, and both are ineffective when mild lesions are produced. The membrane must be destroyed for the treatment to be effective; and, of course, the fovea must be preserved. In treating neovascular nets that are very close to the fovea, the argon laser offers the advantage of being capable of producing a sharper zone of delineation than the xenon arc (Fig. 6). When moderate amounts of subretinal fluid or hemoglobin overlie the neovascular membrane, it is very difficult to achieve the required degree of coagulation. Under these circumstances, it is best first to try to reduce the height of the sensory retinal detachment by means of systemic steroid treatment. If this is not successful, xenon photocoagulation has produced better coagulation effects than the argon laser. Analysis of our data indicates that resultant visual acuity can be correlated with pretreatment visual acuity (Fig. 5), with best results achieved before visual acuity deteriorates beyond the 20/40 level. The closer the edge of the neovascular membrane is to the fovea, the more risky it is to treat. However, these lesions are also those most apt to destroy central vision if left alone. It is encouraging to note that in only 3 of the 16 lesions in which the foveal edge was within 1 degree of the fovea did the visual acuity deteriorate to the 20/200 level, compared to 50 percent deterioration reported in the natural history of this disease [3].


Argon laser photocoagulation in the treatment of presumed histoplasmic  choroiditis. Our experience with the evolving techniques we have reported has not resulted in significant increases in visual acuity over pretreatment levels. However, argon laser photocoagulation, properly given, does destroy subretinal neovascularization. The most significant points of technique are (1) heavy treatment of the entire frond;  (2) accomplishment of this usually by a 200-mu spot size, 0.2 to 0.5 second, at 300 to 400 mW. power; (3) the eye under retrobulbar anesthesia, and (4) following the case at intervals of three to five days until the neovascular frond is destroyed. If the edge of the neovascular frond is within 200 mu of the fovea, treatment presents a very definite hazard to foveal vision and should be attempted only in the most experienced hands and on only the best-informed patients.


Noradrenaline release by nicotinic acid. In doses (from 100 mug to 1 mg) nicotinic acid produced positive inotropic and chronotropic action on isolated frog heart. This effect was blocked by pronethalol and guanethidine administration. This effect was not observed in reserpinised frogs. Repeated administration of the same dose of nicotinic acid caused development of tachyphylaxis, in frog's heart preparation. The observations indicate that nicotinic acid induced a release of noradrenaline in frog's heart. On other preparations, such as isolated rabbit heart, rabbit's intestine and guinea pig seminal vesicles, nicotinic acid produced a nonspecific direct depressant action.


Photocoagulation of presumed histoplasmic choroiditis. Regadless of the etiology of the disciform lesion in the presumed ocular histoplasmosis syndrome, and regardless of our ignorance as to whether the pathogenetic mechanism relates in part to hypersensitization, or can be explained solely on a mechanistic interpretation (that is, chronic vascular decompensation [9]), the question of therapy can be evaluated independently. However, our knowledge regarding the natural history of these lesions is similarly incomplete and thus, without a controlled study, e cannot compare any of the therapeutic modalities with the natural history. Therefore, we cannot make any definitive statements regarding the value of therapy, let alone compare the different modalities. For these reasons, conclusions as to the results of photocoagulation of the macular lesions in the ocular histoplasmosis syndrome must remain incomplete...


Comparison of xenon arc and argon laser photocoagulation in ocular histoplasmosis. Argon laser and xenon arc photocoagulation can be utilized to obliterate choroidal neovascularization in selected cases of macular histoplasmosis. Central vision can be preserved in many instances if criteria for patient selection, treatment techniques, and method of follow-up, as described in this chapter, are adhered to rigidly. Of 40 patients treated with argon laser photocoagulation, 75 percent maintained or improved central vision an average of one year following treatment. Nonetheless, there is a definite need for a prospective controlled study to document the efficacy of this mode of treatment on a long-term basis.


Prognostic criteria in macular histoplasmic choroiditis. 1. Fifty percent of 22 patients "desensitized" to histoplasmin developed subsequent activity, as compared to 44% of 23 patients without "desensitization." 2. Prednisone-induced remission of subclinical activity in patients monitoring their own central fields appears to be the most rewarding therapy for these desperate patients.


Expansion of bladder capacity by the use of intact sigmoid. An experimental study and two case reports. To enlarge bladder capacity after extensive segmental bladder resection, the authors sutered bladder margins to the serosal aspect of intact sigmoid (Heeg's method). Experimental data and two clinical cases have proved this technique to be of practical value.


Contribution to the evaluation of operability limits of tumours. The case of a patient with cancer of the sigmoid is presented. Thanks to surgical procedures, radiological treatment and chemotherapy, his life was prolonged by 8 years. It is worth noting that the original tumour gave later distant metastases to the ureter, right kidney, bladder, intestines and lymph nodes.


