[Morphokinetic effect of PMSG and sex steroids on parts of the cerebral-hypophyseal-gonadal axis of anestrous sheep].

The action of gonadotropins and of sexual steroids on links of the cerebro-hypophyseo-gonadal axis can be morphologically quantified in sheep. In that context, karyovolumetry is a highly dependabel and information-yielding quantitative morphological method. In studies conducted with anoestrous sheep and described in this paper that method has helped to detect an inhibitory effect of PMSG and progesterone upon the activity of neurons of the medial preoptic nucleus of the hypothalamus. The two sexual steroids produced even stronger inhibition of neuronal activity of the arcuate nucleus of the hypothalamus. Such results, when evaluated and re-used under the adequate test conditions might be helpful in identifying structures of central nervous disorders along the cerebro-hypophyseo-gonadal axis and produce reliable information on acting points or general action (activation or inhibition) of active substances as well as on the course of control and regulatory mechanisms.


[Trials of rut induction with prostaglandin F2alpha in gilts].

The possibility of oestrus induction by means of F-2-alpha prostaglandin was checked on nine gilts. The animals received intramuscular injections of 7.5 mg of 10 mg of PG F2alpha on the tenth or twelfth day of cycle. The sexual behaviours of the animals was followed up, and after slaughter followed macroscopic assessment of the ovaries as well as histomorphological and histochemical examinations of the uterus wall. The results have shown that no oestrus or ovulation could be induced by such injection on the tenth or twelfth day of cycle. Regression of corpora lutea and follicle growth five days following application on the twelfth day of cycle were somewhat faster than the same phenomena when observed following injection on the tenth day. However, oestrus and ovulation failed throughout to occur earlier than they would have occurred any way without any treatment. The cycle was not shortened by application of F-2-alpha prostaglandin.


The coupling of transcription from influenza virions to translation in vitro.

The optimum conditions for the coupling of fowl plague virus (FPV) transcription to an in vitro reticulocyte translation system have been established and shown to be close to those required for maximum RNA synthesis by purified FPV virions. Products have been characterized by the peptides they yield on limited proteolysis in SDS and it has been shown that virus nucleoprotein (NP) and matrix (M) protein are made. The smallest virus coded polypeptide, the non-structural protein (NS), is made in only small amounts in the coupled system although it is a major virus coded product of infected cells early in infection.


[Klüver-Bucy syndrome and primitive motor reflexes after heavy brain trauma (author's transl)].

A 16-year-old physically and mentally retarded male developed a complete Klüver-Bucy syndrome similar to that demonstrated in animal experiments and characterized by so-called psychic blindness, oral tendencies, hypermetamorphosis, emotional disturbance, and hypersexuality after severe brain trauma with loss of consciousness and a transitory hemiplegia. In addition, transitory oral and grasp reflexes were observed. Despite the severity of the clinical symptoms, the patient was able to realize and report on his subjective experience of the reflex and on the instinct-motivated behavior associated with the Klüver-Bucy syndrome. In the case described, two basic behavior patterns could be differentiated, each influencing drive and the abnormally increased sexuality. The first phase of the illness was dominated by relatively constant automatic reactions. These had the character of pre-determined instinctive behavior and were more or less emotionally neutral. In the second phase of the illness, the instinctive behavior became less evident and the patient was able to respond more normally to his sensory-motor impulses. Also, emotional experience such as frustration, pleasure, and displeasure regained their meaning for the patient.


The use of marsupial x eutherian somatic cell hybrids to study marsupial cell surface antigens.

Buck and Bodmer (1976) have developed a technique for identifying an antigen on the surface of human x mouse somatic cell hybrids, specified by a gene on a particular human chromosome. We have successfully adapted this technique to a study of marsupial cell surface antigens. Somatic cell hybrids between Macropus rufus (Marsupialia) lymphocytes and the mouse cell lines PG19 and 1R were injected intraperitoneally into mice of the same inbred strain from which the above cell lines were derived (C57B16J and C3H, respectively). The only identified M. rufus chromosome present in the hybrid cells was the X chromosome. The antisera, after adsorption with PG19 or 1R, were tested using indirect immunofluorescence, against the hybrid cells, and also against sub-clones (derived from hybrids) which had apparently lost the M. rufus X chromosome, or at least its long arm. The results of these tests showed that the absorbed antisera contained reactivity against an M. rufus cell surface antigen (or antigens). The reactions of one of the antisera were most simply interpreted by supposing that it was detecting an M. rufus X-lined antigen(s).


The early development of white adipose tissue. Effects of litter size on the lipoprotein lipase activity of four adipose-tissue depots, serum immunoreactive insulin and tissue cellularity during the first four weeks of life in the rat.

1. Newborn rats were reared in litters of either four or sixteen individuals. The animals from the small litters gained body weight more rapidly than those from large litters during the first 29 days of postnatal life studied. 2. The relative weights of the perigenital, perirenal, subcutaneous and intramuscular white-adipose-tissue sites in the animals from small litters indicated their relative obesity compared with controls. 3. The adipose depots from animals reared in small litters had a greater proportion of lipid present, by weight, and had a greater number of larger fat-cells present in them compared with the depots of animals reared in large litters. 4. Compared with both normal-sized litter controls and animals reared in sixteens, during the period of study the animals from small litters were hypertriacylglycerolaemic but normocholesterolaemic. 5. During suckling the blood glucose concentrations of animals reared in fours were increased, as were the concentrations of circulating immunoreactive insulin. 6. During the 29 days of life studied, in general, the lipoprotein lipase activity of adipose depots from animals reared in fours was greater than for animals in large litters when expressed as mumol of nonesterified fatty acid released from the substrate/h per g fresh weight of tissue, per depot, or per million fat-cells, but were similar per cm(2) of fat-cell surface area. 7. The previously noted [Cryer & Jones (1978) Biochem. J.172, 319-325] pattern of mid-suckling elevation, late-suckling decline and post-weaning increase in the lipoprotein lipase activity of the four white-adipose depots studied was not obliterated by the nutritional manipulations employed. 8. The relation of the enzyme-activity changes and their hormonal stimuli to triacylglycerol accumulation in fat-cells of animals from large and small litters is discussed in relation to the possible significance they may have to our understanding of neonatally induced obesity.


Relationship of free fatty acids and magnesium in ethanol withdrawal in dogs.

A group of dogs was conditioned to drink 4-6 g ethanol/kg/day for long periods. Ethanol ingestion was interrupted at monthly intervals in order to study some metabolic changes of the withdrawal period. Plasma long chain free fatty acids (FFA) increased by a maximum mean of 1.4 meq/liter (threefold), and magnesium (Mg) decreased by a maximum mean of 0.4 meq/liter (75% of control during the first 24 hr of simple ethanol withdrawal. Because magnesium salts of FFA are very insoluble, these divergent changes of Mg and FFA suggest that lipolysis may be responsible for the hypomagnesemia that occurs in ethanol withdrawal. In order to control lipolysis, glucose-insulin, glucose alone, and fructose alone were given intravenously for a 4-hr period beginning 14 hr after withdrawal. FFA fell by a maximum of 65% or 0.44 meq/liter and Mg fell by a maximum of 0.31 meq/liter during the glucose-insulin infusions. Nicotinic acid (10-20 mg/kg) in saline produced an identical drop in FFA and a slight rise in Mg. After stopping the nicotinic acid infusion, a sharp rebound rise in FFA and a sharp fall in Mg occurred similar to the simple withdrawal experiments. The sharp divergent changes in FFA and Mg after cessation of nicotinic acid infusion support the prime role of FFA-effecting movements of Mg and the thesis that FFA bind Mg. Control of lipolysis is theoretically sound in therapy of the ethanol withdrawal syndrome.


Electrophysiological studies on embryonic heart cells in culture. Scorpion toxin as a tool to reveal latent fast sodium channel.

Trypsin-dispersed heart cells were obtained from 11-day-old chick embryos. After culture as unstirred suspensions in dimethylsulfoxide-containing medium, spherical aggregates of cells beating spontaneously and apparently synchronously for months were obtained. Two kinds of cell were characterized by electrophysiological recordings: (1) cells with a slow rate of depolarizing phase showing tetrodotoxin-resistant action potential and blocked by D 600 ('slow' cells); (2) cells with high value of rising phase which was strongly decreased by tetrodotoxin and in which D 600 provoked uncoupling of excitation-contraction ('fast' cells). Toxin II from Androctonus australis scorpion venom increased the duration of action potential, which was ascribed to a slowing down of Na+ current inactivation and enhance the maximum rate of depolarization, especially in slow cells. Effects were antagonized by tetrodotoxin in both fast and slow cells. Washing experiments confirmed the results of previous studies, namely that tetrodotoxin and scorpion toxin bind to different receptors. It is concluded that slow cells with tetrodotoxin-resistant action potential contain latent fast Na+ channels that are revealed (activated) by toxin binding to the membrane.


The effect of charged synthetic polymers on proteoglycan synthesis and sequestration in chick embryo fibroblast cultures.

The polycation, poly(L-lysine), repressed the synthesis of glycosaminoglycans in secondary cultures of chick embryo skin fibroblasts and caused sequestration of glycosaminoglycans around the cells. The synthesis of chondroitin sulphate, dermatan sulphate, hyaluronic acid and a fourth component, thought to be heparan sulphate, were all inhibited to the same extent but the sequestration of the sulphated polymers were greater than that of the unsulphated. The sequestered material was retained around and not within the cells. Incubations with the polyanion, poly(L-glutamate), showed a slight stimulation of glycosaminoglycan synthesis and in these and control incubations (no additions to medium), most of the glycosaminoglycan synthesised appeared in the culture medium. The subsequent addition of poly(L-glutamate) to incubations containing poly(L-lysine) reversed the inhibitory and sequestering effect of the polycation. It was concluded that the inhibition of synthesis by poly(L-lysine) was either a direct effect of poly(L-lysine) on the cell membrane or a result of the high local pericellular concentration of sequestered proteoglycan.


Uptake of fatty acids by cultured cardiac cells from chick embryo: evidence for a facilitation process without energy dependence.

Cultured heart cells from chick embryo accumulate fatty acids up to 50 fold at a steady-state level under defined conditions [ref.1]. Studies of fatty acid uptake as a function of different cellular parameters (intracellular ATP and pH, membrane potential and electrochemical gradients for monovalent and divalent cations) show the lack of effect of these factors. The rate of uptake is temperature-dependent. The maximum velocity V is affected with no change in the Km value of the saturable component; the activation energies were found to be 35.5 kJ.mol-1 for palmitate and 42 kJ.mol-1 for oleate. The results are in favour of a facilitation process which leads to an accumulation of fatty acids without energy dependence. The accumulation of fatty acids could be due to their association to intracellular membraneous and/or cytosolic components.


