Effects of adrenaline and methylisobutylxanthine on adenosine 3':5'-monophosphate levels in cultures of beating heart cells of the newborn rat. (-)-Adrenaline caused concentration-dependent increases in cAMP levels and the rate of beating in eight-day-old heart cell cultures of newborn rats. Half-maximal increases in both parameters (5- and 0.2 -fold, respectively) occurred at about 10(-6)M. Following the addition of 3 X 10(-7) M adrenaline, the cellular cAMP level rose to a max imum in 30 sec. The rise was abolished by 5 X 10(-8) M (-)-propranolol and was greatly magnified by 10(-4) M 1-methyl-3-isobutylxanthine. In the presence of the latter compound, the average rate of accumulation of cAMP in thecultures during the first 10 seconds of exposure to 3 X 10(-7) M adrenaline was 8.78 pmol/mg of protein-sec, which is 230 times more rapid than the basal accumulation rate. These findings may be taken as evidence in support of the view that cAMP is involved in the positive chronotropic action of adrenaline on cardiac pacemaker cells.


The effect of the reciprocal relationship of Ca2+ and cAMP on the control of beating in cultured rat heart cells. The demonstration of Ca2+ control of the cAMP level in heart cells and the localization of the Ca2+ activator protein of cAMP phosphodiesterase on the sarcoplasmic reticulum (SR) have led us to postulate a model whereby the Ca2+ flux is related to the cAMP flux. The model suggests that the increase in cytosol Ca2+ automatically results in an increase in SR Ca2+ and a subsequent decrease in cAMP to allow for the periodic flux of Ca2+ and cAMP in the contraction cycle.


cAMP activity and isoproterenol-induced myocardial injury in rats. Isoproterenol-induced myocardial necrosis (ISO-MN) was obviated by the cardioselective beta-blocker, practolol, suggesting that ISO-MN is caused by specific activation of myocardial beta-adrenergic receptors. Because cAMP is the "second messenger" in such activation, enhanced activity of cAMP should aggravate ISO-MN. Pretreatment of rats with bretylium in various amounts, elicited no ill effects but enhanced the effects of ISO on the cAMP activity and also intensified the ISO-induced structural changes in the myocardium.


Arteriography of the hand.

Arteriography of the hand. Eight cases of vascular lesions of the hand are presented to demonstrate the value of arteriography in these entities. Arteriography provides a valuable tool not only to establish a diagnosis but also for the preoperative planning of repair of injuried vessels in the hand.


Cardiomyopathy in vitro.

Cardiomyopathy in vitro. Phase contrast microscopy of cultured embryonic heart cells showed the beating frequency decreased more rapidly and the regularity the rhythm of of the beating cells was lost sooner in heart cells from cardiomyopathic hamsters than from the control hamsters. Studies of cultured heart cells by differential interference contrast (with Nomarski's prism) and by electron microscopy revealed a significant impediment in the maturation of the sarcomeric units in the diseased animals compared to controls. The incorporation of [14C] leucine into acid-insoluble fractions was studied, and no significant difference in incorporation between the two groups was found. An analysis of polyacrylamide gel electrophoresis revealed the possible existence of a quantitative difference in one of the composing proteins of the erythrocyte membrane between the two groups. The protein kinase activity of ghosts from the control group was more sensitive to cAMP than that from the diseased animals. In addition, the binding of [3H] cAMP to the ghost was almost identical between the two. The morphological and biochemical observations lead one to the plausible supposition that there are some differences in the interaction of the so-called catalytic and regulatory subunits between the two groups and that there is an impairment of the higher arrangement of myofibrils from their building blocks in the diseased hamster. The significance of the existence of abundant corpuscles resembling neurosecretory granules was not established by this study. They may have an etiological significance or they may be related to a disturbed function in the cultured cells of the cardiomyopathic hamster.


Electron microscopic cytochemistry of cytochrome oxidase activity in the conduction system of the canine heart. Histochemistry and electron microscopic cytochemistry of cytochrome oxidase in the conduction system were studied with the 3,3'-diaminobenzidine (DAB) method in adult canine hearts. This enzyme was distinctly less active in the entire conduction system than in the working myocardium. By electron microscopy, enzymatic activity per cristal membrane was apparently similar in both specialized and working cardiocytes. However, the volume fraction of cell occupied by mitochondria and the density of cristal membranes in mitochondria were smaller in the specialized cells in the sinus node, atrioventricular (AV) node, His bundle, and Purkinje fibers. These observations define the nature of decreased histochemical activity of cytochrome oxidase in cells of the conduction system, which is caused entirely by the decrease in activity per unit of mitochondrial volume and unit of cell volume in the specialized cardiac tissues.


Characterization of high density lipoproteins in human cholestasis. High density lipoproteins (HDL) of plasma from patients with long-standing cholestasis were studied by several methods including crossed immunoelectrophoresis, gel filtration, and zonal ultracentrifugation. The crossed immunoelectrophoretic pattern against anti-HDL was characterized by the presence of several immunoprecipitates, in striking contrast to the pattern formed by normal HDL. One of these precipitates corresponded to a lipoprotein species dominated by apoprotein A-II (apo A-II). Zonal ultracentrifugation of cholestatic plasma showed a decrease of HDL and a disappearance of the normal delineation of HDL2 and HDL3. In addition a new component designated HDL1-C was observed. Consistent results were found at studies of the molecular size distribution of cholestatic HDL by gel filtration on Sephadex G-200. The lipid and apoprotein composition of isolated cholestatic HDL fractions differed considerably from normal. Most notable were the high proportions of phospholipids and free cholesterol and the occurrence of the apoprotein E (arginine-rich protein) in remarkably high amounts especially in the abnormal HDL1-C.


Complement-dependent cytotoxicity against hepatoma cells mediated by IgM antibodies in serum from tumor-bearing rats. Complement-dependent cytotoxic antibodies in syngeneic serum from rats carrying transplanted aminoazo dye-induced hepatomas (D23 and D33) and from rats immunized with irradiated tumor cell or homogenates were studied by a short-term 51Cr release assay. The tumor-bearer sera (TBS) were subjected to chromatography on unsolubilized protein A and Sepharose 4B. The cytolytic activity of D23 TBS was recovered in the IgM molecular weight region, whereas no such activity was obtained in the IgG fraction. As judged from immunodiffusion experiments, the IgM molecular weight fraction did not contain any aggregated or complexed IgG. Moreover, in immunofluorescence tests against viable hepatoma cells, using a specific anti-rat IgG conjugate, the TBS were negative. Cross-testing of D23 and D33 TBS against the two hepatomas and cross-absorption of the sera with tumor plasma membranes revealed no tumor specificity in these cytotoxicity reactions. Furthermore, neither fetal nor early postnatal liver cells could absorb out the activity. Absorptions with adult liver plasma membranes, however, abrogated the cytotoxic activity, and even more effective in this respect were homogenates from kidney and small intestine, thus indicating that the cytotoxic antibodies are directed against 'normal' adult antigen(s) present also in tissues other than liver.


Cytochemistry--a tool in thyroid pathology. The authors studied the cytoenzymic pattern of various thyropathies. The highest enzymic activity was found in Graves' disease, especially for peroxidase, glucose-6-phosphate dehydrogenase and succinate dehydrogenase. Lactate dehydrogenase showed a great activity in thyroid cancer. The lowest activity was found in Hashimoto's thyroiditis with strong fibrosclerosis. The cytophotometrical data in form of histograms showed dextro-deviation of curves and plurimodal, irregular aspects of nuclear volumes and nucleic acid content in agreement with the cytological features of the investigated thyropathies. The linear regression analysis between the nuclear volumes and the nucleic acid content disclosed a diminished correlation in thyroid carcinoma and in euthyroid goitre.


Migration inhibition produced by sodium periodate oxidation of the macrophage membrane, and reversal by sodium borohydride. Guinea pig peritoneal exudate cells were harvested 3 to 4 days after the intraperitoneal injection of Marcol oil. The washed cells were exposed to various concentrations of sodium periodate in phosphate-buffered saline (PBS) at pH 7.4 for 10 min at +4 degrees C. The cells were then used in the in vitro migration assay, and migration was consistently inhibited at concentrations from 10(-3) to 10(-5) M. The viability of the macrophages was not affected by this treatment. Sodium borohydride (10(-3) to 10(-5) M) in PBS for 10 min at pH 7.4 reversed the periodate effect. Experiments with purified macrophages showed that sodium periodate has a direct effect on macrophage function rather than an indirect effect via the potentiation of migration inhibition factor. In support of this, the in vitro spreading of macrophages on glass substrate for 1 h has been shown to be inhibited. This spreading inhibition can also be reversed by treatment with sodium borohydride. These results provide a new approach to understanding the biological significance and role of macrophage migration inhibition.


The inhibitory effect of coli-endotoxin on alpha-adrenergic receptor functions in the lower urinary tract. An in vitro study in cats. The effects of endotoxin from E. coli 06 on alpha-adrenergic receptor functions have been investigated in muscle strips from the outlet region of the feline bladder. The endotoxin from this strain, known to cause urinary tract infections, inhibited the alpha-adrenergic contractions induced by phenylephrine and noradrenaline. This inhibition was dose-dependent, correlated to time of exposure, and reversible. Alpha-adrenergic receptor function in muscle strips from cat aorta was also inhibited, but not cholinergic stimulation of muscle segments from the bladder.


Adult nephroblastoma.

Adult nephroblastoma. A case of adult nephroblastoma in a 51-year-old woman is reported. A percutaneous aspiration biopsy did not lead to the right diagnosis presumably because the histologic structure of the tumour consisted exclusively of more or less differentiated epithelial-like elements, while mesenchymal tumour components were not demonstrated. It is concluded that this type of nephroblastoma, resembling a renal adenocarcinoma, should be borne in mind with a view to an optimal postoperative treatment.


