[Influence of cortisone on the levels of pyruvic and lactic acids and the activity of the enzymes of gluconeogenesis in the tissues of newborn and adult animals]. There are considerable changes in the lactic and pyruvic acid contents and fructoso-1,6-diphosphatase and glucose-6-phosphatase activities in some tissues of newborn and adult guinea pigs and rabbits 24 hours after cortisone-acetate (2 mg per 100 g of body weight) injection. In the newborn animals of both species the hormone causes a decrease in the lactic and pyruvic acid concentrations and an increase in fructoso-1,6-diphosphatase activity when in the adult ones--an increase in the lactic and pyruvic acid levels and in the glucose-6-phosphatase. In the liver and kidney cortex of adult animals as compared to the newborn ones the fructoso-1,6-diphosphatase activity is significantly increased and in other tissues under study it is decreased. Certain species differences in lactic and pyruvic acid contents and in the activities of both enzymes as well as in the character of their changes under cortisone influence are found.


[Influence of muscular activity on changes in the metabolism of tendotomized muscle]. The muscular activity is established to inhibit the development of atrophic and dystrophic changes and accelerates the restoration of normal biochemical status in a tendotomized muscle. Surgical desympathization does not remove this effect of the increased muscular activity. However surgical desympathization lowers the degree of compensatory biochemical changes in the symmetrical intact muscle of the other leg. Atrophical phenomena is little expressed and dystrophical changes are absent in the tendotomized trained muscles.


[Abdominoanal resection of the rectum with a lowering of different sections of the left half of the colon]. In tumor localization at the level of 7--12 cm aside from the anus the authors performed 168 abdominoanal resections of the rectum with descending of different portions of the left colon. Among these patients in 126 subjects descending of the sigmoid in the anal canal was performed, in 30 of the splenic angle of the transverse colon, and in 12 of a proximal portion of the descending left colon. Some characteristic features of surgery for descending of different portions of the left colon are described.


Dose response to a single injection of azoxymethane in rats. Induction of tumors in the gastrointestinal tract, auditory sebaceous glands, kidney, liver and preputial gland. Male Fischer rats, 6 weeks old, were injected once with one of five doses of azoxymethane. There was a dose response to the carcinogen as determined by weight gain and tumor induction. Rats given the three highest doses developed tumors of the gastrointestinal tract, auditory sebaceous glands, kidney, liver, and preputial gland, whereas rats receiving the lowest doses had tumors mainly of the intestine. Chronic liver lesions in high-dose rats were cirrhosis with megalocytosis, mild fibrosis, nodular hepatocellular hyperplasia, and hyperplasia of bile ductules.


[Noncoenzymic function of vitamin PP].

[Noncoenzymic function of vitamin PP]. The article deals with the experimental data of the authors and those from literature on interrelation between NAD and DNA metabolism in hepatocytes and the role of nuclear NAD-glycohydrolase and NAD-pyrophosphorylase in these processes. Considerable attention is paid to the information on biosynthesis, structure and biochemical functions of poly(ADPR)--a new polymer formed in eucariots nuclei from NAD. The data on the effects of vitamin PP and its biologically active derivative--NAD on DNA synthesis, proliferation of cells and on their genic activity are presented and discussed from modern view points on noncoenzymatic functions of this vitamin.


Naturally occurring intracytoplasmic inclusions in the canine exocrine pancreas. Bodies similar to acidophilic intracytoplasmic inclusions were found by light microscopy in the pancreatic acinar cells of 56 of 174 (32%) healthy male and female purebred Beagles and 14 of 97 (14%) of healthy male mongrel dogs. The inclusions were ovoid, acidophilic and often granular with basophilic particulates. Many seemed to be enclosed within halos of various widths. Electron microscopically the inclusions consisted of whorls of rough endoplasmic reticulum, vacuoles, and cytoplasmic organelles in various stages of decomposition. These inclusion bodies were interpreted as evidence of focal intracytoplasmic degradation. They appeared similar to the dense ribosomal autophagic vacuoles, hitherto described only in association with various experimental procedures.


Tissue-steroid interactions in canine hormone-dependent tumours. Mammary tumour tissue from two bitches and an anal adenoma from a dog were investigated for steroid receptor interaction. Both mammary tumours possessed cytoplasmic macromolecules sedimenting with coefficients of 4S and 8S that bound oestradiol-17beta. These receptors had molecular weights of approximately 60,000 and 180,000 respectively. Transfer of the oestrogen to the nucleus was shown and the presence of a 4-5S nuclear protein demonstrated. The anal adenoma had a cytoplasmic receptor, with a sedimentation value in a sucrose density gradient of 4-5S with respect to bovine serum albumin, that bound tritiated 5alpha-androstane-3alpha, 17alpha-diol. No affinity could be demonstrated for other C19-steroids examined. The significance of these findings in terms of the hormone dependence of the tumours investigated and the possible development of these studies to promote rational therapy in such cases is discussed.


Synovial sarcoma of the larynx.

Synovial sarcoma of the larynx. There have been several reports in the literature2-5 of synovial sarcomas of the head and neck. The consensus of these authors is that the tumor is not as aggressive in this localization as in the extremities, where the recurrence rate is 60% to 70%, and the five-year long-term follow-up of such cases should be made available. Thereby, a reasonably clear and effective modality of treatment could be recommoneded.


[Functional exchange of metabolic regulators in endocrinology and neurochemistry]. On the basis of the authors and their collaborators studies and the data of other investigators, the paper deals with significance and development of the idea of the role in the regulation of the processes and functions not only of unchanged adrenergic hormones-mediators (catecholamines) but also of the products of their metabolism as well as of those ways by which this metabolism occurs. Diversity in the processes of catecholamines and other hormones transformation makes it possible the shunting of this metabolism from one ways to others, that has an effect on many key enzymes of the intracellular metabolism. The products of quinoid and monoaminoxidase transformation of catecholamines affect directly the enzymatic processes and may change the character and intensity of the subsequent and simultaneous effect of the native hormones-mediators. The data obtained when studying adrenaline and noradrenaline metabolism may be extrapolated to certain aspects of the action mechanism of other hormones and mediators of nervous processes. An attempt is made to generalize theoretically the data on the role of hormones-mediators of metabolism in the mechanism of their action with the idea of "induced fit" of the enzymes and with certain problems of biochemistry of the effector cells receptors.


[Complement fixation reaction (CFR) in adenovirus infections of calves]. Studied was the complement-fixation reaction in the diagnosis of the adenovirus infections in calves. It was found that the test is specific and sensitive. A virus suspension of tissue cultures was used as an antigen, its titer varying from 1:8 up to 1:16. Specific complement-fixing antibodies were detected mainly in survivals at serum dilution of up to 1:64. Specific antibodies were established in undiluted sera too taken from animals of infected herds. In some of the tested sera there were both complement-fixing and precipitating antibodies. In calves treated with a live vaccine against adenoviruses the dynamics of the complement-fixing antibodies was followed up.


[Adaptation and cultivation of the Perego strain of ovine smallpox virus in tissue culture and an evaluation of its immunogenic properties]. The strain Perego of the sheep pox virus, used for the production of the ovinized vaccine in this country, was adapted and cultured in tissue cultures of lamb testes. A total of ten passages in succession of the virus were performed with the manifestation of a characteristic cytopathic effect in the cultures. The titer of the virus was found to be within the range of 10(3.5)CPE50, for the initial passages, to 10(4.5)CPE50, for the final passages. The activity and harmlessness of the virus was tested on sheep. The inoculated 14 sheep with one vaccinal dose each, containing 100 CPE50, and two sheep treated with tenfold higher dose of the virus showed that sheep in general tolerate well the rates at which the virus was applied within the range cited. The general state of the sheep did not exhibit deviations, however, the animals' body temperature rose, and there were reactions at the site of the inoculation. Serum-neutralizing antibodies were established in the blood of sheep one month following vaccination.


[Metabolism of nucleic acids in normal, regenerating and neoplastic tissues of the liver]. Under study was the kinetic growth of three hepatomas-22A, 60 and 46, characterized by a various degree of differentiation. There was found a correlation between the degree of differentiation and parameters of the hepatomas growth. For the hepatomas a correlation between the DNA content and rate of growth was observed, for hepatoma 46 a value of the DNA content proved to be near to that of normal liver. Moreover, in a regenerating liver the DNA content is the same as normal, that indicates the difference between normal and neoplastic actively proliferating tissues. The processes of DNA synthesis, studied by thymidine-C14 incorporation, showed a linear correlation with the rate of growth in regenerating, normal and neoplastic tissues. The ratio RNA/DNA in tumors is regularly decreased with respect to normal liver (a linear correlation between RNA/DNA and the maximum rate of growth). In a regenerating liver the ratio is high. Variations in the ratio RNA/DNA reflect changes in the functional activity and related disorders in the metabolism of nucleic acids in hepatomas. There was found a suppressed DNA decomposition in autolysis of homogenates from hepatoma tissues. It is essential to note that in a minimum deviated hepatoma some inhibition of the DNA decomposition is the only observed disorder in the nucleic acids metabolism. Spin-labelled DNA preparations of tissues under study were obtained. The presence of structural differences between separate DNA samples has been demonstrated.


[Functional state of the adrenal cortex in patients with cancer of the rectum]. The level of 17-ketosteroids and 17-ketogenic steroids in the diurnal urine was determined in 70 patients with rectal cancer prior to and after ACTH administration. In most patients the initial excretion of the steroids under study was found to be decreased. 17-ketosteroids excretion is reduced more frequently in patients over 50 years of age and in females. In a predominant number of patients functional reserves of the adrenal cortex are decreased.


[Serologic diagnosis of brain tumors using Clostridium butyrium spores (experimental and clinical studies)]. Spores of the Clostridium butyrium M 55 strain, introuduced intravenously, proliferate selectivity in tumours of individual with newgrowths forming bacilli and then multiply evoking the appearance of antibacillary antibodies. In persons with no tumours there emerge only antispore antibodies. Since the spores and bacilli of this strain have antigens of a different nature their antibodies are encountered separately. The finding of antibacillary antibodies following injection of spores thus serves as an indirect proof for the presence of a malignant tumour. In experiments on animals (rats) with neurogenic tumours induced with ethylnitosole urea and also in patients with brain tumours this phenomenon has been studied in detail.