[Parental resistance of irradiated mice (CBA X M523)F1 to lymphocytes: fate of transplanted cells, duration of resistance and its specificity].

The immune response of (CBA X M523)F1 mouse lymphocytes to the antigen (sheep red blood cells) in CBA mice after lethal irradiation was studied. When irradiation, cell transfer and antigen test-injection were performed at the same day the graft activity was inhibited, in comparison with syngeneic system. The activity of donor cells restored on increasing the interval between these processes up to 3 days. Retransplantation of the spleen cells from recipients to irradiated CBA and F1 mice revealed viability of transplanted cells and lack of their readaptation to insyngeneic microenvironment. The recipient's resistance could be specifically overcome by the preinjection of mouse cells combined with cyclophosphamide or without it. The results obtained allow a conclusion that genetic parental resistance of CBA mice to F1 mouse cells is due to the recipient immunocompetent cells which are inactivated 3 days following irradiation. They do not produce cytotoxic effects with respect to donor cells, blocking, however, their activity for some time.


[Diurnal rhythm of changes in the DNA-synthesizing cell count and the mitotic activity of the cells of jejunal epithelium under conditions of subdiaphragmatic vagotomy].

Bilateral subdiaphragmatic vagotomy in rats 7 days after surgery results in increasing proliferative activity of the jejunum epithelium not changing circadian rhythm of the mitotic process. Vagotomy induces changes in the diurnal rhythm structure of DNA-synthesis in the jejunum epithelial cells, i.e. monoapical rhythm in the norm becomes biapical.


Experimental homocystinemia, endothelial lesions and thrombosis.

A single intravenous injection of homocystine led to an increase in the number of circulating endothelial cells in the blood of rats. We observed also increased permeability of the lung capillaries, platelet sequestration and activation of the venostatic thrombosis. Endothelial injury is probably the key mechanism of thrombotic and atherosclerotic complications in homocystinuria, an inborn error of the amino acid metabolism.


Manipulations of dietary tryptophan: effects on mouse killing and brain serotonin in the rat.

Maintaining rats on a tryptophan-free diet for 4--6 days induced mouse killing in non-killer rats, and significantly facilitated killing in killer rats, as indicated by shorter latencies to kill the mice. The killing responses were similar in topography to the natural killing responses. These changes in killing behavior did not appear to be due to generalized changes in irritability. The increased killing after maintenance on a tryptophan-free diet was accompanied by a 26% reduction in brain serotonin (5-HT) and a 29% reduction in brain 5-hydroxyindoleacetic acid (5-HIAA). When the tryptophan-free diet was supplemented with L-tryptophan (0.5 or 2%), brain 5-HT and 5-HIAA were increased above control levels, and the rat's killing response appeared normal both in terms of latency and topography, similar to that seen in control chow fed animals. While rats consumed less of the tryptophan-free and tryptophan supplemented diets, control subjects deprived of chow such that they lost as much weight as rats fed the tryptophan-free diet, did not show changes in killing behavior. These results are consistent with the hypothesis that central serotonergic systems exert inhibitory control over mouse killing behavior in rats.


Healing of trabeculectomies in rabbits.

We studied the healing of trabeculectomies in rabbits with photographs, fluorescein filtration and histological sections. Initially all except 1 developed proven filtration. However, vigorous fibroblastic proliferation (and collagen production) from the subconjunctiva, uvea and sclera combined to close off the fistula by day 14. Groups of eyes treated with 8 mg of prednisolone injected subconjunctivally at operation showed slightly delayed wound healing but by day 30 there was little difference between treated and untreated groups. The steroid treated eyes had complications ranging from endophthalmitis in 1 eye to tissue necrosis in 3 eyes.


Anaerobic mediastinitis and septic shock secondary to esophageal perforation.

The authors report unusual complications arising from the ingestion of a small fish bone by a 68-year-old man. These included mediastinitis, empyema, pericarditis and septic shock, probably secondary to a small perforation of the esophagus. After appropriate surgical drainage, antibiotic therapy and supportive therapy the patient made a good recovery.


Autoimmune disorders complicating adolescent Hodgkin's disease.

Four adolescents with Hodgkin's disease also developed autoimmune diseases. There were two idiopathic thrombocytopenic purpura (ITP), one polymyositis, and one scleroderma. The first two patients developed ITP in the absence of a spleen, and with their Hodgkin's disease in remission. The first patient with Hodgkin's disease has been continuously free of cancer for over five years. The second patient was a 17-year-old male whoe Hodgkin's disease recurred, but whose disease was in remission at the time the ITP occurred. The polymyositis occurred in an 18-year-old youth when he was in his initial remission for his Hodgkin's disease, but his disease subsequently recurred two years later. This youth presented with Coombs positive autoimmune hemolytic anemia. The polymyositis did not respond to therapy, and he is left with severe muscle wasting and weakness; however, the polymyositis is now quiescent. The scleroderma occurred in an 18-year-old female who had been continuously free of Hodgkin's disease for eight years. The scleroderma did not respond to drug therapy and she now has moderate skin changes, but remains in continuous remission of her Hodgkin's disease. Although there are a few reports of Hodgkin's disease and concurrent autoimmune disorders, physicians dealing with cancer in adolescents should be aware of this association.


Cellular binding proteins for vitamin A in the normal human uterine cervix and in dysplasias.

Cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein are present in the cytosol of normal human uterine cervical tissues, as detected by ultracentrifugation analysis. Both binding proteins have characteristically high specificity for their respective ligands. In sucrose gradients, both proteins sediment in the 2S region and are of similar molecular weight (M.W. approximately 14,000). In blind analyses of cervical biopsies, obtained under direct vision by colposcopy of normal women (control) or from patients histopathologically diagnosed to have dysplasias or carcinoma in situ (study group), CRBP was not detectable by sucrose gradient analysis in 78.8% of the 33 abnormal biopsies, compared to 23.5% of the 34 controls. This difference was statistically significant (p less than 0.005). In biopsies in which CRBP was detected, the mean levels were 2.76 and 0.72 pmol/mg protein in the cytosol for the control and study groups, respectively. In some subjects from each group, cellular retinoic acid-binding protein but not CRBP was detected in the biopsied tissue. The presence and role of these binding proteins in vitamin A metabolism, epithelial maturation and differentiation in cervical dysplasias, and in situ lesions remain to be investigated.


Efficacy of 6-diazo-5-oxo-L-norleucine and N-[N-gamma-glutamyl-6-diazo-5-oxo-norleucinyl]-6-diazo-5-oxo-norleucine against experimental tumors in conventional and nude mice.

The chemotherapeutic effects of 6-diazo-5-oxo-L-norleucine (DON) and N-[N-gamma-glutamyl-6-diazo-5-oxo-norleucinyl]6-diazo-5-oxo-norleucine (azotomycin) were evaluated in a spectrum of transplantable experimental tumor systems including xenografts of human tumors in athymic mice. Both drugs displayed remarkable activity against the murine leukemia L1210 and P388, the Colon Tumors C26 and C38 and the CD8F1 mammary tumor. No significant activity was observed against Lewis lung carcinoma, B16 carcinoma, B16 melanoma, and intracranial ependymoblastoma. DON and azotomycin also exhibited striking inhibitory effects on the growth of s.c. human tumor (MX-1 mammary, LX-1 lung and CX-1 and CX-2 colon) xenografts in athymic mice. With the exception of one colon xenograft (CX-1), all tumor lines were markedly responsive to both drugs. Tumor regressions below the initial tumor sizes of 100 to 300 mg, albeit temporary, were brought about by one course of treatment every 4 days for 3 doses (at optimal dose) with either drug. Although these drugs have been tested previously in the clinic and have shown only limited therapeutic effectiveness, they seem to worthy of a second and closer look in light of the recent laboratory results.


Granule secretion by the luteal cell of the sheep: the fate of the granule membrane.

The ultrastructure of the corpus luteum of the sheep has been examined at the mid-stage of the estrous cycle when progesterone secretion is active. Secretory granules are associated with the secretion of this hormone, and the evidence indicates that the granule membrane becomes incorporated into the plasma membrane during exocytosis. Further evidence of this process has been obtained from studies on the uptake of horseradish peroxidase by the luteal cells.


Idiopathic hypertrophic subaortic stenosis and ventricular preexcitation.

Two patients who had idiopathic hypertrophic subaortic stenosis (IHSS) and type A ventricular preexcitation were studied and showed variations of the subvalvular flow gradients. The increase in subvalvular gradient, occurring at a time when preexcitation developed, was associated with significant increase of the systolic murmur and the systolic anterior motion of the mitral valve. In patient 1, the significant increase in subvalvular gradient during ventricular preexcitation was also confirmed by catheterization of the left side of the heart. The increase of the gradient with the development of the ventricular preexcitation was apparently due to decreased end-diastolic volume. The importance of ventricular volume considered as a variable affecting outflow tract gradient in idopathic hypertrophic subaortic stenosis is emphasized.


Nucleus-anchoring cytoskeleton in chicken red blood cells.

Cytoskeleton of chicken erythrocytes was studies studied after extraction of the cells with Triton X-100. In phase contrast microscopy the extracted cells were seen as ghost-like structures with preserved morphology, distinct nucleus and surrounding plasma membrane remnant. In electron microscopy, dense matrix-like nucleus, fibrillar plasma membrane residue and filaments, ca. 10 nm in diameter, traversing the cytoplasmic domain, were seen. Distinct bands of molecular weight 68000, 53000, 32000 and bands of both higher and lower molecular weight were obtained by polyacrylamide gel electrophoresis of the extracted cells. These results indicate that intermediate filaments, forming the nucleus-anchoring cytoskeleton, are present in nucleated chicken erythrocytes as part of cellular cytoskeleton.


Mitochondrial division in non nucleated sea urchin eggs.

An electron microscopic analysis of non nucleated and parthenogenetically activated sea urchin eggs shows figures that can be interpreted as dividing mitochondria. This is in agreement with our previous observations showing that the egg nucleus negatively controls mitochondrial DNA synthesis.


[Diagnostic problems in poisoning with the agaric Cortinarius orellanus Fr. having a nephrotoxic effect].