Morphology and function of the bladder and urethra in female urinary incontinence. The conventional investigations, gynaecological examination and cystoscopy give very little information about the causes of incontinence. History taking makes it possible to divide the symptoms into either stress- or urge incontinence. Cystometry, lateral voiding cysto-urethrography and urodynamic examination including sphincter EMG enable us to divide the pathological conditions into suspension defects and bladder dysfunctions. The suspension defects are bladder base insufficiency, vesical descensus and trigonocele. The operation of choice for these conditions depends on whether the suspension defect is anterior or posterior. The bladder dysfunctions are supranuclear and infranuclear neurogenic dysfunctions. The treatment in these cases will ordinarily be medical.


Prostatic infarction.

Prostatic infarction. Prostatic infarction is a relatively frequent complication of adenoma of the bladder neck. Nevertheless its importance is minimal as compared with infarctions of vital organs like the brain, heart, lungs or kidneys. General and local factors may play a role in its pathogenesis. Besides other factors, it may contribute to the development of acute retention. Attention is called to the difficulties of differential diagnosis at both gross and microscopic examinations. A misdiagnosis is most frequently made in neoplastic diseases of the prostate.


[The treatment of anorgasmia in males].

[The treatment of anorgasmia in males]. Primary anorgasmia is defined as the inability, in spite of nocturnal pollution and complete erection, ever to achieve orgasm either by masturbation or by sexual intercourse. 30 patients with primary anorgasmia were treated with an electro-vibrator, 26 of them with a positive result. The preceding unsuccessful therapeutical attempts with medicaments and psychotherapy allow the conclusion that with primary male anorgasmia time should not be wasted unnecessarily. Instead, a mechanical ipsation-aid should be employed, regardless of the etiology. Simultaneous intensive psychological guidance including instruction about normal sexual behavior is necessary. Some cases of secundary anorgasmia also react favourably to this treatment.


Demonstration of a diurnal variation in serum parathyroid hormone in primary and secondary hyperparathyroidism. It had been reported previously that there is a diurnal variation in serum parathyroid hormone (PTH) in normal subjects but not in patients with primary hyperparathyroidism. Studies were performed to determine whether there is a diurnal variation in serum PTH in primary or secondary hyperparathyroidism and whether the nocturnal increase in serum PTH, if present, could be prevented by induced hypercalcemia. Serum PTH and calcium were measured in five normal subjects, two patients with pseudohypoparathyroidism, and fourteen patients with primary hyperparathyroidism, twelve of whom were subsequently found to have parathyroid adenomas. In the normals, there was a mean decline in serum PTH of 0.07 ng/ml before noon and a mean increase of 0.04 ng/ml after 8 PM. In primary hyperparathyroidism there was a mean decline in serum PTH before noon of 0.11 ng/ml and a mean increase of 0.11 ng/ml after 8 PM. In both groups, the lowest mean serum calcium values were noted between midnight and 6:00 AM. Patients with pseudohypoparathyroidism showed a nocturnal increase in serum PTH. In each of two normal subjects, two patients with primary hyperparathyroidism, and two patients with pseudohypoparathyroidism, calcium, 4 mg/kg body weight per hour for 4 hours (8:00 PM to 12 midnight), produced hypercalcemia and prevented the nocturnal increase in serum PTH. We have concluded that a diurnal variation in serum PTH often occurs in both normal subjects and in patients with primary or secondary hyperparathyroidism and that nocturnal increases in serum PTH can be prevented by induced hypercalcemia.


Non-chromatographic radiotransinassay for cortisol: application to human adult serum, umbilical cord serum, and amniotic fluid. Rapid (1-2 hour) non-chromatographic radiotransinassay using horse transcortin can be used to measure cortisol in umbilical cord serum (after hexane-carbon tetrachloride prewash and methylene chloride extraction), in amniotic fluid (after methylene chloride extraction only), and in adult serum (after dilution and boiling without extraction). Since horse transcortin has high affinity (2.4 x 10(9) l/mol) for cortisol, only a few microlitres of sample is required. The assay appears to be highly specific for cortisol clinically except in congenital adrenal hyperplasia.


Stability of aflatoxin M in milk.

Stability of aflatoxin M in milk. This three-part study was designed to determine aflatoxin M recovery from pasteurized and/or stored cow's milk. (a) Aflatoxin M was added to samples of raw Holstein milk at a concentration of 2.0 mug/liter. Half of each sample then was pasteurized at 63 C for 30 min, and both raw and pasteurized portions were stored at 4 C up to 17 days. (b) Samples of raw milk, pasteurized (77 C, 16 s) skim milk, dry cottage cheese curd, and cottage cheese whey were taken from a commercial operation in an area in which natural contamination had been encountered. (c) Milk from a cow dosed with aflatoxin B1 was stored frozen (-18 C) in bulk and in assay-size sample containers for 120 days. Aflatoxin M was recovered completely after either storage or pasteurization in (a) and (b). In (c), a recovery deficiency was detectable after 68 days of storage, which increased to 45% of the original value by 120 days. These observations differ from those of others in that loss of aflatoxin M was significant after pasteurization or storage of raw milk, totaling 87% loss after 120 days of frozen storage. Aflatoxin M partitioning between curd and whey in the preparation of cottage cheese agrees with more recent studies, but differs from previous reports. Three possible explanations for the differences are offered.


