[Histological and histochemical studies of the stickleback Gasterosteus aculeatus L. kidney. III. Activity of various phosphatases depending on secretion]. 1. The activity of alkaline phosphatase is intensely positive in proximal tubule I and II during the breeding season. In the kidney of secretion producing the enzyme is detectable as against to kidney of winter on the whole proximal tubule II. 2. In the kidney what is able to build a nest, concentration and size of acid phosphatase granules are very increasing in proximal tubule II. 3. The detection of unspecific esterase was negatively already. 4, The reaction of glucose-6-phosphatase is slightly demonstrable in cells of proximal segment of secretion producing what are enlarged fourfold. 5; From the varied reaction of acid and alkaline phosphatase we conclude that both are to set in relation to excretory activity, but not to process of synthesis in kidney of late-spring fish.


Metastatic Wilms' tumor in the right atrium propagated through the inferior vena cava. A patient with a rare case of cardiac tumor in the right atrium secondary to Wilms' tumor of the right kidney, underwent open heart surgery and removal of the mass was presented. This is the 10th. case of intracardiac tumor secondary to renal malignancy. Careful auscultation of the heart is necessary in patients with malignancy in the kidney to detect the possible right heart metastases through the inferior vena cava. Cardiac symptoms precede the renal manifestations in most cases. Malignant renal metastases to the heart should always be in mind in space occupying masses of the right heart chambers.


[Pathomorphologic studies of the endocrine cells in the gastrointestinal mucosa. Physiology, cytochemistry and ultrastructure (author's transl]. With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable electron density. According to most authors, they represent a distinct cell type and not just a variant of the G-cells. It may be very difficult, however, to separate certain forms of D1-cells from functionally altered G-cells. 5. The A-cell can be found in the gastric mucosa of certain animal species, where it has been demonstrated by immunocytochemistry with antisera to gut-glucagon. This cell type does not occur in the human gastric mucosa. 6...


[Clinical picture of prenatal virus infections]. Review about virus infections in pregnancy. The kind of damage, the incidence, the diagnostic possibilities and the management are discussed.


[Sulphated glycosaminoglycans as virus inhibitors. 4th communication: clinical aspects of zoster with the proposal of a new treatment (author's transl)]. On the base of plaque inhibition tests in at least three virus-host-systems and successful treatment of mice with experimentally induced yellow fever encephalitis a well known sulphated glycosaminoglycan (GAGPS) "L5" was used as therapeutic agent in cases of zoster infection in man. The material was applied as 1% solution in water continuously on lint and rewettet for several days until nearly complete healing was achieved. The clinical course of 18 patients of former years (12 women, 6 men) was compared with 26 cases (19 women, 7 men) treated additionally with the new substance. All of them were carefully observed in the Rudolf-Virchow-Hospital in Berlin. Besides of registrating data as age and sex of the patients and the seasonal distribution of cases the course of illness was analyzed. The mean duration before admission to the hopsital was 4,9 days in the control group and 7,2 days in the L5-patients. Signs of organ diseases possibly acting as trigger mechanism for the remanifestation of the zoster were nearly twice in number in L5 cases than in the controls. Despite of this unfavorable stiutation the main parameters showed a clear tendency to return earlier to normal values in the GAGPS group. The fever was shortened. The blood lymphocytes normalized better with mean absolute values of 2400 in the L5-group and 3029 per m(3) in the control cases. The fall of the cell number in the liquor cerebrospinalis was more rapidly in the GAGPS treatment. The mean stay in the hospital was 33,2 days in L5 cases and 44,6 days in control patients respectively in the main group of age between 60 and 80 years. One death in the GAGPS group corresponded to four in the control group.  In the local skin area the edema disappeared rapidly with beginning of treatment. Confluent vesicles flattened within 24 to 48 hours and no further efflorescences were seen. Pain diminished in few days. The good results justify continued trials.


Typing of Group A streptococci from an urban area (Köln) in West Germany. Two-hundred and twenty strains of Streptococcus pyogenes (group A streptococcus) from the urban area of Köln, West Germany have been typed by M precipitin and T agglutination tests. Determination of streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADase) production and the serum opacity reaction (SOR) have also been performed. 65.5% of the isolates could be typed by the M precipitin reaction. 92.1% of the remaining strains could be identified by their T protein antigens and could be further subdivided according to their NADase/SOR pattern. Most of the M typable strains originated from upper respiratory tract infections (including scarlet fever), whereas the majority of the M nontypable streptocci had been isolated from skin, wound, and other non-respiratory sites.


Primary carcinoma of the liver in Zambia. A review of liver biopsies over a three year period revealed 166 cases of carcinoma of the liver. Hepatocellular carcinoma constituted the commonest malignant tumour in male Zambians. The different histologic sub-types were studied and compared wth a study of liver cell cancer in Uganda. Trabecular carcinoma was the commonest histological type. A significant association of hepatocellular carcinoma with macronodular cirrhosis was noted.


[Blood pressure and pulse frequency during oral intake of cadmium sulfide in animal experiment (author's transl)]. Female wistar rats were given cadmium sulfide in various concentrations in their chow (26 mg CdS/kg feed and 52 mg tcdS/kg feed). After a three month trial no significant changes in blood pressure could be seen. The pulse frequencies showed the falling tendency with increasing weight, as already seen in healthy rats.


[Microbial resistance to formaldehyde. I. Comparative quantitative studies in some selected species of vegetative bacteria, bacterial spores, fungi, bacteriophages and viruses]. The resistence of different microorganisms to formaldehyde was determined. As test objects served gram-negative and gram-positive vegetative germs (Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella paratyphi-B, Staphylococcus aureus, Streptococcus faecalis), bacterial spores (Bacillus cereus, Bacillus pumilus, Bacillus stearothermophilus, Bacillus subtilis), fungi (Aspergillus niger, Candida albicans), bacteriophages (Escherichia coli phages, T1, T2, T3), and viruses (adenovirus, poliomyelitis virus, vaccinia virus). For the studies, suspensions of germs were exposed at identical temperature (20 degrees C) and pH (7.0). The microbicidal effect of formaldehyde was measured by the decrease of the proportion of germs capable of multiplication in the suspension (lg (N/N0); where: N0 equals initial number of germs capable of multiplication; N equals number of germs capable of multiplication after exposure to formaldehyde). For all germs the dependence of the microbicidal effect on the concentration of formaldehyde was determined. In all experiments, the duration of exposure was two hours. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Salmonella paratyphi-B were found to be more susceptible than Staphylococcus aureus (vf. Fig. 1 A). The strains of Pseudomonas aeruginosa used were widely varying as to their susceptibility. To obtain equal microbicidal effects, concentrations of formaldehyde almost three times as high had to be used for the most resistant strain than were necessary for the most susceptible strain of Pseudomonas aeruginosa. All strains of Klebsiella pneumoniae examined were found to have an identical resistence to formaldehyde. Streptococcus faecalis was even more resistant to formaldehyde than Staphylococcus aureus. In the case of Streptococcus faecalis, a concentration of formaldehyde about three times as high had to be used to obtain microbicidal effects of identical magnitude. For the killing of Candida albicans cells concentrations of formaldehyde not higher than those needed for the killing of vegetative gram-negative bacteria were necessary. The conidia of Aspergillus niger were found to be more resistant than the cells of Candida albicans but did not require any higher concentrations than for the killing of Staphylococcus aureus (see Fig. 1 B). In the case of bacterial spores, a special phenomenon was observed. If the spores had been exposed to a temperature of 80 and 95 degrees C, respectively (depending on the species involved) for one or two hours following exposure to formaldehyde, a considerably higher number of spores was found to be capable of germination and colony formation than without such treatment (heat activation: cf. Fig. 2A and Fig. 2B). The spores of Bacillus cereus had only a relatively low resistance to formaldehyde. To reduce the proportion of the spores capable of colony formation to 1/10000, a 2.9% formaldehyde concentration was necessary without heat activation and one of 10.8% with heat activation...


[Rational method of producing sera with high titers of virus neutralizing antibodies]. A possibility of obtaining the diagnostic specific sera with a high titre against the poliovirus, type I, was studied experimentally. Five different immunization schemes by the same antigen were tested in parallel experiments. A method of the viral antigen (both of the concentrated and of the unconcentrated) mixed with complete Freund's adjuvant injection into the popliteal lymph nodes with the subsequent single reimmunization proved to be most effective. In this way it was possible to obtain type-specific sera with a high titre (1:20 000--1:40 000) in the course of five weeks.


[Isolation and purification of a preparation possessing leukocytosis-stimulating properties from pertussis bacteria]. A homogeneous protein LSF-2 preparation was extracted from the cultural fluid of Bordetella pertussis strains of the 1.0.3 serological type by means of precipitation with ammonium sulphate and electrofocussing; this preparation proved to produce a marked leukocytosis-stimulating and a weak toxic action of delayed type in experiments on animals. Intraperitoneal administration of 5 mug of the LSF-2 preparation caused a rise of leukocytosis in mice to 100,000 cells per 1 mm3, a delay in the gain in weight beginning from the 3rd day of the administration and a late death of the animals in 5% of cases. The LSF-2 preparation protected the mice in infection with a virulent pertussis strain No. 18323 in the amount of from 12 to 91%, depending on the immunizing dose; its ImD50 was equal to 2.0 -2.4 mug of protein. The results of investigations carried out permitted to assess the role of this substance in the formation of specific immunity in pertussis infection.


[Purification of the toxoids of Cl. Perfringens and Cl. pedematiens using silicagel]. A possibility was shown of purification of the concentrated toxoids of the Cl. perfringens and Cl. oedematiens species in examination of KSK-2, KSK-2,5; MCA-2 silicagels. The specific activity of the preparations obtained and the yield approached the analogous indices obtained in stratification of Sephadex G-75. The effect of preliminary silicagel treatment and also of the nature of buffer solutions on the efficacy of the process of purification of the gangrenous toxoids was established.


[Influence of spontaneous arousal during hibernation of the activity of the pituitary-adrenal system in the suslik Citellus erythrogenis]. Periodic spontaneous arousals of ground squirrels during hibernation are accompanied by activation of the hypophyseal-adrenal system. However, together with a 3-fold increase in hypophyseal ACTH and 2-fold increase in 11-oxycorticosterioid secretion by the adrenals, more than 2-fold decrease in the content of these hormones in the peripheral blood was observed. The latter may result from the increased corticosteroid metabolism. It is suggested that spontaneous arousals may act as a synchronizer of endogenous rhythm of the activity of the hypophyseal-adrenal system during winter hibernation.