The authors present a case of fungus poisoning involving nephrotoxic effects. Diagnosis was derived from the typical course of the conditions as well as from the postmortem and mycological investigations of intestinal contents. This is the first case of death due to this kind of poisoning ever described in Czechoslovakia.


Separation of bound from free hormone in radioimmunoassay of lutropin and follitropin.

A new technique in which polyethylene glycol is added to double-antibody assays of lutropin and follitropin eliminates the need for an incubation period during the separatory phase. After the antigen-first-antibody equilibrium reaction, the second antibody and polyethylene glycol (30 g/L final dilution) are added, the tubes are immediately centrifuged, each supernate is aspirated, and the precipitated antibody-bound hormone is counted. With this combined polyethylene glycol-second-antibody separatory method, the incubation time is shorter than the usual double-antibody separation procedure, but avoids the problem of high nonspecific precipitation, which occurs with polyethylene glycol alone. In addition, the combined separation technique allows the use of sera containing low titers of second antibody and use of smaller volumes of sera containing high titers of second antibodies, thus conserving second-antibody reagent.


Enzymic assay for serum theophylline.

We describe an original procedure for determination of theophylline in serum. The drug is extracted from 0.4 mL of serum at pH 7.4 with chloroform/isopropanol (20/1 by vol) and back-extracted into sodium hydroxide (1 mmol/L). The inhibition of beef-liver alkaline phosphatases by theophylline in this alkaline phase is measured at 25 degrees C, with p-nitrophenyl phosphate as substrate, in 2-amino-2-methyl-1-propanol buffer, pH 9.4- The reciprocal of enzyme activity and theophylline concentration are linearly related in the range 2 to 60 mg/L. The maximum interference to be expected from 3-methylxanthine would increase apparent theophylline concentration by no more than 1 mg/L. The method is accurate, free of interference by other xanthines and often-coadministered drugs, and results correlate well with those by the immunoenzymic assay. Major advantages are reagent stability, low cost, and simplicity of instrumentation.


Creatine kinase isoenzyme--antibody reactions in immuno-inhibition and immunonephelometry.

I have raised, in rabbits, antibodies against MM and BB isoenzymes of creatine kinase. The antibodies produced were homogeneous by Ouchterlony double immunodiffusion and did not cross react with their opposite antigens. Both antisera, however, appeared to be mixtures of antibodies, displaying different equivalences for activation, inactivation, and, possibly, precipitation. Inactivation studies indicated the presence of antibodies effective against dimer only and antibodies effective against monomer or dimer. Both antisera cross reacted with MB and displayed antibodies that appeared to block only half of the activity as well as antibodies that blocked all of the activity. The antisera produced were useful for measuring MB by both immuno-inhibition and immunonephelometry, but neither appears to be advantageous over current electrophoresis or ion-exchange methods. A comparison of decay of MB in patients between activity and mass measurements indicated that activity decay is about 12-fold faster than mass decay.


Functional significance of antibody formation after long-term salmon calcitonin therapy.

Twenty patients with Paget's disease were challenged with porcine (PCT) and salmon (SCT) calcitonin before and after 6 months SCT therapy. Acute hypocalcaemia was clearly related to the prevailing rate of bone turnover but responses to PCT showed that treatment had not disturbed this relationship. Although antibodies to SCT developed in eight patients during the period of treatment the acute hypocalcaemic response to SCT was not diminished in relation to bone turnover. It is suggested that antibodies which develop during the course of SCT therapy do not necessarily exert a functionally effective neutralizing action.


Inter- and intrasubject variation in diazepam free fraction.

The extent of intersubject variation in diazepam free fraction was measured in fasting plasma of 74 unrelated subjects. Free fraction differences between subjects were significant and ranged from 0.97% to 1.99%. Diazepam free fraction in 29 males was normally distributed about a mean of 1.25% (range, 1.05% to 1.47%), but the distribution in females was skewed to higher free fractions and 40% had values above the highest in males. Albumin concentration (r = -0.27, p less than 0.002) and age (r = 0.44, p less than 0.001) only accounted for a small part of the variation. Within-pair variances were not greater in 11 dizygotic than in 18 monozygotic twin pairs, indicating a greater contribution of environmental than of genetic factors to diazepam binding. The prehemodialysis free fractions of diazepam in 9 uremic patients ranged from 3.44% to 6.69%, and decreased (p less than 0.005) in 7 after 6 hr of hemodialysis. In 10 subjects determination of intrasubject variation in diazepam free fraction between 14-hr fasting and 2-hr postprandial plasma samples indicated that because subjects differ in their pattern of change in free fraction (p less than 0.001), the overall decrease in mean free fraction did not achieve statistical significance (p = 0.10). The mean relative percent change in free fraction within subjects after feeding was 15.2%.


DNA measurements of mitotic chromosomes of the rabbit (Orytolagus cuniculus).

DNA cytophotometry was used to obtain the relative DNA content of mitotic chromosomes of Orytolagus cuniculus. DNA ranking of the rabbit chromosomes is presented, and related to the quinacrine and Giemsa-banded karyotype. In addition, the relative DNA content of the short and long arms of each chromosome was calculated and the DNA-based centromeric index, (i.e., the ratio of long-arm DNA to total chromosomal DNA) determined. The Y chromosome is clearly a submetacentric chromosome on the basis of the DNA measurements.


Echocardiography in the diagnosis of idiopathic hypertrophic subaortic stenosis coexisting with pericardial effusion.

Of 89 patients with idiopathic hypertrophic subaortic stenosis who had M-mode echocardiagrams recorded, seven patients with coexisting moderate to large pericardial effusions were identified. The clinical profile, M-mode echocardiograms, and cardiac catheterization and angiocardiographic studies in two of the seven patients were analyzed. That the two entities were not associated was suggested by the identification of an etiology for the pericardial effusion in four of the patients. Although the "swinging heart" phenomenon was exhibited in the echocardiograms of each patient, the presence of a significant pericardial effusion did not preclude the ability to establish a diagnosis of idiopathic hypertrophic subaortic stenosis by M-mode echocardiography.


Angiosarcoma of the heart. Diagnosis by echocardiography.

Angiosarcoma of the heart is a rare tumor infrequently diagnosed ante mortem. The clinical presentation is usually that of pericarditis or congestive heart failure. This case report illustrates the contribution of echocardiography in suggesting the diagnosis.


Cerebrospinal fluid pathways in a murine mutant.

The hy-3/hy-3 mouse is a model of congenital hydrocephalus. The development of the subarachnoid space and extracellular space were studied in normal and hydrocephalic animals. A previous space in the mesenchyme is altered to form the subarachnoid space. Changes in the extracellular space demonstrate that this space is dynamic and acts to compensate for events occurring in the ventricular system. The aqueduct and central spinal canal are also involved in the hydrocephalic process. Change in cerebral vasculature may indicate the processes which lead to irreversibility.


[Glucose-homeostasis in resection and non-resection procedures of the stomach].

Antrectomy or truncal vagotomy with pyloroplasty induces an abnormal alimentary hyperglycemia after ingestion of oral glucose. Low doses of secretin normalize the glucose homeostasis in dogs after antrectomy and truncal vagotomy.


[Healing process of unpreserved homologous articular cartilage transplantation in animal experiments].

Our experimental work was concerned with the healing process of fresh homologous osteochondral grafts in the knee joints of 45 sheep. The ultrastructural investigations pointed clearly to the fact that the cells of fresh homografts completely survive under optimal conditions. Neither transformation nor metaplasia were evident.


[Studies on organ-related postoperative utilization of administered amino acids].

The exclusive postoperative supply of carbohydrates resulted in a significant improvement (24%) of cumulative nitrogen balance, because increased insulin production apparently caused augmented recycling of amino acids liberated during catabolism. Through addition of amino acids the decreased branched chain amino acids returned to normal levels, whereas the significant fall in plasma proteins with short half-life remained unchanged. Therefore it is assumed that the available amino acids (64% of supply) have predominantly anabolic functions in peripheral tissues and fewer are used to synthesize plasma proteins in the liver.


Discordance for achalasia in identical twins.

Twenty-year-old twin sisters, believed monozygotic on the basis of extensive blood grouping and cytogenetic studies, are reported. One twin demonstrated classical clinical, radiologic, and manometric features of achalasia, while similar studies in her sister documented perfectly normal esophageal motor function. Genetically determined damage to the esophageal parasympathetic innervation is, therefore, not a likely cause for the esophageal motor dysfunction in achalasia.


[Treatment of diabetes during pregnancy with Des-Phe insulin: preliminary results (author's transl)].

Seven pregnant diabetics were treated with Des-Phe insulin (Hoe 01-S and Hoe 02-S). Daily blood glucose profiles were obtained for 7 to 32 weeks, a total of 4182 measurements. The blood glucose level was well controlled with the insulin preparation. Postprandial blood-glucose increase was counteracted so that even one hour after food the preprandial blood sugar concentration had been reached (Des-Phe insulin Hoe 01-S). This ensured normal carbohydrate metabolism during pregnancy. There were no side effects or skin allergies. The pregnancy proceeded uneventfully in all patients resulting in seven normal infants.


Studies on pituitary follitropin. IV. A conformation specific radioimmunoassay for the ovine hormone.

An antiserum to partially purified ovine follitropin (50 x NIH-FSH-S10) shows species specificity. It is conformation dependent and requires the proper recombination of the alpha and beta subunits for maximal reactivity. The isolated alpha subunit is essentially inactive and the hormone specific beta subunit is weakly reactive. The homologous radioimmunoassay is valuable for estimating native ovine follitropin in the presence of free subunits. It also provides a sensitive method to study association-dissociation and structure-function relationships.


Reversal by insulin of concanavalin A inhibition of myotube formation and evidence for common binding sites.

Concanavalin A (Con A) inhibits fusion of trypsin-treated myoblasts. This inhibition is reversed by the addition of supraphysiological concentrations (4 micrograms/ml) of insulin either during continuous presence in culture or by pulse additions at 36 and 48 h of culture, just before the time that cultures not treated with Con A undergo myoblast fusion. This reversal is not due to the mitogenic effects of insulin. Under reversal conditions, no specific displacement of bound [125I]iodo-Con A was detected nor did insulin stimulate metabolite uptake. Cell surface replicas of hemocyanin-tagged Con A showed that insulin reversal of the inhibition of myotube formation correlated with the alteration of Con A-binding sites from a clustered configuration present in the inhibited cells to a dispersed state correlated with normal myotube formation. Although a causal relationship has yet to be shown, the data suggest that insulin-mediated reversal of Con A inhibition of myoblast fusion may be related to the ability of insulin at supraphysiological levels to alter the translational mobility of cell surface components containing glucose and/or mannose residues capable of binding Con A. Evidence is presented which suggests that insulin and Con A share common binding sites, since in the physiological range of insulin concentrations (1 ng/ml), Con A pretreatments results in an inhibition of specific [125I]iodo-insulin binding, and antagonistic interactions of insulin and Con A on metabolite uptake and cell proliferation occur. Thus, it appears that the insulin receptors of developing skeletal muscle are glycoproteins containing glycopyranosides.