Influence of environmental heat on peripheral plasma progesterone and cortisol during the bovine estrous cycle. Plasm progesterone and cortisol were measured in jugular blood by competitive protein-binding assay. Six cycling, estrus-synchronized Guernsey heifers were followed for four consecutive estrous cycles under two controlled temperature (18.2 C, 55% relative humidity; and 33.5 C, 55% relative humidity) conditions. Prolonged exposure to heat of Guernsey heifers increased plasma progesterone on days 2 to 19 of the first cycle and only on days 2 to 8 of the second cycle. However, heat stress depressed plasma cortisol in both cycles and reduced the correlation coefficient between these steroids relative to specific stages of the estrous cycle.


Effects of temperature on hatching and development of Nematospiroides dubius in aerated water. Fresh eggs obtained from female Nematospiroides dubius were cultured at temperatures ranging from 5 degrees C to 33 degrees C. Hatching occurred between 5 degrees C and 30 degrees C; third stage larvae were obtained between five degrees C and 25 degrees C. The minimum time required from hatching to development to the third stage was 3-6 days (at 20 degrees C) and the maximum was seven days (at 5 degrees C). Larvae cultured at higher temperatures were smaller than those cultured at lower ones.


[Prognosis of cancer of the corpus uteri]. A statistical study of 240 cases of cancer of the body of the uterus treated throughout at the Institute Gustave-Roussy has led us to the following conclusions. The number of patients who survive drops rapidly after the first year of follow-up and this phenomenon is particularly marked in women who are more than 60 years of age. Mortality linked to other causes of death does not account for the total falling off in the number of those who survice among the older patients. A study of the clinical spread of the disease shows that most cancers stay confined to the body of the uterus and this really lessens the value of a classification based on spread of the disease for prognostic purposes. A systematic study of hysterograms taken before any treatment is started does on the other hand give us two prognostic pointers. The first is the size of the endometrial cavity and the second the maximum diameter of the tumour. These two radiological characteristics allow us to make an interesting division of cancers that are limited to the body of the uterus. The overall survival rate after 5 years is 61 per cent. When we take into account the dimensions of a tumour we can place patients into two groups; those with tumours that are less than 45 mm in diameter have a 71 per cent survival rate and those with tumours of greater than 45 mm diameter have a survival rate of 45 per cent.


Preovulatory changes in the ovaries during the first spontaneous pro-oestrus in the rat. Events in the ovaries during the first spontaneous pro-oestrus were compared with those in the adult rat. The occurrence of first spontaneous pro-oestrus was determined from vaginal smears after surgical opening of the vagina. Pubertal rats showed a remarkable increase in ovarian weight from 10.00 to 15.00 h on the day of pro-oestrus, which was absent in the adults. They also showed an earlier and more pronounced interstitial oedema. Dispersion of cumulus cells, resumption of meiosis and ovulation also occurred slightly earlier in pubertal rats. A distinct difference was found in the growth rate of follicles of ovulatory size, i.e. follicles of larger than or equal to 500 X 10(5) mum3. At the first pro-oestrus these follicles showed a slower and less pronounced increase in size from 10.00 to 17.00 h compared with the adult follicles at this time, although this disparity was made up by a marked increase in growth from 17.00 to 24.00 h. The development of a new crop of follicles progressed similarly in the pubertal and adult animals. Follicular atresia seemed to progress more rapidly from 10.00 to 15.00 h in the pubertal animals compared with adults but from 15.00 h onwards no further differences were observed. The possible causal factors underlying the observed differences between the pubertal and adult animal are discussed.


Gonadotrophin and steroid levels around the time of first ovulation in the rat. Luteinizing hormone, FSH, prolactin, oestradiol and progesterone concentrations were measured by radioimmunoassay in the blood of female rats from 7 days before the first ovulation (the day of first ovulation is designated day 0) until the day after the second ovulation. Serum LH concentrations varied between 29 and 59 ng NIAMDD-rat-LH RP-1/ml from days -7 to -2. On the day preceding first ovulation (day -1) a steep increase in serum LH was found between 13.00 h and 15.00 h reaching a maximal value of 2100 ng/ml at 17.00 h. Thereafter LH levels decreased to undetectable values (less than 15 ng/ml). Serum FSH concentrations from days -7 to -2 varied between 108-154 ng NIAMDD-rat-FSH RP-1/ml; increased concentrations were found on the afternoon of day -1 and on the morning thereafter (first oestrus) with a maximal value of 1150 ng/ml at 19.00 h on day -1. On the day preceding the second ovulation (day +4) LH and FSH peaks were again found. Prolactin concentrations on the days preceding first ovulation were generally low. A small rise was found nearing first ovulation (12-7 ng/ml, day -6; 23-9 ng/ml, day -2). On day -1 a peak (118 ng/ml) was found at 15.00 h, similar to that found on day +4 in adult pro-oestrous rats. Plasma progesterone concentrations also reached a peak value (50 ng/ml) on day -1, at 17.00 h, preceded by concentrations between 3-5 ng/ml from days -6 to -2. Progesterone concentrations after the first ovulation showed a pattern characteristic of the adult cycle. Plasma oestradiol levels were un-etectable (less than 10 pg/ml) from days -6 to -2; a clearly increased oestradiol concentration was found on day -1, reaching a value of 98 pg/ml. One and two days before the second ovulation, oestradiol levels rose again. The differences and similarities between pubertal and adult pro-oestrous hormone peaks are discussed.