[Clinico-electrophysiologic studies of experimental herpetic encephalitis]. Studies on animals demonstrated that in experimental herpetic encephalitis there is a diffuse retardation of background bioelectric brain activity and a proxysmal activity of 2 types: peek complex-slow waves 3 per 1 sec. and periodical paroxysmal complexes. There is also an increase of latent periods, duration and amplitudes of visual evoked potentials. Electrophysiological data correlate with the clinical picture of herpetic encephalitis and pathomorphological changes in the CNS. The obtained data are discussed with consideration bor the theory of neuron epileptization and hemodynamical disturbances.


[Clinical and biochemical heterogenicity of phenylketonuria in adults]. The authors carried out a clinical and biochemical investigation of 23 phenylketonuric patients at the age of 17--49 who were not treated specifically. The clinical examination showed that behavioural reactions, attacks of psychomotor excitation, neurological status, presence or absence of strokes and other symptoms of the disease were heterogenous. It has been established that disturbances of acid, protein, adipose and carbohydrate metabolism have different degrees of expressiveness. The clinical manifestation of the disease is conditioned by heterogeneity of monolocus mutations of the PAH gene.


[Functions of the adrenal cortex in patients with supratentorial brain tumors and their prognostic value for surgical intervention]. The functional activity of the adrenal cortex was studied pre- and postoperatively in patients with pituitary adenomas, craiopharyngiomas and supratentorial meningiomas. With the hypothalamus function preserved, the patients developed varying degrees of stress-responses in the postoperative period. Severe morphological injuries to the hypothalamus make the normal response to surgical trauma impossible. With some functional centers preserved, the diencephalo-catabolic syndrome develops. Severe injuries of the diencephalon, with its adaptative function completely lost, result in the development of the diencephalic areactive syndrome.


Effect of vertebrate hormones on the cyclic AMP level in Tetrahymena. Epinephrine, insulin, glucagon and theophylline produced a significant increase in the cAMP level of Tetrahymena, while the enhancing effect of TSH was not significant. The experimental results suggest that Tetrahymena possesses receptors for hormones of higher animals, but has no receptor for the nonsense hormone TSH. The cAMP enhancing effect shown by many hormones of higher animals irrespective of their different functions indicates that apart from the general mediator action of cAMP, some special mediation is also taking place.


Biological activities of ACTH-analogues varied in the active site. The steroidogenic and lipolytic activities of corticotrophin-(1-24)-tetracosapeptide and [Lys17,18]corticotrophin-(1-18)-octadecapeptide amide were compared with those of corresponding analogues substituted in position 8 with norarginine and homoarginine, and in position 9 with phenylalanine and pentamethylphenylalanine. The norarginine containing analogues demonstrated a rewarding activity, although they were generally somewhat less active than the homoarginine containing compounds. This confirms the previous conclusions concerning the indispensability of arginine as a guanidinium derivate. The analogues in which phenylalanine was a substitute for tryptophan, constituted partial agonists with a low activity in steroidogenesis and lipolysis but a rather high melanophore stimulating activity. Insertion of the permethylated derivative of phenylalanine in this position, which ensures the presence of an aminoacyl residue with the full electron donor properties of tryptophan, destroyed the low steroidogenic and lipolytic activity, but increased the MSH-activity about 2-fold.


Stimulation of longitudinal bone growth by hypophyseal hormones in the hypophysectomized rat. The stimulating effect of different pituitary hormones on longitudinal bone growth was determined with tetracycline as intravital marker in hypophysectomized rats. Growth hormone was found to be the most effective growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating activity. TSH exerts its effect via the production of thyroxine, whereas the growth stimulation by prolactin seems to be a direct effect of this hormone, similar to the effect of growth hormone. The LH, FSH, ACTH, MSH, vasopressin and oxytocin preparations did not stimulate longitudinal bone growth.


Altered responsiveness to hypophysiotrophic hormones of perifused rat pituitary tumours. Since growth hormone (GH) and prolactin (Prl) secretion by human pituitary tumours is often influenced by the hypophysiotrophic hormones thyrotrophin-releasing hormone (TRH) and somatostatin (SRIF), we have examined the responses of several transplantable rat pituitary tumours to these substances in a perifusion apparatus. The MStT/W15 tumour did not alter its secretion of GH and Prl in response to TRH, SRIF, or a partially purified porcine hypothalamic extract containing GH-releasing activity; normal rat pituitaries show clear responses to each of these substances. Theophylline and dibutyryl cyclic AMP each provoked increased GH and Prl release from the tumour. A second specimen of the MStT/W15 tumour and a specimen of the MStT/W5 tumour behaved in a manner identical to the original MStT/W15, showing no response to TRH or SRIF, but releasing both GH and Prl when theophylline or dibutyryl cyclic AMP was given. The MtT/F4 tumour increased its secretion of GH in response to TRH, 10 mug/ml, and theophylline, but no effect was seen with lower concentrations of TRH or with SRIF; Prl secretion by the F4 tumour was increased by theophylline, but TRH and SRIF had no effect. The autonomy demonstrated in these experimental tumours may be due to a loss of specific hypophysiotrophic hormone receptors or of secretory activating mechanisms.


The effect of treatment of hyper- and hypothyroidism on urinary excretion of cyclic adenosine 3',5'-monophosphate. The urinary excretion of cyclic adenosine 3',5'-monophosphate (cyclic AMP) was examined in patients with hyperthyroidism and primary hypothyroidism, before treatment and at least six months later on return to euthyroid status. Urinary cyclic AMP excretion was significantly greater in the hyperthyroid group than in the hypothyroid group both in the basal state (P less than 0.01) and the ambulant state (P less than 0.001). In ambulant hyperthyroid patients absolute urinary cyclic AMP excretion (mumol/24 h) was significantly greater (P less than 0.05) prior to treatment than on return to euthyroid status. In the hypothyroid group no significant change occurred after treatment with 1-thyroxine (P greater than 0.05). The mechanism of changes in urinary cyclic AMP excretion in thyroid disease are discussed.


Studies of a thyroid hormone and androgen dependent protein in rat liver cytosol. Sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the liver cytosol of euthyroid male rats revealed a prominent band (molecular weight, 26 000 daltons), designated Protein II, which was virtually absent in the cytosol of hypothyroid animals. Injection of 500 mug triiodothyronine (T3) per 100 g body weight resulted in a maximal increase in the level of Protein II, reaching 90% of the euthyroidal level 3 days after hormone administration. Concomitant studies with the liver mitochondrial enzyme alpha-glycerophosphate dehydrogenase (alpha-GPD) indicated that this T3 dose also resulted in a maximal enzyme response in this time period. Since we have estimated that 500 mug of T3 will saturate nearly all nuclear T3 binding sites, these results support the concept that the synthesis of both proteins is limited by nuclear binding. Protein II was absent in the liver cytosol of female rats but could be induced in ovariectomized female rats by androgens. Treatment of male rats with oestradiol resulted in disappearance of Protein II. Since administration of testosterone to hypothyroid male rats caused only a minimal increase in the amount of Protein II, the absence of the protein in hypothyroid animals was not due to androgen deficiency. Similarities in the molecular weight and the response to hormonal manipulation of Protein II and of the urinary alpha2uglobulin, previously reported by Roy (1973) raise the possibility that these proteins are the same. The high concentration of Protein II in male rat cytosol and the relative ease in its identification by SDS polyacrylamide gel electrophoresis make it a potentially useful model protein for the study of thyroid hormone action at the cellular level.


Oestrogen formation from C19 precursors in human choriocarcinoma in culture. A cloned cell line of human choriocarcinoma was evaluated as a model of human placental oestrogen production. Oestrone formation from dehydroepiandrosterone (D), D-sulphate (DS) or 4-androstenedione (A) was less than or equal to 5% of oestradiol-17beta (Oe2) formation. Oe2 formation from D and A was similar (100-150 pmole/h/10(7) cells); that from DS was 10 times less. Omitting serum from the medium increased Oe2 yield from DS 4-fold; addition of albumin restored these yields to control values (P greater than 0.05, t-test), presumably by binding DS. N6,O2'-dibutyryl-adenosine 3',5'-cyclic monophosphoric acid and theophylline treatment for 72 h stimulated (P less than 0.01) Oe2 formation from D (36%), DS (66%) and A (183%). In intact cells, sulphatase activity, Oe2 formation from D and Oe2 formation from DS equalled those in homogenates (P greater than 0.05) but Oe2 formation from D was greater than that from DS in both systems (P less than 0.001), indicating a deficiency of sulphatase relative to subsequent enzymes of oestrogen synthesis. Steroids, at concentrations previously shown to inhibit placental sulphatase or 3beta-hydroxysteroid dehydrogenase, did not inhibit choriocarcinoma enzymes. Except for its relative sulphatase deficiency and insusceptibility of oestrogen synthesizing enzymes to steroid inhibitors, choriocarcinoma appears to be a useful model of placental oestrogen synthesis.


Inherited erythrocyte pyruvate kinase deficiency: Studies on 15 members of two related families. The case of a haemolytic non-spherocytic anaemia with pyruvate kinase (PK) deficiency is reported. The investigation concerns two families with a low level of PK. In the propositus and in the members of his family we have also examined the behaviour of some enzymes and the concentration of red cell metabolites. We confirm the heterogeneity of the manifestation and agree that anaemias due to PK deficiency are complex forms in which the enzyme defect is only one of the symptoms.


Fine structure of myomedulloblastoma.

Fine structure of myomedulloblastoma. Electronmicroscopic studies in a case of myomedulloblastoma support the concept that the medulloblastoma and the myoblastoma component of the tumor derive drom different cell lines. The myoblastoma component shows bundles of myogenic elements, whereby quite undifferentiated cells lacking myofilaments are tightly attached to differentiated elements having well organized myofilaments. These bundles are encompassed by a common basement membrane, and their cells are joined by junctions, helping the identification of the undifferentiated elements. No comparable structures were seen in the medulloblastoma component. The fine structure of the myoblastoma is reminiscent of aspects of normal fetal development of skeletal muscle.