[Diabetogenic and atherogenic effects of glucose]. Tests were set up on 59 albino male-rats with reproduced functional overstress and depletion of the insular system of the pancreas thorough a long-term (for 50, 100 days) peroral introduction of glucose (2 g/100 g body weight, every other day) and with and alloxan-induced diabetes (achieved by poisoning the animals with a 2.5% alloxan solution, 15 mg/100 g administered in a single dose intraperitoneally). A comparison of the data obtained ascertained the presence of a number of similar pathobiochemical changes in the metabolism, viz. hyperglycemia, an increase of the free cholesterol fraction, a diminution of the bound cholesterol fraction and a fall of the insulin-like activity (ILA) in the blood serum, a rise in glycogen and beta-lipoproteids in the liver; morphologically--a reduced count of Langerhan's islands beta-cells, less intensive colouration of the specific granulation in their cytoplasma manifestations of vacuolar and granular dystrophy of the liver. Further tests were staged on 23 rabbits involving a long-term introduction of glucose (in amounts of 25 g/kg every other day) and a cholesterol-induced atherosclerosis (by administering 0.2 g/kg of cholesterol in oil, daily), which also showed similar changes in the figures of the carbohydrate and fat-lipoids metabolism, such as hyperglycemia, an increased level of total lipids, cholesterol and its fractions, beta-lipoproteids, a fall of ILA in the blood serum, as well as variations in the morphological picture of the aortic wall. The above findings suggest that a protracted administration of glucose can produce both diabetogenic and atherogenic effects.


[Level of nicotinic acid and NAD in the organs of rats during complete starvation]. In the liver, heart, brain and pancreas of control rats and of test animals fasting for 2, 4, 7 and 11 days the content of nicotinic acid in the organs was determined by the microbiological method and that of NAD- biochemically. After 2, 7 and 11 days of fasting a statistically significant increase in the level of nicotinic acid per 1 g of tissue was ascertained in all the organs. After 4 days of fasting an increase in the vitamin content proved insignificant. With the calculation covering the entire organ the fall of the PP level in the liver proceeded uniformly and after the 11th day of fasting it amounted to 46 per cent, whereas in the heart the decline was insignificant, the content of the vitamin in the brain, however, rose by 21 per cent. The NAD level in the organs, calculated to 1 g of the tissue, changed but little and with the estimates covering the whole of the organ there could be noted its substantial drop in the liver, especially after 11 days of fasting (by as much as 62 per cent), and to a lesser degree--in the heart and pancreas and rise in the brain (by 13 per cent).


[The intestinal parasite fauna in patients, returned from the tropics, from the Dresden district]. It is reported on the affection with intestinal parasites in 438 persons who returned from the tropics. In these test persons were also established only those species of parasites which were proved in the Dresden inhabitants. However, there were remarkable quantitative differences between the affection of the persons returning from the tropics and the Dresden inhabitants. Thus by laboratory examinations in Dresden in the persons returning from the tropics were established infections with Entamoeba histolytica (7.0%), with Dientamoeba fragilis (17.9%), with Lamblia intestinalis (9.0%) as well as with Trichuris trichiura (3.4%), where as the extensity of affection with the corresponding parasites is for the Dresden inhabitants 1.9%, 4.7%, 5.0%, and 1.6%. It is referred to the fact that all persons who returned from the tropics should parasitologically be examined for an infection with Entamoeba histolytica.


Microfilaments in human epithelial cancer cells. The occurence, distribution, and ultrastructural morphology of microfilaments in malignant epithelial cells of invasive squamous cell carcinoma of human oral cavity were studied by electron microscopy. The findings are compared with those in malignant oral epithelial cells of carcinoma-in-situ. In the malignant cells of invasive carcinoma, microfilaments 50-70 A in diameter are prominent in the cortical cytoplasm of the lateral and basal cell surfaces, adjacent and parallel to the plasma membrane, and extending into cell processes and microvillous extensions. Additional microfilaments are found to run from the peripheral cytoplasm to the perinuclear region. The microfilaments are aggregated into bundles aligned parallel to the long axis of the cell and display foci of increased electron density. They also tend to be aggregated into complex polygonal arrays. These microfilaments are similar in organization, concentration and ultrastructural architecture to those of various other nonmuscle cells, where they are thought to be capable of contraction and associated with cell motility. The presence of a microfilament system believed to be associated with contractile and motile cell processes may be an important characteristic of malignant cells of invasive tumors. The lack of abundant organized microfilaments in malignant cells in the absence of tumor invasion, and the presence of a prominent microfilament system in cells of invasive tumors, suggest that the microfilaments are related to the invasive properties of malignant tumor cells.


[Comparative studies of simultaneous intraoperative frozen sections and imprint cytology of the mamma (author's transl)]. 250 tissue biopsies of the mamma were examined simultaneously by intraoperative histology (frozen sections) and imprint cytology. In 95% of the cases there was a good agreement between the histologic and cytologic diagnoses. The reliability of the imprint cytology was tested in some complicated cases such as proliferating fibroadenomas, sclerosing adenosis and carcinomas and the significance of the imprint cytology for the diagnosis of difficult cases was pointed out in detail. The results have demonstrated, that such a cytologic examination can not be a substitute for intraoperative frozen sections - but the simultaneous cytologic examination of unfixed mamma biopsies can be a good searching method and can be helpful in the intraoperative diagnostic.


[Nucleotide alterations of 18 S and 28 S ribosomal RNA from rat liver during carcinogenesis induced by N-nitrosomorpholine (author's transl)]. After administration of N-nitrosomorpholine (NNM) to female Wistar-rats the ribosomal RNA (18 S and 28S rRNA) of the livers contained "abnormal" dinucleotides which were resistant against treatment with alkali or with spleen phosphodiesterase. These and further observations are discussed in view of the hypothesis that during the induction of liver tumors a metabolite of NNM causes crosslinks of nucleic acid bases. The application of this hypothesis on the effects of NNM upon DNA permits to explain the additional results that have been obtained. Observations on NNM metabolism as reported in the literature are not inconsistent with this interpretation.


Spermatogenesis in free living mite, Pergamasus viator Halaŝ (Parasitidae, Mesostigmata). I. Fine structure of spermatozoa. The spermatozoa of Pergamasus viator Halaŝ. from Parasitidae family (Acarina, Mesostigmata) were studied in light and electron microscopy. The spermatozoa are motionless (in vitro) rod-shaped cells 110 mum long, in which six morphologically different zones can be distinguished: acrosomal zone, mitochondrial zone, zone of granular bodies, zone of striated bodies, nuclear zone and retronuclear zone. The acrosomal zone filled with the granular subacrosomal material contains at the top the acrosomal vesicle. Plasmalemma forms 19--21 folds running longitudinally along the spermatozoon. Within each fold there is a flattened canaliculus, and under each fold is found a stoff band. Between the stiff bands flattened cisternae are observed. Apart from the above structures the spermatozoon contains: the nucleus, striated bodies, granular bodies and mitochondria. The flagella-like structures or centrioles were not found. A possible origin and role of the structures decribed in spermatozoa of P. viator are discussed.


Adenyl cyclase activity in lymphocytes stimulated with immunologically specific and nonspecific stimuli. Adenyl cyclase activity was determined in suspensions of rat lymphocytes from animals with postadjuvant polyarthritis and from healthy animals. Adrenaline was used as activator of the enzyme. Adenyl cyclase activity was determined by the method based on synthesis of 3H-cAMP from 3H-ATP in intact cells. The influence of imidazole on blastic transformation of lymphocytes sensitized in the process of postadjuvant polyarthritis and subjected to the action of antigen, i.e. Old Tuberculin, was also studied. The response of sensitized lymphocytes to antigen in the presence of a nonspecific stimulus, adrenaline, was also investigated. In addition, the action of adrenaline on incorporation of 3H-thymidine in cultures of nonsensitized lymphocytes was observed. Adenyl cyclase activity in suspensions of lymphocytes from animals with postadjuvant polyarthritis was higher than in suspensions of lymphocytes from healthy animals. Following administration of adrenaline as activator of the enzyme, lymphocytes from healthy animals showed higher activity of the enzyme than lymphocytes from the sick rats. Imidazole inhibited the response of lymphocytes sensitized to antigen. Adrenaline had no influence on blastic transformation of lymphocytes sensitized to antigen. Adrenaline slightly inhibited incorporation of H-thymidine in cultures of sensitized lymphocytes in absence of antigen in cultures of nonsensitized lymphocytes.


[Disorders in conditioned reflex activity and morphologic changes in the brains of rats deprived of paradoxical sleep]. Reproduction of defensive conditioned reflexes elaborated before a 96-hour deprivation of paradoxal sleep (DPS) in rats was sharply disturbed immediately after DPS, but became normal 24 hours later. Elaboration of conditioned reflexes immediately after DPS is followed by a disturbance of their reproduction, while such elaboration 24 hours after DPS does not affect their subsequent reproduction. It is assumed that dissociated learning plays an important part in the origin of the disclosed disturbances of conditioned activity. Morphological investigation of the animals' brain immediately after DPS revealed activation of neuroglia with productive-dystrophic changes of astrocytes, an increase in the sizes of nuclei of neurones in the motor cortex and hippocampus, and pronounced vascular changes. A day after DPS the changes of the astrocyte glia and the vessels are less pronounced, and the sizes of neurone nuclei in the motor cortex diminish.


[Duration of possible detection of cysts of Entamoeba histolytica in stool samples (author's transl)]. Stool samples containing large numbers of cysts of Entamoeba histolytica were stored at room temperature (+22 degrees C - +25 degrees C) and at +4 degrees C respectively. After 1 h, 6 h, 12 h, 20 h, 36 h, 5 d, 7 d, 10 d, 15 d, 20 d, and 30 d smears were performed and stained according to the method of HEIDENHAIN. In both groups cysts remained easily detectable for about one week; after that time, however, distinct changes of the morphology of the cysts occurred and the number of detectable individuals decreased rapidly. After 30 days storage of the stool cysts could be recognized only exceptionally and only in samples stored at 4 degrees C. At that time the microscopic picture of the smears had undergone heavy changes; yeasts predominated over bacteria. In addition it was shown, that freezing of stoll samples (at - 20 degrees C and -80 degrees C) destroyed practically all cysts.


Phenotypic chain formation in Clostridium welchii by suramin. Cl. welchii NCTC 6785 was grown in 1% glucose containing medium having 1% Suramin w/v. The cells grew into long chains of thirty units. This effect was not found beyond 0.5% concentration. On transfer into Suramin free medium the chains reverted to normal morphology indicating the change in morphology to be phenotypic.