Effects of oestradiol-17beta, oestradiol benzoate and the synthetic oestrogen RU 2858 on sexual differentiation in the neonatal female rat. Groups of neonatal female rats were treated for the first 5 days of life with oestradiol-17beta, oestradiol benzoate or a synthetic oestrogen, 11beta-methoxy-17-ethynyl-1,3,5(10)-oestratriene-3,17beta-diol (RU 2858), in daily doses ranging from 0-5 to 1000 ng. Oestradiol-17beta had no effect on adult ovarian cyclicity or sexual receptivity after ovariectomy and oestrogen+ progesterone treatment. Ovarian cyclicity was prevented by 100 ng or more oestradiol benzoate/day, and by all doses of RU 2858. Only rats receiving 50 ng oestradiol benzoate/day or 0-5 ng RU 2858/day showed normal receptivity. The defeminizing action of RU 2858 was at least 100 times greater than that of oestradiol benzoate; it is suggested that this greater potency is due to the low affinity of RU 2858 for the oestradiol-binding protein in the plasma of neonatal rats. These results indicate that defeminization of the neonatal rat brain can be induced by physiological amounts of oestrogen, and are discussed with reference to the action of testosterone.


Ureolytic bacteria in sheep rumen.

Ureolytic bacteria in sheep rumen. Estimates were made of the numbers of viable bacteria in the rumens of sheep receiving different rations. Representative colonies were isolated and tested for urease production. Some urease-positive isolates were characterized and identified. The ureolytic activities of the urease-producing isolates were determined and compared with the activity of rumen fluid. The rations fed to the sheep did not exert a significant influence on the relative numbers of the urease-producting organisms in the rumen. No obligately anaerobic ureolytic bacteria were found. All urease-positive isolates were facultatively anaerobic, Gram-positive, catalase-positive cocci. Out of ten isolates, nine were identified as Staphylococcus saprophyticus and one as Micrococcus varians. The total urease activity of the different isolates based on the lowest numbers in which they were present in the rumen, compared favourably with the urease activity of rumen fluid. The facultatively anaerobic Gram-positive cocci were probably responsible for a large proportion of the urease activity of the rumen fluid. Conditions prevailing in the rumen were found to be conducive to urease production by the isolates tested.


Leghaemoglobin and the supply of O2 to nitrogen-fixing root nodule bacteroids: presence of two oxidase systems and ATP production at low free O2 concentration. Studies of rates of consumption of dissolved O2 by suspensions of bacteroids (Rhizobium japonicum, strain CB1809) from soybean root nodules showed the presence of two different terminal oxidase systems. A high-affinity system, sensitive to inhibition by N-phenylimidazole and by carbon monoxide, was most active when the dissolved O2 was between 0-01 and 0-1 muM. At 1 muM-O2 or higher, this oxidase system had little activity and O2 was consumed largely by a low-affinity system insensitive to these inhibitors. At low concentrations of dissolved O2, bacteroid respiration rates appeared to be diffusion-limited. When purified oxyleghaemoglobin was added to such systems, this restriction was relieved and respiration was maintained to much lower concentrations of free dissolved O2, where nitrogenase activity was greatest. Analysis of reactions which were terminated at various stages during the depletion of O2 from oxyleghaemoglobin showed that at low free O2 concentration, the high-affinity pathway produced up to five times greater bacteroid ATP concentrations than the low-affinity oxidase pathway operating about 1 muM free O2 in the absence of leghaemoglobin. At intermediate free O2 concentrations, occurring during the later stages of deoxygenation of oxymyoglobin, intermediate concentrations of ATP were found in the bacteroids.


Interferon induction by viruses and polynucleotides: a differential effect of comptothecin. The plant alkaloid comptothecin inhibits interferon production induced by Newcastle disease virus (NDV) or ultraviolet-irradiated NDV in chick and human cells, and by Sindbis virus in chick cells. It has no effect on interferon production induced by poly (rI).poly(rC) in chick and human cells. No effect of comptothecin could be detected on the multiplication of NDV, and it is concluded that the inhibition reflects a difference between interferon induction by viruses and by polynucleotides.


The regressive effects of frustration upon the concrete reasoning ability of seven and eight-year-old-boys. Forty-four seven- to eight-year-old boys were divided randomly into a experimental group and a contro group. All children took Forms A and B of the Concrete Reasoning Test as arranged by Siegelman and Block (12) and originally constructed by Smedslund (13). In the experimental group, each boy took Form A first and then was told that he could win a prize, which he selected from several items offered, if he could put together an easy puzzle (which was difficult in actuality). Each boy was given three minutes to work on the puzzle and was then given Form B. After each item he was allowed to work again on the puzzle for three more minutes. The individuals in the control group followed the same procedures, except that they had a much easier task to perform. It was hypothesized that (a) frustrated boys at a high level of concrete reasoning ability will regress less than frustrated boys at a lower level with the exception that (b) boys in the transitional period of thinking will regress more than those who are not, and (c) those boys who are frustrated will tend to regress more than those who are not. The results supported all of these hypotheses.