The target phenomenon in rat muscle following tenotomy and neurotomy. A comparative light microscopic and histochemical study. Target fibers were checked at regular intervals in two groups of rat gastrocnemius muscle namely after tenotomy and neurotomy. The highest amount of target fibres was observed during the first week following tenotomy and around the seventh week, when the muscle became again functional by spontaneous union of the tendon. The target phenomenon was restricted to the type II fibres. It appeared also in the early stage of re-innervation, 5 weeks following neurotomy and remained present subsequently in a transitional zone between denervated and re-innervated muscle fibres and was restricted to the type I muscle fibres. The target phenomenon was not the only histochemical alteration observed following tenotomy and neurotomy. This experimental study allowed to determinate more precisely the causal factors of the target phenomenon.


The incidence of ultrastructural abnormalities in the cortex of two retarded human brains (Down's syndrome). In a quantitative electronmicroscopic study, autopsy samples from the frontal and temporal lobes of two severely defective mongoloid brains were examined for the presence of abnormalities in the ultrastructure of the cerebral cortex. Particular attention was paid to the occurrence of atypical neuronal and glial inclusions similar to those which occur in small numbers (1 in 5000 mu2 of cortex) in neurologically normal brain (Rees, 1975). An area of 3.6 x 10(5) mu2 of cortex was examined from each brain. Within the cortical parenchyma, there was no gliosis, neuronal death or areas of degeneration.  Atypical neuronal and glial inclusions were observed in both of the retarded brains, but they did not occur in substantially different numbers from normal brains. There were no inclusions or structural abnormalities peculiar to the retarded brains. Thus, in these two defective brains, it has not been possible to demonstrate any specific abnormalities in the ultrastructure of the cortex.


Corpora amylacea in the peripheral nerve axons. Deposits similar to corpora amylacea were observed by electron microscopy within myelinated axons in the peripheral nerves in a case of familial spastic paralysis. Ultrastructurally the deposits consisted of randomly interlacing short filaments which were closely related to glycogen granules present in the periphery of the deposits. A possible relationship between the filamentous structures and glycogen granules is discussed. The significance of this inclusion and of related bodies is also discussed.


Pituitary growth hormone cell adenoma with cytoplasmic tubular aggregates in the capillary endothelium. Electron microscopy revealed the presence of cytoplasmic tubular aggregates in the capillary endothelium of a sparsely granulated growth hormone cell adenoma removed surgically from a 25-year-old female patient with acromegaly. To our knowledge, this is the second publication describing these structures in hypophysial growth hormone cell adenomas.


Chorionepitheliosis: A rare benign tropholblastic disease. Chorionepitheliosis, a benign trophoblastic disease, is a rare entity since only 26 cases have been published. The diagnosis was made in two instances and microscopic, biological and clinical data are presented. The lesion must be distinguished from syncytial endometritis, chorioadenoma destruens and choriocarcinoma. The possible histogenesis is discussed.


Herpes encephalitis.

Herpes encephalitis. Four cases of herpes encephalitis treated with dexamethasone and cytarabine. Cases were all verified by brain biopsy and immunofluorescent techniques. Attention is called to the need for early diagnosis, but the difficulty of deciding when to perform brain biopsy is discussed. Early treatment with effective drugs is necessary to prevent permanent brain damage.


Chemical modification and characterization of enterotoxin from clostridium perfringens type A. Enterotoxin from Clostridium perfringens type A has been purified. The enterotoxin was shown to be heat-labile, but re-activation of heat treated enterotoxin did occur down to an activity of 15 per cent of the native enterotoxin. The molecular weight was shown to be 34,000 by ultracentrifugation, and the molecular weight did not change significantly after treatment with 0.1 M beta-mercaptoethanol and 6 M guanidine hydrochloride. It was concluded that the enterotoxin consists of one single polypeptide chain. The enterotoxin did not lose any activity after treatment with iodoacetic acid and iodoacetamide, but a complete loss of activity was observed after succinylation.


In vitro stimulation of human lymphocytes by Bordetella Pertussis. Bordetella pertussis (B.p.) induces blast transformation of human lymphocytes; whole killed B.p. are more efficient than extracts obtained by sonication. Similar responses were obtained with each of the four strains used in the Danish pertussis vaccine. B.p. with low amounts of Protective Antigen and Histamine-Sensitizing Factor also induced lymphocyte transformation, but were less toxic to the lymphocytes at high concentrations. The supernatants of B.p. cultures were purified with respect to Lymphocytosis Promoting Factor; evidence is presented that these purified fractions possess T-lymphocyte mitogenic activity. Lymphocytes from all normal humans were stimulated by B.p., including cells from cord blood. Cells from childbearing women, obtained immediately after delivery, showed a general depression of lymphocyte transformation including the response to B.p. Children with whooping cough had a lower lymphocyte response to B.p. than healthy children. A highly significant correlation was observed between the responses to B.p. and to E. coli in the adults and newborn examined. It is concluded that the major part of the lymphocyte transformation induced by B.p. is non-specific.


In vitro modulation of human leucocyte migration and migration inhibitory factor (LIF) activity by cyclic 3',5'-AMP and cyclic 3',5'-GMP. The effects of cyclic 3', 5'-AMP (cAMP) and cyclic 3', 5'-GMP (cGMP) on the in vitro migration of human peripheral blood leucocytes under agarose and on the activity of leucocyte migration inhibitory factor (LIF) was studied. Leucocyte migration was not influenced by dibutyryl cAMP, while the dibutyryl derivative of cGMP significantly stimulated cell migration (1 x 10(-5)M). LIF-treated leucocytes partially escaped migration inhibition in the presence of dibutyryl cAMP (greater than or equal to 1 x 10(-6)M), while dibutyryl cGMP was inefficient. If the parent compounds cAMP and cGMP were tested, almost similar results would be obtained, although at higher concentrations of the drugs. These results represent initial experiments with a view to investigating the possible role of cyclic nucleotides in the expression of LIF activity.


Sympathetic influence on the nasal mucosa. The tone of the resistance vessels determines the capillary flow and the tone of the capacitance vessels --the nasal patency. Lower impulse frequencies in the sympathetic nerves affect mainly the capacitance vessels, while higher frequencies affect both types of vessel. The existence of both alpha- and beta-adrenoreceptors and their distribution offer pharmacological ways to affect mainly one type of the vessels.


The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo (b) furan-7-carboxamido)-ethyl)-benzenesulphonyl]-N'-cyclohexylurea (NOVO CS 476). II. Pharmacological studies on the mechanism of action. The new sulphonylurea CS 476 does not potentiate the effect of insulin on plasma glucose levels in diabetic dogs in which an oral glucose load does not cause insulin release. In normal dogs propranolol 0.3 mg/kg intravenously inhibites the insulin release and the hypoglycaemia due to CS 476 suggesting involvement of beta-adrenergic receptors in its action on the pancreas. Pretreatment of dogs with phentolamine leads to an augmentation of the insulin response to CS 476.


A simple and inexpensive protein binding assay for cyclic AMP in biological materials. We have developed a simple and inexpensive method for largecapacity cAMP determination in biological materials. The assay is based on competitive binding of 3H-cAMP to proteins isolated from rabbit skeletal muscle. Bovine serum albumin is added to the incubate to reduce non-specific interference. Separation of free and bound radioactivity is performed by (NH4)2SO4 precipitation allowing determination of either free or bound fraction. In the latter case, all procedures are performed in the same tube, to which is finally added 1.2 ml of scintillation fluid for counting. By this only one fourth. The method has been applied to rat tissue extracts and urine with satisfactory sensitivity, precision and accuracy.


Plasma levels and electrophysiological effects of acebutolol (M & B 17.803) in the dog heart in situ. The effect of acebutolol a beta-adrenergic receptor blocking agent was tested on the dog heart in situ. The drug decreased heart rate, and caused a reduction in the conduction velocity and a significant increase in the functional refractory period of the atrioventricular node. The functional and the effective refractory period of the right atrium was increased by acebutolol. During sinus rhythm, the drug did not affect conduction velocity in the rest of the conduction pathway. During atrial pacing, however, the intra-atrial and His-Purkinje conduction times were slightly increased. The plasma concentrations of acebutolol were in the range between 0.09 and 0.5 mug/ml, which is far below those values expected to cause a membrane-stabilizing or quinidine-like effect. The clinical applications of the results are discussed.


Effects of cholinergic drugs and imidazole on Ca release and cyclic AMP formation in microsomal fractions from rabbit colon. Following the addition of carbachol or acetylcholine to microsomal fractions isolated from rabbit colon which were preloaded with Ca, the ions were rapidly released. In the 35-45% fraction Ca was completely released within 10 min., but in the 35% fraction only 30% was released. Carbachol reduced the adenylate cyclase activity of the 35-45% fraction. Both these effects were blocked by atropine. Exogenous cyclic AMP completely inhibited the Ca-releasing action of carbachol in the 35% fraction and markedly reduced it in the 35-45% fraction. Imidazole released Ca from the 35-45% fraction and stimulated its phosphodiesterase activity. It is suggested that the microsomal fractions are parts of a Ca-sequestering system in smooth muscle which are able to bind Ca and which on the addition of some contracting drugs release the ions and thereby activate the contractile system. The release of Ca may partly at least be due to a reduction of the adenylate cyclase activity, although other mechanisms must also be considered.


Antidiuretic and urinary cyclic AMP response of vasopressin in normal rats and in rats with lithium-polyuria. The antidiuretic and urinary cyclic AMP response to supramaximal vasopressin infusion was studied in normal rats and in rats with lithium-polyuria. The animals were anaesthetized and then infused with a solution designed to produce excessive water diuresis and to lower basal cyclic AMP excretion. In 6 control animals not infused with vasopressin (1) urinary cyclic AMP excretion decreased during the infusion period. Vasopressin infusion (300 muU/min.) consistantly induced antidiuresis in all of 13 control rats (II); but the urinary cyclic AMP response varied individually from a significant increase in 6 animals to either no change or to a decrease in the remaining animals. The antidiuretic response to vasopressin was inhibited by 85% in 10 animals with marked polyuria induced by lithium administration (III). None of the animals in this group showed a significant increase of cyclic AMP excretion in response to vasopressin. The average rate of cyclic AMP excretion, which was equal in the two groups before vasopressin, was signifimantly lower in group III than in group II during vasopressin infusion. It is suggested that the increase in cyclic AMP excretion during vasopressin antidiuresis, although not consistant, most likely reflects hormone-induced changes of intracellular cyclic AMP levels in the renal medulla. Thus, the data suggest that the nephrogenic diabetes insipidus syndrome produced by lithium is associated with a defect in the renal formation of cyclic AMP in response to vasopressin.