Properties of the methane mono-oxygenase from extracts of Methylosinus trichosporium OB3b and evidence for its similarity to the enzyme from Methylococcus capsulatus (Bath).

1. The methane mono-oxygenase from Methylosinus trichosporium OB3b was soluble. The only suitable electron donor was NAD(P)H, neither sodium L-ascorbate nor electrons derived from the oxidation of methanol could substitute for NAD(P)H. Evidence is presented for the existence of an NAD+-linked formaldehyde dehydrogenase. 2. Mono-oxygenase activity was not inhibited by a range of potential inhibitors including potassium cyanide, amytal, carbon monoxide or various metal-chelating agents, although 8-hydroxyquinoline and ethyne were effective in this respect. 3. Although the enzyme preparations were unstable on storage, the crude extract could be resolved into two components by ion-exchange chromatography. Activity could be restored to one of the components on addition of purified components from Methylococcus capsulatus (Bath). 4. Cross-reactivity of mono-oxygenase components and other similarities between the enzymes from M. trichosporium and M. capsulatus are discussed. The properties of the M. trichosporium methane mono-oxygenase reported here are contrasted with the properties of the same enzyme reported by others.


Nucleotide sequence coding for the N-terminal region of the matrix protein influenza virus.

After polyadenylation in vitro of the influenza virus RNA segment which contains the coding information for the matrix protein, a cDNA copy can be made using the primer p(dT)8-dA and reverse transcriptase. The sequence of 166 nucleotides of the cDNA was determined by a modification [Brownlee, G. G. & Cartwright, E. M. (1977) J. Mol. Biol, 114, 93--117] of the plus/minus method [Sanger, F. & Coulson, A. R. (1975) J. Mol. Biol. 94, 441--481] and adaptation of the "dideoxy" method [Sanger, F., Nicklen, S. & Coulson, A. R. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 5463--5467] for sequencing DNA. The cDNA sequences is of the same sense as the mRNA for matrix protein and contains a potential initiating codon, d(ATG), at position 26--28. When matrix protein purified from virus particles was digested with chymotrypsin or trypsin and the amino acid compositions of separated peptides determined, one peptide containing nine amino acids found which had a composition corresponding to that predicted by the cDNA sequence following the first methionine codon, confirming that protein synthesis initiates at this position. The compositions of four other peptides matches those predicted from the nucleotide sequence. There is no processing of the N terminus of the protein before incorporation into the virus particle except for removal of the N-terminal methionine and addition of a "blocking" group on the resulting N-terminal serine residue.


Presynaptic subsensitivity as a possible basis for sensitization by long-term dopamine mimetics.

A possible cellular basis for dopaminergic sensitization by long-term dopamine mimetics was examined in rat brain striatum. Long-term apomorphine or amphetamine administration (10 mg/kg/day for 14 days) resulted in a decrease in the specific binding of 3H-apomorphine, but no change in 3H-haloperidol binding. Long-term apomorphine treatment also enhanced the cataleptogenic action of haloperidol, with many rats being spontaneously cataleptic after apomorphine withdrawal. It is suggested that the reduced 3H-apomorphine binding signifies less presynaptic receptors. This permits less autoregulation and enhanced dopamine agonist action, possibly accounting for the dopaminergic sensitization by long-term agonists.


The effect of an intrauterine device on myometrial glycogen in the hamster.

The myometrical glycogen content of the uterine horns of cycling, castrated and castrated hormone-treated hamsters was basically unaffected by the presence of an intrauterine device (IUD). The study also indicates that visual evaluation of histochemical localization of glycogen is not adequate to determine minor differences in staining intensity. The "estrogen-like" effect or stimulatory effect of the IUD on uterine glycogen in the rat is not duplicated in the hamster.


[Dynamics of hormone secretion during chronic emotional stress].

Study of spontaneous secretion of corticosteroids and thyroid hormones and the direct hormonal response to stress revealed the pathogenic effect of chronic combined emotional stress upon the hormonal function of adrenal glands. The hippocampus takes part in formation of the emotional tension in response to stress stimulus and of the following hormonal secretion.


The effect of polyanion on the enzymatic degradation of modified deoxyribonucleoprotein samples.

The degradation of DNA in modified deoxyribonucleoprotein samples by DNase II in the presence of a polyanion (polypentose sulphate) was studied. The behaviour of DNP samples partially depleted of histone and treated with acetic anhydride is characterized by an increased accessibility of their DNA to DNase II, by a decreased polyanion amount needed for the maximum enzymatic degradation of their DNA, and, finally, by a more profound inhibitory effect of higher polyanion amounts on the DNase II-catalyzed degradation. On the other hand, the behaviour of DNP samples treated with formaldehyde is characterized by a decreased accessibility of their DNA to DNase II, by a limited increase in the enzymatic degradation of their DNA in the presence of the polyanion, and finally by a less profound inhibitory effect of higher polyanion amounts on the DNase II-catalyzed degradation.


[Effect of pellet size on respiratory activity and motility of cryopreserved spermatocytes].

The effect of different pellet volumes at freeze preservation in human semen was studied. It was measured the motility of spermatozoa during an incubation time of several hours at 37 degrees C and the alteration of oxygen consumption after adding rotenone, succinate, digitonine or 2,4-dinitrophenol. - The motility of cryopreserved spermatozoa does not show significant differences after preservation procedure. In respect of oxygen consumption the smallest differences from native material were obtained at a pellet volume of 0,2 to 0,3 cm3. Explanations for this behaviour are discussed.


Effect of neonatal stunting on development of rats: large litter rearing.

As nurslings, rat pups reared in large litters showed reduced frequencies of returns to their nest from other parts of the home cage and reached maximum levels of nest returns at older ages than control animals from small litters. These differences were not due to differences in activity level or attraction to the nest but appeared to be perceptual in nature. As adults, animals from large litters showed deficits in learning the 1st 2 problems in a series of visual discriminations in a modified version of the Lashley jumping stand technique in which food reinforcement was not used. The deficits were confined to male animals only and were the result of stronger position habits in the early part of training, rather than an inability to make the discriminations. A comparison of these results with those obtained when other methods of stunting animals are employed revealed that different methods of stunting may result in both common and divergent effects on behavior. One long-term consequence of large litter rearing appears to be increased emotional response to noval situations.


Three parameters affecting interlitter variations.

We studied 3 parameters affecting average body weight differences between mouse litters and have arrived at an approximation of the contribution that each makes to such differences. These parameters are birth weight, genetically based growth potential variations, and maternal competence. We have developed methods for controlling these parameters and show that through their application we can reduce litter-average body weight differences from our normal value of more than 24% to about 3%. The vanished 21% consists of 12% due to differences in maternal competence, 6% due to growth potential differences, and 3% due to initial weight differences.


Argon vs. neodymium YAG laser photocoagulation of experimental canine gastric ulcers.

A neodymium YAG (Nd:YAG) laser was evaluated in a dog ulcer model used in the same manner as is recommended for bleeding patients (power 55 W, divergence angle 4 degrees, with CO2 gas-jet assistance). The experiments were performed during sterile laparotomy in heparinized dogs. Bleeding gastric ulcers were photocoagulated until bleeding stopped and then examined histologically 7 days later when depth of tissue injury was maximal. In the first series of experiments, the Nd:YAG laser was compared with the 7-W argon laser in the same dogs. Both lasers stopped bleeding from all experimental ulcers. The 55-W Nd:YAG laser caused full-thickness injury to the gastric wall beneath 11 of the 14 treated ulcers, whereas the 7-W argon laser caused no full-thickness injury beneath 14 treated ulcers. In a second series of experiments, we tried to determine whether varying exposure times with the 55-W Nd:YAG laser would make it less injurious; it did not. In a third series of experiments, the 55-W Nd:YAG laser was tested with and without CO2 gas-jet assistance in order to determine if this would affect the depth of injury; it did not. In the final series of experiments, the wattage of the Nd:YAG laser was varied to see if this would reduce depth of injury; lower wattage did not stop bleeding, and intermediate and higher wattages did stop bleeding but did not reduce depth of injury. We conclude that the 55-W Nd:YAG laser as it is currently used clinically produces deeper tissue damage than the argon laser in our animal model. This damage is not reduced by changes in power, duration of exposure, or the presence of gas-jet assistance.


Inhibition of hepatic regeneration in rats by acute and chronic ethanol intoxication.

We studied the effects of acute and chronic ethanol feeding on hepatic regeneration in rats after partial hepatectomy and toxic liver injury produced by D-galactosamine. Ethanol, when administered as a single dose (6 g/kg), inhibited 3H-thymidine incorporation into hepatic DNA; this effect depended in part on the time of ethanol feeding after partial hepatectomy. Multiple ethanol feedings produced an even greater inhibition, which persisted for at least 48 hr after partial hepatectomy. Rats chronically fed ethanol for 30 days also failed to achieve a hepatic proliferative response to either partial hepatectomy or D-galactosamine-induced hepatitis, comparable with isocaloric pair-fed controls. These investigations suggest that there may be a certain metabolic state in the hepatocyte cell cycle that is most susceptible to the action(s) of ethanol; inhibition of liver regeneration by acute or chronic ethanol consumption may result in delayed recovery from prior or coincident liver injury.


Nematocide effect of entomophilic and entomophagous fungi.

Study of nematocide effect of 48 species of entomophilic and entomophagous fungi from the class Fungi imperfecti against Panagrellus redivivus and Rhabditis oxycerca nematodes revealed a high frequency of fungi with nematocide effect. A close correlation between these two effects was disclosed by measuring the intensity of the nematocide and insecticide effect of fungal extracts.


Personality traits of 47,XYY and 47,XXY males found among juvenile delinquents.

The mental features of nine 47,XYY males and six 47,XXY males found among Japanese juvenile delinquents were examined. The results of intelligence tests suggested a slight impairment among 47,XYY and 47,XXY males. The psychiatric interviews and the psychological tests revealed that 47,XYY males had a high activity level while 47,XXY males had a low one. Analyses of the offense type and psychophysiological features supported these findings. As the activity level is considered to be largely determined genetically, the extra Y is suspected to be responsible for the high activity level and the extra X in males to be responsible for the low activity level.