Quantitative determination of tocopherols by high-speed liquid chromatography. A high-speed liquid chromatographic method for the determination of alpha-, beta-, gamma- and delta-tocopherols using a spectrophotometer or a spectrofluorometer, is described. The best results were obtained using a 2.3 mm i.d. x 500 mm normal phase partition column, JASCO-PACK WC-03-500 and a spectrofluorometer as a specific detector. A mixture of diisopropyl ether and n-hexane (2:98) was used as the mobile phase. A flow rate was set at 0.8 ml/min. A mixture of pure alpha-, beta-, gamma- and delta-tocopherols or natural tocopherols in vegetable oils were separately determined by this method.


The nature of extraversion: a genetical analysis. A biometrical-genetical analysis of twin data to elucidate the determinants of variation in extraversion and its components, sociability and impulsiveness, revealed that both genetical and environmental factors contributed to variation in extraversion, to the variation and covariation of its component scales, and to the interaction between subjects and scales. A large environmental correlation between the scales suggested that environmental factors may predominate in determining the unitary nature of extraversion. The interaction between subjects and scales depended more on genetical factors, which suggests that the dual nature of extraversion has a strong genetical basis. A model assuming random mating, additive gene action, and specific environmental effects adequately describes the observed variation and covariation of sociability and impulsiveness. Possible evolutionary implications are discussed.


Desirable versus undesirable life events: their relationship to stress and mental distress. The research of Holmes, Rahe, and their associates disclosing that life events and stress are related to the onset of physical illness is extended to the psychological domain in the present study. Using a modified version of their life events checklist, it is shown that an accumulation of life events is correlated with self-reported tension and distress, with emotional disturbances manifested by depression, paranoid thinking, suicidal proclivity, and anxiety, as well as with behavioral indications of stress such as drinking and traffic accidents. Most importantly, it is shown that these relationships do not hold for desirable life events but primarily for undesirable events. Thus, the authors suggest that the quality of the events in terms of their desirability is the crucial determinant of stress and the above-mentioned relationships rather than simply the life change produced by the events, as suggested in earlier studies. Methodological and theoretical implications for future research are discussed, emphasizing the importance of studying additional stress-relevant dimensions such as anticipation of the events and control over their outcome.


[Relations between the changes of the phagocytic activity of the reticuloendothelial system and the alterations in protein and nucleic acids contents of the rat liver (author's transl)]. The phagocytic activity of the reticuloendothelial system (RES) was evaluated after a single oral administration of soya-bean oil to male rats (15 g/kg). 1. An emulsion of soya-bean oil administered to the rat by gastric intubation activated the phagocytosis of colloidal carbon; the stimulation appeared on the 2nd day after treatment and persisted up to the 3rd day. There was also a relation between the stimulation of RES activity, under our experimental conditions, and the increased level observed in the protein and nucleic acid contents of the liver. 2. In contrast, without emulsion, soya-bean oil depressed the phagocytic activity on the 2nd and 3rd days after administration of the oil. These changes were associated with a diminution in ribonucleic acid and protein contents of the liver. Although the mechanisms of soya-bean oil-induced alterations of phagocytic activity were not clarified, there was a relationship between the RES stimulation or inhibition and the modifications in nucleic acid and protein contents of rat liver.


The role of the rete ovarii in meiosis and follicle formation in the cat, mink and ferret. Ovarian morphology was studied from the inception of meiosis in the cat, mink and ferret. It was shown that "open connections", allowing cellular contact, existed between the intra-ovarian rete cords and the groups of germ cells as well as between the surface epithelium and the germ cells. The germ cells in the innermost part of the cortex and lying in contact with the rete cells were those which were the first to enter meiotic prophase. Later, the more peripheral oogonia transformed to oocytes. The first follicular formations occurred at the innermost part of the cortex. The granulosa cell layers were in open connection with the intra-ovarian rete cords. In the mink and ferret, a certain part of the rete system at the hilus differentiated into the hilar rete body. In all animals, the extra-ovarian rete cells were actively secreting. It is proposed that the rete system interacts with the cortex, initiating the start of meiosis and that the rete cells as well as cells of the surface epithelium contribute to the granulosa cell layer.


Long-term effect of HCG on plasma testosterone in bulls. The spontaneous diurnal variation of peripheral plasma testosterone concentrations in four bulls was established and then the long-term effect of a single intravenous or intramuscular injection of HCG on testosterone levels was studied. Intravenous and intramuscular HCG injections produced, within 1/2 hr and 3 hr, respectively, a rapid rise of testosterone to levels equivalent to the highest values seen in the diurnal pattern. A second increase of up to x2 to x3 the highest values of the diurnal cycle was observed 2 days after the injection of HCG, and the testosterone level remained high for at least 3 to 4 days after plasma levels of HCG were no longer detectable. The pattern of diurnal variation after HCG revealed an attenuation of the extensive spontaneous variation and high levels with only slight fluctuations were maintained.