Primary bronchial carcioma. An analysis of lung operations performed at Kolding hospital during the 10-year period 1965--1974. A clinical material consisting of 88 patients with primary bronchial carcinoma, treated at the Department of General Surgery, Kolding Hospital, during the 10-year period 1965--1974, is presented. It was possible to operate on 98% of the patients. Resection was performed in 76%: 75% as pneumonectomies and 25% as lobectomies. All the operations were performed by the same surgeon. The 5-year survival rates for the total number of patients were 19% during the period 1965--69 and 22% during the period 1970--74. The survival rates after resection were 26% and 28%, respectively, during the same periods. On the basis of the above-mentioned material and results, it may be concluded that an operation such as resection of the lung can be performed with the same degree of safety in operating theatres other than those of departments of thoracic surgery.


[Therapeutic results using VP 16-213 alone or in combination with 5-fluorouracil in liver cancer (hepatoma)]. The podophyllotoxin derivative VP 16-213 was used as monotherapy in 6 patients and combined with 5-fluorouracil in another 6. Of the 12 patients treated, 11 had measurable tumor criteria and 5 of these responded to treatment. These responses were attributed mainly to the effects of VP 16-213. Patients responding to chemotherapy lived significantly longer than non-responders. Each case of objective tumor response was accompanied by subjective improvement. In view of these results, a more active approach to the treatment of hepatocellular carcinoma would seem to be justified.


Assembly of type C oncornaviruses: a model. The salient features of this model for oncornavirus assembly are that uncleaved precursor molecules to the internal virus polypeptides possess specific recognition sites both for viral envelope constituents already inserted in the cell membrane and for the viral RNA. After orderly alignment of these components at the budding site, virus maturation proceeds through specific proteolytic cleavage of the precursor components and association of the resultant molecules into the characteristic type C virion substructures revealed by electron microscopy.


Intercellular communication in insect development is hormonally controlled. Cellular coupling in the insect epidermis changes in a characteristic way during metamorphosis. In vitro, beta-ecdysone mimics the initial phase of these changes by increasing electrical coupling. Both adenosine 3',5'-monophosphate (cyclic AMP) and Ca2+ reverse natural and beta-ecdysone-stimulated changes, which suggests that ecdysone could work on communication through changes in cyclic AMP and Ca2+ levels. The transient changes in intercellular communication before metamorphosis may reflect the timing of the signals that trigger proliferation and the generation of new spatial patterns in the epidermis.


Tricyclic antidepressants: therapeutic properties and affinity for alpha-noradrenergic receptor binding sites in the brain. Tricyclic antidepressants vary in their capacity to cause psychomotor activation, to relieve agitated depressive states, and to cause sedation and hypotension. We have quantified relative potencies of tricyclic antidepressants in competing for the binding of 3H-labeled WB-4101 to alpha-noradrenergic receptor sites in rat brain membranes. Affinities of tricyclic drugs for alpha-noradrenergic receptor sites in the brain correlate well with the capacity of these agents to relieve psychomotor agitation and to induce sedation and hypotension; these affinities also correlate inversely with tendencies to elicit psychomotor activation.


Intracellular analysis of trigeminal motoneuron activity during sleep in the cat. Intracellular recordings were made from trigeminal motoneurons of normally respiring, unanesthetized cats during naturally occurring sleep. The transition from quiet to active sleep was accompanied by tonic motoneuron hyperpolarization. Stimulation of the reticular formation induced a depolarizing potential in trigeminal motoneurons during quiet sleep and a hyperpolarizing potential during active sleep. The results provide a synaptic explanation for the phenomenon of reticular response reversal and insights into the basic mechanisms controlling motor activity during the sleep states.


Particle-mediated membrane uptake of chemical carcinogens studied by fluorescence spectroscopy. The fluorescence emissions of chrysene, N-ethylcarbazole, and 1,6-diphenylhexatriene undergo large spectral shifts or changes in quantum yield, or both, upon their uptake from particulates by phospholipid vesicles. This membrane uptake of carcinogen and carcinogen-like molecules by model membranes does not result in any disruption of the lipid bilayers. The fluorescence emission of chrysene, when bound to silica, was found to be sensitive to the surface density of chrysene on the silica. These observations demonstrate the feasibility of using fluorescence spectroscopy to measure the rates of exchange of carcinogens from particulate matter to cell membranes and to characterize the surface distribution of chemical carcinogens on particulate matter. Comparison of the uptake rate of chrysene from the unperturbed crystal state, sonicated crystals, and the silica-adsorbed state demonstrated that the last condition results in the most rapid transport of chrysene into model membranes. This information should prove valuable in understanding the cocarcinogenic effects of particulates and polynuclear aromatic hydrocarbons.


Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3',5'-monophosphate may be signal for "turnoff". Dispersed pinealocytes have been used to study the role of adenosine 3',5'-monophosphate (cyclic AMP) in the "turnoff" of N-acetyltransferace activity. Activity was first stimulated 100-fold by treating cells with 1-norepinephrine. 1-Propranolol acted stereospecifically to rapidly reverse this, resulting in a 70 percent loss of enzyme activity within 15 minutes. An even more rapid 1-propranolol-induced decreased in cyclic AMP also occurred. This together with the observation that the inhibitory effect of 1-propranolol on N-acetyltransferase was blocked by dibutyryl cyclic AMP and phosphodiesterase inhibitors indicate that an abrupt decrease in cyclic AMP may be the signal for the rapid decrease in pineal N-acetyltransferase activity.


Regulatory role of guanosine 3',5'-monophosphate in adrenocorticotropin hormone-induced steroidogenesis. The relation between steroidogenesis induced by adrenocorticotropic hormone and the concentrations of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) was studied at different time intervals in isolated adrenal cells. Submaximal and supramaximal steroidogenic concentrations of the hormone did not cause detectable changes in cyclic AMP during the first 30 minutes, whereas there was an increase in the concentration of cyclic GMP that was accompanied by phosphorylation and steroidogenesis. It is therefore suggested that cyclic GMP, rather than cyclic AMP, is the physiological mediator of adrenocorticotropic hormone-induced adrenal steroidogenesis.


Guanosine 3',5'-monophosphate: a central nervous system regulator of analgesia. The dibutyryl derivative of guanosine 3',5'-monophosphate (cyclic GMP), administered centrally, totally abolishes response to noxious stimuli without depressing the central nervous system. Analgesic properties of the nucleotide are not reversed by naloxone. Microinjected intracerebrally into different sites, dibutyryl cyclic GMP does not mimic the action of morphine. Pharmacological effects of dibutyryl cyclic GMP suggest that endogenous cyclic GMP modulates an inhibitory pain pathway distinct from that on which morphine acts.


Maternal behavior as a regulator of polyamine biosynthesis in brain and heart of the developing rat pup. Rat pups removed from the mother and placed in a warm incubator for 1 hour or more show a 50 percent reduction in ornithine decarboxylase activity in the brain and heart. The decline is not caused by lack of nutrition. Instead, these studies suggest that active maternal behavior is necessary to maintain normal polyamine metabolism in brain and heart of the pup during development.


Pentobarbital: differential postsynaptic actions on sympathetic ganglion cells. The frog sympathetic ganglion has been used as a model to elucidate the cellular mechanism of barbiturate anesthesia. Anesthetic concentrations of pentobarbital markedly reduced the fast nicotinic excitatory postsynaptic potential while having no effect on the slow excitatory postsynaptic potential or slow inhibitory postsynaptic potential, even though all three synaptic potentials depend on the presynaptic release of acetylcholine. A similar differential effect was seen for nicotinic and muscarinic responses to exogenously applied agonists, while the depolarizing action of gamma-aminobutyric acid (GABA) was enhanced. These results indicate that pentobarbital has remarkably selective actions on the sympathetic ganglion and further indicate that blockade of ganglionic transmission by anesthetic concentrations of pentobarbital can be entirely explained by a postsynaptic action. The present results strengthen the concept that pentobarbital anesthesia results from a postsynaptic blockade of central excitatory synapses which increase sodium conductance coupled with a postsynaptic enhancement of GABA-mediated synaptic inhibition.


Nelson's syndrome: case report and review of the literature. A patient who developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome) is presented. The literature reviewed shows less than a 10 percent incidence of this disorder for which extremely elevated plasma ACTH levels are diagnostic. Special radiologic technics may be required to detect small pituitary tumors, but pituitary hormone levels may be elevated in the cerebrospinal fluid if there is suprasellar tumor extension. The different modalities available for treatment of Nelson's syndrome are discussed.


Visceral leishmaniasis acquired in Greece: diagnosis and treatment in an American child. Reported is a case of visceral leishmaniasis acquired in Greece by a 3-year-old American child. Untreated, this protozoan infection causes a high mortality. Specific treatment is available, making early recognition of the illness important. This child's infection responded dramatically to a course of sodium antimony gluconate. Repeat bone marrow cultures demonstrated persistent organisms and a second course of treatment was required. Monitoring of his response to therapy suggested that serial bone marrow cultures and the neutrophil response may be sensitive means for following the course of this infection.


Hypothalamo-pituitary-adrenal function in pituitary adenoma and craniopharyngioma. Part I: Insulin test, lysine-vasopressin test, and rapid ACTH test. For the assessment of hypothalamo-pituitary-adrenal function in the presence of pituitary adenomas and craniopharyngiomas, insulin tests, lysine-vasopressin tests, and rapid ACTH tests were performed and plasma cortisol was assayed. Rapid ACTH test and lysine-vasopressin test, which examine adrenal and mainly pituitary function respectively, showed normal function in ten among 14 cases. But insulin test, which examines the whole hypothalamo-pituitary-adrenal function, showed various levels of abnormality in eight among 14 cases. Frequent association of functional disturbances of this axis in these diseases was stressed.


False positive complement fixation tests with respiratory virus preparations in bird fanciers with allergic alveolitis. False positive raised complement fixation titres to egg-grown virus preparations were found in six pigeon fanciers suffering from extrinsic allergic alveolitis but not in six similar budgerigar fanciers. The raised titres in the pigeon fanciers fell fourfold over a short interval in the absence of avian exposure and were attributable to antibodies directed against antigens from hen's egg in which the test virus preparations were grown. Such antigens were shown to be present in the virus preparations. In view of the clinical similarities between influenza and acute extrinsic allergic alveolitis, it is essential that a diagnosis of influenza in bird fanciers is not based on either a single raised titre or a fourfold fall in complement fixation titre without appropriate control tests with avian antigens.