Combination of differential sister chromatid staining, G-banding pattern, and X-inactivation pattern.

A method is presented for obtaining a combination of differential sister chromatid staining. G-banding and X-chromosome inactivation pattern. The result of this method enables a precise localization of the sister chromatid exchange points to particular bands of individual chromosomes.


X-linked mental retardation with macro-orchidism and the fragile site at Xq 27 or 28.

Data are presented suggesting that the form of X-linked mental retardation with macro-orchidism and the form associated with a fragile site at Xq27 or 28 are the same entity.


Regulation of radiation pollution: its possible usefulness in strategy for intervention against chemical mutagens.

Over the last 25 years, a large amount of work has been carried out in the field of safety with regard to ionizing radiations. This has resulted in the establishment of norms of security which have been accepted in most countries. These norms are not perfect; they are constantly reviewed and, from time to time, revised; but, such as they are, they are of tremendous usefulness. These standards may serve as a model of what must be achieved in the field of pollution by chemical mutagens. Further, the norms already in force for radiation may serve as a reference for the establishment of similar norms for the major environmental mutagens. It is not possible to assign a specific factor of equivalence with radiation (rad-equivalence) to a given chemical pollutant; but it is possible to establish point-equivalences with regard to well-defined biological systems under well-defined conditions. When they are accurately determined, such point values may be useful and sensible. In this area, as with radiation, it is impossible to find perfect solutions; however, approximate solutions can be arrived at that would already represent a reat progress with regard to the present situation, and which could later be improved as work in the field allows.


Effects of antimicrotubule agents, potassium and inhibitors of energy production on hCG secretion.

The BeWo trophoblastic cell line was employed to assess the requirement for microtubules and cellular energy in human chorionic gonadotropin (hCG) secretion. In contrast to the general inhibitory effect of colchicine and vincristine on hormone secretion in systems involving exocytosis, wide concentration ranges of these antimicrotubule agents caused enhancement of hCG secretion. Similarly, cytochalasin B, an agent that interferes with microfilament function, doubled both basal hCG secretion, and secretion of hCG stimulated by 1 mM dibutyryl cyclic AMP plus 1 mM theophylline (dbT). Inhibitors of cellular energy production (2,4-dinitrophenol, malonate, azide) decreased both secreted and cellular levels of hormone. High concentrations of K+ gave no enhancement of basal or dbT-stimulated hCG secretion, nor any reduction of cellular hCG levels. These findings contrasted with observations of others in secretory systems involving exocytosis, in which high K+ potentiated basal or stimulated hormone release and depleted cellular stores of hormone. It was concluded that the process of hCG secretion in the malignant trophoblast is fundamentally different from the mechanism of protein hormone secretion in other tissues.


[Comparative studies on the use of equimolar 14C-labeled glucose and fructose infusions in normal subjects and patients with liver cirrhosis].

In 11 normal subjects (NS) and 12 patients with liver cirrhosis (LC) the utilisation of 14C-glucose and 14C-fructose infusions (0.75 g/kg/h for 4 h) was compared. There were nor relevant side effects. Lactate and pyruvate were in both groups during fructose infusion slightly increased compared to glucose infusion. The free fatty acids were significantly decreased. The serum glucose level rose more in LC than in NS when given fructose infusion. During glucose and fructose infusion in LC higher insulin concentrations were calculated than in NS. 15 min after infusion of 14C-fructose 20% of the total serum activity was 14C-glucose, after 2 to 4 h the level was 30%. Differences between NS and LC were not found to be significant. The specific activity of 14CO2 was the same in both the 14C-glucose infusion and the 14C-fructose infusion. The glucose oxidation was impaired in LC, but not the 14CO2-exhalation during infusion of 14C-fructose. Unimpaired 14CO2-exhalation, and normal utilisation and conversion to glucose are arguments for the use of fructose in infusion treatment of cirrhotics.


[Effect of a 3.6 o/o dextran Ringer acetate solution on moderately hypovolemic patients in intensive care].

The effects of 1000 ml 3.6% dextran Ringer's acetate solution (Mw 61,800; infusion time 60 min) on circulation, blood and plasma volume, blood viscosity and renal function parameters were investigated, the renal elimination of dextran also being measured. During the entire investigation period no significant alterations of cardiocirculatory parameters, blood and plasma volume and rheological properties of blood could be demonstrated, the same holding true for kidney function values. Dextran excretion was about 33% three hours after the end of infusion, reaching 51% of the whole amount given 21 hours later. It has to be assumed that mainly macromolecular dextran components of less efficiency are retained intravascularly. Taking into consideration the practically absent volume expanding effect - even at the end of infusion period - this dextran solution cannot be recommended as a blood substitute during acute hemorrhage or as an "expander" in other shock states.


[Behavior of the serum fatty acid patterns during administration of an MCT-containing fat emulsion].

After a continuous intravenous 3-hour infusion of 500 ml fat emulsion containing MCT, composed of 25 g soybean oil and 25 g MCT oils, there was an infusion-induced increase of all fatty acids administered. The medium-chain fatty acids (C8-C12) revealed ideal steady-state conditions and were quickly eliminated after the infusion. The reaction of linoleic acid (C18:2) was not as favorable. Linoleic acid increased steadily during the infusion, and its elimination rate from the serum was delayed.


[The effect of formula diets with a modified fat content on human plasma phosphatide fractions].

Variation of human plasma phospholipids by formula diets with different composition of fat are caused by changes of the lecithin fraction, which amounts to 70 to 80% of total phospholipids. The changes of lysolecithin correspond to that of lecithin. The absolute amounts of sphingomyelin are unchanged by the different formula diets, while the relative amounts are negatively correlated to the lecithin fraction.


Intramuscular inoculation of live respiratory syncytial virus induces immunity in cotton rats.

Intramuscular inoculation of infant or weanling cotton rats with 10(2.2) to 10(4) plaque-forming units of respiratory syncytial virus induced significant or complete resistance to infection in both the upper and lower portions of the respiratory tract. This resistance did not appear to be the result of in vitro neutralization of virus during homogenization of tissue. Virus was not recovered from the local site of inoculation after 5 min and was never detected in the respiratory tract of intramuscularly inoculated rats. Attempts to detect viral antigens at the site of inoculation by using indirect immunofluorescence were unsuccessful. However, inactivation of infectivity of three different strains of respiratory syncytial virus markedly reduced or completely ablated antigenicity and protective efficacy by the intramuscular route. This suggests that these viruses underwent limited replication, perhaps restricted to an abortive cycle, at the local site of inoculation. An immunosuppressive effect of passive maternally derived immunity was observed. Only 50% of weanling rats possessing passive maternal serum antibody were successfully immunized by intramuscular vaccination with live virus.


Splenic influence on the development of a local pulmonary immune response.

The role of the spleen in the development of specific antibody-forming cells (sAFC) in the pulmonary draining lymph nodes (pdLNC) of hamsters after local inoculation of sheep erythrocytes (SRBC) was evaluated. The role of the spleen was viewed from two vantage points. Panels of animals were either splenectomized with appropriate sham-operated controls before intratracheal inoculation of SRBC, or panels were immunized intravenously simultaneously with the local inoculation of antigen. The presence of an intact spleen was not necessary for the induction of a sAFC response to occur in the pdLNC. Similar numbers of immunoglobulin M (IgM) sAFC were recorded in the pdLNC on day 4 of both sham-operated and splenectomized animals. However, an enhancement of this local response occurred on day 7 if the animals were systemically immunized and therefore demonstrated active participation of the spleen in the specific immune response. The results support the hypothesis that although a local response may occur in the pdLFC in the absence of a spleen or a splenic response, the presence of a systemic or splenic response appears to be important for the enhancement of local IgM sAFC response. These observations suggest that the immune defenses involved in the lower respiratory tract may differ from those in upper respiratory tract and other mucosally lined organs in that the response of the spleen to the antigen affects the local response to that antigen.


Comparison of intratracheal and intravenous inoculation of sheep erythrocytes in the induction of local and systemic immune responses.

The interdependence of the local and systemic immune systems in the development of the immune responses relating to the lung was evaluated. Hamsters were inoculated with 10(9) sheep erythrocytes (SRBC) via local (intratracheal) or systemic (intravenous) routes of immunization. The local immune response was quantitated by the specific antibody-forming cell (sAFC) response in the pulmonary draining lymph nodes (pdLNC). sAFC in the spleens and serum hemagglutination titers evaluated the systemic immune response. The local inoculation of antigen was superior for induction of the maximal numbers of immunoglobulin M (IgM) and non-IgM sAFC in the pdLNC at 4 days post-immunization. However, the local response coould be enhanced by a concomitant splenic response. The local route of inoculation did not consistently induce an sAFC response in the spleen, but when the spleen was involved, two unique observations were recorded regarding the IgM response: (i) an approximate twofold increase in the numbers of sAFC was seen in the pdLNC on day 7 post-inoculation in animals that had a splenic sAFC response; and (ii) the appearance of an early (day 4) serum IgM hemagglutination titer was observed in the animals with a splenic sAFC response. However, the appearance of IgG serum hemagglutination titers was independent of the indirect sAFC response in the spleen but correlated with the appearance of indirect sAFC response in the pdLNC. As expected, intravenous inoculation of antigen was superior for inducing a systemic IgM response. We concluded that the local and systemic immune responses are related and interdependent in providing immune reactivity related to the lung. Whereas the systemic response enhanced both the serum IgM titer and the specific IgM antibody-forming cell response in the draining nodes, we observed that the local response was sufficient for the IgG serum hemagglutination titer even in the absence of a splenic sAFC response.


Effect of immune status on dengue 2 virus replication in cultured leukocytes from infants and children.

Cord blood leukocytes from neonates with maternal dengue antibody supported dengue 2 virus replication in vitro; those from neonates without maternal antibody did not. Cord bloods of infants born to dengue-immune mothers contained a potent enhancing factor which gradually decayed with age and which was absent from neonates born to nonimmune mothers. Permissiveness of cultures of washed peripheral blood leukocytes from infants with maternal antibody declined steadily with increasing age in parallel with the decay of maternal antibody, and the leukocytes were no longer permissive after 10 to 12 months. The demonstration of a dengue maternal infection-enhancing factor in human cord blood from dengue-immune mothers supports the hypothesis that severe primary dengue hemorrhagic fever with shock seen in Bangkok infants is related to maternal immune status.