Environmental factors and reproduction in the female hopping mouse, Notomys alexis. Australian hopping mice (Notomy alexis) were subjected to short or long photoperiods, different social environments and/or water deprivation. The age at which vaginal opening and first oestrus occurred was delayed by short photoperiods and by the absence of male proximity. Water deprivation prevented normal maturation. The normal 7 to 8 day oestrous cycle was prolonged by short photoperiods or water deprivation. Animals deprived of water had lighter body, ovarian and uterine weights, and follicular growth seemed to be impaired. No differences in organ weights were found between animals in the two photoperiods. The significance of the findings is discussed.


Further evidence of normal fertility and the formation of balanced gametes in sheep with one or more different Robertsonian translocations. Mating experiments are described for sheep with three different Robertsonian translocations in the single heterozygous t1, t2 and t3, homozygous t1t1 and t3t3 and double heterozygous t1t2 and t1t3 state. The experiments were designed to investigate several previously reported unusual chromosome segregation ratios in sheep, to test the fertility of translocation heterozygous ewes mated to rams of normal karyotype and to test both the fertility and segregation patterns of sheep which were double translocation heterozygotes. The fertility of the translocation heterozygous ewes was normal as assessed from conception to first service, numbers of non-conceiving ewes and lambing percentages. Two types of double translocation heterozygous rams mated to ewes of normal karyotype produced regular chromosome segregation patterns in their progeny and the matings were of normal fertility. Double translocation heterozygous ewes were also fertile. Four sheep were bred with 51 chromosomes. Two of these were triple heterozygotes with three different Robertsonian translocations 51,xy,t1t2t3 and 51,xx,t1t2t3 and two were homozygous for one translocation and heterozygous for the others, namely 51,xx,t1t2t3 and 51,xxt1t3t3. All sheep were phenotypically normal. It is concluded that the t1,t2 and t3 Robertsonian translocations of sheep do not affect reproductive performance significantly.


Plasma relaxin immunoactivity during the oestrous cycle of the ewe. Plasma relaxin immunoactivity was measured every 2 hr during 4-day periods in a series of sheep to cover the 17-day period of the ovine oestrous cycle. The immunoactivity fluctuated considerably throughout eacn 4-day period, and a large betwee-animal variation was found. A marked episodic release, occurring at approximately 12.00 and 24.00 hours, was identified and shown to occur more regularly either at certain times of the cycle or in certain animals. Relaxin immunoactivity was high throughout the late pro-oestrous phase of the cycle (Days 15 and 16), and at 24 hr after the onset of the LH peak, conincidnet with the approximate time when ovulation occurs. Bursts of relaxin activity were found on Days 8 to 9 in one ewe, and Days 10 and 11 and 13 to 14 in another. There was no significant correlation between prolactin levels and relaxin immunoactivity in one ewe studied throughout the oestrous period.


Production of mastitis in mice with human and bovine ureaplasmas (T-mycoplasmas). Five ureaplasmas (T-mycoplasmas) of human origin and four of bovine origin were inoculated into the mammary glands of mice. The strains multiplied and neutrophils were observed in sections of infected glands. Some of the glands were macroscopically inflamed, albeit slightly, at necropsy but none of the mice showed any sign of disease during the course of the experiments. All nine ureaplasma strains produced mastitis in BSVS mice and the mammary glands of mice appear more susceptible to ureaplasmas than the udders of cows or goats. Mouse mastitis is suggested as being a suitable small animal model for studying ureaplasma infections.


Reversible loss in suspension culture of a major cell-surface glycoprotein of the TA3-Ha mouse tumor. A major cell-surface glycoprotein of the TA3-Ha ascites mammary adenocarcinoma diminished during transfer from ascites growth to cell growth in suspension culture. A sensitive, hemagglutination-inhibition assay that used a lectin from Vicia graminea seeds indicated approximately a 50% loss after 7-10 days of culture and a 90% loss after 2 months. These findings were corroborated by carbohydrate and amino acid analysis with gas-liquid chromatography of trypsin glycopeptides released from the cell surface. Repassage of the cultured cells in vivo caused the reappearance of the surface glycoprotein.


Electron microscope study on human lymphocyte-sheep erythrocyte rosettes. Nonimmune rosette formation of human peripheral blood lymphocytes and cultered MOLT 3 and MOLT 4 cells with sheep red blood cells was studied by transmission electron microscopy. At the cell contact area of the rosette, lymphoid and red cell membranes were parallel and 80-100 A apart. The inner leaflet of the lymphoid cell membrane seemed denser, and amorphous substance attached to its cytoplasmic face. The cell contact area was 100-1000 nm wide and frequently on the lymphoiid cell body rather than on microvilli, though some cells extended microvilli near red cells.