Effects of prostaglandins, derivatives of cyclic 3':5'-AMP, theophylline, cholinergic agents and colchicine on clot retraction in dilute platelet-rich plasma and gel-separated platelet test systems. In dilute suspensions of platelet-rich plasma (PRP) or gel-separated platelets (GSP), dibutyryl-cAMP (DBcAMP) and monobutyryl-cAMP inhibited platelet-mediated fibrin clot retraction in concentrations of 2--3 X 10(-6) M, with complete inhibition at 1--3 X 10(-4) M. Prostaglandin E1 (PGE1), which inhibited fibrin clot retraction in concentrations greater than 1.5--3 X 10(-8) M, was a more effective inhibitor than either PGE2 or PGF2 alpha. In the presence of theophylline (10-4 M), concentrations of DBcAMP, PGE1, PGE2 and PGF2 alpha necessary to inhibit fibrin clot retraction were reduced 50-fold for DBcAMP and 2.5 to 20-fold for the prostaglandins. In dilute PRP or GSP, inhibition of fibrin clot retraction does not result from inhibition of thrombin-induced platelet aggregation. Thus, compounds which increase platelet cAMP levels result in the inhibition of platelet-mediated fibrin clot retraction, and this inhibitory effect may be mediated, at least in part, through suppression of platelet contractility. Cyclic GMP, dibutyryl-cGMP and carbamylcholine-Cl (which stimulate guanylate cyclase) did not influence fibrin clot retraction, and did not prevent inhibition of fibrin clot retraction by DBcAMP and PGE1. Colchicine, in concentrations known to disrupt platelet microtubules (2.5 X 10(-6) M to 2.5 X 10(-3) M), had little inhibitory effect on either fibrin clot retraction or platelet (3H)-serotonin release.


The epidemiology of infection with Entamoeba histolytica in the Gambia, West Africa. A country-wide stool survey of The Gambia showed the prevalence of Entamoeba histolytica cysts to range from 13.7% up-country in the dry season to 52.3% near the coast. A longitudinal survey showed a near 100% infection rate over one year and a sharp rise in prevalence as the rains commence with an equally sharp fall as the rains progress. Specific antibody levels are elevated and reasonably constant through the year. Carriers generally show no specific lymphocyte reactivity to amoebic antigen but consistently parasite-negative individuals tended to show elevated lymphocyte reactivity. Attempts to discover the presence of cysts in the environment of villages by cultivation of specimens of water, soil, food, flies and washing from clothes and hands generally failed though E. histolytica was recovered once from a well.


The relationship between hepatitis B virus infection and hepatic cell carcinoma in Mozambique. Hepatitis B surface antigen and antibody were sought in sera collected from patients with hepatic cell carcinoma and from healthy blood donors. The frequency of the antigen among the patients was significantly higher than that among blood donors who served as controls (p = less than .01) but no significant difference was found in estimated exposure to hepatitis B virus between hepatic cell carcinoma patients and African blood donors. However, exposure to hepatitis B virus was significantly less frequent (p = less than .01) among European blood donors when compared to African blood donors.


Experimental infection of Nigerian sheep and goats with bovine virus diarrhoea virus. Apart from leucopenia and a low grade pyrexia Nigerian goats showed no ill effects following inoculation with bovine virus diarrhoea virus. Sheep showed a variable leucopenia without pyrexia. No difficulty should arise in differentiating BVD infections from peste des petits ruminants.


[Test of an attenuated viral strain of TGE as a vaccine]. A live vaccine was produced using a local strain P of the virus of the transmissive gastroenteritis, arrenuated in cell cultures. The vaccinated pregnant sows had high-titer serum and colostrum virus-neutralizing antibodies. In the first days following farrowing there were in the colostrum ummunoglobulins of the Igg class that prevailed, however, IgA and IgM proved more effective in the virus-neutralizing test. Newborn pigs acquired passive immunity at about the 24th hour after the intake of colostrum. They withstood a challenge with a virulent virus.


[Serological response of rabbits following immunization with M. parainfluenzae-3, adenovirus I and infectious bovine rhinotracheitis virus associated antigens]. The immunization of rabbits separately with virus suspensions of Myxovirus parainfluenzae-3, adenovirus serotype I, and bovine rhinotracheitis virus or with combinations of each two of them and with a combination of all three viruses led to the production of sera having titers of virus-neutralizing antibodies acting against each of the antigens that participated in the combination. Results showed that no inhibition existed of the antigens during immunization as established by the serologic response of the rabbits. The demonstrated specificity of the monovalent sera points to the fact that the latter could be used for the diagnostic purposes.


[Use of the plaque method for isolating Aujeszky's disease virus from meat, organs and meat products]. Comparative virologic studies were carried out to isolate the virus of Aujesky's disease from meat, viscera, and raw smoked products by the plaque method as modified by Sullivan and Read as well as by the method with which the presence of the virus is recorded visually by the cytopathic effect observed in the infected cell monolayer. It was found that at the veterinary and sanitary inspection of meat and meat products produced from diseases or survived animals the modified plaque method proved more suitable as against the other method. The former made it possible to determine directly and at low titers the virus of Aujeszky's disease for the needs of research and practical activities associated with rendering the meat harmless as coming from diseased pigs.


Degenerative processes in the pathogenesis of pulmonary alveolar lipoproteinosis. Electron microscopy in an infant of 4 months with pulmonary alveolar lipoproteinosis showed filling of the alveoli with osmiophilic lamellar bodies. Similar structures were present in the cytoplasm of type I alveolar epithelial cells and to a lesser extent in the capillary endothelium and interstitium. These changes represent widespread degenerative processes in the lung caused by an unidentified cytotoxic agent. In this patient the disease is comparable to the drug-induced cytotoxic animal model and differs from the dust-induced hypersecretory animal model.


Further observations on the relationship between the matrix and the calcifying fronts in osteosarcoma. Human osteosarcoma biopsies were studied with the SEM using sequential etching with sodium hypochlorite solutions after removal of aluminium or gold coatings. Osteosarcomas differ from normal hard tissues in that the matrix never proceeds to complete mineralization, so that the specimens fragment on hypochlorite treatment. Details of the fibrillar pattern and calcospheritic type of mineralization pattern can be seen in hypochlorite etched, fractured surfaces and mineralizing fronts.


Benign epithelial nephroblastoma. A contribution to its histogenesis. The occurrence of a malignant Wilms'tumor in the right kidney and of a benign epithelial nephroblastoma in the left kidney of a 5-year-old girl is reported. Both kidneys contained foci of persistent well differentiated blastema. In the left kidney a direct transformation of the primitive metanephric epithelium into a benign nephroblastoma is shown. This finding suggests an origin of epithelial nephroblastoma from persistent nephrogenic tissue and indicates that the former represents the benign counterpart of the malignant Wilms'tumor.


[Paget's disease of bone: ultrastructure and cytogenesis of osteoclasts (author's transl)]. The cytogenesis of giant osteoclasts in Paget's disease of bone was studied by means of electron microscopy. 26 iliac crest biopsies were made and divided for light and electron microscopic investigation. A special procedure was used for electron microscopic preparation of bone without previous decalcification. Paget osteoclasts are characterized by their high content of nuclei. Several nuclei may show paracrystalline inclusions pointing to a possible virus infection of these cells. Giant osteoclasts have an increased mobility and a high resorptive activity, manifest by the dissection of bone fragments from endosteal bone surfaces. Cell membrane interdigitations between mononuclear cells and osteoclasts occur as a morphologic concomitant of cell fusion. Frequent occurence of such cell membrane contacts seem to indicate an increased tendency to cell fusion among the mononuclear precursors of Paget-osteoclasts. Precursor cells are located in the pericapillary region, and morphologically resemble pericytes. The assumption of an increased rate of cell fusion amoungst the precursor cells of osteoclasts might explain the development of giant osteoclasts in this disease. Further studies of the paracrystalline nuclear inclusions of Paget-osteoclasts are necessary to determine whether this process can be considered to be a cytopathogenic effect of virus infection.


Rod-shaped tubulated bodies in the endothelia of mesenteric arteries of hypertensive rats. Weibel-Palade bodies were found in the endothelial cells of the mesenteric arteries of hypertensive rats. They were spherical or rod-shaped and bounded by a single membrane. They measured approximately 0.1 to 0.2 mu in diameter and up to 0.4 mu in length. The majority of them showed microtubular subunits, measuring about 200 A in width. These bodies are thought to originate from Golgi apparatus.


[Role of the oxidation-reduction state and phosphate potential in regulating rat liver gluconeogenesis during inclusion of 1,3-butanediol in the diet]. Gluconeogenesis was stimulated in rat liver tissues if 38.5% of carbohydrates were substituted in the diet by 1,3-butane diol used as a source of energy. Under these conditions concentration of substrates (phosphoenol pyruvate, malate, oxalacetate), participating in coupling of glycolysis and gluconeogenesis, was increased in liver tissue; activity of gluconeogenesis key enzymes (phosphoenolpyruvate carboxykinase and fructose-1,6-diphosphatase) was also increased. Decrease in the ratio NAD+/NADH showed that the nicotinamide nucleotide pool acquired the most distinct reducing properties of cytoplasma and mitochondria of rats maintained on the diet. The value of phosphate potential (the ration ATP/ADP/Pn) was decreased during the experiment due to increase of ATP utilization in gluconeogenesis.


[Adenylate kinase and creatine kinase activity of rabbit blood serum following application of a tourniquet to the thigh]. A colorimetric method is described for estimation of the adenilate kinase activity in blood serum; the method is based on coupling of adenilate- and creatine kinase reactions and on estimation of the amount of creatine formed. Adenilate kinase activity in blood serum, estimated by the method, was shown to increase 4-fold after removing of tourniquet with subsequent normalization within the next day. The same data were obtained using a spectrophotometric method for estimation of adenilate kinase based on NADP reduction in coupled reactions with hexokinase and glucose-6-phosphate dehydrogenase. An increase in creatine kinase activity in blood serum occurred later on after removing of the tourniquet; it was more distinct (8.5-fold) and maintained longer as compared with the increase in adenilate kinase activity.