Adherence of human peripheral blood lymphocytes to measles-virus infected cells: modulation by solubilized rhesus erythrocyte membranes and carbohydrates.

The adherence of human peripheral blood lymphocytes to HeLa cells persistently infected with measles virus (HeLa-K11) was studied. The following data were observed. (i) The proportion of HeLa-K11 cells with adherent human peripheral blood lymphocytes of rhesus monkey erythrocytes was similar over a wide range of ratios of HeLa-K11 cells to lymphocytes or erythrocytes. (ii) The great majority of human peripheral blood lymphocytes and erythrocytes reacted with the same HeLa-K11 cell (iii). The adherence of lymphocytes or erythrocytes to HeLa-K11 cells was blocked by rabbit anti-measles virus antibody or solubilized monkey erythrocyte membranes. The pretreatment of erythrocytes or lymphocytes with receptor-destroying enzyme did not alter their adherence properties. (iv) The pattern of inhibition observed with several carbohydrates was similar in both the erythrocyte and the lymphocyte adherence assays. These data are consistent with the possibility that the receptor present on both rhesus monkey erythrocytes and human lymphocytes has similar specificities and biochemical composition.


Partial purification and characterization of two Cladosporium herbarum allergens.

Two important Cladosporium herbarum allergens (Ag-54 and Ag-32) were partly purified by means of diafiltration, gel filtration and isoelectric focusing. Modifications of quantitative immunological techniques, including autoradiography, were used as assay systems for allergenic activity and to provide a basis for evaluation of the immunological purity of the allergens. Ag-54 appeared to have a molecular weight of approximately 25,000 daltons and an isoelectric point of 5.0. The molecular weight of Ag-32 appeared to be approximately 13,000 daltons. It consisted of 5 molecular species differing in isoelectric points from 3.4 to 4.4 in intervals of approximately 0.25 pH units. These variants of Ag-32 seemed to be antigenically and allergenically identical.


Serum amyloid protein SAA, C-reactive protein and lysozyme in leprosy.

Serum amyloid protein (SAA) appears to be the precursor of amyloid protein AA, the non-immunoglobulin fibril protein of secondary amyloidosis. Since amyloidosis is known to occur in high frequency associated with lepromatous leprosy (LL), we have examined the SAA levels in untreated LL patients and compared them to the levels observed in patients with tuberculoid leprosy (TT) and a large number observed in healthy controls. We found that SAA is markedly elevated in LL when compared to TT and controls. No clear correlation could be established with C-reactive protein, a well-documented acute phase reactant, or serum lysozyme levels that reflect the presence of monocyte activity. This study showed that SAA levels in leprosy do not appear to be a reflection of inflammatory activity or monocyte turnover. Whether amyloidosis will be more prevalent in patients who have higher SAA levels remains to be determined.


Lucio's phenomenon: a comparative histological study.

To study further the pathogenesis of Lucio's phenomenon, we have made a comparative histological study of 11 patients with Lucio's phenomenon and 12 with ENL. Confirming the findings of others, Lucio's reaction could be distinguished from ENL by epidermal necrosis and by necrotizing vasculitis manifesting necrosis in the walls of superficial vessels and severe, focal endothelial proliferation of mid-dermal vessels. Furthermore, in Lucio's phenomenon large numbers of AFB were found in evidently normal and in swollen or proliferating endothelial cells. We hypothesize that patients with Lucio's phenomenon have an exceptionally deficient defense mechanism, allowing unrestricted proliferation of AFB in endothelial cells, facilitating contact between bacterial antigen and circulating antibody and leading to infarction; also, this nadir of resistance allows unimpeded dissemination of AFB, accounting for the clinical features of diffuse non-nodular leprosy. Thus, an explanation is offered for the restriction of Lucio's phenomenon to patients with diffuse non-nodular lepromatous leprosy.


In vivo effect of DDS on phytohemagglutinin (PHA)-induced lymphocyte transformation cultures in normal healthy volunteers.

Depression in PHA-induced lymphocyte transformation in peripheral blood has been observed in 15 healthy volunteers after administration of DDS (100 mg/day) for seven days. In vitro culture of lymphocytes obtained from these volunteers in DDS-free normal AB serum has not altered the blast cell numbers. Lymphocytes of these volunteers have been found to contain a significant amount of DDS, ranging from 0.42 to 3.2 micrograms per 10.6 lymphocytes.


Unusual electrocardiographic presentation of idiopathic hypertrophic subaortic stenosis.

A patient with idiopathic hypertrophic subaortic stenosis and normal coronary arteries, with dynamic electrocardiographic changes resembling acute myocardial ischemia, is presented. A definite association between the electrocardiographic changes and the idiopathic hypertrophic subaortic stenosis cannot be absolutely confirmed; however, the findings demonstrate the broad spectrum of electrocardiographic presentation in this disease.


Studies on relationships between the structure and the glycosidase-inhibiting activity of HPAAO and its analogs.

p-Hydroxyphenylacetaldoxime (HPAAO) (anti and syn forms) obtained by fermentation and its analogs chemically synthesized were tested for their activities to inhibit various glycosidases. HPAAO inhibited bovine liver beta-galactosidase in a competitive manner at pH 7.0 with an apparent Ki value of 8 x 10(-8) M. HPAAO also inhibited various mammalian beta-glycosidases which had pH optima between 6.0 and 8.0. The syn form of HPAAO was found to be more active than the anti form against bovine liver neutral beta-galactosidase. It was concluded that the oxime moiety of HPAAO and its analogs was essential for their enzyme-inhibiting activity and the activities of aromatic or aliphatic oxime derivatives were dependent on the number of carbon atoms in their alkyl-chains.


A cytochemical and ultrastructural study of the "S.I.F." cells in cat sympathetic ganglia.

According to the hypothesis of Eccles and Libet, the small intensely fluorescent cells (S.I.F. cells) in the sympathetic ganglion would represent an essential element in the inhibition of the principal neuron. As a contribution to the study of this important problem, we have investigated serial sections in superior cervical (S.C.G.) and celiac (C.G.) ganglia of the cat, a species that has not been extensively studied up to now, both by fluorescence and electron microscopy. We have shown that the "S.I.F." cells are three times fewer in the cat S.C.G. than in the rat S.C.G. There are five times more "S.I.F." cells in the C.G. of the cat than in the S.C.G. of the same species. Moreover we have described two types of "S.I.F." cells. Type I is composed of cells characterized by highly polymorphous large dense-cored vesicles. These cells lack processes and are grouped in clusters centered on fenestrated capillaries. They could be endocrine function cells. Type II is formed of isolated cells which exibit long processes and establish synaptic junctions with the dendrites of the principal neurons. In this case, the dense-cored vesicles are very regular and much smaller. These cells could be equivalent to interneurons. Type I very strongly predominates in the S.C.G. and C.G. of the cat where it represents more than 90% of the "S.I.F." cell total observed by fluorescence microscopy. A priori such a quantitative and qualitative heterogeneity hardly consistent with Eccles and Libet's hypothesis based on the existence of dopaminergic interneurons only, allows the question to be raised as to the functional significance of the "S.I.F." cells in ganglion physiology. The notion of modulation of ganglionic transmission does not seem to be quiered by these new data but could be founded on different forms of action embodied in the broader conception of the neuromodulation phenomenon.


Formation of molecules of biological interest from formaldehyde and hydroxylamine in a modified sea medium.

As reported previously, glycine, serine, aspartic acid, and beta-alanine are the predominant amino acids produced from equimolecular formaldehyde and hydroxylamine in a modified sea medium enriched with essential transition metal ions. The time course of formation of the amino acids, and related substances was studied. Among the amino acids, glycine was produced earlier. Urea was produced initially and disappeared rapidly. Formation of cyanide, glycinenitrile, and glycinamide preceded the formation of amino acids. Probable pathways for the formation of amino acids and urea are suggested.


Preparation of ruthenium(II) and ruthenium(III) myoglobin and the reaction of dioxygen, and carbon monoxide, with ruthenium(II) myoglobin.

Ruthenium myoglobins have been prepared by the reconstitution of horse heart apomyoglobin with either ruthenium(II) or ruthenium(III) mesoporphyrin IX (MpIX) derivatives. The ruthenium(II) and -(III) myo globins (RuMb and RuMb+, respectively) contain one ruthenium porphyrin/heme binding site; the species are readily interconverted using dithionite for reduction and bromine for oxidation. RuMb binds carbon monoxide to give the known carbonyl complex. Reversible oxygenation occurs readily with protein-free RuII(MpIX) species in dimethylformamide, but RuMb in phosphate buffer is irreversibly oxidized by dioxygen to give RuMb+ via an outer sphere electron transfer mechanism.


Intermediate (skeletin) filaments in heart Purkinje fibers. A correlative morphological and biochemical identification with evidence of a cytoskeletal function.

Cow Purkinje fibers contain a population of free cytoplasmic filaments which consistently differ in ultrastructural appearance from actin and myosin filaments, irrespective of preparation technique. The fixation and staining techniques, however, influenced the filament diameter, which was found to be 7.4--9.5 nm for filaments in plastic-embedded material, and 7.0 nm in cryo-sectioned material, thus intermediate as compared to actin and myosin filaments. Cross-sectional profiles suggested that the intermediate-sized filaments are composed of four subfilaments. To provide a basis for further biochemical investigations on the filaments, extraction procedures were carried out to remove other cell organelles. Electron microscopy showed that undulating bundles of intermediate filaments converging towards desmosomes still remained, after the extractions, together with Z-disk material. In spite of the extensive extraction, the shape of the individual cells and the assemblies of cell bundles remained intact. This confirms that the intermediate filaments of cow Purkinje fibers together with desmosomes do in fact have a cytoskeletal function. On account of (a) the cytoskeletal function of the filaments, (b) the similarities to the smooth muscle "100-A filament" protein subunit skeletin, and (c) the inadequate and confusing existing terminology, we suggest that the filaments be named "skeletin filaments."


Nucleation of polar actin filament assembly by a positively charged surface.

Polylysine-coated polystyrene beads can nucleate polar assembly of monomeric actin into filamentous form. This nucleation has been demonstrated by a combination of biochemical and structural experiments. The polylysine-coated beads accelerate the rate of actin assembly as detected by two different biochemical assays. Subsequent examination of the beads by electron microscopy reveals numerous actin filaments of similar length radiating from the beads. ATP promotes this bead-induced acceleration of assembly. Decoration of the filaments with the myosin fragment S1 shows that these filaments all have the same polarity, with the arrowhead pattern pointing toward the bead. The relevance of the system to in vitro mechanisms and its usefulness in other studies are discussed.