[Study of the interrelationship between the content of immunizing units and the immunogenicity of C1. perfringens anatoxins]. Comparative experiments were conducted on rabbits and guinea pigs; a study was made of the immunological efficacy of the toxoids with a different content of the immunizing units (IU/ml). There was revealed a regular quantitative interrelationship between the content of the IU/ml in the toxoids, the level of the antitoxin formation and the extent of protection against the experimental gas gangrene in the immunized animals.


[Comparative characteristics of the toxic properties of the whooping cough microbes]. The author presents materials concerning the study of the toxic properties of 12 pertussis cultures used in the USSR for the production of vaccines. As a result of studying the toxic properties of the microbes in the test of the change of the weight of mice, and in experiments of testing the anaphylactogenic and histamine-sensitizing activities it was revealed that the strains of pertussis microbes differed by the quantitative content in them of the thermolabile toxin, endotoxin, lymphocytosis-stimulating and histamine-sensitizing factors; therefore, the period of keeping the pertussis suspensions for 1.5 months from the moment of detoxication proved to be inadequate for some of the strains. Since the toxic properties of the strains failed to correlate with their protective activity, in recommendation of pertussis strains for the production of pertussis vaccine preference should be given to the strains with lesser toxic properties.


[Effect of a chronic iodine deficit in the ration on the development of the infectious process]. It was revealed that the infectious process in albino rats kept for 4-5 months on an iodine-deficiency diet was characterised by a tendency to dissemination. The seeding efficiency from the parenchymatous organs increased in such animals significantly, whereas the bactericidal properties of the plasma and the phagocytic activity of blood neutrophils decreased; this was apparently associated with depression of the intracellular metabolism reflected in reduction of the cytochromoxidase and peroxidase in the neutrophils.


[Modelling of biological encoding mechanisms as a system with distributed parameters]. The encoder region in receptors and neurons is represented by the inhomogeneous origin of the axon. The axon diameter and the excitability are in fact space-dependent. For the analysis the soma is described by a system with concentrated parameters followed by an inhomogeneous axon. The membrane properties are approximated by the slightly modified Hodgkin-Huxley equations. The assumption that the space-dependence of the excitability originates in variations of the conductance value for sodium ions accounts for a number of experimental results. The influence of other membrane parameters upon the mechanism of impulse generation and transmission has also been analysed.


LP-X in cholestasis.

LP-X in cholestasis. Extrahepatic and intrahepatic biliary obstruction of different etiology were studied in 62 patients, who were investigated for the presence of lipoprotein X (Lp-X). It was found present in 19 of 20 cholestasis by lithiasis, in all three primary biliary cirrhosis patients, in 2 of 4 cirrhosis, in 5 of 13 hepatitis, in all three benign recurrent intrahepatic cholestasis and in 1 of 2 recurrent juandice of pregnancy. It was found in a Dubin Johnson. Lp-X disappeared in 4 patients within two weeks after relief of the obstruction. It was found in patients with cholestatic hepatitis during the first week of jaundice. It was found in the first 48 hours in three patients with cholestasis by lithiasis. Lp-X does not help in differential diagnosis between extrahepatic and intrahepatic biliary obstruction, but the time of its appearance could contribute to it in some cases. A word of caution is raised in indicating surgery in a cholestatic patient without the presence of Lp-X.


Immune responses to treatment with natural and synthetic ACTH in bronchial asthma. Two comparable groups of asthmatics each with 10 patients were treated during 2 years at scheduled intervals with either natural or synthetic ACTH up to a total dose of 2000-95-- IU. All patients had previously been given the natural but never the synthetic hormone. Intradermal tests with natural and synthetic ACTH were performed before treatment and after 1, 12 and 24 months. Serum samples were also taken on these occasions and analysed for antibodies against ACTH, vasopressin and porcine gamma-globulin. No sign of clinical allergy to ACTH was noted in any of the patients during the 2-year period. The incidence of intradermal reactions against natural ACTH was high at the onset of treatment but was not increased by treatment with either synthetic or natural ACTH, while the reactivity rate against synthetic ACTH was increased after both types of treatment. The incidence of IgE reactions against synthetic ACTH at the 20 U/ml level was significantly increased after 12 months' treatment with either natural or synthetic hormone. A high incidence of low-titered agglutinating antibodies against natural or synthetic ACTH was demonstrated before treatment in both the groups, but no significant change in incidence or mean titre against natural or synthetic ACTH or porcine gamma-globulin was noted during treatment with the natural or the synthetic preparation. A few patients, however, did display an increased agglutinating titre against ACTH after 12 months' treatment. Rather unexpectedly, most sera reacting with ACTH were found to react also with vasopressin and a significant increase of the incidence of these reactions and of the titres occurred during the treatment with synthetic as well as with natural ACTH. Two cases have been examined in detail, one because of a fulminant shock after synthetic ACTH and the other because of very high antibody titres without clinical symptoms of ACTH allergy.


Pathology of the human spinal ganglia in varicella-zoster virus infection. Spinal ganglia from a patient who died on the 6th day of varicella infection were examined by immunofluorescence and electron microscopy, and were compared with spinal ganglia from a patient dying on the 17th day of herpes zoster infection. In herpes zoster, typical intranuclear inclusion bodies were found in neurons, satellite cells and fibroblast-like cells of the ganglia, which contained numerous naked virus particles. In varicella, few changes were found by light microscopy but viral antigen was detected in a few neurons and satellite cells by immunofluorescence. Electron microscopy revealed scattered virus particles near the nuclear membrane of a neuron, satellite cells and capsular cells and enveloped particles in the cytoplasm of satellite cells. The particles in the nuclei were mostly naked virions with specific crescent-like inner-nuclear structure; those in the cytoplasm had complete and incomplete envelopes and showed pleomorphism. A "virus-like" intranuclear filament found in mononuclear cells in herpes zoster and a "plexiform vermicellar array" found in the nuclei of neurons in varicella are at present considered to be non-specific nuclear changes caused probably by viral infections.


Rod-shaped filamentous inclusions and other ultrastructural features in a cerebellar astrocytoma. A biopsy specimen of a cerebellar astrocytoma from a 14-year-old girl was studied by light and electron microscopy. Histologically the tumor showed a mixture of loose and compact areas with numerous Rosenthal fibers. By electron microscopy most tumor cells contained, besides the usual organelles, large amounts of 70 to 100 A thick filaments. Classical Rosenthal fibers were also identified. In addition many cell bodies and processes were sprinkled with fragments of Rosenthal fiber material. Ordered filamentous arrays (so-called Hirano bodies) were seen in a number of tumor astrocytes. They are considered to be a nonspecific arrangement of filament units largely devoid of cytopathologic significance. Other ultrastructural features of some tumor cells were inchoate forms of the granulated bodies of conventional histology, paired cisternal elements of rough endoplasmic reticulum, and honeycomb-like profiles of transversely cut cylindrical units of smooth endoplasmic reticulum. Microtubular bodies were numerous in the endothelial cells of the tumor vessels.


Double encephalitis with herpes simplex virus and cytomegalovirus in an adult. A 51-year-old housewife developed symptoms of a cold followed by high fever, delirium, coma, rigidity of extremity muscles, positive Babinski sign and generalized convulsions, while complement-fixing antibody titre to herpes simplex virus in the sera raised over 128 X and declined to 8 X in the course. She finally expired of bronchopneumonia following status epilepticus after 94 days of illness. Severe necrosis with extensive hemorrhage in the white matter was predominant in the temporal, insular and orbitofrontal cortex, thalamus and globus pallidus. Focal rarefaction of the cerebral cortex with a very few eosinophilic intranuclear inclusions in the oligodendroglia and nerve cells, nerve cell destruction in the substantia nigra with glial nodules and perivascular inflammatory cell cuffs were observed. Abundant cytomegalic inclusion cells, originating from hypertrophic astrocytes, were present in the necrotic areas of cerebrum as well as in the rarefied tissue in the subependymal layers of the brainstem and cerebellum. Electron-microscopic study of the cytomegalic cells demonstrated the presence of numerous virions in both nucleus and cytoplasm. Fortuitour infection of the brain by cytomegalovirus with necrotizing encephalitis by herpes simplex virus is unique. The cause of double viral infections and severe lesions by less virulent strains is discussed.


Electron microscopic investigation of inclusion material in a case of adult metachromatic leukodystrophy; observations on kidney biopsy, peripheral nerve and cerebral white matter. The fine structural characteristics of storage products in peripheral nerve, kidney and cerebral white matter, from a case of adult metachromatic leukodystrophy are described. There were pronounced differences from the fine structural aspects in late infantile cases. A large proportion of the inclusions did not exhibit a unit membrane. An hypothesis is proposed to clarify the delayed manifestation of this type of metachromatic leukodystrophy until childhood.


Quantitative analysis of radioisotopic angiography in trophoblastic neoplasia. The diagnostic significance of radioisotopic angiography in the clinical management of trophoblastic neoplasia was studied by analyzing the patterns of radioisotope (RI)-dynamic curve obtained by processing sequential image with a computer, and an attempt was made to express numerically the size of tumors present in vivo. It was demonstrated that the total activities of RI in the abnormal phase of RI-dynamic curves in trophoblastic neoplasia were closely correlated with the sizes of the intrauterine tumors actually resected.


A case of multiple sclerosis associated with defective neuromuscular transmission. A 38-year-old woman developed relapsing disseminated sclerosis associated with myasthenic syndrome. The cerebrospinal fluid showed 12 lymphocytes per 1 mul and paretic colloidal curve. The serum contained antibody against smooth muscle antigen (titre 1 : 10) but no antibody against nuclear antigen or VDRL antigen. Repetitive stimulation of the right ulnar nerve at 35 c/sec. demonstrated typical decrements between 70 and 72%. The prostigmine test showed significant diminishing of decrements. The possible immunopathological mechanism of myasthenic syndrome in multiple sclerosis was briefly discussed.