The interaction of cyproheptadine with agents affecting neuromuscular transmission. Using the rat phrenic nerve diaphragm, cyproheptadine at concentrations of 1 to 8 mug/ml did not affect or slightly augmented indirect muscle twitches, but potentiated blockade by tubocurarine, decamethonium and succinylcholine, and antagonized the augmentation of twitches by neostigmine. Ketamine, choline and tetraethylammonium at concentrations causing no blockade produced, when given after cyproheptadine (6 mug/ml), a high degree of blockade. At concentrations of 9 to 20 mug/ml, cyproheptadine induced neuromuscular blockade which was slow in onset, more apparent at higher rate of stimulation and was not reversed by neostigmine, choline or tetraethylammonium. In the cat tibialis anterior muscle, it potentiated blockade by tubocurarine, decamethonium and succinylcholine, and blocked acetylcholine twitches. In the chick biventer cervicis muscle, the durg was more effective in blocking indirect twitches than responses to carbachol.


Potentiation by carbachol and aminophylline of histamine- and db-cAMP-induced parietal cell activity in isolated gastric glands. The response to combinations of gastric acid secretagogues was studied in isolated glands from the rabbit gastric mucosa in terms of changes in oxygen consumption and accumulation of the weak base aminopyrine (AP). The latter reflects the acid secreting status of the glands. The following secretagogues were investigated: histamine, carbachol, aminophylline and db-cAMP. The histamine respiratory dose-response curve was shifted to the left in the presence of the phosphodiesterase inhibitor aminophylline. Both ED-50 and maximum response were significantly increased. Histamine-induced AP accumulation was also strongly enhanced by aminophylline (5 X 10(-4) M). These results are consistent with the hypothesis that histamine stimulation of acid secretion is mediated by cyclic AMP. Carbachol-stimulated oxygen consumption could not be potentiated by aminophylline and the combined effect was only additive. The response to a combination of histamine and carbachol was a significant increase in oxygen consumption above what could be expected from an additive effect alone. Carbachol addition to glands prestimulated with histamine gave a rapid increase in the respiratory rate resulting in a new steady state level within 10-15 min, as compared with a time constant of about 40 min when both drugs were added simultaneously. Likewise AP accumulation increased more rapidly and reached a higher value after addition of histamine + carbachol as compared with histamine alone. The db-cAMP-stimulated oxygen consumption was in all respects equally affected by carbachol as was histamine stimulation. This indicates that the well known cholinergic potentiation of histamine stimulation is not due to an increased sensitivity of the histamine receptor but is of a more general nature. A mechanism involving intracellular availability of Ca2+ is proposed as one possible explanation of this potentiation.


Pineal serotonin metabolism in non-innervated perinatal glands before and after intraocular maturation: supersensitivity of adrenoceptors that have never been innervated. Transplantations were made of fetal pineal glands (crown-rump length, CRL, 19-30 mm) or pineal glands from adult male rats to the anterior chamber of the eye of the rat. Studies were performed with regard to the importance of the age of the donor animal (and thereby the degree of maturation and innervation of the gland to be transplanted) for the possible development of denervation supersensitivity. The transplants were cultured in a medium containing 14C-serotonin. Increased production of 14C-N-acetylserotonin (NAcS) was used as the main criterion for beta-adrenergic stimulation. 4 experimental groups were obtained by transplanting fetal or adult pineals to intact or sympathetically denervated eyes. In all 4 groups beta1-stimulation (KWD 2033 10(-6) M) increased 14C-NAcS formation. The response to beta-stimulation was significantly higher in denervated fetal pineal transplants than in innervated fetal transplants and thus demonstrating beta-receptor supersensitivity. It was concluded that a) the ability to respond to beta-adrenoreceptor stimulation with increased 14C-NAcS formation develops between the 18th and 20th day of gestation, b) transplants derived from fetal as well as from adult rats can respond to beta-adrenergic stimulation, c) this sensitivity also develops in oculo in transplants that at the time of transplantation lacked the capacity to increase their 14C-NAcS formation in response to treatment with beta-agonist, d) denervation supersensitivity occurs in fetal transplants that became mature in sympathetically denervated eyes.


Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity. Succinate dehydrogenase (SDH) and cytochrome oxidase activities in the lateral vastus of the human quadriceps femoris muscle together with total body VO2 max were followed during an 8-10 week period of endurance training (n = 13) and a successive 6 week period without training (n = 8). During the training period there was a gradual increase in both VO2 max and muscle oxidative enzyme activities, all being significantly different from the pre-training levels after 3 weeks of training. After 8 weeks of training VO2 max was 19%, vastus lateralis SDH 32%, and cytochrome oxidase activity 35% above the pre-training levels respectively. 6 weeks post training VO2 max was still 16% above the pre-training level, and not significantly different from the level at the end of training (p greater than 0.2). In contrast vastus lateralis SDH activity had returned to the pre-training level. Cytochrome oxidase activity had returned to the pre-training level within two weeks post-training. The significantly faster post-training decline in skeletal muscle oxidative enzyme activities in contrast to that of the VO2 max indicates that an enhancement of the oxidative potential in skeletal muscle is not a necessity for a high VO2 max. Moreover, the fast return to the pre-training level of both SDH and cytochrome oxidase activities indicate a high turnover rate of enzymes in the TCA cycle as well as the respiratory chain.


Conjugated catechol derivatives in a transplantable islet cell tumour of the golden hamster. Two glucuronidated catechol have been identified in a transplantable islet cell tumour of the golden hamster, i.e. dopamine-4-O-glucuronide and 3-methoxytyramine-4-O-glucuronide. L-dopa is rapidly metabolized in the tumour to one or both of these glucuronides. Incubation of tumour homogenates in the presence of beta-glucuronidase shows that dopamine-4-O-glucuronide is present in the tumour in extremely high concentrations.


Actomyosin ATPase, myokinase, CPK and LDH in human fast and slow twitch muscle fibres. The enzyme activities of Mg2+ stimulated ATPase, creatine phosphokinase (CPK), myokinase (MK) and lactate dehydrogenase (LDH) were determined in pooled fast twitch (FT) and slow twitch (ST) human skeletal muscle fibers, dissected out from freeze-dried muscle biopsy material. All enzymes investigated demonstrated higher activities in FT fibres. The ratio in enzyme activity between fibre types was greatest for Mg2+ stimulated ATPase (3:1) and smallest for CPK (1.3:1). In addition, the isozyme patterns of CPK, MK and LDH were studied by means of isoelectric focusing (CPK and MK) and discelectrophoresis (LDH). A difference was observed between fibre types with respect to the isozyme distribution of MK and LDH, whereas the CPK isozyme pattern was similar in both fibre types. These results on separated human FT and ST fibres were essentially in conformity with what has earlier been indicated from experiments on mixed muscle homogenates.


Electron microscopic studies of the parathyroid gland of senile dogs. The parathyroid gland of healthy senile dogs aged 8.5 to 15 years was compared with that of mature control dogs by examination with the electron microscope. Preparations fixed by perfusion with glutaraldehyde showed the cytoplasmic matrix of most parenchymal cells to be uniformly dense. None of the cells were of the extremely light type and dark cells were much less frequently noted than in preparations fixed by immersion in glutaraldehyde or osmium tetroxide. Syncytial cells and so-called coloid follicles were more frequent in senile dogs than in control dogs. It was suggested that the content of the latter structures is not colloid but necrotic substance hiving origin from the parenchymal cells and that perhaps the occasional cells containing large, membrane-bound inclusions may be degenerating cells which ultimately produce this necrotic substance. Oxyphil cells and mitochondria-rich cells of another type were found in all senile dogs, but not in the controls. These cells, especially the mitochondria-rich cells, frequently contained bizarre mitochondria that were modified in shape, size and arrangement. The most striking feature of these mitochondria was the concentric arrangement of elongated mitochondria which seemed to consist of densely layered cup-shaped mitochondria. Such mitochondria were noted in all senile dogs aged ten years and over. The significance of mitochondrial ple-morphism in the parathyroid gland of senile dogs was discussed.


Treatment of toxic megacolon. A comparative review of 29 patients. A review of 29 patients with toxic megacolon complicating ulcerative colitis was undertaken to (1) compare the results of medical and surgical treatment; (2) determine the optimal timing for surgical intervention, and (3) identify possible precipitating factors. Twenty-one patients were treated medically with nasogastric suction, steroids, parental fluids, blood transfusions, and antimicrobial agents. Of the 21 patients, 11 (53%) showed improvement by subjective and objective criteria  and 10 (47%) failed to respond. Sixteen patients were treated surgically. This group was subdivided into 8 patients who failed to respond to medical treatment and 8 treated surgically. Total proctocolectomy with ileostomy was performed in 8 and subtotal colectomy and ileoproctostomy in 8, with subsequent proctectomy and ileostomy in 6 patient. Six of 8 patients (75%) treated primarily surgically improved, and 2 (25%) died. Seven of 8 patients (87.5%) treated surgically after failure of medical trial showed definite postoperative improvement, and 1 (12.5%) failed. Those who were operated on within the first 48-72 hr after the diagnosis of toxic megacolon was made responded uniformly well. Anticholinergics, opiates,, barium enema, and colonoscopy were identified as possible precipitating factors in 70% of cases. The results of this tudy in this patient population indicate that early surgical therapy in toxic megacolon is associated with better results than medical therapy (P less than 0.025). Although intensive, optimal medical therapy plays a significant role in the management of toxic megacolon, failure to induce rapid improvement within 48-72 hr constitutes an indication for definitive surgical treatment.