Induction of interferon and erythropoietic differentiation in cells transformed by Friend virus. Two lines of Friend virus (FV)-transformed mouse spleen cells have been analyzed in respect to their interferon production capacity: neither F4 cells, which liberate infectious FV when kept under tissue culture conditions, nor the thymidine kinase-deficient B8 cells, which do not produce significant amounts of FV, release detectable amounts of autogenous interferon into cell supernatants. However, interferon is produced in these cells in amounts comparable to that in L-929 cells when interferon induction is initiated with UV-inactivated Newcastle disease virus. Conversely poly(I)-poly(C), a potent interferon inducer in L-929 cells, proved ineffective in this capacity in F4 or B8 cells. When erythropoietic differentiation is induced in these cells by dimethyl sulfoxide, no autogenous interferon production occurs, but with NDV-induction a four- to fivefode increase of interferon production is observed. A similar elevation of interferon production is achieved during 5-bromodeoxyuridine stimulation of differentiation in the thymidine kinase-deficient B8 cells. The refractiveness against poly(I)-poly(C) displayed in unstimulated cells is not overcome at any stage of differentiation, indicating major differences of Newcastle disease virus and poly(I)-poly(C) induction mechanisms.


Evidence for an "early early" vaccinia virus-induced protein which causes a density change of infected L-M cells. The density decrease of vaccinia virus-infected L-M cells observed in a Ficoll density gradient by 2 h postinfection was found to be dependent on RNA synthesis and protein synthesis but independent of DNA synthesis. Using low multiplicities of infection, the required RNA and protein species appeared to be synthesized before parental viral DNA became sensitive to DNase, i.e., while the bulk of input virus was still at the core stage of uncoating. To date only thymidine kinase and a vaccinia virus-specific cell surface antigen (as well as the putative uncoating protein) have been shown to be "early early" proteins, i.e., synthesized while parental viral DNA is still enclosed within the core. Both heat- and UV-inactivated virus failed to cause the cell density decrease. The need for a functioning viral genome implies that the required early early RNA and protein species are virus specific and not cell specific. Thus the protein leading to the density decrease of L-M cells, induced very early after infection with vaccinia virus, represents one of the first bits of viral genetic information expressed after infection. Since antibody-neutralized virus is still capable of causing the phenomenon of cell density decrease, the basis of neutralization of vaccinia virus by specific antibody must be other than by inhibiting early early transcription and/or translation.


Physical dependence on morphine, phenobarbital and diazepam in rats by drug-admixed food ingestion. To produce physical dependence on morphine, phenobarbital and diazepam in rats, these drugs were mixed with powder form of rat food in concentrations of 0.5 mg/g, 1 mg/g and 2 mg/g of food. One group of rats (the lower dose group) was continuously exposed for 1 week to two morphine-admixed foods with morphine to food ratios of 0.5 mg/g and 1 mg/g in a cage. The other group (the higher dose group) could choose between two morphine-admixed foods with morphine to food ratios of 1 mg/g and 2 mg/g. After 1 week, morphine-admixed foods were replaced with morphine free food for 2 days. Both groups of rats showed greatly reduced body weight and food intake after the first 24-48 hr withdrawal. The body weight decrease was greater for rats in the higher dose group. Control groups of morphine dependent rats were kept on the morphine added food diets and showed the same body weight increase as well as normal control rats during the course of these experiments. Physical dependence on phenobarbital and diazepam was produced using the same dosage schedules as with morphine. Both the lower and higher dose groups showed significant decrease in body weight due to withdrawal after 1 week of drug-food exposure. Levallorphan (0.5, 1, 3 and 5 mg/kg, s.c.) administered to morphine dependent rats had dose-dependent effects on the intensity of abstinence symptoms (e.g., diarrhea, piloerection and wet shakes phenomena), maximal decrease in body weight and duration of decreased body weight. Cross-physical dependence between phenobarbital and diazepam was demonstrated by this method.


[Malignant melanoma in a child (author's transl)]. The rare case of a ciliary malignant melanoma in an 11-year-old boy is reported. Signs of a subacte iridocyclitis with secondary glaucoma were the main clinical changes. The striking histological details were numerous wide blood vessels with thin endothelial walls within the tumour, and the sparse invasion of the tips of the ciliary processes, and between the sphincter pupillae and the pigment layer of the iris; many tumor cells displayed more than one nucleolus. Finally, a survey is given on the intraocular tumours in children.


[Double-sided occlusion of the great vessels of the neck after X-ray treatment in childhool (author's transl)]. This paper reports on two cases of bilateral blockage of the carotid vessels many years after X-ray treatment of the neck lymph nodes in childhood. The X-ray overdoses resulted in the damage and shrinkage of the skin and upper connective tissue of the neck. The time of delay from X-ray treatment to the first signs of vessel blockage was 45 years and 51 years. The first patient, male aged 62 years, has dilated vertebral arteries. Nine years after bilateral antiglaucomatous operation (with cataract removal) the intraocular vessel processes have slowed and there is good compensation of the carotid vessels as shown by CNS function. The second patient, female aged 62 years, exhibited moreover a block of the right vertebral artery and stenosis of the left vertebral artery. This resulted in acute blindness of the left eye and then of the right eye 1 1/2 years later. Puncture of the anterior chambers and Iridencleisis (right eye) were performed, but without success. Together, with loss of acuity, she had constantly increasing neurological deficiencies and psychopathological changes consistent with thrombosis of the left vertebral artery. Pathiological and anatomical stenosis in the region of X-ray treatment should have warranted surgical intervention to restore normal circulation.