Antibodies to herpesvirus hominis types 1 and 2 among women with neoplastic change of uterine cervix. The occurrence of antibodies to herpesvirus hominis types 1 and 2 was studied in Finland among patients with a neoplastic change of the uterine cervix. The following groups were studied: 220 patients with malignant or premalignant lesions of the uterine cervix, 143 control patients matched for age, socioeconomic level, marital status, home district and number of deliveries and 82 patients with breast or stomach cancer. Antibodies to HVH types 1 and 2 were determined using the neutralization test. Sera showing an index of less than or equal to 100 were accepted as positive to type 1 and those of greater than or equal to 85 as positive to type 2. Among patients with a neoplastic change of the uterine cervix the frequency of type 1 antibodies varied between 70% and 79%. In the control group the frequency was 84% and among patients with some other malignancy 91%. These differences in the frequencies of type 1 antibody were not statistically significant. Type 2 antibodies were present in 35 to 47% among dysplasia and malignancy of the cervix. In the control group it was 18% and in other malignancies 20%. The differences between these groups and the controls were almost significant, significant and highly significant, respectively. Differences could also be observed in the distribution of neutralization indexes. The average index calculated from all sera was 48 both in the control group and in the group of other malignancies, while in sera of patients with dysplasia, carcinoma in situ and invasive carcinoma the respective vlaues were 70, 66 and 79. The results are discussed in terms of the role of herpesvirus hominis type 2 in the development of cervical cancer.


Inhibitory processes in the medial geniculate body. Inhibition in the medial geniculate body was studied with a double click technique. A conditioning click caused a marked inhibition of field potentials and unit discharges to a subsequent test click. Cyclic inhibition with a period of about 150 ms was seen in the medial geniculate body and the auditory cortex, but not in the inferior colliculus. The postsynaptic excitability was tested by recording from the killed ends of the thalamocortical fibres. A preceding click reduced the direct response to a test stimulus delivered to the medial geniculate body indicating the presence of postsynaptic inhibition. The excitability of the fibres from the inferior colliculus terminating in the medial geniculate body was tested with a modified Wall (1958) method. The results suggest the presence of a presynaptic inhibitory mechanism in the medial geniculate body. The techniques employed do not allow an estimation of the relative contribution of the two inhibitory mechanisms to the inhibition at the medial geniculate level.


Histopathological studies on the tumourlet of the lung with special reference to the cytogenesis of proliferating cells. Eight foci of tumourlets of the lung and one allied lesion obtained from autopsy cases were histologically examined. The tumourlet of the lung consisted of epithelial cells and was considered to be a benign lesion. Small sized-lesion, uniformity of proliferating cells with very few mitosis and existence of associated lung lesions were documented as characteristic findings. However, the histopathogenesis of the tumourlet was not fully clarified. It was found that proliferating cells of tumourlets often show argyrophilia and contain numerous neurosecretory-like granules in their cytoplasm. These characteristics are very similar to Kultschitzky-like cells of the lung.


Histopathological studies on experimentally induced pulmonary adenomatosis in guinea-pig lungs. The main purpose of our experimental series was to induce, in experimental animals, diffuse pulmonary fibrosis resembling that in human lungs. In the lungs of guinea-pigs injected with a soluble immune complex and continuously exposed to a 40-60 per cent oxygen-rich atmosphere, diffuse pulmonary fibrosis occurred in many cases in the course of 2 to 3 months after the injection. After the 100th experimental day, multiple foci of pulmonary adenomatosis occurred. The morphology was similar to that of Jaagsiekte. Electron microscopic observations revealed that these hyperplastic cells originated from type II pneumoncytes.


Congenital stapes fixation, symphalangism and syndactylia. An autosomal dominant hereditary syndrome is described consisting of congenital deafness, characteristic finger and toe deformities, with absence of the proximal interphalangeal joint together with syndactylia. The syndrome has been observed in 5 members of a Danish family, and the study confirms the autosomal dominant trait.


Tumor of glomus jugulare report of a case. A typical case of glomus jugulare tumor was presented. This 42-year-old man suffering from a left-sided impaired hearing progressive over a five year period was found to have a small hemorrhagic polypoid tumor in the left external auditory canal. After repeated surgical treatments the tumor removed was light and electron microscopically diagnosed as glomus jugulare tumor which corresponded to the 13th case in this country. The implication that this tumor may constitute a distinctive group of tumor among the neuroendocrine tumors from other sites was discussed from the facts of the presence of a large number of rather small argyrophilic granules of secretory type in the cytoplasm of tumor cells including the present case and of the appearance of increasing cases with functioning glomus jugulare tumor secreting catecholamine in the recent medical literature.


Cochlear innervation in the guinea pig. II. The spiral tunnel bundle. The organization of nerve fibers in the spiral tunnel bundle (STB) of the guinea pig organ of Corti has been studied by light and electron microscopy. In the basal turn STB fibers were found to run toward the base or apex in about equal numbers while in the upper turns they ran predominantly in an apical direction. Long spiral fascicles of 100 microns or more in length were abundant in the third and fourth turns, but were rarely seen in the lower turns. No synaptic contacts between tunnel bundle fibers could be found and no afferent nerve fibers were seen in the bundle. Furthermore, interruption of the efferent nerve supply resulted in complete degeneration of the STB. The tunnel bundle does not, therefore, appear to be a site of synaptic interaction between afferent and efferent neutral elements.


High-energy protons in the postoperative treatment of malignant glioma. Fractionated irradiation with high-energy protons was given postoperatively to seven patients with malignant glioma. In four cases in which detailed microscopic examinations were performed, radiation induced tumour necrosis was evident but in all four cases viable tumour cells were also observed. No abnormalities that could be attributed to radiation were observed in brain tissue free from tumour. The therapeutic results were comparable to the results achieved by other modern therapies. The results support the view that the RBE of high-energy protons is similar to that for 60Co radiation. It is suggested that a larger radiation dose, delivered by a homogeneous, well-defined proton field could possibly result in an improved therapeutic result without undue risk of injury to normal brain tissue.


Effects of cholinergic agonists and antagonists of nucleus vestibularis lateralis unit discharge to vestibular nerve stimulation in the cat. Unit discharge in nucleus vestibularis (NVL) was studied in locally anesthetized cats. The mean firing rate +/-S.E. of spontaneous unitary discharges of NVL neurons was 19.8+/-0.9 Hz and that of spinal-transected animals was 18.0+/-1.6 Hz. The mean firing rate of these neurons in animals with cerebellum ablation and the administration of scopolamine in a dose of 0.5 mg/kg i.v. was relatively low. After administration of physostigmine in a dose of 25 mug/kg i.v. the firing rate was enhanced. The effects of physostigmine were antagonized by scopolamine. About 95% of NVL neurons activated by single electrical shocks to the ipsilateral vestibular nerve showed regular firing following administration of physostigmine. These neurons changed to a gamma distribution at lambda=2 following administration of scopolamine.


The effect of acute exercise on plasma corticosterone in the ovariectomized rat. Levels of plasma corticosterone were determined by a fluorometric method in female rats, subjected to acute treadmill exercise. It was found that physical exercise causes a twofold rise in the plasma corticosterone concentration. This increase was slightly lower in the ovariectomized animals. Duration of the effort until exhaustion varied with age und hormonal status of the animals.


Serum lipoprotein composition in different types of hyperlipoproteinemia. Fasting serum lipoproteins (LP) were separated into VLDL, LDL and HDL by ultracentrifugation and the content of cholesterol and triglycerides analyzed in each LP class in 69 consecutive men attending a lipid clinic. The effect of using different cut off points in the definition of HLP was discussed. It was pointed out that by using lower values for the cut off points there is only an increase in the number of subjects with hyperlipoproteinemia (HLP) but also shifts in the proportions between the various types of HLP, particularly with increase in the amount of types IIB and IV. In addition to the LP abnormalities inherent in the definition of each type of HLP other LP abnormalities were observed. Thus type IIA HLP had cholesterol rich VLDL with an increased ratio cholesterol/triglycerides. The types of HLP with increased VLDL triglycerides had characteristic changes in both LDL and HDL. For LDL its triglyceride content was increased and HDL showed a lowering of its cholesterol content and a rise in triglycerides. These changes were more pronounced the higher the VLDL triglyceride concentration was. Both normo- and hyperlipoproteinemic subjects having the second pre-beta LP on agarose gel electrophoresis of the VLDL fraction called LPB (Late Pre Beta) had two characteristic LP features. VLDL had an increased cholesterol/triglyceride ratio. LDL had a raised triglyceride content. The relation of LPB to so called intermediary particles was discussed. When the SPB (Sinking Pre Beta) LP variant was present this had negligible effects on the LP composition. Type IIA was present in 14 percent of the 609 men. None had tendinous xanthomata. The LP pattern of this common type IIA was compared to the LP pattern of the uncommon type IIA where tendinous xanthomata are present, called IIA-X. Type IIA-X had much higher LDL cholesterol and in relation to the triglyceride content a more cholesterol rich LDL. Furthermore type IIA-X had lower VLDL lipids than the common type IIA, but type IIA-X was more cholesterol rich. The differences in clinical appearance as well as in quantitative and qualitative LP composition between the common type IIA and type IIA-X makes it important to separate these two types of HLP from each other.


The heritable hyperlipoproteinemias and atherosclerosis. 1. The genetic hyperlipoproteinemias are common, are easily diagnosed and are often expressed in children or in infants. 2. Familial combined hyperlipidemia, hypercholesterolemia and hypertriglyceridemia are all associated with a markedly augmented atherosclerotic cardiovascular event rate. 3. The clinical importance of early diagnosis, family screening, and lipid sampling in high risk or free living populations must be emphasized. 4. Exciting progress at a biochemical molecular level (in tissue culture, for example) provides better understanding of the genetic hyperlipoproteinemias and possible avenues for its better therapy.


Lipoproteins and lipid transport.

Lipoproteins and lipid transport. Continued advances in the delineation of pathways of lipid transport in lipoproteins now provide substantial information on all phases of plasma triglyceride transport. Analysis of certain genetic human disorders, together with studies in experimental animals, has begun to show how lipoproteins transport cholesterol as esters of long chain fatty acids. Both triglycerides and cholesterol are esters of long chain fatty acids. Both triglycerides and cholesteryl esters are transported in the "core" of lipoproteins, but the polar lipids and the apoproteins at the aqueous interface critically determine the interactions with enzymes and cellular receptors that control this complex transport system. Differences in pathways as well as in rates of lipid transport appear to underlie the large interspecies variations in lipoprotein concentrations.