The biochemistry of the renin-angiotensin system and its role in hypertension. The renin-angiotensin system has an important role in maintaining elevated blood pressure levels in certain forms of experimental and human hypertension. Renin, an enzyme produced by the juxtaglomerular cells of the kidney, acts on a protein substrate found in the alpha 2-globulin fraction of the plasma to produce a decapeptide, angiotensin I. This decapeptide is not directly pressor, but on passage through the pulmonary circulation is converted to an octapeptide, angiotensin II, a very potent pressor substance which acts by causing constriction of arteriolar smooth muscle. In addition to its direct action which increases blood pressure, angiotensin II acts on the adrenal cortex to cause the release of the sodium-retaining hormone aldosterone. Recent evidence suggests that this action may be mediated by the heptapeptide, angiotensin III. Both renin and its protein substrate exist in multiple forms and renin may also exist as a high molecular-weight "pro-hormone," although the physiologic significance of these forms is not clear. The elucidation of the biochemistry of the renin-angiotensin system has provided us with inhibitors which allow the system to be blocked effectively in vivo. Thus, angiotensin antagonists such as Sar 1, IIe 8-angiotensin II and converting enzyme inhibitors such as BPP 9a (SQ 20881) have proved useful in the study of experimental and human hypertension.


Conversion of angiotensin I to angiotensin II. The angiotensin I converting enzyme has two important functions: it inactivates bradykinin and converts angiotensin I to angiotensin II. Inhibition of the enzyme blocks the renin-angiotensin system and decreases systemic blood pressure if the pressure is maintained or increased by renin. The enzyme occurs in a variety of tissues and cell forms. The vascular endothelial cells of the lung and of peripheral blood vessels, and the epithelial cells of the kidney tubules are major sources of the enzyme. In addition to inactivating hypotensive peptides and activating a hypertensive one in the systemic circulation, the enzyme may affect organ functions by hydrolyzing peptides that are formed and released locally.


Unexpected pressor responses to propranolol in essential hypertension. An interaction between renin, aldosterone and sympathetic activity. The blood pressure response to propranolol treatment was analyzed retrospectively in 187 patients with benign essential hypertension. In most patients (102 patients, 54 per cent) systolic and/or diastolic blood pressure was decreased by more than 10 per cent (responders). No significant change in blood pressure occurred in 35 per cent (65 patients) of the patients (nonresponders). Surprisingly, in 20 patients (11 per cent) systolic (8 patients) and/or diastolic (14 patients) blood pressure was increased by more than 7 per cent (pressor-responders). All three subgroups received similar amounts of propranolol and irrespective of the effect on the blood pressure, propranolol produced a similar reduction in pulse rates, suggesting similar degree of beta blockade. The three subgroups did not differ in their clinical characteristics, except that the nonresponders were significantly older than the responders. Pretreatment renin values were highest in the responders, somewhat lower in the nonresponders and significantly lower in the pressor-responders. In a representative subset of 66 patients, control and treatment values for plasma renin activity and aldosterone excretion were compared. The responders had the most pronounced decreases in both renin and aldosterone. In striking contrast, no significant changes were observed in the two hormones in those patients whose blood pressure levels rose. Moreover, in the pressor-responders, the drug produced the greatest increases in body weight, reflecting sodium retention. The differences in blood pressure responses observed in different patients may be explained by various interplays between the drug-induced suppression of renin and aldosterone, and the operation of unapposed or reactive alpha sympathetic activity. The latter is presumably active in all patients tending to cause vasoconstriction and hence an increase in peripheral resistance. In the pressor-responders such unopposed alpha-tone combined with the demonstrated lack of renin and aldosterone suppression with attendant fluid retention could work to produce the paradoxical pressor responses. In contrast, in those whose blood pressure levels drop, the drug-induced suppression of renin leads to decreased peripheral resistance despite the unopposed alphatone. The accompanying decrease in aldosterone limits sodium retention and contributes to the fall in blood pressure levels.


Role of anaerobic bacteria in spontaneous peritonitis of cirrhosis: report of two cases and review of the literature. The role of anaerobic or microaerophillic bacteria in spontaneous peritonitis of cirrhosis has not been clearly defined. Among 126 cases recorded in the literature, in only eight (6 per cent), including the two reported here, was bacterascites associated with anaerobic or microaerophilic bacteria. Clinical features in these cases were indistinguishable from those associated with aerobic bacteria. However, polymicrobial bacterascites occurred in four of eight cases associated with anaerobes, as contrasted with only 10 of 118 cases (8 per cent) associated with aerobes alone. On the other hand, concurrent bacteremia occurred in only one of eight cases associated with anaerobes as contrasted with 52 of 118 cases (44 per cent) of aerobic spontaneous peritonitis. Experimental evidence is cited in an attempt to explain this relatively low incidence of spontaneous peritonitis associated with anaerobic or microaerophilic bacteria, despite the high density of these organisms in the normal bowel flora.


Cytomegalovirus mononucleosis in a healthy adult: association with hepatitis, secondary Epstein-Barr Virus antibody response and immunosuppression. A 35 year old previously healthy physician had clinical manifestations of a mononucleosis illness complicated by arthralgia, vesicular pharyngitis and hepatitis. Initially, the patient had cytomegalovirus (CMV) viremia (predominantly in polymorphonuclear leukocytes) followed by the presence of CMV in the urine, throat and semen. He also had an antibody response to the Epstein-Barr virus which appeared to be a secondary type. During the acute phase of illness, only 7 per cent of the patient's lymphocytes formed spontaneous T cell rosettes as compared to a normal value of 65 to 70 per cent. Concurrently, evidence of abnormal delayed hypersensitivity was manifested by the loss of reactivity to mumps skin test antigen. All clinical and laboratory abnormalities except for the persistence of CMV in the pharynx, urine and semen returned to normal after resolution of the clinical illness.


Exogenous estrogen and endometrial carcinoma: case-control and incidence study. Recent independent case-control studies have indicated that treatment with exogenous estrogen is associated with an increase in the risk of endometrial cancer. This question was studied in Olmsted County, Minnesota, by identifying all cases of endometrial cancer among residents over a 30 year period (1945 through 1974) and by matching four controls to each of the 145 patients. The rate of past exposure to any exogenous estrogen for any duration was about the same for patients as for controls. However, the estimated relative risk of endometrial cancer associated with conjugated estrogen treatment of 6 months or longer was 4.9 (P less than 0.01), and this increased to 7.9 (P less than 0.01) with exposure for 3 years or longer. The risk increased with larger doses (1.25 mg. or more) and continuous administration of conjugated estrogens. The incidence of endometrial carcinoma over the three decades of the study, corrected for an increasing rate of hysterectomy, was constant. Thus to this time, the low rate of use of conjugated estrogens in this region over the past 30 years apparently has not had an appreciable impact on the incidence of endometrial cancer.


The value of urinary steroid analysis in chorionic neoplasia. The profile of urinary neutral steroids was investigated in normal pregnancy and chorionic neoplasia by gas-liquid chromatography. The whole chramatogram was divided into three metabolically distinct fractions. The excretion of fraction 2, including four menstruation-dependent steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetrial), was remarkably increased in normal pregnancy as compared with that in nonpregnant controls. But the same parameter was differentially reduced in hydatidiform mole (HM) and chorioadenoma destruens (CA) as compared with normal pregnancy, and the ratio of fraction 2 to fraction 1 (11-deoxy-17-ketosteroids) was found useful in separating normal pregnancy, HM, and CA from each other. In choriocarcinoma (CC), reduced excretion was observed in both fraction 1 and fraction 2 steroids. The linear relationship between the logarithm of fraction 2-fraction 1 ratio and that of pregnanediol excretion, as observed in the reproductive cycle of a healthy woman, was not detectable in women with CA, whose urine revealed a low value of log (fraction 2/fraction 1) in spite of an abundant HCG content. It is indicated that the above findings reflect the deficiency of ovarian steroidogenesis under the influence of abnormal HCG from tumors.


Ultrastructure of a polysome-lamellae complex in a human paraganglioma. Study of a human abdominal paraganglioma under electron microscopy revealed an unusual cytoplasmic inclusion appearing as a hollow cylinder made up of one or several concentric lamellae surrounded by single or aggregated granules. Cross sections of the lamellar element show a discontinuous juxtaposition of particles. It is moderately dense and is bordered by 140--to 250-A granules of sure ribosomal nature. The inclusion is closely connected to the rough endoplasmic reticulum. The origin and significance of this complex are discussed.


Pulmonary carcinoma (Jaagsiekte) of sheep. Ultrastructural study of early and advanced tumor lesions. Lung carcinoma of sheep (Jaagsiekte) is a bronchiolar-alveolar cell carcinoma. Differences in the ultrastructural patterns of early and advanced lesions of the disease are described. A-type and C-type viruses were observed in advanced tumors and were absent in early lesions. Numerous microtubules were characteristic in the epithelial tumor cells of the early lesions and were absent in the advanced tumor. In comparison to the early lesions, extensive cytosome production, surfactant secretion, and glycogen accumulation were observed in the advanced tumor. The immune response to the early tumor lesion was restricted to the peribronchiolar lymph aggregates, while in the advanced stages of the disease the systemic immune response was markedly increased.


Excitation conduction in Meissner's plexus of rabbit small intestine. Excitation conduction in Meissner's plexus of the rabit small intestine was investigated by analyzing the records of potentials evoked by a single electrical stimulus applied to this plexus. Experiments were performed on the Meissner's plexus that remained attached to the circular muscle after the longitudinal muscle and mucous membrane were removed from intestinal segment. Conduction velocities of nerve impulses were 0.3-0.7 m/s, chronaxie of the nerve bundle was 0.06-0.12 ms. While the distance between the stimulating and recording electrodes was increased, the latency of evoked potentials was prolonged, the number increased, and the amplitude decreased; no potentials could be recorded when the distance  was more than 4 mm. Evoked potentials recorded at relatively long conduction distance were reduced in amplitude or abolished after a repeated stimulation with high frequencies above 50/s, after hexamethonium application, and in a state of lack of oxygen. It was concluded that, in Meissner's plexus, nerve impulses spread through multiple pathways and make synaptic transmission at a relatively short conduction distance.