[Vessel wall lipids in human atherosclerosis]. Relative content of linoleic acid in the fraction of cholesterol esters was increased in "unaltered" intima of human aorta in course of aging. Due to this phenomenon the fatty acid composition of this lipid fraction became similar to the composition of cholesterol esters in lipoproteins of low density, observed in blood of persons at the age of 50 and older. Lipids were accumulated extracellularly in intima of aorta in the course of aging. The high ratio of linoleic acid was also typical for the fatty acid composition of cholesterol esters in fibrous patch with area of atheromatosis (amorphous accumulation of fat, localized out of the cells). These data demonstrate that lipoproteins of low density from blood serum may serve as a source of accumulation of lipids both in "unaltered" intima in the course of ageing and in fibrous patch. The lower ration of linoleic acid and relatively higher content of oleic acid were the characteristic properties of cholesterol esters from lipid spots ("early impairment") as compared with intima and atheroma. Cells of lipid spots, filled with fat, might apparently degrade the liproproteins from blood serum and the liberated cholesterol could be esterified by fatty acids, newly synthesized or preformed in the cells.


[Changes in skin enzyme activity in experimental burns]. Activities of proteolytic enzymes--cathepsins B and D, trypsin-like proteases, leucine aminopeptidase--as well as of lactate dehydrogenase and its isoenzymes were studied in area of thermic burns of skin and hypodermic tissue, in the zone surrounding the burns area and in intact skin of burned rats. Within a day after burns activities of the enzymes studied were distinctly decreased. The low levels of the activities were within the next three weeks. The activities of the proteolytic enzymes were gradually restored and exceeded the normal level in the tissues situated under crust, in boundary zone and in leukocytes of demarcational zone; the increase in activity appears to affect the subsequent deepening of burn wounds.


[Energy metabolism disorders in the myocardium due to alcoholic intoxication]. Energy metabolism was studied in rat myocardial mitochondria by estimation of respiratory enzymes activity and content of the Krebs cycle substrates under conditions of acute and chronic intoxication with ethyl alcohol. In the acute intoxication mitochondrial redox enzymes were inhibited (glutamate- and malate dehydrogenases, NADH cytochrome C oxidoreductase and cytochrome C oxidase), succinate- and lactate dehydrogenases were activated; at the same time, contents of pyruvate, succinate, and alpha-ketoglutarate were elevated and the content of oxalacetic acid was decreased. Prolonged administration of alcohol (within 2 months) caused an intensification of glycolysis and an increase in NADH cytochrome C oxidoreductase pathway with preferable oxidation of succinate and activation of cytochrome C oxidase; the phenomenon appears to be an adaptation to chronic "alcohol hypoxia". Discontinuation of alcohol administration led to deficiency of native substrates in myocardium (primarily, oxalacetic and succinic acids) due to decrease in NAD reduction via alcohol dehydrogenase reaction and to increase in oxidation of NAD-dependent endogenous substrates.


[Phospholipid composition of high density lipoproteins in hyperalphalipoproteinemia]. Content of lecithin as related to the total content of phospholipids was increased in alpha-lipoproteins of healthy men with hyper-alpha-lipoproteinemia (concentration of cholesterol exceeded 72 mg% in the lipoproteins). The alpha-lipoproteins accumulated considerably more free cholesterol than its esters; this caused a decrease in the molar ration "phospholipids/free cholesterol". The surface of phospholipid-cholesterol monolayer of alpha-lipoproteins is apparently responsible for retaining of increased amounts of cholesterol in the complex as well as for participation of these structures in enzymatic reactions in blood serum.


[Serum factors that inhibit in vitro immunological reactions in malignant tumor development in experimental animals]. In two immunological reactions (immunocytoadherence and inhibition of macrophage adherence in the presence of specific antigens) it was shown that autologous and homologous native sera in some percentage of cases render an inhibitory effect. One of the blocking factors of sera proved to be rather thermostable, the other, on the contrary, to be thermolable.


[Cyclic adenosine monophosphate and atherogenic factors]. Hypercholesterolemia caused a decrease in the activity of adenylcyclase in rabbit liver tissue and in thrombocytes; hypertriglyceridemia, which developed after administration of hydrocortisone, led to an increase in the activity of adenylcyclase and in the content of 3,5-AMP in adipose tissue. Activities of adenylcyclase, phosphodiesterase and content of prostaglandines E1 and F2alpha were measured in thrombocytes of 39 healthy men without any symptoms of of ischemic heart impairment, in 52 patients with coronary atherosclerosis of the III degree (by Myasnikov's classification) as well as in 12 patients during the period of rehabilitation after myocardial infarction. The activity of adenylate cyclase system was impaired in atherosclerosis. This phenomenon might be caused by alteration in concentration of glucocorticoids in the organism.


[Effect of cortisol on adenylate cyclase and 3',5'-AMP phosphodiesterase activity and 3',5'-AMP concentration in tissues and biological fluids in experimental atherosclerosis]. Administration of hydrocortisone into healthy rabbits activated adenilate cyclase and phosphodiesterase in liver tissue; activity of the enzymes was normalized within 5 days after the treatment. The hormone, administered into animals with experimental cholesterol-induced atherosclerosis, caused an activation of adenilate cyclase and inhibition of phosphodiesterase; due to the phenomenon more distinct and long-term increase in cAMP concentration was observed in kidney, liver and fatty tissues. Concentration of cAMP exceeded considerably its initial content in the tissues within 5 days after the hydrocortisone administration. Hydrocortisone inhibited the adenilate cyclase system activity in adrenal cortex of experimental and control animals at early period of the experiment. In health rabbits content of cAMP was increased in adrenal cortex within 5 days after the hormone administration. As the similar effect was not found in animals with experimental atherosclerosis these data suggest that the hypophysis-adrenal cortex system under the experimental conditions studied was inhibited.


[Cholesterol metabolism in rabbits with resistance to experimental atherosclerosis acquired by immunological treatment]. Development of resistance to experimental atherosclerosis due to immunization of newborn rabbits with homologous fraction of beta- and pre-beta-lipoproteins was accompanied by increased oxidation of cholesterol to biliary acids and by accelerated excretion of cholesterol. The phenomenon appears to be caused by two mechanisms: 1 (cholesterol, occurring in the fraction of free lipoproteins "unblocked" by the antibody (immunzied animals), is more readily oxidized to biliary acids in liver tissue than cholesterol, occurring in the autoimmune complex "lipoprotein-antibody" (non-immunized animals)); 2) the enzymes and biological systems, responsible for elimination of cholesterol from an organism (oxidation to biliary acids, excretion with bile), are activated after immunization of the newborn animals by the lipoprotein fraction endriched with cholesterol.


[Use of EDP (electronic data processing) in the after care for heart-infarct patients]. It is demonstrated an after-treatment model for patients with myocardial infarction as a part of a complex project of electronic data processing within prevention and treatment of selected diseases of the heart and circulatory system (electronic data processing project myocardial infarction). The aim of the after-treatment project is the establishment and ambulatory medical after-treatment of all patients with myocardial infarction of a territory, by means of which without any additional manual expenditure by giving standardized evidences of data and using electronic data processing automatic letters of doctors and working lists may be established and scientific evaluations may be made possible.


[Pyridoxal kinase activity in human tumor tissues]. Activity of pyridoxal kinase (per 1 g of tissue or per 1 mg of protein) varied in the range from 7 to 39 un or from 0.079 to 0.4 un in human malignant neoplasm tissues (adenocarcinoma of various localization, squamatous cell carcinoma of lungs, skin melanoma). The direction of alterations in the pyridoxal kinase activity differed in various tumors studied as compared with the respective controls (unimpaired tissues used for growing malignant cells).


[Bone tissue collagen and vitamin D in chronic kidney insufficiency in rats]. Chronic kidney insufficiency, caused by subtotal nephrectomy, did not lead to distinct alterations in hydroxyproline concentration in blood and to its excretion in rats within 1-1.5 months after the operation. Content of salt-soluble collagen was decreased in diaphyses of rat tubular bones in chronic kidney insufficiency; in the epiphyses (with metaphyses) content of the collagen fraction was increased, but the concentration of non-soluble collagen was unaltered. Decrease in content of salt-soluble collagen in diaphyses in chronic kidney insufficiency was similar to that in experimental vitamin D deficiency. The decrease might be due to impairment in formation of the active form of vitamin D-1,25-dihydroxycholecalciferol. Other pathogenetic factors (effect of uremic toxins and stress) were apparently of primary importance for development of impairments of collagen metabolism in epiphyses. Dihydrotachysterol, the structural analogue of 1,25-dihydroxycholecalciferol, normalized the alterations in content of salt-soluble collagen in diaphyses and did not affect the impairments of collagen metabolism in epiphyses of rat bones in chronic kidney insufficiency.


Induction of liver tumors in rats by sodium nitrite and methylguanidine. The carcinogenicity of sodium nitrite and methylguanidine singly and together were examined in rats. A hepatocellular carcinoma, a hemangiosarcoma and a spindle cell sarcoma  were found in 3 of 15 rats fed continuously on pellet diet containing 0.16% sodium nitrite and 0.16% methylguanidine. Hemangiomas and bile duct adenomas of the liver were also found in 6 and 8, respectively, of the 15 rats in this group. Hemangiomas and bile ducts adenomas of the liver were found in 2 and 3, respectively, of the 4 rats fed on pellet diet containing 0.16% sodium nitrite. Only 1 of 5 rats fed on pellet diet containing 0.16% methylguanidine developed a hemangioma. No tumor was found in the control group. All the tumors were found in rats that survived for over 12 months. No significant changes were detected in the esophagus or stomach.


Chemotherapy studies in autochthonous rat tumors: hepatomas. Diethylnitrosamine (DEN) was applied orally to a total of 250 female Wistar rats in a single dose (d) of 3 mg/kg body weight 5 times a week for a duration of 20 weeks. After approximately 150 days exploratory laparotomy was performed to all animals. By inspection of the liver they were divided into 4 stages of disease according to the extent of cancer formation. The reaction of rats with DEN induced liver tumors was tested using a 4-drug combination chemotherapy with different equitoxic doses of Adriamycin (Adm), Methotrexate (Mtx), 5-Fluorouracil (5-FU) and Cyclophosphamide (CP). No benefit of drug treatment could be noted. In drug treated animals no decrease in the development of the liver tumors, in the frequency of metastases nor in the frequency of tumors of other origin could be demonstrated. The parallels of chemotherapy in chemically induced liver cancer to clinical experience are discussed.