The cockerel as an animal model for atherosclerosis research. The chicken is a good animal model for the study of atherosclerosis research because it is: 1. Omnivorous. 2. Small and suitable for prolonged laboratory investigation. 3. Able to develop spontaneous atherosclerosis. 4. Capable of producing atherosclerosis after cholesterol feeding with elevated hypercholesterolemia. A diet of 1/4% cholesterol plus 5% cottonseed oil added to starter-grower-mash resulted in aortic atherosclerosis with a slight but significant increase in plasma cholesterol. 5. Plasma levels of cholesterol and triglyceride are similar to those in humans. 6. Lipid composition of high and low density lipoproteins as well as chylomicrons resembles those of humans. 7. Has been noted that there is no essential difference between vascular lesions seen in chickens as a result of cholesterol diet and that of atherosclerosis observed in man.


How good is thermography in breast cancer screening? With the present level of experience and with current equipment, thermography does not seem sufficiently reliable to substitute for either clinical examination or mammography in breast cancer detection. It is, however, of adjunctive value and can be used in frequent screening and in younger individuals. Women with positive thermograms should be followed more closely, both clinically and radiographically, than the average patient.


Metabolic and cardiovascular abnormalities in patients with peripheral arterial disease. Twenty-eight consecutive patients of an average age of 63 years with intermittent claudication secondary to underlying peripheral arterial disease were studied for evidence of metabolic or other cardiovascular abnormalities and the results obtained were compared with those of 28 matched control subjects free of vascular disease. Patients with peripheral arterial disease had significantly higher levels of systolic and diastolic blood pressure, a greater incidence of ECG abnormalities, lipoprotein abnormalities, elevated serum triglycerides, and serum copper. The incidence of smoking and abnormal glucose tolerance, while higher in peripheral arterial disease patients, was not statistically significant. Hematocrit and serum cholesterol levels were nearly indentical in both groups of patients. Twenty-six of the 28 patiens with peripheral arterial disease had either a cardiovascular or a metabolic abnormality, indicating the high incidence of multisystem illness in this disorder. The epidemiologic data in peripheral arterial disease are similar to those in coronary artery disease but some measurements contrast sharply, such as the apparent normal level of serum cholesterol in patients with peripheral arterial diseases.


Idiopathic cardiomyopathy and skeletal muscle abnormality. The skeletal muscle of three cases presenting with idiopathic congestive cardiomyopathy has been studied, histologically, histochemically, ultramicroscopically, and electromyographically. In all three there is clinical evidence of skeletal muscle weakness, and in all three, pathologic changes were found in the muscle. These changes were different in each case and varied from mitochondrial myopathy to spinal atrophy to vacuolar myopathy. Other reported cases of cardiomyopathy demonstrating skeletal muscle pathology are discussed.


On acupuncture analgesia and the mechanism of pain. The effect on the experimental tooth pain threshold of conditioning electrical stimulation via needles or surface electrodes applied to the hands and cheeks was studied in 34 dental students. Conditioning stimulation with 2/sec. gave a slowly increasing pain threshold followed by a slow return to the control level in the post-conditioning period. In each individual the amplitude of the threshold increase was reproduceable. It was concluded that these effects are not due to motivational but to more basic neurophysiological mechanisms. The pain threshold was increased mainly by segmental conditioning stimulation; segmentally unrelated stimulation gave usually only small effects. Conditioning stimulation with 100/sec. produced only a strict segmental short-lasting effect. Effects with characteristics of both 2/sec. and 100/sec. were obtained by conditioning at 10/sec. It is suggested that the transmission of impulses from the pain afferents to ascending pathways is controlled at the segmental level by (a) presynaptic inhibition within the group of afferents giving rise to the flexion reflex of which the pain afferents are assumed to be a part; (b) postsynaptic inhibition between alternate pathway excited by flexion reflex afferents; and (c) descending control from supraspinal systems which may utilize similar segmental mechanisms as the primary afferents.


Use of immunoperoxidase on brain tissue for the rapid diagnosis of herpes encephalitis. An indirect immunoperoxidase method to detect herpes simplex viral antigen in brain cell suspensions from patients suspected to have herpes encephalitis is described. The method is rapid, reliable and specific, and successfully identified the herpes virus infected cells in four of five culture-proven cases. There was one false-negative reaction, but no false-positive. The immunoperoxidase technic offers a number of advantages over immunofluorescence for routine diagnosis.


Fluorescent antibody studies of alpha-1-antitrypsin in adult human lung. The histologic distribution of alpha-1-antitrypsin in frozen sections prepared from four specimens of human lung was determined by the indirect fluorescent antibody technic. Three of the specimens were obtained directly from surgical procedures and were peripheral tissue excised with tumors. The tumors were a mixed-cell "scar cancer" (Case 1), a bronchiolar carcinoma (Case 2), and a benign hemartoma (Case 3). The fourth specimen (Case 4) was obtained at autopsy following death by myocardial infarction. Specific fluorescence for alpha-1-antitrypsin was observed lining the terminal airways and alveoli throughout the sections from Cases 1 and 4. In specimens from Cases 2 and 3, a few focal areas of specific fluorescence were observed. The results of this study suggest that alpha-1-antitrypsin may be distributed in lung in variable concentration in association with pulmonary surfactant.


The epidemiology of cancer of the breast. A summary of the most relevant facts and hypotheses concerning breast cancer epidemiology is made. It is suggested that the statistical associations with suspected etiologic factors might be diluted by the heterogeneity of the disease. It is suggested that breast cancer is composed of several epidemiologic sub-entities determined by such factors as familial aggregation, histology and hormone profile.


Cellular composition of the nipple aspirate specimen of breast fluid. II. Abnormal findings. Studies of cellular findings in nipple aspirate specimens from 796 women revealed 50 women with abnormal cells and/or microcalcifications. The clinical correlation of these abnormalities with breast cancer appears to be highly significant: abnormal cells were found in 50% of the satisfactory specimens from women who had breast cancer or who had had a previous mastectomy for breast cancer. Continued observation of the women for evidence of regression, persistence, or progression of the cytologic abnormalities is required to determine the significance of the abnormalities. Microcalcifications were present in nipple aspirates from 27% of the women whose mammograms were interpreted as showing calcification. The absence of mammographic confirmation of the cytologic findings of microcalcifications may be an indication for re-evaluation of the existing mammograms and repeat clinical and mammographic examination at more frequent intervals for early localization of small lesions.


Breast specimen radiography. Obligatory, adjuvant and investigative. The development of mammography and that of breast specimen radiography, which have paralleled one another, are reviewed. The preparation of radiographs of breast specimens is obligatory when biopsy is performed for purely mammographic indications and when no palpable mass is present. Such cases are being encountered with increasing frequency because of the development of centers for breast cancer screening. Close collaboration among pathologists, radiologists and surgeons and precise attention to procedural detail are necessities wherever this situation arises. The application of specimen radiography as a routine to all breast specimens is regarded as an adjunct to gross examination. While useful, its yield of otherwise undetected occult carcinoma is low. Whether other advantages outweigh the cost appears to be a matter for individual decision. Investigative uses of breast specimen radiography have received little attention. Some possible applications are suggested.


Staging in the therapy of cancer of the breast. Clinical and pathologic staging of breast cancer are discussed. A new pathologic staging system is presented: numerical scores are assigned, in cases of infiltrating ductal carcinoma of no specific subtype, for tumor size, histologic grade, amount of stromal infilttration, vascular invasion, axillary lymph nodal metastases, and sinus histiocytosis in axillary lymph nodes. Staging by this system correlates well with survival in cases treated by radical mastectomy. The essential features to be studied in pathologic specimens of breast cancer are also indicated.


Endocrinology in cancer of the breast. Status and prospects. Breast cancer is the result of a multistage carcinogenic process. Initiation, promotion, dependency and autonomy make up a sequence of experimentally distinguishable phases of this process. Progression--the transition from dependency on hormonal support to autonomy--is demonstrable clinically. High-affinity saturatable estrogen binding by breast cancer cytosols distinguishes endocrine-responsive mammary neoplasms from autonomous breast cancers. Approximately 70% of neoplasms containing estrogen-recepor protein at a level of 2.5 femtomoles per mg. protein or higher regress after endocrine ablation (ovariectomy in premenopausal women; adrenalectomy or hypophysectomy in postmenopausal women). Only about 5% of neoplasms lacking the receptor will respond to these maneuvers. Estrogen-receptor content also predicts clinically for estrogen and androgen responsiveness, and experimentally for prolactin dependency. Fifty per cent of primary breast cancers in women are receptor-positive. Normal breast tissue and benign breast lesions characteristically lack receptor protein. The receptor proteins appear to be induced in neoplastic cells during mammary carcinogenesis in endocrinologic settings where non-cancerous breast cells do not contain free receptor in large amounts and fail to manifest endocrinologic growth stimulation. Implications of these findings for endocrinologic management of disseminated mammary cancer, adjuvant therapy, and breast cancer prevention are discussed.


Primary hypothyroidism. Differentiation from primary hypopituitarism. Five patients with growth failure but few other abnormal clinical signs are presented. Two were shown to have primary hypopituitarism, three had primary hypothyroidism. All received levothyroxine sodium and grew 7.0 to 12.5 cm during the first year and 6.2 to 8.7 cm during the second year of treatment. Three of the adolescent patients developed signs of signs of puberty within six to nine months of initiation of levothyroxine therapy. One hypopituitary patient had femoral epiphysial dysgenesis, hypopglycemia, and undescended testes. One hypothyroid patient had been treated for diabetes mellitus for 8.5 years and may be the youngest patient reported with such a disease combination. We conclude that in a few patients with growth failure without specific clinical signs, diagnosis and differentiation between primary hypothyroidism and primary hypopituitarism can only be made by specific endocrinologic testing.


Prostaglandin E in cholera toxin-induced intestinal secretion. Lack of an intermediary role. Prostaglandin E1 (PGE1) and cholera enterotoxin stimulate small-intestine mucosal adenylate cyclase and intestinal secretion of water and electrolytes. The previous suggestion that PGE may mediate cholera-toxin effects was explored in these studies. Closed rabbit jejunal loops were injected in vivo with cholera toxin and compared to similar loops in the same animal injected with buffer. Loop mucosal homogenates and intestinal secretions were analyzed by radioimmunoassay for cAMP and PGE concentrations. Cholera toxin produced significant increases in mucosal and intestinal fluid cAMP; however, there were no significant increases in PGE in the toxin-treated loops when compared to the control loops. In addition, there was no correlation between cAMP and PGE in the same samples. These studies indicate that cholera toxin stimulates intestinal cAMP anc secretion independent of PGE synthesis and provide evidence against a specific role for PGE in mediating cholera-toxin effects.