Role of spindle microtubules in the control of cell cycle timing.

Sea urchin eggs are used to investigate the involvement of spindle microtubules in the mechanisms that control the timing of cell cycle events. Eggs are treated for 4 min with Colcemid at prophase of the first mitosis. No microtubules are assembled for at least 3 h, and the eggs do not divide. These eggs show repeated cycles of nuclear envelope breakdown (NEB) and nuclear envelope reformation (NER). Mitosis (NEB to NER) is twice as long in Colcemid-treated eggs as in the untreated controls. Interphase (NER to NEB) is the same in both. Thus, each cycle is prolonged entirely in mitosis. The chromosomes of treated eggs condense and eventually split into separate chromatids which do not move apart. This "canaphase" splitting is substantially delayed relative to anaphase onset in the control eggs. Treated eggs are irradiated after NEB with 366-nm light to inactivate the Colcemid. This allows the eggs to assemble normal spindles and divide. Up to 14 min after NEB, delays in the start of microtubule assembly give equal delays in anaphase onset, cleavage, and the events of the following cell cycle. Regardless of the delay, anaphase follows irradiation by the normal prometaphase duration. The quantity of spindle microtubules also influences the timing of mitotic events. Short Colcemid treatments administered in prophase of second division cause eggs to assemble small spindles. One blastomere is irradiated after NEB to provide a control cell with a normal-sized spindle. Cells with diminished spindles always initiate anaphase later than their controls. Telophase events are correspondingly delayed. This work demonstrates that spindle microtubules are involved in the mechanisms that control the time when the cell will initiate anaphase, finish mitosis, and start the next cell cycle.


Actin microfilaments, cell shape, and secretory processes in isolated rat hepatocytes. Effect of phalloidin and cytochalasin D.

The effects of phalloidin and cytochalasin D, drugs which, respectively, stabilize and destabilize actin microfilaments, have been tested on isolated rat hepatocytes. Both drugs produced a modification of cell shape, characterized by protrusions bulging from the cytoplasm. In phalloidin-treated hepatocytes, an accumulation of actin microfilamentous network was detectable at the base of each protrusion by electron microscopy, immunofluorescence, and HMM decoration. This accumulation of microfilaments was absent in cytochalasin D-treated cells. The release of triglycerides, an index of very low density lipoprotein secretion, was inhibited by phalloidin or cytochalasin D, and accompanied by an increase in cellular triglycerides. At the electron microscope examination, triglyceride accumulation was represented by fat droplets and vesicle-enclosed, very low density lipoprotein-like particles. Total protein and albumin secretion was only very slightly modified by either one of these drugs. With the use of various phalloidin analogs, a correlation was observed between their respective ability to stabilize F-actin in vitro, and their effects on cell shape and triglyceride secretion. In conclusion, phalloidin, and cytochalasin D: (a) modify the shape of isolated hepatocytes; (b) inhibit lipoprotein secretion. These effects possibly result from a modification of actin microfilament function.


Polymerization of actin. VI. The polarity of the actin filaments in the acrosomal process and how it might be determined.

The polarity of the actin filaments which assemble from the nucleating body or actomere of Thyone and Pisaster sperm was determined using myosin subfragment 1 decoration. The polarity was found to be unidirectional with the arrowheads pointing towards the cell center. When polymerization is induced at low temperature with concentrations of actin near the critical concentration for polymerization, elongation of filaments occurs preferentially off the apical end. If the sperm are induced to undergo the acrosomal reaction with an ionophore, the polarity of the actin filaments attached to the actomere is the same as that already described, but the filaments which polymerize parallel to, but peripheral to, those extending from the actomere are randomly polarized. These randomly polarized filaments appear to result from spontaneous nucleation. When sperm are induced to undergo the acrosomal reaction with eggs, the polarity of the actin filaments is also unidirectional with the arrowheads pointing towards the cell center. From these results we conclude: (a) that the actomere, by nucleating the polymerization of actin filaments, controls the polarity of the actin filaments in the acrosomal process, (b) that the actomere recognizes a surface of the actin monomer that is different from that surface recognized by the dense material attached to membranes, and (c) that egg myosin could not act to pull the sperm into the egg. Included is a discussion of how the observation that monomers add largely to one end of a decorated filament in vitro relates to these in vivo observations.


Size classes of replication units in DNA from sea urchin embryos.

Sea urchin DNA containing replication structures was isolated from two to four cell stage and blastula stage embryos, and examined by electron microscopy. In addition to the expected eye forms, we also observed molecules with large internal single-stranded gaps. Such structures were not present in DNA devoid of replicating molecules such as that isolated from sea urchin sperm. When the size of eye forms and interbubble distances between the two stages were compared, there was no detectable difference. In both stages, we observed two distinct size classes of bubbles and of interbubble distances. In the case of bubble sizes, the smaller size class was comprised of clustered microbubbles that ranged from 200 base pairs to 1 Kilobase (kb) with a mean of 432 base pairs. The large eye forms measured 1--35 kb with a mean of 6.8 kb. Interbubble distances also yielded two distinct populations, with the smaller class ranging from 400 base pairs to 2.3 kb (mean = 1.1 kb) and the larger population ranging from 2.8 to 36 kb (mean = 10.9 kb). Although other possibilities cannot be entirely excluded, the data support the contention that a substantial fraction of the larger eye-form population arises from the fusion of the clustered microbubbles.


Ultrastructure of the endoplasmic factor responsible for cytoplasmic streaming in Chara internodal cells.

Previous investigators have proposed that cytoplasmic streaming in Chara internodal cells results from the interaction between an endoplasmic factor and fibrils composed of microfilaments in the stationary cortex. Using the internal perfusion technique, we confirmed the observation that organelles which had been attached to the fibrils by decreasing the internal concentration of ATP moved along the fibrils after ATP was introduced. Thin-sectioned specimens revealed that endoplasmic organelles of various shapes were linked to microfilament bundles in the absence of ATP. Linkage was effected by regularly arranged electron-dense materials with a spacing of 100 -- 130 nm at definite regions on each organelle. The organelles in question were studied in negatively stained preparations of endoplasm. The organelles had some common features. (1) They were all membrane-limited.(2) Their sizes and configurations varied largely. (3) One or more protuberances were present on them. (4) The protuberances were usually rod- or horn-like. (5) Small globular bodies 20--30 nm in diameter were found in ordered array with the same spacing as those in thin sections at the surface of the protuberances. (6) Many fine filaments were always attached to the surface of the protuberances. These fine filaments differed from F-actin in diameter (less than 4 nm) and inability to react with heavy meromyosin from rabbit skeletal muscle. The role of such components of the organelles in cytoplasmic streaming is discussed. A paracrystalline array of microfilaments with a transverse periodicity of about 38 nm is presented, together with its optical diffraction pattern.


The effects of ovariectomy and estrogen treatment on the dopamine inhibition of gonadotropin and prolactin release.

The suppressive action of dopamine (DA) on circulating gonadotropin and PRL levels is found to be positively correlated with their basal serum concentrations. Thus, DA inhibition is greater in ovariectomized (agonadal) women than in normal women on day 2 of their menstrual cycles, and the reverse is observed for PRL. Pretreatment of agonadal subjects with estrogen lowers the basal levels of LH and FSH and thereby proportionately decreases the suppressive effects of DA. Estrogen treatment elevates the basal level of PRL in agonadal subjects and also the PRL-inhibiting effect of DA. These findings indicate that castration and estrogen treatment significantly influence the inhibitory effect of DA on gonadotropin and PRL release.


Diurnal variation in the response of plasma prolactin, cortisol, and growth hormone to insulin-induced hypoglycemia in normal men.

Plasma PRL, cortisol, and GH responses to a standard iv dose of regular insulin were studied during the morning and evening in seven normal young men. Hypoglycemia achieved during morning and evening in the same aubjects was equal. There was a substantially greater maximal increment in PRL in the evening compared to the morning (P less than 0.01). The peak levels of cortisol achieved in the morning and evening were equal, but the evening maximal increase was greater (P less than 0.05) because of the significantly lower evening basal cortisol level. Evening increases in GH were greater than in the morning in five subjects and were essentially the same in two subjects; for the group, the evening maximal increment in GH was significantly greater (p less than 0.05 after log transformation). Since serotonergic mechanisms appear to be involved in the PRL, GH, and cortisol responses to hypoglycemia, we suggest the possibility of a diurnal variation in hypothalamic serotonin activity which may partly mediate these differential diurnal hormonal responses to hypoglycemia (although other neurotransmitters may also be involved). The data on cortisol are discussed with regard to the reset hypothesis of feedback inhibition.


Exotoxin activity associated with the Legionnaires disease bacterium.

Hemolysis occurred around growth of the Legionnaires disease bacterium on supplemented Mueller-Hinton agar containing sterile defibrinated blood from each of five mammalian species. Hemolysis was most pronounced with guinea pig or rabbit blood, was less intense with horse or sheep blood, and was slight with blood from a human donor. Sterile filtrates of allantoic fluid from embryonated hen's eggs that had been infected with this organism displayed hemolytic activity in a radial hemolysis assay with guinea pig cells in agar. Growth of the Legionnaires disease bacterium on F-G agar with 5% hen's egg yolk was surrounded by a zone of clearing and more circumscribed zones of iridescence and increased opacity on and in the medium. Attempts to detect activity analogous to that of Escherichia coli heat-labile or heat-stable enterotoxin in allantoic fluid from infected eggs or in cultures of the Legionnaires disease bacterium were not successful.


First isolation of Peptococcus indolicus from a human clinical specimen.

Peptococcus indolicus was isolated from a skin lesion of a sheepherder. A case report is given, and microbiological features of this organism are described.


Relationship of scores on the Escapism Scale of the MMPI to escape from minimum security federal custody.

Investigated the ability of the Escapism (Ec) scale of the MMPI to differentiate between escape and non-escape minimum security federal prisoners. At the .05 level there was no difference between the scores of the two groups on the Ec scale or on comparisons of other correctional data, age, and ethnic composition. It appears that the Ec scale alone or in combination with other data will be a poor predictor of escape. Also, the rate of escape was so low as to make accurate prediction from any criteria extremely unlikely.


Isolation-induced facilitation of male sexual behavior in mice.