[Comparative study of the morphofunctional organization of tissues of different regions of the rat brain in culture]. The morphological organization and spontaneous electrical activity of neurones of the hippocampus, visual cortex and cerebellum of one- two-day old rats were studied during prolonged cultivation (up to 35 days) of explants under indentical conditions in vitro. Differentiation of cells, myelinization of axons and formation of synapses between the neurones were observed. A continuous and periodic types of unit activity were recorded which, for the hippocampus did not depend on the time of cultivation and units' location in the explant. The cerebral cortex cultures displayed a transition of continuous unit activity to a periodic one after a two-week development of the explants in vitro. The process coincides with the increase in the number of synapses in the culture and their structural maturation. The periodic discharges observed in mature cultures of the cerebral cortex and in the central part of the cerebellum explants, are transformed into continuous ones under the action ofmagnesium ions.


A mixed outbreak of epidemic keratoconjunctivitis due to adenoviruses types 29 and 8. An outbreak of epidemic keratoconjunctivitis (EKC) occurred in northern Bohemia in the summer of 1975. One hundred and four patients were treated. Four strains of adenovirus type 29 with low or strong pronounced cross-neutralization against anti-Ad 15 reference serum, and 2 adenovirus type 8 were isolated of 4 patients. Type 8 strains were only obtained from conjunctiva, type 29 also from stools. From one patient, type 8 from conjunctiva and type 29 from stool were isolated simultaneously. Out of 22 patients with demonstrable antibody rise, a monotypic response in virus-neutralization test against type 29 was detected in 13 and a mixed response against types 29 and 8 in nine. An antibody rise was most frequently demonstrated by virus-neutralization test, the frequence for VNT alone being equal to the frequency of antibody rise as detected by VNT, hemagglutination-inhibition test and complement-fixation test in combination.


[Development of action potentials spreading antidromally from an acute epileptogenic focus through the corpus callosum]. The activity of callosal neurones located in the sensorimotor cortical area was studied in unanaesthetized rabbits. An epileptogenic focus was produced by application of penicillin or strychnine in the homotopic region of the contralateral hemisphere. During hyperpolarization of the membrane, corresponding to the appearance of paraxysmal discharges in the homotopic area, some of the neurones exhibited a group of antidromic action potentials (APs) in their soma with a 70-80 msec latency. Analysis of the APs form and of interspike intervals between the tested APs and antidromic APs evoked by stimulation, allowed to identify spontaneous antidromic APs in the extracellular records of callosal neurones as well. The data obtained show that under the influence of epileptogenic agents in the axon terminals located in the focus of the epileptic activity APs may appear, spreading antidromally through the corpus callosum to the soma of the callosal neurones.


[Lipoproteins as serum inhibitors in rubella hemagglutination inhibition test and their elimination (author's transl)]. Lipoproteins of 20 human sera were isolated by flotation centrifugation and tested for inhibitory activity in rubella HI-test. Low density lipoproteins (LDL) showed the highest titers with an average of 1:238,0, whereas the others (VLDL, HDL) had lower titers (see tab. 2). The greatest reduction of all classes of lipoproteins was achieved with kaolin treatment. Heparin-manganous chloride and dextran sulfate-calcium chloride method mainly reduced the LDL (84.4 resp. 78.7%). In a comparative test sera treated with the heparin procedure showed higher antibody titers than those treated with dextran sulfate.


Detection of collagenase-activity in RA synovial fluids using soluble 14C-labelled collagen. 14 RA synovial fluids and 7 non-RA synovial fluids were investigated as to their collagenase-activity using 14C-labelled type I human collagen in soluble form. Breakdown products were fractionated by gel filtration on Sephadex G 200 superfine. Cleavage of native and denatured labelled collagen was compared. 11 RA synovial fluids showed significant collagenase activity as manifested by degradation of native collagen, while only one synovial fluid of the control group displayed a significant collagenolytic activity. Results were compared with cleavage of reconstituted collagen fibrils. Influence of EDTA and KSCN on collagen degradation was also studied: EDTA completely blocked degradation of native or denatured collagen, while KSCN caused an increase of collagenolytic activity in two cases.


[Immunogenicity and toxicity of soluble trichloroacetic acid precipitate from pertussis microbes and its fractions]. The authors studied the biological properties of the preparations of pertussis protective antigens obtained by the disintegration of the microbial mass of Bordetella pertussis, with the subsequent purification with trichloracetic acid (TCA-preparations). TCA-preparations proved to possess a stable protective activity and by the ratio of the protective dose to toxic and histamine-sensitizing doses considerably exceeded the corpuscular vaccine. A TCA-preparation fraction with a greater immunogenic activity than the initial preparation was obtained by chromatography on sepharose 4B.


[Changes in the nervous system in kidney diseases]. A total of 150 patients with renal pathology (chronic glomerulonephritis, pyelonephritis, urolithiasis, etc.) accompanied by the development of psychoneurological disturbances were examined. In the initial stage of the renal insufficiency the authors observed neurasthenic, radicular, polyneuritic, renovisceral syndromes, in a more remote stage--encephalopathies and disturbances of the brain circulation. The important part in the above-mentioned disturbances is played by azotemia, metabolic acidosis, disturbances of fluid-electrolyte and albumine balance, as well as arterial hypertension.


Histochemical studies on reserve substances and enzymes in female gametophyte of Zea mays. Cytochemical changes during the early development of maize caryopsis are reported. Changes in the localization of different reserve substances (e.g. polysaccharides, proteins, nucleic acids and lipids) and enzymes (acid phosphatase, esterase, lipase, phosphorylase, succinate dehydrogenase, cytochrome oxidase and peroxidase) have been studied in unfertilized and fertilized ovules. Before pollination very feeble enzyme activity (acid phosphatase, succinate dehydrogenase, cytochrome oxidase and peroxidase) was observed. Reserve substances were present in low amounts before pollination. Pollination stimulated the accumulation of several substances and enzymes in the tip of the nucellus, micropylar zone. Just prior to, during and after fertilization, the cells in the micropylar zone had strong reaction for several enzymes indicating temporary enhancement of metabolic activity in the micropylar zone. The role of antipodals in the storage of reserve food products and nutrition of embryo and early stages of endosperm development is discussed. The pattern of enzymatic changes within the embryo sac reflected the biochemical changes operative during quiescent and active stages. The nucellus of Zea mays contains many enzymes required for hydrolysis of reserved food substances. A role of acid phosphatase in autolysis of nucellar cells, after fertilization is suggested. Post-fertilization increase in the activity of enzymes and accumulation of reserve materials is interpreted as reflecting a presumed increase in the metabolic rate relative to growth and differentiation.


Phosphatases in the accessory respiratory organs of two fresh-water fishes. The distribution of enzymes, viz., alkaline phosphatase, acid phosphatase, adenosine monophosphatase and adenosine triphosphatase was studied by histochemical methods in the accessory respiratory organs of two fresh-water fishes (Clarius batrachus and Heteropneustes fossilis). Enzymes have been used as markers to differentiate between functional and non-functional cells of the dendritic organ of Clarius and of the air chamber of Heteropneustes. The variations in the enzyme activities have been correlated with the functional capacity of each respiratory organ. It is attempted to understand the physiological role of these enzymes in the process of aerial breathing.


Low-density lipoprotein complexes with histones. Low-density lopoproteins (LDL) form soluble and insoluble complexes with the total histone and its fractions. The bulk of these complexes is formed by the arginine-rich histone fraction. LDL are bound with histones by means of ion binding.


Studies on NAD+ permeability in intact mitochondria from rabbit reticulocytes. Functionally intact mitochondria from rabbit reticulocytes are characterized by a low NAD+ level after the preparation (0.29 nmoles NAD+ + NADH/mg protein). They are apparently impermeable for NADH and exhibit a slow net uptake of NAD+. From the increase of O2-uptake in state 3 and the increase of NADH concentration in state 4 of respiration after the addition of NAD+ we concluded that 3--10 min are necessary for the saturation with NAD+ at 23 degrees C. 2mM NAD+ extramitochondrially are not sufficient to saturate the mitochondria with NADH and probably NAD+, too. Because of the net uptake of NAD+ we assume that reticulocyte mitochondria lose NAD+ during their preparation. If they are incubated with the physiological concentration of 300 micrometer NAD+, which was found in reticulocytes, a value of 1.9 nmoles NAD+ + NADH mg protein was calculated. At an extramitochondrial NAD+ concentration of 300 micrometer, reticulocyte mitochondria exhibit an almost maximal O2-uptake in the presence of oxaloacetate or alpha-ketoglutarate. It is concluded that the mitochondria in intact reticulocytes contain the "normal" complement of NAD+ + NADH.


Degradation of mitochondria by cytosolic factors in reticulocytes. The degradation process of mitochondria in rabbit reticulocytes proceeds predominately directly in the cytosol rather than in secondary lysosomes as judged by electronmicroscopy. At least five cytosolic protein factors are present in reticulocytes, which could be related to the degradation of mitochondria: the two inhibitory proteins of the respiratory chain RF and RC and three enzymes which cause a lysis of mitochondria in vitro (lipoxygenase, proteinase, phospholipase A). The properties of these factors are the subject of this paper. A hypothetic scheme of the degradation of mitochondria in reticulocytes is proposed. The degradation of mitochondria in reticulocytes is viewed as a complex interplay of various cytosolic factors and the functional state of the mitochondrial membranes. The lipoxygenase damages the membranes and triggers the penetration of the respiratory inhibitors. In this manner, a catastrophic cycle is initiated which leads to the complete breakdown of the mitochondria.