Evaluation of a measles-smallpox vaccination campaign by a sero-epidemiologic method. An assessment technique has been devised whereby children from 30 randomly chosen sampling sites are visited within three days of measles-smallpox vaccination and one month later. Vaccination coverage is measured at house visits and immunologic status is determined by collection of early and late blood samples on filter papers from substratified children in priority age-groups, and by looking at vaccination scars. The methodology was employed in a rural area of the Ivory Coast during the maintenance phase of a measles-smallpox vaccination program; 1762 children from 0--72 months old were inspected. Children in the target age groups, 6--24 months, had a vaccination coverage of 53.6% whereas children outside of the target group had a 10.5% coverage. Of 571 target age children, 94.6% had a measles hemagglutination-inhibition antibody titer of less than 1:10 dilution at the first visit, and were presumed susceptible to measles or vaccine. Of 247 substratified children 6--8 months, 98.3% were susceptible to measles before vaccination; 84.3% of 127 vaccinated children in this age-group sero-converted when re-tested. Of 324 children 9--24 months, 91.7% were susceptible before the campaign; 94.7% of 170 vaccinated children in this age-group converted. A positive history of prior measles or prior measles-vaccination was not a good indicator of measles serologic status. The smallpox vaccination major reaction rate was 93.2%; 91.4% of children with a recent vaccination scar sero-converted to measles vaccine. Thus, the smallpox scar read at the second visit proved the best clinical marker for determining both coverage and immunologic effectiveness of the campaign.


Human erythrocyte galactokinase and galactose-1-phosphate uridylyltransferase: a population survey. Erythrocyte (RBC) galactokinase (GALK) and galactose-1-phosphate uridylyl-transferase (GALT) activities were measured in a random sample of 1,700 (1.082 black and 618 white) pregnant women from the Philadelphia area to estimate the frequency of the genes GALKG and GALTG responsible for the two biochemically distinct forms of galactosemia. Blacks have significantly lower mean RBC GALK activities than whites (P less than .0005). The distribution of individual GALK activities for blacks differs from a normal distribution (X227=43.0, P less than .03) whereas that for whites does not (X224=25.5, P approximately equal to .30). These results are consistent with the thesis that reduced RBC GALK activity in blacks is due to the Philadelphia variant (GALKP), which is common in blacks and rare in whites. The frequency of heterozygotes (GALKG/GALKA, GALKG/GALKP) for GALK galactosemia observed in this sample is 1/340 for the total, 1/347 for blacks, and 1/309 for whites. The existence of the GALKP variant allele has been considered in this determination. However, because a method for distinguishing the GALKP and GALKG alleles became available only in the latter part of the study, the frequency of the GALK G allele in the black population may be underestimated. The mean RBC GALT activity for blacks is higher than that for whites, a difference that may be due to a higher frequency of the Duarte variant allele GALTD in whites. Heterozygotes (GALTG/GALTA) for GALT galactosemia were distinguished by family studies and starch gel electrophoresis from individuals who have half-normal RBC GALT activity due to the GALTD allele. The GALTG/GALTA frequency is 1/212 for the total, 1/217 for blacks, and 1/206 for whites. Of the 1,700 individuals surveyed three had atypically high RBC GALK activity, similar to that found in red blood cells of newborns.


Galactose tolerance studies of individuals with reduced galactose pathway activity. The galactose tolerance of individuals with mutant genotypes affecting the activities of galactokinase (GALK) and galactose-1-phosphate uridylyltransferase (GALT) was examined. Genotypes studied were heterozygotes for the GALK and GALT forms of galactosemia, the Duarte-variant GALT, and Philadelphia-variant GALK alleles. The measurements used were urinary concentration of galactose during pregnancy in adults and in infants from the newborn period through the first 5 months of life; the rate of elimination of an intravenous infusion of galactose; and slit-lamp examination of the lens for evidence of cataracts. No unusual urinary excretions of galactose were noted in any of the age groups studied. Intravenous galactose tolerance tests were normal in all but two women, a mother and daughter heterozygous for the GALK-deficient form of galactosemia (GALKG/GALKA). Six other GALKG/GALKA subjects had normal tolerance studies. The intrafamilial consistency and interfamilial differences in the galactose tolerance of GALKG/GALKA individuals suggest heterogeneity of the genes responsible for the GALK-deficient form of galactosemia. Although subclinical cataracts were observed in several individuals, their significance relative to the mutant genotype cannot be resolved with the available data.


Evaluation of a possible sex difference in recombination for the ABO-AK linkage. Thirty-five informative families were scored for linkage between the ABO and AK loci. The recombination fractions were estimated separately in females and males and were compared with values reported in the literature. A 1.33:1 ratio for the female:male recombination fraction was obtained by combining all sources, but the difference between the recombination fractions was not significantly different from zero. The present data, combined with those reported earlier, show that the most likely recombination fraction is about 14%.


Determination of estrogens in pregnancy urine by hemoagglutination inhibition reaction. A simple and rapid hemoagglutination inhibition reaction system for the estimation of estrogens in pregnancy urine is described. Results obtained by this method showed a good correlation with those measure by a conventional radioimmunoassay method and Brown's colorimetric method. Ninety-seven pregnancy urine samples from various gestational weeks were subjected to the assay, and the usefulness of this method as a screening test for high-risk pregnancy is discussed.


The ultrastructural response of human endometrium to medroxyprogesterone acetate. Medroxyprogesterone acetate is a steroid compound similar to progesterone in structure and function. Thirty women were given 150 mg. of medroxyprogesterone intramuscularly, and samples of the endometrium were examined by light and electron microscopy. The initial response of normal human endometrium was maturation and then inhibition. By 50 days after injection, the atrophic changes began to reverse, and by Day 90, after injection the tissue resembled normal proliferative endometrium. A previously undescribed nuclear inclusion body is present; however, its significance is unclear at this time. On the basis of ultrastructural changes, medroxyprogesterone appeared not to exert a significant influence on the endometrium past 90 days at this dosage.


Acute posterior multifocal placoid pigment epitheliopathy associated with an adenovirus type 5 infection. A 19-year-old black man with acute posterior multifocal placoid pigment epitheliopathy had concurrent positive viral cultures and rising antibodies to adenovirus type 5. This finding, considered together with earlier reports of viral-like syndromes accompanying the disease, supports the implication of a respiratory virus as a possible etiologic factor.


Interaction of anabolic steroids with glucocorticoid receptor sites in rat muscle cytosol. While glucocorticoid hormones act catabolically on skeletal muscle through their binding to glucocorticoid-specific receptors in the cytosol, androgens exert anabolic responses but no androgen-specific binding proteins could be detected in this responsive tissue. However, various nonradioactive androgens were effective in displacing labeled dexamethasone or cortisol from their respective cytoplasmic receptors in muscle, both in vitro and in vivo. The inhibition of glucocorticoid binding by androgens is competitive, and could be observed following a single or repeated administration of the androgens to adrenalectomized-castrated animals. The synthetic androgen fluoxymesterone and the hormone testosterone displayed Ki values of 7.5 X 10(-6) M and 1 X 10(-5) M, respectively, for the inhibition of [3H]dexamethasone binding in muscle cytosol. On the basis of competition experiments it is postulated that interaction of androgens with glucocorticoid receptors prevents the binding of glucocorticoids and might be responsible in part for the anabolic effects of pharmacologic doses of androgens in muscle.


Renal cyclic AMP accumulation and adenulate cyclase stimulation by erythropoietic agents. The regional distribution of cyclic AMP in the kidney was determined following erythropoietic stimulation with hypoxia and cobalt. Following these stimuli, increases in renal cyclic AMP concentrations were restricted to the cortex. The basis for this localization in the case of cobalt treatment was found to reside in the stimulation of renal cortical adenylate cyclase activity in vitro by concentrations of cobalt similar to those found in vivo. The level of cobalt in the cortex after cobalt treatment was found to approach 500 mumol/kg of tissue, whereas no detectable levels of cobalt were found in the renal medulla. Additionally, other agents such as parathyroid hormone and lactic acid, that are known to lack stimulatory effects on medullary adenylate cyclase, were found to stimulate the cortical enzyme. This stimulation of renal cortical adenylate cyclase correlates with enhanced erythropoiesis as demonstrated by increased radiolabeled iron incorporation into erythrocytes. These results support previous reports which suggest that renal cortical cyclic AMP mediates erythropoietin production in response to erythropoietically active agents.


Alpha-Glycerol phosphatase and glycerol kinase activities in tissues of the silkmoth Hyalophora cecropia during the larval-pupal transformation. Magnesium metabolism has been studied in Hyalophora cecropia during the larval-pupal transformation (LPT) (Jungreis, A. M., Am. J. Physiol. 224: 27--30, 1973). Throughout this period, it accumulated in midgut (0.5 M at ecdysis), presumably as osmotically inactive Mg3(PO4)2. Glycerol accumulation in hemolymph was also first noted during this period. Since total alpha-glycerol phosphate present in hemolymph declined between the larval and pupal stages of development, the relationship between magnesium and alpha-glycerol phosphate metabolism was studied. Specific and total alpha-glycerol phosphatase (degradative) and glycerol kinase (synthetic) enzyme activities were measured in fat-body and midgut tissue throughout the LPT. At both feeding larval and diapause pupal stages in development in both tissues, total glycerol kinase activity is greater than that of alpha-glycerol phosphatase with degradative/synthetic activity ratios of 0.2--0.5. In fat body, ratios remained constant or shifted in the direction of synthesis during the LPT, whereas those measured in midgut tissue increased in the direction of degradation with a maximum ratio of 5.8 noted following spinning. The increase in degradative/synthetic activity ratios in midgut tissue is attributed to a greater rate of loss of glycerol kinase than alpha-glycerol phosphatase enzyme activity. Orthophosphate, presumably released from alpha-glycerol phosphate within the cells of the pharate pupal midgut tissue, combines with magnesium to form osmotically inactive Mg3(PO4)2 crystals.