Sexual performance of male mice housed individually or in groups of 3 or 12 was compared. Experiment 1 examined naive males presented at weekly intervals with ovariectomized, estrogen-primed, progesterone-treated females. Performance in isolates was consistently superior and reached an asymptote that was twice that of grouped animals. Reversal of housing conditions reversed performance. Experiment 2 varied intervals of isolation among subjects, finding facilitation at several intervals. Experiment 3 compared animals under different population densities. Density did not alter the effects of isolation and grouping. In all experiments, additional tests with target males indicated that aggressive and sexual performance were moderately correlated and responded similarly to parametric manipulations. These results parallel and extend studies of isolation-induced aggression.


Copulation and intermale aggression in rats.

Attack behavior of reliably aggressive male Long-Evans rats against unfamiliar male intruders was observed immediately following copulation to one or more ejaculations. Compulatory series to five ejaculations did not differ from copulation to a single ejaculation or from a noncopulatory control in affecting aggressive behavior. Repetitive biting attacks occurred in all conditions, with comparable wounding. Evidently, the male postejaculatory state of insensitivity to sexual stimuli does not extend to stimuli eliciting intermale aggression. A second experiment determined the attack-eliciting capacity of foreign males placed in the home cage of an actively copulating male. As intromissions increased and the interval to ejaculation decreased, the probability of intermale aggression and interruption of copulation diminished. The results are discussed in reference to sexual and aggressive strategies of the copulating male.


Defensive behaviors in rats following septal and septal--amygdala lesions.

Rats with anterior septal lesions showed a pattern of consistent enhancement of defensive behaviors normally elicited by threatening conspecifics, with no enhancement of attack or general reactivity. Further division of this group indicated that damage to sites anterior and ventral to the septal area, sites previously implicated in the "septal syndrome," produces maximal effect on these behaviors. When amygdala lesions are combined with septal damage this enhanced defensive responding is almost completely eliminated. These results were interpreted as indicating that the septal syndrome represents hyperdefensiveness to conspecific threat stimuli rather than aggression or increased general reactivity, and that amygdaloid mechanisms are also involved in the regulation of conspecific defensive behaviors.


Common mammary pathogens and factors in infection and mastitis.

Inflammation of the mammary gland, commonly known as mastitis, is considered a complex disease in view of its complexities of etiology, pathogenesis, sequela, therapy, and related aspects. The disease of most concern is the one produced by pathogenic microorganisms. However, as a prerequisite the pathogen must not only enter the mammary gland but also be able to survive and multiply in numbers sufficient to produce pathogenic effects. The normal bovine mammary gland is protected from such attacks by several anatomic and biologic armamenta which must be overcome by the invading pathogens. Organisms involved in causation of mastitis vary in their habitat, virulence, and susceptibility to host barriers. Similarly cows vary in their resistance to microbial entry into the mammary gland and subsequent response to overcome the infection. Only a few organisms, however, need to survive in the milieu of the mammary gland to produce mastitis. This paper is a general discussion of these aspects concerning bovine mastitis in relation to common mammary pathogens.


Endocrine control of energy metabolism in the cow: correlations of hormones and metabolites in high and low yielding cows for stages of lactation.

Measures of hormones and metabolites in blood plasma of high and low yielding cattle matched for diet and stage of lactation were investigated for relationships between milk yield, body weight, and concentrations of hormones (prolactin, growth hormone, insulin, and thyroxine) and metabolites (glucose, nonesterified fatty acids, beta-hydroxybutyric acid, and L-lactic acid) for stages of lactation. A first approach correlated total milk yields of 15 cows with average constituents during the four 24-h blood samplings through the first 27 wk of lactation. The second examined associations of changes with sampling periods in milk yield or body weight with changes in hormones and metabolites. Total milk yield of the high yielding group was correlated positively with ratios of growth hormone/thyroxine and glucose/thyroxine and correlated negatively with thyroxine. Changes in growth hormone and its ratio to insulin, and changes in yield were correlated positively for groups combined. Changes in thyroxine were correlated negatively with changes in yield. Changes in liveweight gain were related positively to insulin and lactic acid and negatively with changes in growth hormone. Changes in growth hormone were related positively to changes in nonesterified fatty acids.


Heat inactivation of superoxide dismutase in bovine milk.

Superoxide dismutase, and enzyme normal to bovine milk, may be inactivated partially by heat during processing of milk and milk products. A minimal pasteurization temperature (71.7 C for 15 s) does not cause heat inactivation of superoxide dismutase. Higher temperature of pasteurization or systems including a 'vac-heat process' will inactivate a substantial portion of the enzyme. Heat treatments greater than 75 C inactivated more than 20% of the superoxide dismutase. Purified superoxide dismutase fractionated from bovine milk was more sensitive to thermal processing than the superoxide dismutase in bovine milk serum.


Studies on the life cycle of Asymphylodora tincae (Modeer, 1790) (Trematoda: Monorchiidae) in a small lake near Amsterdam. Part 1. The morphology of various stages.

Aspects of the life cycle of Asymphylodora tincae have been studied in a small lake near Amsterdam. Bithynia tentaculata, being the only snail species that was very numerous in the lake, was the first as well as the main second intermediate host; adult trematodes were found exclusively in the tench, Tinca tinca. A small part of the cercariae that penetrate into B. tentaculata was able to develop into progenetic specimens. A morphological description is given of the following stages of A. tincae: adult, egg, redia, cercariaeum, metacercaria and progenetic stage. The cercariaeum is identified as Cercariaeum paludinae impurae De Filippi, 1854. It is concluded that A. tincae is a species, capable of large variation regarding both morphological structure (e.g. body spination, size) and life cycle.


Ascaridoid nematodes of amphibians and reptiles: Multicaecum and Brevimulticaecum.

The genus Multicaecum Baylis 1923, sensu Hartwich 1957, was found to be heterogeneous, comprising species which are released to two distinct genera, namely Multicaecum Bavlis, 1923 and Brevimulticaecum. The latter name is derived from the subgenus Brevinulticaecum Mozgovoy, in Skrjabin, Shikhobalova, and Mozgovoy, 1951 by raising it to generic rank and emending the definition. Multicaecum contains a single species, agile Wedl, 1861 occurring in Crocodylus spp. in Africa, India and Australia, and is characterized by smooth rounded lips, each with a dentigerous ridge comprising small sharp denticles. The excretory pore is level with the nerve ring or behind it, and the ventricular appendices are long and slender. The species gangeticum Maplestone 1930 and quadrata Linstow 1904 are excluded from Multicaecum and regarded as species inquirendae incertae sedis. Brevimulticaecum contains five species occurring in the caimans and the alligator of the New World: baylisi Travassors, 1933 (type species; acuticauda Schuurmans-Stekhoven, 1937 is placed in synonomy under baylisi); stekhoveni Baylis, 1947; tenuicolle Rudolphi, 1819; and two new species. Brevimulticaecum spp. are characterized by flat lips with alate margins and notches, without dentigerous ridges, excretory pore in front of or at nerve ring and the ventriculus with short appendices. The significance of this proposal is discussed in relation to the other genera of ascaridoid nematodes in crocodilians.


Freeze-fracture studies on the plasma membranes of normal human, thrombasthenic, and Bernard-Soulier platelets.

The description of severe molecular deficiencies of different membrane glycoproteins in thrombasthenic and Bernard-Soulier platelets has led us to investigate the intramembrane organization of their plasma membranes using freeze-fracture electron microscopy. An initial examination of the cleaved plasma membranes of freeze-fractured normal human platelets revealed randomly distributed MAPs on the fracture faces of both the outer and inner phospholipid leaflets of the bilayer. Particle densities of 925 +/- 52/micrometer22 on the EF and 427 +/- 29/micrometer2 on the PF were calculated with a computer-linked picture analyzer. The particle size was heterogeneous on both fracture faces, and the number of particles decreased exponentially in the 5 to 13 nm size range. Examination of the platelets of three thrombasthenic patients revealed a low particle density (36% to 69% of the normal range) on the PF of the cleaved plasma membrane and a reduced particle coefficient between the two fracture faces (PF/EF). This abnormality was accompanied by a preferential decrease in the larger sized particles. In marked contrast 8 to 13 nm particles predominated on both fracture faces of the plasma membranes of the platelets of a Bernard-Soulier patient, and a greater concentration of particles on the PF rather than the EF was uniquely observed. The results further define the modified structure of thrombasthenic and Bernard-Soulier platelet plasma membranes and suggest a structural heterogeneity within the total MAP population of the membranes of normal human platelets.


Chronic polioencephalitis with cerebral atrophy in infantile X-linked hypogammaglobulineaemia.

The development of a chronic polioencephalitis is reported in a patient with infantile X-linked hypogammaglobulinaemia (IXH Bruton type agammaglobulinaemia). In early childhood, the patient had multiple episodes of purulent inflammation involving the meninges and respiratory tract. He was given continuous administration of gammaglobulin and intermittent treatment with antibiotics, and survived for 21 years. The neuropathological lesion, which revealed severe cerebral atrophy, is described.


Menstrual cycle affects kinesthetic aftereffect, an index of personality and perceptual style.

Research suggests that kinesthetic aftereffect (KAE) scores reflect status on a postulated stimulus intensity modulation (SIM) mechanism that damps down subjective stimulus intensity for some (reducing) and increases it for others (augmenting). Such a mechanism would help account for empirically observed individual differences in such behaviors as pain tolerance, sensory deprivation reactivity, and stimulation seeking. It was hypothesized and confirmed in three adult female samples that KAE varies curvilinearly over the menstrual cycle: Greater KAE reduction occurs at the cycle's beginning and end. Neither tiredness, oral contraception, medication, attention, nor social expectations can explain this finding. Of the behaviors studied in the KAE literature, only five are also encompassed by the menstrual cycle literature. Four of these (antisocial behavior, acute schizophrenic episodes, accidents, and activity level) show similar curvilinearity over the cycle. We hypothesize that cyclical variation in the SIM mechanism mediates the curvilinear pattern observed for both these four behaviors and KAE.


Acquired monocular nystagmus in monozygous twins.

Twins girls presented with monocular nystagmus, head-nodding, and tilting in early infancy. This disorder resolved without therapy or residual defect. This case represents the first documented report of spasmus nutans presenting with only monocular nystagmus in twins. The etiology of spasmus nutans and monocular nystagmus is discussed in light of recent clinical and experimental observations.


Inherited Duane's syndrome: mirror-like localization of oculomotor disturbances in monozygotic twins.

Abnormal innervation hampered the left eye in one twin, while producing the same effect in the right  eye of the other twin and in that of his mother.