[A clinical experimental study on the therapeutically effective component of retinal phosphatides (author's transl)]. In the present study it was demonstrated that neither the relation of the single phosphatide components nor the organ which serves as the source of the phosphatides have any importance on the therapeutic effect on the retina. The therapeutic effect of the phosphatide depends on their content of C 22:6. The phosphatide complex from livers of pigs, feeded with fish, has a particularly high content C 22:6. Its therapeutic effect and its production offers great technical and economical advantages.


Reproductive biology and postnatal development of the neotropical climbing rat, Tylomys. Neotropical climbing rats (Tylomys), offspring of animals from Mexico and Panama, were maintained in the Michigan State University Museum-Live Animal Colony for the purpose of collecting data on reproduction. Vaginal smears indicated an estrous cycle 6.8 +/- 0.4 da under natural winter lighting, 12.0 +/- 2.5 da when exposed to a 12:12 light:dark cycle, and 4.3 +/- 0.3 da when utilizing an activity wheel and under a 14:10 lighting scheme. The earliest recorded mating for a female Tylomys was 90 da of age. The gestation period was 40.6 +/- 0.5 da, and there was no statistical difference between the gestation lengths of lactating and non-lactating females. The average litter size was 2.3 with a range of 1-4. Weight at birth averaged 20.2 +/- 0.3 g, or about 8% (litter about 16%) the weight of the adult. The daily instantaneous rate of growth (weight) for the first wk was about 5.6%. Graphs were presented indicating changes with time of weight, total body length, and tail, hind foot, and ear lengths. Young respond to loud noises at 6-14 da of age, and eye opening occurs slightly later, at 7-15 da of age. The young cling tenaciously to the female's nipples nearly continuously for the first 3 wk. Females did not perform any nest-building activities. Weaning occurred at approximately 3-4 wk of age.


The effect of canavanine on the capsid protein of Sindbis virus. In the presence of the arginine analogue canavanine, Sindbis virus-infected BHK 21 cells synthesize a capsid protein of somewhat larger molecular weight than that of controls. This protein can also be seen in short pulse-labelled cells, and probably represents a precursor of the normal capsid protein. In our experiments canavanine had no effect on the viral envelope proteins, and the canavanine containing capsid protein formed nucleocapsids and virus particles as well as normal capsid protein does.


Effect of cycloheximide on viral precursor protein B in Sindbis virus-infected BHK cells. The possible role of B protein, a postulated precursor of viral envelope proteins was studied in Sindbis virus-infected BHK cells. Although tryptic digestion of the B protein produces tryptic peptides of the viral envelope proteins it seems unlikely that B molecules accumulated in the cytoplasm of infected cells are subsequently cleaved into structural proteins. We suggest that if B is really the precursor of E1 and PE2 viral envelope proteins, the cleavage takes place on the ribosomes during the synthesis of the second part of the B protein. Low concentrations of cycloheximide completely blocked the synthesis of B protein but did not inhibit the synthesis of viral structural proteins.


[Introcution to the Topic "The Problem of Cancer" (author's transl)]. How will things progress with cancer? Main facts: cancer increase until 1964. Reversal of sexual proportion (now greater mortality of men). Cancer of different organs changing their relative frequency. In 80% cancer acquired. Enviromental carcinogenes. Percental increase of cancer without carcinogenes by decreasing causes of death (infectious diseases). Future problem: Experimental cancer prevention (tests upon germinal cells for mutagenicity). Since 1964 the level of cancer mortality has remained constant. Decrease is in sight: an anti-cancer future has begun.


[Urinary diversion through isolated bowel segments (author's transl)]. 80 cases of urinary diversions by means of an ileal or colon conduit are reported. Indications and the operative technique with several variations especially of the bowel-ureter-anastomosis are described. The significance of intestino-uretero-renal reflux and the role of urinary infection in different compartements of the isolated segment are discussed: if the stoma is large enough no reflux can be observed; in the majority of cases infection is limited to the distal part of the segment. Urinary diversion by isolated bowel segments seems to be a safe procedure especially for the protection of the upper urinary tract, preferable to diversion into the non-isolated colon.


[Unnatural death and its causes (forensic autopsy cases in Budapest during 1974)]. In Budapest in 1974, 4766 medicolegal autopsies were carried out. The cause of death in 2589 cases was natural disease, in 1246 cases an accident, in 878 cases suicide, in 43 cases death was caused by violence and in 10 cases stillbirth. Data of decreased by sudden and unexpected death are presented according to the internationally accepted nomenclature, accidental cases are analysed according to the type of the accident. Cases of violent death are analysed with regard to the form of them and the age of the victims.