Corticosteroids and ACTH are not required for compensatory adrenal growth. We have tested the hypothesis that unilateral adrenalectomy results in decreased glucocorticoid secretion, reflexly elevated ACTH secretion, and consequently, compensatory adrenal growth. Plasma ACTH and corticosterone and right adrenal weight were measured during the first 10 days after left adrenalectomy or sham adrenalectomy in young male rats. There is a decrease in plasma corticosterone after unilateral adrenalectomy compared to sham adrenalectomy that persists for 1 h. ACTH is elevated only at 2 h after unilateral adrenalectomy compared to shamoperated rats. Treatment with dexamethasone, shown to abolish the ACTH and corticosterone responses to laparotomy with intestinal traction, resulted in significantly increased adrenal weight after unilateral adrenalectomy by 6 h (wet or dry weight), and at 24 h. Compensatory adrenal growth also occurs after unilateral adrenalectomy in hypophysectomized rats (wet or dry weight). We conclude the compensatory adrenal growth after unilateral adrenalectomy requires neither a virtual decrease in circulating corticosterone levels nor elevated ACTH levels, and speculate that the phenomenon is neurally mediated.


Minimal deviation hepatoma. A new entity. The term minimal deviation hepatoma has been applied to a specific clinical, pathological, and angiographic entity. It is a tumor, composed of atypical cells, which is neither frankly malignant nor so well organized as a benigh tumor. This lesion occurs in females with otherwise normal livers and has a relatively benign course, although life threatening hemorrhage may occur. The diagnosis may be strongly suggested in the presence of hypervascularl or hypovascular discrete masses without evidence of frank malignancy, with a defect in the colloid liver scan and with normal liver function tests. Surgical resection when possible and aggressive chemotherapy may be corrective in many cases.


Percutaneous transhepatic cholangiography. Problems in interpretation. The patient who presents with jaundice, regardless of the etiology, cannot be adequately examined by a gallbladder series and intravenous cholangiography. Clinical evaluation aided by laboratory analysis will not always differentiate between primary liver parenchymal disease and biliary tract obstruction. Percutaneous transhepatic cholangiography, when successfully performed, answers the question of whether the jaundice is due to primary liver parenchymal disease or due to biliary tract obstruction. The point to emphasize is that under no circumstances is it appropriate to presume any information if the biliary system is not entered and visualized successfully. The proper interpretation of the level of block can fall prey to the mistake of incomplete aspiration of the thick, inspissated bile in the obstructed biliary tree before injection of contrast material. The problem will be worsened by a peripheral entrance into the biliary system rather than a more central one. Gastrointestinal series should always be available to aid in identifying pathology at the entrace of the common bile duct into the duodenum. Lastly, identifying the etiology at the site of the block will require additional procedures. Selective visceral angiography has contributed greatly in this area. During the 20 years of clinical usage of percutaneous transhepatic cholangiography, we feel it has become the single examination capable of preventing unnecessary exploration of the jaundiced patient with primary liver parenchymal disease and the most useful potential source of practical information if laparotomy is necessary to correct biliary tract obstruction.


Hepatic echography.

Hepatic echography. There are 2 kinds of echographic investigations: those which are only complementary and those which are specific by themselves. To improve this latter category, we would like to emphasize two useful echographic signs. First, the attenuation sign, which indicates the fibrotic nature, therefore practically speaking, the cirrhotic nature of a diffuse echogenic pattern. Secondly, the posterior echo accumulation sign, which indicates the liquid nature, and therefore in general the cystic nature of a localized sonolucent pattern.


Compensatory renal hypertrophy after treatment for Wilms' tumor. In children who undergo nephrectomy for Wilms' tumor, compensatory renal hypertrophy occurs rapidly despite concomitant irradiation and chemotherapy. Review of preoperative and postoperative intravenous pyelograms of 21 children showed all to have significant enlargement of the remaining kidney. Sixty-five per cent renal hypertrophy occurred during the first 2 months after nephrectomy; by 11 months, renal hypertrophy is complete and renal growth is no longer accelerated.


A new concept in the measurement of neuromuscular transmission and block. The discovery of the safety margin of neuromuscular transmission has brought forth the requirement for an improvement in the clinical examination of curarization, since the safety margin, i.e. the reserves, should also be measured. For this purpose a peripheral nerve stimulator and an electromechanical recorder unit have been produced, suitable for both the examination of manifest curarization and of the neuromuscular reserves. The measurements of muscle relaxation are performed making use of 30 Hz stimulation, while the safety margin of neuromuscular transmission is measured using stimulation at 200 Hz one.


Equine serum lipids: serum lipoprotein profiles of Morgan and Thoroughbred horses. The serum of lipoproteins of 10 Morgan and 8 Thoroughbred horses were examined by 2 methods of polyacrylamide gel electrophoresis. A significant breed difference in the beta-lipoprotein to alpha-lipoprotein ratio was seen in gradient slab electrophoresis. A breed difference in the number of peaks, but no difference in beta-lipoprotein to alpha-lipoprotein ratio, was found in disc gel electrophoresis. These results have been correlated to indicate differences in charge of alpha-lipoprotein components and in size of beta-lipoprotein components between these 2 breeds of horses.


Equine serum lipids: lipid composition and electrophoretic mobility of equine serum lipoprotein fractions. The serum lipoprotein fractions from 5 Morgan and 5 Thoroughbred horses were isolated by preparative ultracentrifugation, chemically analyzed for lipid composition, and studied by 2 methods of polyacrylamide gel electrophoresis to determine electrophoretic mobility. Breed differences were not seen in the relative percentages of the lipid classes found in the various fractions. Normally, horses, like most animals, carry the majority of their lipid in high-density lipoproteins. Electrophoretically, the only difference seen between breeds occurred on disc electrophoresis where the extra band, which is characteristic of lipoprotein profiles of Morgans, was found in the high-density lipoprotein fraction.


Pathogenicity of a caprine herpesvirus.

Pathogenicity of a caprine herpesvirus. A herpesvirus isolated from neonatal Angora kids (Capra hircus) with a relatively severe generalized infection was shown to be infective for adult goats as well as for kids. However, the virus lacked pathogenicity for either lambs or calves. Although a nonreciprocating serologic overlap exists between the caprine virus and the antibody to bovine herpesvirus (BHV-1), results of cross immunity tests in calves indicated that the 2 viruses are immunologically distinct. On the basis of these findings, the caprine virus seems to be a specific pathogen of goats. Accordingly, the designation of Herpesvirus caprae or caprine herpesvirus 1 seems taxonomically appropriate.


[Peripheral neuropathies i- Waldenstrom's disease. Histological and ultrastructural studies of 5 cases]. In four cases it was the existence of peripheral neuropathy which led to the discovery of macroglobulinemia within an interval from 1 to 11 years. The treatment of the disease also markedly improved the peripheral neuropathy in three cases. Two patients died. Two of the biopsies of the peripheral nerve showed infiltration by atypical lymphocytes. Ultrastructural changes in the five cases were variable. Marked axonal involvement in the two cases with cellular infiltration. In one of these two cases it was combined with segmental demyelinization. This lesion was clearly predominant in the three other cases. In one of them demyelinization occurred in a very peculiar way with dilation of the internal part of the mesaxone going on in the most peripheral layers of the myelin. Discussion of the mechanisms of the involvement of the peripheral nervous parenchyma in Waldenström's disease. Cellular infiltrations, amorphous deposits, changes in the capillaries and macroglobuline may occur.


Synthesis of fibroma viral deoxyribonucleic acid complexes in rabbit kidney cells. Cytoplasmic extracts of primary rabbit kidney cells inoculated with fibroma virus revealed 2 peaks of DNA complexes (120S and greater than or equal to 410S) in a linear sucrose gradient. Pulse-chase experiments demonstrated a shift in the gradient profile of lighter complexes toward heavier complexes. Synthesis of DNA complexes was inhibited by adding puromycin or actinomycin D. The DNA from virus-infected cultures hybridized 7 to 9 times greater with fibroma virus DNA than did the DNA from noninfected cultuures. The DNA complexes became increasingly resistant to deoxyribonuclease digestion as a function of time during viral growth cycle and produced tumors in rabbits.


Angiographic assessment of resectability in primary hepatic carcinoma. The nature of primary hepatic malignancy and the magnitude of operative procedures for treatment dictate that hepatic resection be carried out only when there is the chance of cure. Following resection, a sufficient amount of liver with an intact afferent and efferent vascular system must remain to sustain life. Complete hepatic angiographic evaluation by arteriography, inferior vena cavography, hepatic venography and portal venography provides valuable information about extent of tumor involvement and the anticipated hepatic remnant. Complete preoperative knowledge of hepatic vascular anatomy should permit better selection of patients for potentially curative resection and avoid operation in patients with incurable tumors.


Diagnostic error in breast disease.

Diagnostic error in breast disease. Fifty-six breast biopsies, incorrectly assessed by preoperative clinical or mammographic examination, were reviewed to define the characteristics in the tumor or patient that caused the clinician and mammographer to be diagnostically inaccurate. The most important patient characteristic associated with error was the use of hormones. Failure to recognize that oral contraceptive use significantly reduces the incidience of benign breast disease contributed to the frequent misdiagnosis of lesions in those patients. Twelve of 16 masses in oral contraceptive users were malignant. In seven, their resemblance to cysts or fibroadenomas resulted in treatment delay of two weeks or 18 months. Because benign disease is uncommon in women who have used contraceptives two or more years, all new lesions in those women should be studied by biopsy promptly. Neither clinical nor mammographic evaluation of lesions in postmenopausal women who used estrogens was accurate. Twelve postmenopausal patients with carcinoma had used estrogens. Three of these lesions were considered benign clinically and four, by mammogram. In one, treatment was delayed four years. In women over 50 not using hormones, clinical diagnosis of malignancy was accurate. Ten carcinomas in those women were missed by mammogram. Eight had negative nodes; thus a negative mamogram when the clinical diagnosis is correct may be an effective guide in predicting the status of axillary nodes. Paget's disease was not recognized clinically in two of eight patients with that disease, and an additional two were not recognized on mammography. The initial examiner did not identify three of six inflammatory carcinomas. Ten percent of benign lesions were intraductal hyperplasia or papillomatosis with atypia and were the benign lesions most often misdiagnosed clinically and by mammogram. No microscopic lesions were noted on mammography without an associated palpable mass. Twenty-five per cent of the lesions in women aged 40-49 were incorrectly assessed by mammography or clinical examination. Four (15%) of the 27 carcinomas in this age group were not recognized by either modality. Mammography helped delineate the characteristics of masses in premenopausal women. With recognition that any mass that appears in a woman using oral contraceptives must be studied by biopsy, combined clinical and mammographic study in primenopausal women should minimize diagnostic error. Unfortunately, neither clinical nor mammographic evaluation of the women with irregular periods approaching menopause or within three years past menopause is accurate. It is in that age group that new diagnostic modalities are needed and when reported their efficacy in that age group should be stressed.