Grouping of patients with hyperparathyroidism by clinical signs, correlated to some biochemical findings. Serum parathormone (S-PTH), total and free fractions of serum calcium (Cat and Caf), urinary excretion of cyclic 3',5'-adenosine monophosphate (cAMPu), serum phosphate and serum magnesium were analysed in 68 patients with hyperparathyroidism verified by operation and PAD. The diagnostic significance of the analyses was examined. It was shown that Caf was consistently above normal even in patients in whom the other tests were normal. The best diagnostic sensitivity was thus found for Caf followed by Cat, S-PTH and cAMPu. The results of these tests were generally correlated to each other except in patients with impaired renal function in whom S-PTH increased out of porportion to the other tests. Cat and Caf were significantly correlated to each other. However, Caf was pathologic even when Cat was normal. It is concluded that for hypercalcemic patients Cat and Caf are the most reliable tests. S-PTH is elevated only in some hypercalcemic patients. In normocalcemic patients all tests except Caf show normal values.


Isolated gastric involvement in Crohn's disease. Report of a case simulating scirrhus carcinoma. A 63-year-old woman suffered a short period of nausea and vomiting. X-ray examination of the upper gastrointestinal tract was suspicious of scirrhus carcinoma of the stomach. At operation the suspicion was strengthened, and total gastrectomy was performed. Microscopic examination showed chronic, granulomatous gastritis compatible with Crohn's disease. The patient died on the 8th day postoperatively with caval thrombosis obliterating the inlet to the right auricle. No other localization of the disease could be demonstrated on thorough microscopic and macroscopic examination of the whole gastrointestinal tract.


Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles stimulated with LH and FSH. Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles was determined after in vitro stimulation by LH and FSH. Combined time course and dose response experiments determined that the acute response of the follicles (0-30 min) to LH and FSH was similar with respect to cyclic AMP accumulation. The pattern of cyclic GMP accumulation was, however, distinctly different in LH and FSH stimulated follicles. LH increased follicular cyclic GMP only at the lowest dose (0.005 IU/ml), while higher doses of LH had no effect. In contrast, FSH at all doses stimulated cyclic GMP accumulation. The different cyclic AMP to cyclic relationships generated in the follicles by LH and FSH may be determinants in specificity of hormone action in pre-ovulatory follicles.


Induction of premature parturition in sheep: adrenocorticotrophin and corticosteroid changes during infusion of Synacthen into the foetus. Synacthen (10 microgram/h) infused into foetal sheep at about day 125 of gestation caused premature delivery within 4 days. During the first 24 h of the infusion the secretion of adrenocorticotrophin was depressed and the assayable hormone concentration was within 500-1000 pg/ml. Subsequently, large fluctuations occurred in the adrenocorticotrophin concentration in the plasma of foetal sheep which were consistent with the stimulation of adrenocorticotrophin secretion. No transfer of Synachthen to non-infused twin foetuses was observed. The plasma corticosteroid concentration in the infused foetus also showed a small rise during the first 24 h of the infusion followed by large fluctuations in concentrations that coincided with the changes in adrenocorticotrophin. No consistent changes in the plasma corticosteroid concentration in the non-infused twin foetus were observed. These results are discussed in relation to the hormone changes occurring during normal delivery.


Adrenocorticotrophin and corticosteroid changes during dexamethasone infusion to intact and synacthen infusion to hypophysectomized foetuses. Synacthen has been infused at 10 microgram/h into 4 hypophysectomized foetal sheep. This caused a rise in adrenocorticotrophin to a mean value of 512 pg/ml which remained fairly constant and did not show the large fluctuations seen on infusion into intact foetuses. The Synacthen half-life in the circulation had a mean value of 0.27 min. Hypophysectomy did not necessarily delay the foetal corticosteroid response to Synacthen infusion. The corticosteroid concentration achieved had a mean value of about 50 ng/ml which is substantially below that for intact foetuses and in one case it was maintained at only 20 ng/ml. Despite this delivery occurred within 5 days. Dexamethasone infusion reduced the plasma adrenocorticotrophin concentration by about 70% and the plasma cortisol concentration by about 60%.


Activity of phosphatases and succinic dehydrogenase in the trigeminal ganglion of the corticosteroid-treated mouse. Immature mice were treated for 21 days with daily doses of triamcinolone diacetate. The trigeminal ganglion was studied enzymatically for the activity of alkaline phosphatase, acid phosphatase, ATPase and succinic dehydrogenase. It became apparent that the prolonged treatment with a potent corticosteroid hormone did not affect significantly the in vivo activity of the above enzymes. Some enzymes even appeared to have increased their intracellular activity. The heterogeneous effect of corticosteroid upon their peripheral target organs is discussed.


Evidence for neurosecretory substance in neurons in the small intestine of dogs. Paraffin-embedded sections from the small intestine of the dog were stained for neurosecretory by various methods. Neurons in the submucous plexus show distinct violet granules, indicating the presence of neurosecretory substance. Nerve cells positive to Gomori's stain were not seen in the myenteric plexus.


Enzyme activity in the pulp following preparation of cavities and insertion of medicaments in cavities in monkey teeth. The effect of cavity preparation, calcium hydroxide and a corticosteroid on pulpal enzymes (Alkaline phosphatase, acid phosphatase, beta-glucuronidase, cytochrome oxidase and succinate, lactate and glucose-6-phosphate dehydrogenase) in monkey teeth has been studied by histochemical means. Cavity preparation with an air turbine and sufficient spray apparently did not affect the enzyme activity of the pulp, nor did application of a corticosteroid to the cavity floor. Twenty-four hours after calcium hydroxide application an increase in enzyme activity was found in the ondontoblastic and subodontoblastic cell layers subjacent to the calcium hydroxide-covered dentin. This activity seemed to demonstrate an onset of dentin formation, and 15 days after the application a slight amount of secondary dentin was found subjacent to the cavities in these teeth.


Ocular herpes simplex infection. A clinical evaluation of virus isolation and studies on iodo-deoxyuridine resistance. Fifty-seven patients with ocular herpes simplex (HS) infection were studied for evaluation of existing methods for virus isolation and its application in diagnosis of HS infection. Virus was isolated in 90% of 34 cases with keratitis dendritica, when specimens were taken within eight days of onset of symptoms. The same isolation frequency was obtained in 10 cases of palpebral herpes with conjunctivitis. No isolation was possible in 11 cases of keratitis disciformis. Laboratory confirmation was obtained within four days in 70% of the positive cases. Ten strains of HS virus type 1 were examined for IDU resistance, 5 strains isolated prior to and 5 during IDU treatment. Nine of the strains had the same degree of sensitivity. One strain isolated during treatment was found to be highly resistant.


Selective and non-selective beta-blockade in renin release. The effects of two beta-adrenergic receptor blocking drugs, the non-selective propranolol and the beta1selective metoprolol, were studied on hemodynamics and plasma renin activity (PRA) of healthy volunteers in an ergometric exercise test. Oral doses of 160 mg of propranolol and 200 mg of metoprolol were tested against placebo. The drug plasma concentrations were determined. Heart rate and systolic blood pressure were equal and significantly lower during treatment with both active drugs when compared to placebo. The effect of drugs on exercise heart rate was correlated with the logarithm of drug plasma concentration with both propranolol and metoprolol. Propranolol, but not metoprolol, decreased the basal level of PRA. The ergometric exercise induced a significant rise in PRA after placebo but this increase was partially inhibited by the both active drugs. On the basis of these findings it is suggested that in man the basal level of PRA could be decreased mainly by blocking the beta2-adrenoceptors. Instead the exercise induced increase of PRA could be inhibited by blocking the beta1-adrenergic receptors.


Effect of endurance training on the capacity of red and white skeletal muscle of mouse to oxidize carboxyl-14C-labelled palmitate. Three groups of mice were trained for 1, 4 and 5 months according to different running programs on a motor driven treadmill and the fatty acid oxidation capacity (FAO) and the activities of some enzymes of energy metabolism (cytochrome c oxidase, malate dehydrogenase, triosephosphate dehydrogenase, and lactate dehydrogenase) were determined from m. quadriceps femoris (MQF). Endurance training increased the FAO [5-month training 4 days/week, 30 min/day 22% (p less than 0.05); 1-month training, 7 days/week, 150 min/day 37% (p less than 0.001); 4-month training, 5 days/week, 60 min/day 24% (p less than 0.05)]. The activities of cytochrome c oxidase and malate dehydrogenase increased approx. 30% (p less than 0.001) whereas triosephosphate dehydrogenase and lactate dehydrogenase activities were not prominently influenced by training. The predominantly red part of MQF of untrained animals oxidized palmitate four times faster than the predominantly white part. The activities of cytochrome c oxidase and malate dehydrogenase were two times higher showing pronounced FAO in the red part. Endurance training increased the FAO and activities of oxidative enzymes in the red and white parts and in the whole muscle relatively equally resulting in similar differences between the muscle types after training. The absolute increase in the FAO of the red muscle was, however, manyfold when compared in chemical units to the white muscle.


Role of the adrenergic nervous system in development of training-induced bradycardia. Sprague-Dawley rats, normal and chemically sympathectomized with 6-hydroxy-dopamine, were trained by treadmill running. The normal rats, unlike the sympathectomized animals, showed reduction of the exercise heart rate after the training period. Compared to a sedentary control group the sympathectomized rats showed no difference in intrinsic heart rate after pithing and denervation and no increase in heart weight. The increase of the heart weight/body weight ratio after training was smaller in the sympathectomized group than in the normal one. The results show that a functioning adrenergic nervous system is necessary for an efficient adaptation to physical training. Administration of noradrenaline to pithed trained and untrained rats showed that betaadrenergic receptor sensitivity was not altered by physical training. The intrinsic heart rate of normal trained rats was lower than that of normal control rats.


Opiate receptors and endogenous opioid peptides in tolerance and dependence. The impact of the discovery of the endogenous opioid peptides, the enkephalins and endorphins, on our concepts of the mechanisms of tolerance to, and dependence on, opiates is discussed. After a brief survey of the chemistry of the opioid peptides, the possibility of an interaction between opiates and the peptides is considered and a hypothesis formulated. Experimental proof is presented as far as it has become available. The possible mechanisms involved in the development of tolerance and dependence for alcohol, barbiturates and opiates are compared briefly.