Glucose-stimulated and La3+-nondisplaceable Ca2+ pool in pancreatic islets. To study intracellular pools of calcium tissue specimens from noninbred ob/ob mice were labeled with 45Ca2+ and subsequently washed with La3+. D-glucose, 20 mM, enhanced the labeling of the La3+-nondisplaceable calcium in pancreatic islets but not in pieces of exocrine pancreas or liver. The disappearance of 45Ca2+ from labeled islets was accelerated by the ionophore, X-537A, but not by dibutyryl cyclic AMP, theophylline, or pentobarbital. On fractionation of 45Ca2+-labeled islets, the greatest radioactivity per unit of protein occured in a fraction rich in insulin secretory granules. The radioactivity of this fraction was higher after the islets had been loaded with 45Ca2+ in the presence of 20 mM glucose as compared to 3 mM glucose. It is concluded that the secretory granules make up a considerable part of the glucose-sensitive calcium store in the beta-cells.


Prostaglandins in adrenergic transmission of isolated perfused rat pancreas. In the isolated, perfused rat pancreas, prostaglandins (PGs) E1 and E2 1-5 ng/ml, reduced the vasoconstrictor responses to periarterial nerve stimulation and variably affected those to injected norepinephrine. Prostaglandin F2alpha had no consistent effect on the vasoconstrictor responses to both adrenergic stimuli. Stimulation of adrenergic nerves or administration of norepinephrine released a PGE-like substance from  the perfused pancreas which was abolished by inhibitors of PG synthesis, acetylsalicylic acid, indomethacin, meclofenamate, and eicosa-5,8,11,14-tetraynoic acid. The latter three agents did not potentiate, but rather reduced the vasoconstrictor responses to both adrenergic stimuli. Arachidonic acid that was converted by the pancreas into PGE2 and PGF2alpha inhibited the vasoconstrictor responses to adrenergic stimuli. The latter effect of arachidonic acid was not altered by the simultaneous infusion of PG synthetase inhibitors. Although these results, which could be attributed to a direct effect of inhibitors of PG synthesis and arachidonic acid on adrenergic neuroeffector junction, fail to establish the role of endogenous PGs in modulating adrenergic responses in rat pancreatic vessels, they emphasize the differences in the effect of PGE1 and PGE2 on adrenergic responses in various vascular beds of the rat.


Ileal mucosal cyclic AMP and Cl secretion: serosal vs. mucosal addition of cholera toxin. Changes in ion transport and cyclic AMP (cAMP) concentration produced by addition of cholera toxin to the serosal side of isolated rabbit ileal mucosa (CTs) were compared to the changes produced by addition to the mucosal side (CTm). CTs increased short-circuit current (SCC) as did CTm but it did so more slowly. CTs, unlike CTm, did not significantly decrease electrical conductance. Inhibition of the  SCC response to theophylline, a measure of preexisting secretion, was almost complete 180 min after CTm but was not yet significant 180 min after CTs. Longer (280 min) after CTs, the SCC response to theophylline was reduced by 59%, a significant reduction but less than that caused by CTm. A statistically significant change in net Cl flux could not be demonstrated after CTs, although at 280 min the measured flux was halfway between the fluxes for control and CTm tissues. Cyclic AMP concentrations were determined at 190 min, 10 min after addition of theophylline. CTs, despite little or no effect on ion transport, increased cAMP to the same level as did CTm, and the effect on cAMP of adding toxin to both sides was additive. We conclude that 1) active secretion is  probably stimulated by cholera toxin added on the serosal side, although more slowly than after addition to the mucosal side and 2) much of the toxin-stimulated cAMP content of the mucosa is not coupled to secretion.


Effects of high potassium concentration on theophylline responses of toad bladder. It has been demonstrated previously that a high concentration of potassium in the serosal bathing medium (5-21.5 mM) potentiates the increase in short-circuit current caused by vasopressin or exogenous cyclic AMP. The same concentration of potassium in the bathing medium inhibited the increase in short-circuit current caused by theophylline. The increases in osmotic water permeability caused by vasopressin or cyclic AMP were unaffected by a serosal potassium concentration of 21.5 mM. The increase in osmotic water permeability caused by theophylline was inhibited by 21.5 mM potassium. The concentration of cyclic AMP in either intact total bladder or isolated toad bladder cells was increased two- or three-fold by theophylline. Increasing the concentration of potassium to 21.5 mM did not alter cyclic AMP concentration in either the absence of presence of theophylline. One interpretation of these results is that theophylline increases osmotic water flow and short-circuit current by a mechanism other than by inhibition of cyclic nucleotide phosphodiesterase.


Identification of smooth muscle series elastic component in intact carotid artery. Experiments were performed to indentify the series elastic component (SEC) in intact dog carotid artery held at in situ length. The vessels were studied during excitation of the muscle with norepinephrine and after metabolic poisoning with potassium cyanide and sodium iodoacetate. Static circumferential stress-strain curves and stress-quick-release stiffness curves were examined to evaluate Maxwell and Voigt model elements. The vessels were studied at 33, 36, and 39 degrees C. Temperature variations altered active stress, but did not alter connective tissue properties or the Maxwell SEC stiffness. The Voigt model SEC stiffness was altered, but this was secondary to changes in active stress. Thus, most of the SEC is separate from the contractile apparatus. Other vessels were treated with elastase, collagenase, or hyaluronidase to digest the connective tissue components of the wall. Hyaluronidase had no effect on mechanics. Elastase and collagenase altered connective tissue properties, but only elastase unequivocally altered SEC stiffness. This analysis indicated 1) that the carotid artery wall is better represented by a Maxwell model than a Voigt model, and 2) that the SEC in intact carotid artery is primarily elastin.


Cyclic nucleotide metabolism and vasodilation in canine mesenteric artery. The uptake and extracellular and intracellular metabolism of radioisotopically labeled cyclic 3',5'-adenosine monophosphate (cAMP) and dibutyryl cAMP (DBcAMP) was determined in canine mesenteric arteries incubated in vitro. Intracellular tissue uptake was measured by radioisotope counting and labeled metabolites separated by thin-layer chromatography. Extracellularly, cAMP was extensively metabolized to AMP, adenosine, and Pi. DBcAMP was metabolized to monobutyryl cAMP (MBcAMP) intracellularly. Vasodilation of the mesenteric circulation in vivo was produced by cAMP, its metabolites and DBcAMP. DBcAMP caused greater vasodilation than cAMP but had a response time to its peak effect of 12 min versus 90 s for cAMP. The vasodilator properties of cAMP and DBcAMP were related to their metabolism. It was concluded that the vasodilation caused by cAMP was due to cAMP metabolites produced by extracellular metabolism.


A bone matrix calcification-initiator noncollagenous protein. When completely demineralized, the densely packed structure of bone matrix does not recalcify, neither in physiologic solutions in vitro nor in implants in vivo. Even when inorganic and organic calcification inhibitors (which normally are stored in bone matrix) are removed first by autolytic digestion in neutral buffers at 37C and then by sequential chemical extraction, implants of the EDTA insoluble residue will not recalcify after as long as 4 wk in a muscle pouch. However, if first demineralized in cold dilute HCl, second, extracted and autodigested in buffers solution at 37C, and then further extracted in EDTA and other solutions at 2C, a calcification initiator protein (Cp) is unmasked, and the residue will invariable recalcify. CIP, isolated by gel filtration and column chromatography, is a disulfide-bonded glycoprotein aggregate composed of subunites of a moleclar mass of 55,000. CIP is composed of a large proportion of acidic amino acids and has a calcium binding capacity of about 1.8 times greater than albumin. The affinity constant CaCIP, calculated by ultrafiltration of physiologic solutions of Ca2+, is log K, 2.9. Observations on implants of residues that containe a) CIP but not a bone morphogenetic property (BMP), B) BMP accompanied by CIP activity, or c) neither BMP nor CIP activity suggested that BMP covers CIP and that the two are attached to bone collagen in tandem. Whether CIP plays a part in calcification of the normal skeleton requires further investigation.


New method of quantifying ligand binding based on measurement of an induced response. A new general method is proposed for quantifying ligand-receptor interactions using the biological response induced by the ligand as an index of ligand binding. With this method the binding of human chorionic gonadotropin (hCG), several hCG derivatives, and luteinizing hormone (LH) to rat Leydig cells was measured by analysis of the ability of these materials to stimulate testosterone formation. As applied here, hormone dose-response curves were generated in the presence of increasing numbers of cells incubated in vitro in a successful attempt to alter the concentrations of bound and free hormone in the incubation mixture. Measurements of testosterone synthesis as a function of the total amounts of hormone and numbers of cells enabled us to evaluate the concentrations of both bound and free hormone at any constant fractional response (i.e. quarter-, half-, or three-quarter-maximal). We were thus able to measure hormone binding at the extremely low hormone concentrations (1 pM) within the steroidogenic dose-response range under conditions that would not have been possible using currently available radioiodinated hCG preparations. The results obrained confirmed the presence of spare functional receptors. Specific quantitative results are discussed in the text.


Lipoprotein lipase distribution in rat adipose tissues: effect on chylomicron uptake. Adipocytes in the epididymal (Epi) and perirenal (PR) depots of the rat increased continuously in size in rats ranging fromm 50 to 550  g body wt. In contrast, cell size in the subcutaneous (SC) and mesenteric (M) depots was similar to that in the other two depots only until rats achieved 250-350 g. Thereafter, adipocytes in the latter depots were significantly smaller than in the former. In all four depots, the activity of lipoprotein lipase (LPL) per 10(6) cells increased with increasing size in both fed and fasted rats. No significant differences were noted in LPL activity per 10(6) cells between depots as a function of cell size in either nutritional state. During growth, a greater percentage of whole tissue LPL of all depots was sequestered within enlarging adipocytes, resulting in an absolute decrease in activity extracellulalrly. This effect was least pronounced in the Epi and PR depots. In large adipocytes of fed rats, decreased extracellular localization of LPL was paralleled in vivo by decreased uptake of chylomicron triglyceride fatty acids in all depots. In fasted rats, uptake was low and unaffected by changes in cell size in all sites.


Kinetic analysis of iodide transport in dog thyroid slices: perchlorate-induced discharge. Dog thyroid slices were incubated with methimazole (2 mM) and radioiodide. The medium radioactivity was continuously recorded for 8 h. Multiple data were collected for individual glands to calculate simultaneously by compartmental analysis the influx and efflux rates of iodide from the slices. A two-compartment thyroid model was necessary and sufficient to simulate the transport of inorganic iodide. The two compartments could be defined as the cellular and the luminal spaces, but interferences due to slice thickness, nonuniform follicle sizes, and open follicles were not excluded. Sodium perchlorate (1 mM) inhibited the influx of iodide into the follicles and discharged the trapped radioiode into the medium with increased efflux rates. Our data suggest that perchlorate decreases the inward influx rates by competition and enhances the outward efflux rates by countertransport and support the hypothesis of mobile iodide carriers at the basal and apical membranes of the thyroid cells.