Foodhandler-associated outbreak of hepatitis type A. An immune electron microscopic study. Immune electron microscopy, which can detect hepatitis A antigen and antibody (anti-HA), was used to study a foodhandler-associated outbreak of hepatitis among 136 naval recruits. In stool specimens collected during the acute phase of illness, 27-nm viruslike hapatitis A antigen particles were shown, but only in patients with icteric hepatitis. Detection was possible in stools collected as early as 10 days before peak serum aminotransferase activity and up to the time of peak enzyme activity, but not thereafter. The immunologic similarity of these viruslike particles to those found in acute phase stools of volunteers inoculated with the MS-1 strain of hepatitis A virus was determined, and an increase in anti-HA was shown between acute and convalescent serums from 25 of the recruits. These data support the view that the MS-1 strain of hepatitis A virus is serologically related to naturally acquired type A hepatitis.


Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion. We have studied the effects of demeclocycline on the water metabolism of a patient with the syndrome of inappropriate antidiuretic hormone (ADH) secretion who presented with a serum sodium concentration of 110 meq/litre. Free water clearance was studied before, during, and after treatment with demeclocycline. This study shows that demeclocycline (900 mg/day) can at least partially inhibit the action of ADH in the setting of tumor-induced ADH secretion, with the production of a reversible, partial nephrogenic diabetes insipidus, and with few or no side effects. Demeclocycline may be useful in the treatment of chronic inappropriate ADH secretion.


Islet cell carcinoma, pancreatic cholera, and vasoactive intestinal peptide. Three patients with profuse diarrhea, hypokalemia, metastatic nonbeta islet cell carcinoma, and the absence of gastric hypersecretion were found to have elevated levels of vasoactive intestinal peptide. One patient also had elevated serum gastrin levels. Two patients experienced prolonged remissions of diarrhea after operations in which only tumor biopsies were done. These cases further implicate vasoactive intestinal peptide as the agent mediating the diarrhea in the syndrome of pancreatic cholera.


[Studies on the conidial differentiation of "Neurospora crassa" VI.--Functional anomalies of the conditional aconidial mutant "amycelial" (author's transl)]. Studies using the morphological mutant "amycelial"--a conditional, aconidial strain of N. crassa--have revealed certain consistent functional and biochemical differences from wild type strains showing normal morphology and conidia formation. Thus it was found that the mutant strain showed an abnormal utilization of protein reserves at a time when there is extensive degradation during conidiogenesis in wild type. In addition, the mutant exhibited abnormally low oxygen consumption and free amino acid pools depressed nearly 3/4 with respect to wild type. All of these findings are consistent with earlier work linking conidiogenesis to aerobic oxidative processes and suggest that catabolic reactions particularly regarding protein breakdown may be important to conidiogenesis from the standpoint of the synthesis of new conidial proteins and for the supply of endogenous energy reserves during the process. The aconidial character of "amycelial" could be partially alleviated on solid acetate medium supplemented with amino acids, especially tryptophan or histidine. Conidiation was also induced by cyclic-AMP, even on sucrose medium. A polymer strongly antigenic in rabbits was found to be released into growth medium by the mutant but not by wild type cultures, providing a possible clue to the immediate cause of the abnormal morphology seen in "amycelial". This substance appears to be a glycopeptide containing a few hexoses and amino acids associated with polyphosphate.


Effect of steroidogenesis on ascorbic acid content and uptake in isolated adrenal cells. Isolated adrenal cell preparation was used to investigate the relationship between ascorbic acid and steroidogenesis by two methods: (1) in vivo incorporation of exogenous [1-14C]ascorbic acid into endogenous ascorbic acid of adrenal by intraperitoneal injection of labeled ascorbic acid into rats and studying the depletion of labeled ascorbic acid under a variety of experimental conditions; and (2) study of the uptake of [14C]ascorbic acid by IAC in response to steroidogenic stimuli and various steroids. These studies demonstrate that: 1. IAC preparation by the trypsin digestion method results in almost total depletion of ascorbic acid from adrenal cells, i.e., ascorbic acid content of the cell preparation was less than 1% of the original ascorbic acid in quartered adrenal gland. 2. In spite of such a severe depletion of ascorbic acid, steroidogenesis in response to ACTH and dibutyryl cyclic AMP (dcAMP) is quite pronounced. 3. ACTH and dcAMP affect depletion of endogenously labeled ascorbic acid in IAC by a process that is both concentration- and time-dependent, but is independent of steroidogenic processes. 4. ACTH and dcAMP both inhibit the uptake of exogenous [1-14C]ascorbic acid, which is time-dependent but independent of the steroidogenic phenomenon. 5. The uptake of [14C]ascorbic acid by IAC is independent of extra-to-intracellular gradient of glucocorticoids or mineralocorticoids.


Immunodeficiency to hepatitis B virus infection and genetic susceptibility to development of hepatocellular carcinoma. The high frequency of hepatitis B antigen (HBsAg) in hepatocellular carcinoma (HCC) patients has led to the hypothesis that immunoresponsiveness to hepatitis B virus (HBV) may be deficient in some patients, and that the immune response deficiency may have a genetic basis. Radioelectrocomplexing (REC), a radioimmunoassay in gel based on the principle of counterimmunoelectrophoresis (CIE), has been used to identify four HBV immune status subgroups: 1) HBsAg +ve/HBsAb +ve; 2) HBsAg +ve/HBsAb -ve; 3) HBsAb -ve/HBsAb +ve; 4) HBsAg -ve/HBsAb -ve/HBsAb -ve. These subgroups comprise 2, 6, 70, and 22 percent, respectively, among blood donors, and 32, 19, 23, and 26 percent, respectively, among HCC patients. Although the HBV exposure rates in the two groups were similar, the immune complexemic rates and HBs antigenemic rates were significantly higher in HBB patients than in the blood donors. It is proposed that the failure of termination of HBV infection revealed by these high rates reflects an immunodeficiency state characterized by an inability to produce high-avidity HBsAb. The immunodeficiency might have a primary genetic basis, or it might be secondary to the immunodepressive effects of concurrent viral or parasitic infections.


Carcinofetal alterations in glycogen phosphorylase isozymes in rat hepatomas. As part of a continuing study on the loss or retention of enzymes involved in specific hepatic functions in a series of rat liver neoplasms ranging widely in growth rate and degree of differentiation, isozyme patterns of glycogen phosphorylase in rat hepatomas were compared with those in rat tissues during development. A third phosphorylase isozyme, distinguishable kinetically, immunologically, electrophoretically, and by isoelectric focusing from liver and muscle types is commonly present in various rat hepatomas including Novikoff, Morris, and Yoshida hepatomas with various degrees of retention of liver type according to their degree of differentiation. This isozyme is also the sole type in the placenta and early embryo, and in liver and muscle is replaced with the organ specific liver and muscle types during development. In other organs, the replacement is only partial, and, especially in adult rat brain, this type is retained. Thus, this isozyme seems to be a prototype whose appearance in hepatomas is one of many examples of carcinofetal alterations in isozymes.


Preoperative embolization of juvenile angiofibromas of the nasopharynx. The juvenile nasopharyngeal angiofibroma is a vascular tumor. Careful and complete removal is challenging because of the brisk bleeding during surgery. The means applied to reduce this blood loss have included preoperative estrogens, ligation of feeding vessels, silicone embolization of feeding vessels, and cryosurgery. We have used preoperative Gelfoam embolization of the internal maxillary artery in seven patients. Our clinical impression of significant reduction in loss of blood was confirmed by comparison with 16 previous patients. The average amount of blood lost in the embolized group was half that of the control group. A study of this type comprises many variables; however, the results do suggest that preoperative embolization of the internal maxillary artery is of advantage in the surgical treatment of juvenile angiofibromas.


Differential effects of oxygen and oxidation-reduction potential on the multiplication of three species of anaerobic intestinal bacteria. The sensitivity of three strains of anaerobic intestinal bacteria, Clostridium perfringens, Bacteroides fragilis, and Peptococcus magnus, to the differential effects of oxygen and adverse oxidation-reduction potential was measured. The multiplication of the three organisms was inhibited in the presence of oxygen whether the medium was at a negative oxidation-reduction potential (Eh of -50 mV), poised by the intermittent addition of dithiothreitol, or at a positive oxidation-reduction potential (Eh of near +500 mV). However, when these organisms were cultured in the presence of oxygen, no inhibition was observed, even when the oxidation-reduction potential was maintained at an average Eh of +325 mV by the addition of potassium ferricyanide. When the cultures were aerated, the growth patterns of the three organisms demonstrated different sensitivities to oxygen. P. magnus was found to be the most sensitive. After 2 h of aerobic incubation, no viable organisms could be detected. B. fragilis was intermediately sensitive to oxygen with no viable organisms detected after 5 h of aerobic incubation. C. perfringens was the least sensitive. Under conditions of aerobic incubation, viable organisms survived for 10 h. During the experiments with Clostridium, no spores were observed by spore staining.


Carcinoma of the nasopharynx in children. Seven children with carcinoma of the nasopharynx have been treated and followed for five years. In this group of patients there were no cranial nerve palsies or radiographic evidence of destruction of the base of the skull. Four of the seven patients are living and well. The development of lymphoepithelioma in two siblings is of great interest from an environmental and genetic point of view. The older sibling developed the clinical manifestations of the tumor at 12 years of age and four years later the younger sibling developed them at 14 years of age. The possible etiologic relationship of carcinoma of the nasopharynx to the Epstein-Barr virus is discussed. The good survival rate in these patients under 21 years of age suggests that the prognosis in carcinoma of the nasopharynx is better in the younger age group than in adults. The management of these patients illustrates that carcinoma of the nasopharynx should be managed as a regional rather than a systemic disease. Systemic drug therapy is sometimes advocated because of confusion over the name lymphoepithelioma on the assumption that these tumors are more related to lymphomas and lymphosarcomas than carcinomas. It is clear that lymphoepitheliomas should be managed as carcinomas.