Importance of cardiac and vascular beta-receptors in the action of phentolamine. To determine to what extent the effects of phentolamine (PHE) are mediated by the cardiac and vascular beta-receptors, the action of the drug was studied in anaesthetized cats pretreated with beta-blockers. Blockade of the cardiac beta-receptors with either propranolol or metoprolol entirely prevented the increases in heart rate, dP/dt and cardiac output caused by PHE. In animals pretreated with propranolol (in a dose blocking the vascular beta-receptors) or metoprolol (in a purely cardio-selective dose) PHE significantly lowered blood pressure to the same extent as in untreated controls. The effects of PHE on the heart are thus conditional on the integrity of cardiac beta-receptors, whereas it seems improbable that vascular beta-receptors have any part in its vasodilative action. Evidence presented in the literature rather suggests a predominantly central mode of action.


Ether-dissolved ethiodol for lymphangiography: an experimental study. In order to decrease administration time, the viscosity of Ethiodol was reduced by mixing it with ether; this mixture was evaluated in lymphangiography of dogs. The ether-Ethiodol solution was injected into a cannulated lymph vessel of one hind limb and compared to pure Ethiodol in the other. For the ether-Ethiodol solution, the time required for complete injection was 10-30 min in most cases compared to 60-105 min for Ethiodol alone. The radiographic appearance of the lymph vessels and nodes appeared similar on both sides, and follow-up lymphangiograms in two animals after 1 and 3 weeks showed no difference from the original study. Microscopic examination of the opacified lymph nodes on both sides revealed no histologic differences. The techniques has potential clinical application.


Computed tomography in the evaluation of sarcomatous tumors of the thigh. CT examination of a soft tissue mass in the lower extremity adds substantially to a more precise preoperative histologic diagnosis and anatomic localization of the lesion. An appreciation of the normal cross-sectional anatomy of this region is essential for adequate evaluation of the information provided by the CT scan. Four patients with sarcomatous tumors involving the soft tissues of the thigh are described and the diagnostic information provided by CT is discussed. In two of these cases anatomic cross sections are correlated with the CT scan.


False negative bone scans in neuroblastoma metastatic to the ends of long bones. Studies of 12 children with neuroblastoma were performed to assess the comparative sensitivity of skeletal radiography and 99mTc pyrophosphate bone scintigraphy in the detection of metastases to the ends of long bones. A total of 18 lesions were detected in six patients. Fourteen were demonstrated only by radiography, whereas four were positive by both methods. In no case was a lesion detected by scintigraphy alone. Small lesion size, lytic radiographic appearance, metaphyseal location, and technical difficulties in imaging the knee all contribute to the high incidenmce of false negative scans. Lesions in two of the nine patients with metastatic disease to bone would have been missed on the basis of bone scans alone. Accordingly, the radiographic skeletal survey seems to remain a necessary part of the neuroblastoma workup.


Radiologic appearance of viral disease of the lower respiratory tract in infants and children. The radiologic findings in 123 hospitalized children with viral disease of the respiratory tract due to adenovirus, respiratory syncytial virus, parainfluenza, influenza, measles, or herpes virus were retrospectively reviewed. Bronchial wall thickening, peribronchial shadowing and/or associated perihilar streaking were present in 107 cases. Patchy pulmonary shadowing thought to reflect disease at a sublobular or lobular level was present in 72 cases, while areas of coalescent more homogeneous pulmonary shadowing were present in only 20 cases. In general the pulmonary abnormalities were widespread; on the average, two to three lobes demonstrated abnormal pulmonary findings. Poorly defined small pulmonary nodules, while radiologically unimpressive, were noted in 49 cases. Air trapping was observed in 61 cases. Hilar adenopathy was seen in only four cases and was unimpressive. There was a striking absence of pleural effusion, pneumothorax, pneumatocele, and lung abscess in the patients examined.


The nasal arteries.

The nasal arteries. Thorough knowledge of the normal gross and radiographic anatomy of the nasal fossa is a prerequisite for correct interpretation of external carotid angiograms in patients with lesions in or adjacent to the nasal cavity. This report describes in detail the normal gross and angiographic vascular anatomy of the nasal fossa. The appearance of the sphenopalatine artery and nasal branches of the ethmoidal arteries in a variety of lesions that affect the nasal cavity, nasopharynx, and adjacent structures is also discussed. Typical changes in acute rhinitis, sinusitis, sphenopalatine neuralgia, vascular malformations, neoplasms, and benign bulky nasal masses are illustrated.


Effect of vitamin E on serum cholesterol and triglycerides in hyperlipidemic patients treated with diet and clofibrate. Vitamin E in conventional therapeutic doses (400 mg/day) was given to 17 patients with hyperlipidemia on long-term treatment with diets enriched in polyunsaturated fatty acids and with clofibrate. The effect of this treatment on total serum cholesterol and on serum triglycerides was studied. To avoid influences of other factors (especially changes in dietary habits) the investigation was performed giving the patients tocopherol and placebo randomly, double blind and cross-over. No significant effect of vitamin E on total serum cholesterol or on serum triglycerides was seen.


Androluteoma syndrome of pregnancy.

Androluteoma syndrome of pregnancy. The clinical course of a 26-year-old primigravid woman with a virilizing luteoma of pregnancy is described. It was demonstrated by endocrine studies that the tumor secreted an excessive amount of testosterone. After removal of the luteoma in week 32 of pregnancy, the virilizing symptoms of the mother completely regressed. A normal male infant was delivered in week 39. From 100 luteomas of pregnancy described in the literature, 26 cases have been cited to elicit endocrine virilizing activity. An evaluative synopsis indicates that including the case described in this paper only 13 can be regarded as a clinical, morphologic, and functional entity. This entity should be differentiated from the inhomogeneous group of luteomas as the "androluteoma syndrome of pregnancy." It is characterized by the following major criteria: virilization, beginning with the second trimester of pregnancy; histologic criteria of a luteoma of pregnancy; production of testosterone, leading to excessive plasma levels (exceeding the concentration of androstenedione), and masculinization of female fetuses.


Fibrous histiocytoma of the tarsus.

Fibrous histiocytoma of the tarsus. A 21-year-old white man had an asymptomatic eyelid mass that had slowly enlarged for one year. On clinical examination the lesion was well circumscribed; it appeared subconjunctivally but provoked no conjunctival inflammation, and had a consistency suggestive of cartilage. Microscopic examination showed it was matted and composed of elongated fibro-histiocytes and an evenly distributed population of xanthoma cells and Touton giant cells. The lesion was easily removed by local excision because of a pseudocapsule formed by remnants of the tarsus; there has been no recurrence during a 12-month follow-up.


Mesectodermal leiomyosarcoma of the antrum and orbit. A 39-year-old black man developed a left antral leiomyosarcoma that subsequently extended into the ipsilateral orbit. On light microscopic appearance of the antral tumor the presence of a distinctive myxoid and fibrillar cytoplasmic background suggested the diagnosis of a malignant Schwann's cell tumor. A second biopsy of the orbital extension displayed the same fibrillar character, but the emergence of tumor giant cells with cytoplasmic trichrome positivity also raised the possibility of a rhabdomyosarcoma. Electron microscopy demonstrated the smooth muscle derivation of the tumor, which probably originated from vascular smooth muscle elements. The atypical neural appearance of this myogenous tumor may have been caused by the extensive neural crest contribution to the cephalic connective tissues (mesectoderm). Radiation therapy and chemotherapy were ineffective.


Immunohistochemical and ultrastructural analysis of medullary carcinoma of the thyroid in relation to hormone production. Eighteen cases of medullary carcinoma of the thyroid were analyzed immunohistochemically for calcitonin- and ACTH-containing cells, and tumor cells in 8 cases were examined by an electron microscope and analyzed by manual and computer procedures with particular attention paid to the size and quality of secretory granules. Calcitonin- and ACTH-containing cells were found singly or in clusters in 14 and 11 tumors, respectively. In 4 cases, calcitonin-positive cell clusters and an increase in number of singly scattered C cells were seen apart from the main tumor, suggesting a multicentric nature of certain medullary carcinomas. Some ACTH-containing cells were apparently also positive for calcitonin. In a case of familial Sipple disease, follicular lining cells were replaced in areas with ACTH-containing cells. Three to five frequency distribution curves of the size of secretory granules were obtained in all of 6 cases analyzed, and at least two different types of granule matrix were identified.


The stability of events in the natural history of neoplasia. Previous studies on the natural history of neoplasia, utilizing mouse skin as a model, have demonstrated that the process of epidermal carcinogenesis may be separated into at least two different phases. The first of these, termed "initiation," is essentially irreversible; the second phase, that of promotion, may be modulated or reversed by a variety of environmental conditions. More recently, similar stages have been demonstrated for other organ systems during carcinogenesis, in particular that of murine liver. At the same time, investigations of a variety of systems including those in plants, amphibians, and, most recently, in mammals have demonstrated that the initiation process of neoplasia may not be as irreversible as previously considered, but in several of these systems, including those in plants and in the mouse teratoma, the neoplastic process appears to be reversible from its initial stages under appropriate conditions. A proposed scheme is presented which takes into account the reversibility of the process of initiation in the natural history of neoplasia.


The type 1 alveolar lining cells of the mammalian lung. II. In vitro identification via the cell surface and ultrastructure of isolated cells from adult rabbit lung. Using a newly described dissociation and isolation technique, Type 1 alveolar lining cells were obtained from adult rabbit lung within a heterogeneous population. Identification of many lung cell types in this mixed population was by a) comparison of isolated cells with in situ lung cells in lung sections using identical parallel staining, b) stepwise ultrastructural examination of cells during all stages of lung dissociation so that intercellular associations were monitored throughout, and c) Type 1 cell surface changes following collagenase treatment. This phenomenon was studied with both electron and light microscopy, the latter employing tetrachrome staining of basophilic blebs as well as characteristic staining of nucleus and cytoplasm. Following their isolation, most Type 1 cells lost their surface blebs and assumed a "relaxed" state. In this condition, Type 1 cells were exposed to cytochalasin D (CD) for various times and at several concentrations. Surface knobs, having all the characteristics of zeiotic knobs produced in a number of cultured cell lines by exposure to CD, were produced in isolated Type 1 epithelial cells within 45 minutes. The reaction to CD was temperature-dependent, proceeding maximally at 37 C with inhibition at lower temperatures and was inhibited by antimetabolites such as dinitrophenol and 2-deoxyglucose in the presence of CD. As with established cell lines, formation of zeiotic knobs at the isolated Type 1 cell surface appeared closely related to microfilamentous nets located beneath the plasmalemma. The density of this net appeared to vary as isolated Type 1 cells underwent expansion and contraction in response to CD. Zeiotic knobs were formed as the result of herniation of endoplasm through the cell cortex. The significance of such a labile cortical zone is considered in relation to the deformation changes Type 1 cells undergo during inflation-deflation of alveoli and the folding-unfolding of alveolar lining cells as a result of lung volume changes.