Renin stimulation by isoproterenol and theophylline in the isolated perfused kidney. The intrarenal mechanisms of renin release were studied in the isolated perfused rabbit kidney during stimulation by isoproterenol, 0.01 mug/kg per min, and by theophylline, 0.87 mg/kg per min. In the absence of urinary flow during the early stages of perfusion, isoproterenol caused a 17% increase of renal vein serum renin concentration (RVSRC) (P less than 0.001) without changing renal blood flow, renal vascular resistance, or serum potassium. dl-Propranolol, 2.0 mg/kg per min. abolished this isoproterenol-induced renin release. A moderate reduction in perfusion pressure prior to the infusion of isoproterenol resulted in a marked additional stimulation of renin release. Studies during and following ureteral occlusion demonstrated that theophylline stimulates renin release by decreasing renal vascular resistance, whereas the concomitant increase in sodium transport to the macula densa exerted an opposite effect. dl-Propranolol did not affect theophylline-induced renin secretion. It is concluded that single exogenous stimuli may activate more than one intrarenal mechanism simultaneously. Isoproterenol has a direct renin-stimulatory effect on intrarenal beta-adrenergic receptors that may be reinforced by baroreceptor stimulation. Theophylline stimulates renin via a baroreceptor mechanism, with simultaneous renin suppression via a sodium-macula densa effect.


Pharmacological analysis of sympathetic function in the embryonic chick heart. Sympathetic nerve cells enter the embryonic chick heart on the fifth day in ovo, but it is uncertain when these nerves become functional. Using pharmacological probes known to affect the embryonic circulation, sympathetic nerve function was examined at various stages of development. Exogenous norepinephrine elicited cardioacceleration in the hearts of embryos with intact extraembryonic circulation both before (stage 20-24) and after (stage 28-32) sympathetic innervation of the heart, and this acceleration could be inhibited by propranolol and practolol. In contrast, ganglionic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) elicited cardioacceleration only after stages 27-28 (i.e., after sympathetic innervation), producing a 25-30% increase in heart rate over the predrug levels of 148.7 +/- 1.8 beats/min. DMPP-elicited positive chronotropy was reduced by beta-receptor antagonists, hexamethonium, guanethidine (GuE), and tetrodotoxin. In preparations of the embryonic thorax in which the innervated heart was separated from brain and adrenal influences, DMPP elicited a GuE-sensitive cardioacceleration. It is concluded that during chick embryonic development, no more than a 1-day interval exists between the appearance of sympathetic nerves in the heart and the onset of neuronal function in that organ.


Disulfiram toxicity and carbon disulfide poisoning. The author compared the neurotoxic effects of disulfiram with those of carbon disulfide, a disulfiram metabolite. The results suggest that carbon disulfide is responsible for the behavioral and neurological side effects of disulfiram. If this is so, then some other toxic effects of carbon disulfide, including parkinsonism, choreoathetosis, and thalamic syndrome may follow the ingestion of more than 5 g of disulfiram by adults, and individuals receiving as little as 125 mg of disulfiram per day may be at a three- to four-fold greater risk for arteriosclerotic cardiovascular disease than a comparable population not receiving the drug.


Analysis of clinically occult and mammographically occult breast tumors. Findings by xeromammography and clinical examination were compared in 16,000 self-selected women aged 45-64 who participated in a voluntary breast cancer screening program. A total of 138 malignancies were detected: 108 (78%) by mammography and 78 (57%) by clinical examination. Mammography was more effective for large breasts, fatty breasts, and in older women. Conversely, clinical examination was more effective for small breasts, dense breasts, and retroareolar lesions. Clinical detection decreased strikingly for lesions with negative lymph nodes, in situ and microinvasive lesions, deeply situated lesions, and lesions where microcalcifications were the sole mammographic finding.


Effect of insecticide spraying for malaria control on the incidence of sandfly fever in Athens, Greece. Sera from 637 Athens residents of various age groups were examined by plaque reduction neutralization test for antibodies against Naples and Sicilian Phlebotomus fever viruses. A marked change in the prevalence of antibodies to both agents was observed in persons born after 1946, when residual insecticide spraying for malaria control was initiated in Greece. The prevalence of Naples and Sicilian neutralizing antibodies among residents greater than or equal to 30 years of age was 36% and 13%, respectively. In contrast, only 4% of persons less than or equal to 29 years of age had Naples antibodies and all were negative to Sicilian. These serologic data confirm previous clinical observations that sandfly fever becam uncommon in Athens after initiation of the insecticide spraying program. Presumedly the spraying program was effective in reducing the Phlebotomus population to levels where virus transmission was minimal. New information on the specificity and duration of Phlebotomus fever neutralizing antibodies is also presented.


Experimental milk-borne transmission of Powassan virus in the goat. A lactating goat with a 74-day-old kid was inoculated with 10(3) mouse 50% lethal dose (LD50) of Powassan virus. No ensuing viremia could be detected, but virus was secreted in the milk on postinoculation days 7 through 15, with a titer of 10(5) LD50/ml on day 12. Neutralizing antibody was found in the serum on days 22 through 36 and in the milk on day 36. The offspring was not inoculated but was allowed to continue feeding on its mother's milk. It developed neutralizing antibody by day 22. Since the kid was past the age when it could resorb antibody from the milk, its serum antibody was evidence of active infection. Neither animal showed any clinical sign of illness. A serum survey of 499 goats in New York State showed that 9 had neutralizing antibodies to Powassan virus. These immune goats came from widely scattered localities, including counties where human cases have been confirmed. The findings suggest the possibility of milk-borne transmission of Powassan virus from goat to man.


The ependyma of ventriculus mesencephali in golden hamsters. The ventriculus mesencephali of golden hamsters protrudes, in the form of a short channel, from the upper wall of the aquaeductus Sylvii in dorsal direction, between the third and fourth ventricle. It is lined with ependymal cells of cubic to cylindrical forms. Some of the ependymal cells possess basal processes. On the cell surface, there are cilia, microvilli and protoplasmatic protrusions. The cells contain relatively few endoplasmatic reticulum, a poorly developed Golgi apparatus, free and bound ribosomes and critiform mitochondria. The cell nuclei have round to oval shapes. Supraependymally, there are homogenous globules and intraventricular nerve fibres. The morphological characteristics of ependyma in the region of ventriculus mesencephali, as well as the close contact of the ependymal cells with capillaries, allow to suppose an active participation of these cells in the exchange of various substances also in this part of the brain ventricle system.


Antagonism of general anesthesia by naloxone in the rat. The effect of naloxone, a narcotic antagonist, on the response of animals to painful stimuli during anesthesia was studied. Rats were anesthetized with cyclopropane, halothane, or enflurane in groups of 12. Following induction, inspired anesthetic concentration was gradually reduced to a point at which 35-60 per cent of animals responded to tail clamping. Thereafter the anesthetic concentration was held constant for 30 minutes. Rats in each group then received saline solution or naloxone, 10mg/kg, given intravenously. The response to tail clamping was retested 5 minutes later. In additional experiments EEG's were recorded from rats anesthesized with one of these anesthetics. After a stable light plane of anesthesia had been attained, each animal was given naloxone, 10 mg/kg, iv, and the EEG recorded for an additional 5 minutes. In the tail-clamping experiments, naloxone approximately doubled the number of rats responding during cyclopropane, halothane, or enflurane anesthesia. The EEG patterns of several animals anesthetized with either cyclopropane or halothane changed to patterns consistent with lighter planes of anesthesia after naloxone administration. That naloxone alters the depth of inhalational anesthesia suggests that anesthetics may release an endogenous morphine-like factor (MLF) in the central nervous system.


Evaluation of a feline viral rhinotracheitis-feline calicivirus disease vaccine. An attenuated respiratory disease vaccine against feline viral rhinotracheitis (FVR) and feline calicivirus (FCV) disease was evaluated for safety and efficacy in specific-pathogen-free cats. Twenty cats were vaccinated twice intramuscularly, with 28 days between vaccinations. Ten unvaccinated cats were used as contact controls. Adverse effects were not noticed after vaccination, and the vaccinal virus did not spread to contact controls. Arithmetical mean serum-neutralizing titers against vaccinal FCV strain F9 and challenge FCV strain 255 were 1:13 and 1:15 at 28 days after the 1st inoculation. These titers increased to 1:45 and 1:196 after the 2nd inoculation. After challenge exposure of vaccinated cats to virulent FCV 255 virus, mean titers increased to 1:129 and 1:865, respectively for F9 and 255 viruses. The F9 postchallenge mean titer for vaccinated cats was 21.5 times higher than that for the 8 contact controls that survived challenge exposure. The arithmetical mean serum neutralizing titer for FVR was low (1:2) after the 1st vaccination, but increased to 1:35 after the 2nd vaccination. Challenge exposure to virulent FVR virus resulted in a marked anamnestic immune response (mean titer of 1:207, compared with 1:12 for contact controls). In general, vaccinated cats remained alert and healthy after challenge exposure with FCV-255, whereas unvaccinated contact control cats developed definite signs of FCV disease, including central nervous system (CNS) depression (6 of 10) and dyspnea indicative of pneumonia (5 of 10). Two controls died of severe pneumonia. A mild fibrile response was detected in 28% of vaccinated cats, compared with a more severe febrile response in 78% of control cats. Some vaccinated cats developed minute lingual ulcers that did not appear to be detrimental to the health of the cat. After FVR challenge exposure, vaccinated cats were free of serious clinical signs. Five of 18 vaccinated cats had mild signs of FVR, including an occasional sneeze, low temperature, and mild serous lacrimation for 1 or 2 days. Contact controls developed definite clinical signs of FVR. The combined FVR-FCV vaccine appears to be safe and reasonably efficacious. Vaccination against FCV disease and FVR should be part of the routine feline immunization program.


Effect of infectious bursal disease on the response of chickens to Mycoplasma synoviae, Newcastle disease virus, and infectious bronchitis virus. At 35 days of age, chickens which as 1-day-old chicks were inoculated with the infectious bursal disease virus (IBDV) had significantly lower antibody titers against Mycoplasma synoviae, Newcastle disease virus, and infectious bronchitis virus than did those never inoculated with IBDV. The IBDV also had a marked effect on the development of air-sac lesions. Birds infected with IBDV that were later inoculated with M synoviae (day 14), Newcastle disease virus (days 14 and 28) experienced an increased incidence and greater seversity of airsacculitis than did chicks which were not exposed to IBDV.


Ventilatory and waking responses to CO2 in sleeping dogs. We examined ventilatory and waking responses to hyperoxic hypercapnia in 3 dogs during natural sleep. Progressive hypercapnia was induced by a rebreathing technique, and sleep was determined by electroencephalographic and behavioral criteria. In non-rapid eye movement sleep (high-voltage, slow-frequency electroencephalography) rebreathing continued for 0.99 +/- 0.05 min (mean +/- SE) before arousal occurred, and the alveolar PCO2, at arousal was 54.2 +/- 3.4 mm Hg. In contrast, during rapid eye movement sleep, rebreathing lasted for 1.71 +/- 0.27 min (P less than 0.05) before arousal occurred and the alveolar PCO2 at arousal was 60.3 +/- 4.2 mm Hg (P less than 0.05). Linear regression analysis of breath-by-breath instantaneous minute volume of ventilation, tidal volume, and respiratory frequency against alveolar PCO2 revealed regression coefficients in rapid eye movements sleep that were 14 to 33 per cent of those found in non-rapid eye movement sleep, and correlation coefficients of 0.26 to 0.46, compared to 0.71 to 0.91 in non-rapid eye movement sleep. Thus, the link between CO2 and ventilation appeared to be strong in non-rapid eye movement sleep but considerably disrupted during rapid eye movement sleep. We conclude that centers involved in both waking and ventilatory responses to hypercapnia behave as if they are less aware of or responsive to CO2 in rapid eye movement sleep than in non-rapid eye movement sleep.


Studies of pulmonary and renal immunopathology after nonlethal primary sendai viral infection in normal and cyclophosphamide-treated hamsters. Hamsters were infected by aerosol with a nonlethal strain of Sendai virus. The virus infected mainly bronchial mucosal cells, some alveolar cells, and occasional renal tubular cells. By the third day after infection, there was an impressive local influx of inflammatory and IgG-secreting cells at sites of infection, disruption and desquamation of infected mucosal cells, and destruction of bronchial basement membrane. These findings were associated with the presence of specific antibodies bound to viral antigens in the tissues. Treatment with cyclophosphamide resulted in the ablation of these histologic events, failure to eradicate virus or to produce antibody, and some spontaneous deaths. Viral antigens were regularly detected in kidneys on days 3, 6, and 9 as a fine, granular glomerular and tubular basement membrane staining pattern after elution of tissue sections. The IgG deposition was found in a similar pattern at the same times, persisted after Sendai antigens could no longer be detected, and tended toward linear staining, fading with time. Treatment with cyclophosphamide decreased significantly, but did not completely abolish, the renal abnormalities. It was concluded that the humoral immune response is associated with eradication of virus, excess local tissue damage, and some immunopathologic consequences in the kidney.


The current status of chemodectomas.

The current status of chemodectomas. An analysis of the current status of chemodectomas including the report of two additional cases is presented. One patient with a rare malignant intrathoracic tumor failed to survive palliative pneumonectomy. To our knowledge, this represents the seventeenth histologically proved case. The other patient had the more common carotid body tumor which was managed satisfactorily by subadventitial carotid excision. Comments are made regarding the clinical recognition and treatment of chemodectomas in general. Historical, anatomic, physiologic, and pathologic features are emphasized.


Epstein-Barr virus and human malignancy. The association of the Epstein-Barr virus and two human malignancies, Burkitt's lumphoma and nasopharyngeal carcinoma, is reviewed. Seroepidemiologic, virologic, and immunologic evidence is summarized, and several hypotheses regarding a possible etiologic role for the Epstein-Barr virus in these tumors are presented. With our current state of knowledge we cannot conclude that the Ipstein-Barr virus is oncogenic in man, nor can we yet ascertain the biological and clinical significance of its association with Burkitt's lymphoma and nasopharyngeal carcinoma.


[Identification of two plasmids isolated from a bacteriocinogenic strain of Clostridium perfringens]. Two plasmids were found and studied in the bacteriocinogenic strain N5 of Clostridium perfringens: one is a bacteriocinogenic factor (MW=5.7 X 10(6)) and the other a cryptic plasmid (MW 32.4 X 10(6)). Simultaneous loss of the ability to produce bacteriocin and of the bacteriocin resistance in a "cured" variant corresponds to the loss of the bacteriocinogenic plasmid DNA. The syntheses of haemolysin 0 and phospholipase C do not seem to be coded for by the cryptic plasmid.


[Dermo-neuro-hypsarrhythmia. Association of a congenital dermatosis and hypsarthymia. 9 cases (author's transl)]. These 9 cases confirm that tuberose sclerosis, von Recklinghausen's neurofibromatosis, incontinentia pigmenti, linear warty sebaceous naevus and alopecic naevus resulting in a woolly naevus of the scalp may be complicated by flexion spasms with hypsarhythmia. Early diagnosis of hypsarhythmia makes possible specific treatment with ACTH or hydrocortisone.


[Some African gregarines (Ivory Coast, Gaboon) (author's transl)]. We study in the present paper two collections of Gregarines (all parasite of terrestrial arthropods) from the Ivory Coast and the Gaboon. Among the 17 species studied, three are new for science: Gregarina darchenae, Gregarina pycnoceri and Gigaductus africanus. The other species have been already found in closely related hosts.


[Mechanism of action of tetracycline on the functional state of the adrenal cortex]. The mechanism of stimulation of the adrenal cortex function by tetracycline was studied on albino rats. It was shown that tetracycline administered orally in a dose of 200 mg/kg regularly induced an increase in the corticosterone levels in the peripheral blood of the animals by the 15th day of the antibiotic use. It was shown on the animals with an experimentally suppressed function of the hypophysis by prolonged administration of hydrocortisone acetate that tetracycline primarily stimulated the hypophysis function resulting in production and excretion of increased amounts of the adrenocorticotropic hormone into the blood. The hormone increased the production of corticosterone in the adrenal glands which resulted in its higher levels in the peripheral blood.


[Effect of Actinomyces rimosus ribonuclease on the reproduction of viruses]. Antiviral activity of RNA-ase isolated from the fermentation broth of Actinomyces rimosus was studied. The effect of the enzyme on multiplication of the viruses of vesicular stomatitis, Newcastle and cariolovaccine diseases was investigated. It was found that the enzyme was capable of suppressing reproduction of the vesicular stomatitis virus (VSV) in the culture of chick fibroblast cells. The suppression level directly depended on the enzyme concentration and decreased with an increase in the infection multiplicity. The enzyme had no effect on multiplication of other viruses tested. RNA-ase decreased the infectious properties of the freshly isolated virus-containing material in concentrations showing the antiviral effect. Preliminary incubation of the cells with the enzyme resulted in suppression of the plaque formation by VSV. The RNA synthesis in such cultures treated with RNA-ase was somewhat lower. It was shown that the antiviral effect of RNA=ase was connected with its enzymic activity. RNA-ase has no antiviral effect in the experiments with mice infected with VSV.


[Some ways to eliminate the side effects of antibiotic therapy in experimental pneumonia]. Impairement in the process of tissue respiration at the subcellular level in growing animals with experimental pneumonia are described. Under the conditions of antibiotic therapy such impairements aggravated. A combined use of antibiotics with succinic and glutamic acids resulted in improvement of the tissue respiration and acceleration of reparation. Possible mechanisms of this phenomenon are discussed.


[Effect of polymyxin M on intestinal microorganisms of gnotobiotic chicks]. The effect of polymyxin M on the microflora artifically introduced into the digestive tract of gnotobiotic chickens was studied. It was found that polymyxin M caused dysbacteriosis in the digestive tract. Reduction of the impaired biocenosis after discontinuation of polymyxin use was rapid and practically complete.


Multicentric reticulohistiocytosis.

Multicentric reticulohistiocytosis. Multicentric reticulohistiocytosis is a rare disorder of the skin and joints that possesses distinctive histologic findings. A case is reported from shortly after its onset to a stage of resolution 4 1/2 years later.


Comparative study of carcinoembryonic antigen in rheumatoid synovium, tumour, and normal adult lung. Material reacting like carcinoembryonic antigen (CEA) in the radioimmunoassay has been extracted from rheumatoid synovial membranes. This CEA activity has been compared to that found in hepatic metastases from colorectal tumours and in normal adult lung. The antigen in the rheumatoid synovium has been shown to be more sensitive to perchloric acid and to isolate with a lower weight than that derived from the tumour and lung. Immunodiffusion studies with anti-CEA indicate that the CEA-like determinants in the rheumatoid synovium have partial identity with tumour CEA and that a significant proportion of them are associated with large molecular weight material. Production of an antiserum to these CEA-like components in the rheumatoid synovium should enable further identification of their relationship to tumour CEA and might allow a better judgement of whether or not they represent the expression of neoantigens in the disease.


Transfusion-associated cytomegalovirus mononucleosis. Transfusion-associated cytomegalovirus mononucleosis is generally considered only as a complication of extracorporeal circulation following cardiac surgery. Three cases following trauma were recognized in less than one year. Both massive and limited volume blood transfusions were involved. Hectic fever was a characteristic feature in these otherwise remarkably asymptomatic individuals, without the classic features of heterophile-positive infectious mononucleosis. Since the illness developed several weeks into the post-operative period after extensive thoracic or abdominal trauma surgery, the presence of an undrained abscess was naturally the major diagnostic concern. Atypical lymphocytosis, markers of altered immunity (cold agglutinins, rheumatoid factor) and moderate hepatic dysfunction were important laboratory clues. In one case, focal isotope defects in the spleen scan misleadingly suggested a septic complication. A false-positive monospot test initially obscured the correct serologic diagnosis in the same patient. Failure to consider this selflimited viral infection may be a critical factor leading to unnecessary surgery. Other viral agents capable of eliciting a similar syndrome are cited.