Replication of type I herpes simplex virus in primary cultures of hairy cell leukemic leukocytes. The ability of leukemic leukocytes to support the replication of herpes simplex virus (HSV) was studied. Mononuclear leukocytes (MNL) from the peripheral blood of patients with a variety of lymphoid leukemias were isolated on Ficoll-Hypaque gradients and infected with HSV at a multiplicity of infection of 5 to 10. No virus growth was detected in cells from patients with chronic lymphocytic leukemia (9), acute lymphocytic leukemia (1), or lymphosarcoma cell leukemia (2), HSV replication did occur in hairy cell leukemic MNL from all of 4 patients studied. Maximal titers of 10(3.7) to 10(4.7) PFU/ml occurred 1 to 7 days after incubation. By electron microscopy, herpesvirus particles were seen in the nuclei of these infected cells after 3 days of culture, but none was seen in the cells not exposed to virus. Fluorescent antibody examination confirmed the presence of HSV antigens in the nuclei of infected hairy cells. No difference in the adsorption or penetration of the virus was found with the various MNL studied. Productive infection of the cells thus appeared to depend on the ability of the leukocyte ;o support a later stage of infection, either uncoating or replication of the virus.


Isolation of enzymatically homogeneous populations of human lymphocytes, monocytes, and granulocytes by zonal centrifugation. Human monocytes, lymphocytes, granulocytes, red cells, and platelets were completely separated from each other by zonal centrifugation on linear sucrose density gradient. The monocytes contained only one tenth the amount of myeloperoxidase, one half the amount of lysozyme, one half the amount of acid ,hosphatase, and one half the amount of beta-glucuronidase found in granulocytes; the monocytes contained no alkaline phosphatase or neutral protease. The lymphocyte fraction contained only acid phosphatase and beta-glucuronidase in amounts one half as much as in the monocytes. Fluctuations in enzyme levels of monocytes and granulocytes were noted following infection. In vitro, the isolated monocytes transformed into macrophages. The results suggest that lymphocytes, monocytes, and granulocytes may be linked biochemically in a differentiation sequence through sets of commonly shared enzymes as well as by groups of enzymes specific for each divergent cell line.


Role of insulin during exercise-induced glycogenesis in muscle: effect on cyclic AMP. Skeletal muscle cyclic AMP (cAMP) content and glycogen synthesis were investigated in male rats subjected to exhaustive exercise, alloxan diabetes, and combinations of these conditions. After an exhaustive swim or control treatment of wading, randomly selected animals were administered 500 mg glucose via stomach tube. Two hours after glucose administration, gastrocnemius glycogen levels rose from 1.31 to 10.67 mg/g wet wt in fatigued nondiabetics (FND), producing a 94% supercompensation above control values. Glycogen of fatigued diabetics (FD) increased from 0.88 to 4.21 mg/g wet wt during the first 2 hr after glucose administration and did not reach control values for 24 h. In conjunction with these glycogen changes, cAMP increased from 1.23 to 2.59 and 1.47 to 2.81 pmol/mg wet wt for FND and FD, respectively (P less than 0.05). No difference in cAMP levels between diabetics and nondiabetics was found. These in vivo data suggest that insulin may not be essential for muscle glycogen synthesis, but that after glycogen depletion it plays a prominent role in supercompensation. Also, this hormone's mechanism of action in skeletal muscle does not appear to be mediated through alteration in the tissue cAMP concentration.


Immunofluorescent study on egg-adapted avian encephalomyelitis virus infection in chickens. Fluorescent antibody study showed persistent infection of egg-adapted avian encephalomyelitis virus in the central nervous system and pancreatic tissues of infected embryos and chickens hatched from them. The limited organ tropism of the egg-adapted virus in hatched chickens was in striking contrast to the systemic infection that occurs with a field strain. In chidkens orally infected with egg-adapted virus strains, transient infection of a few organs was found despite occurrence of viremia.


Isolation of bovine adenovirus type 4 from cattle in Oregon. Four isolates of bovine adenovirus type 4 were recovered from Oregon cattle. One isolate was recovered from a 1-week-old calf with pneumoenteritis, and 1 isolate from an 8-month-old bull with fever and respiratory disease. Two isolates were recovered as latent viruses in testicular cell cultures. All 4 isolates of the virus were shown to have certain physical, chemical, biologic, and antigenic characteristics similar to previously described strains of bovine adenovirus type 4. Of 246 adult beef and dairy cattle in Oregon, 51% had serum-viral neutralizing antibodies to the type 4 virus at the 1:8 dilution level.


Demonstration of equine infectious anemia virus in primary leukocyte cultures by electron microscopy. Electron microscopy was used to demonstrate the presence of viral particles in primary cultures of leukocytes taken from a horse after SC inoculation with the Wyoming strain of equine infectious anemia virus. Unlike previous studies, the exposure virus was not passaged through cell culture prior to horse inoculation. Cultures were begun approximately 1 week before and 1 week after the 1st pyrexic period after inoculation. In both samples, viral particles and cytoplasmic alterations were observed resembling those previously reported in equine infectious anemia virus and other retravirus-infected cells.


Prevalence of ovine progressive pneumonia in a sampling of cull sheep from western and midwestern United States. Ovine progressive pneumonia was found to be prevalent in many major sheep-producing areas in the United States. The incidence was determined in a sampling of cull sheep (5 to 10 years of age) at slaughter. Diagnostic criteria were based on finding viral-specific immunoglobulins, virus, or lesions. Each method indicated a high incidence in samplings from midwestern and northwestern states and a relatively low incidence in the sampling from southwestern states. Of those sheep examined, precipitating immuno-globulin to the causal virus was seen in 1.0% to 67.5%, virus was isolated from the lungs of 0% to 46.2%, and lymphoid hyperplasia was seen in the lungs of 0% to 38.5%. The most common lesions in the lungs (from which virus was isolated) were multiple lymphoid nodules and increased fibromuscular tissue.


Oropharyngeal excretion of Epstein-Barr virus by patients with lymphoproliferative disorders and by recipients of renal homografts. In an attempt to associate oropharyngeal excretion of Epstein-Barr (EB) virus with lymphoproliferative disorders other than infectious mononucleosis, we tested throat gargles collected from adult subjects for the EB virus. Nine (16%) of 55 healthy persons were positive. High EB virus-excretion rates were found among patients with active acute lymphocytic leukemia (6/6, 100%), among renal homograft recipients during the third to 12th month after transplantation (26/30, 87%), and among critically ill patients with leukemia-lymphoma (14/19, 74%). Moderately high excretion rates were found among patients with myeloma (7/16, 44%), patients with poorly differentiated lymphocytic lymphoma (5/11, 44%), critically ill patients with solid cancers (15/37, 41%), and patients with chronic myelogenous leukemia (8/21, 38%). Our data suggested that the higher than normal excretion rate is realted to the basic disease process and to the general health status but not to the duration of cancer chemotherapy.


[Corticosteroids determination in pig plasma (author's transl)]. To measure corticosteroid levels in peripheral blood of pig, the competitive protein-binding assay of Murphy was compared to a fluorimetric determination of cortisol and corticosterone previously separated by thin-layer chromatography. Accuracy and precision of each technique were determined. Concentration of corticosteroids were found to be 3.4 +/- 0.3 microgram/100 ml by competitive protein-binding and 2.4 +/- 0.2 microgram cortisol/100 ml and 0.3 +/- 0.03 microgram corticosterone/100 ml by fluorimetric determination. These levels were subject to diurnal variations. They were increased by ACTH administration and decreased by dexamethasone treatment. Both techniques were found to be sensitive and accurate to assess adrenal function in pigs. The competitive protein-binding assay, in spite of its relative lack of specificity, would appear to be suitable for routine analysis.


Early x-ray diagnosis of occult infiltrating nasopharyngeal carcinoma. The occult type of nasopharyngeal carcinoma (NPC) accounts for 30% of all nasopharyngeal carcinomas. The occult NPC is clinically difficult to visualize, because the tumor infiltrates and grows in the submucosa. It then metastasizes to the skull base or draining lymph nodes. When the NPC is finally diagnosed, the prognosis is poor. Three refined x-ray techniques are evaluated for their utilization in earlier diagnosis of the occult NPC: thin section tomography, nasopharyngography, and Eustachian tube function studies. In a consecutive series of 50 patients, these techniques detected 12 infiltrating carcinomas not visible on clinical examination. Five of these patients also had initially negative blind biopsies. Patients having diplopia, facial numbness, cervical adenopathy, and chronic serous otitis media are highly suspect for NPC. The described x-ray techniques, that are safe and noninvasive, can detect these occult infiltrative tumors earlier than clinical examination. Earlier detection and treatment of NPC has resulted in a significant increased cure rate.


[Antiviral properties of analogs of distamycin A]. The effect of 9 analogues of distamycin A was studied in a tissue culture with respect to the virus of a smallpox vaccine and classical avian plague. Three analogues of distamycin A (I, VI, VII) were studied in chick embryos with respect to the smallpox and influenza viruses. The analogues were characterized by a loss or decrease of the activity against the smallpox vaccine virus as compared to distamycin A. In contrast to distamycin A analogue VII had an inhibitory effect on influenza infection in chick embryos.


ATP formation associated with fumarate and nitrate reduction in growing cultures of Veillonella alcalescens. Molar growth yields, fermentation balances and enzyme activities were measured in Veillonella alcalescens grown anaerobically with different substrates in the absence or presence of fumarate or nitrate. The molar growth yields on malate (14.3 g dry wt bacteria/mole substrate) and citrate (19.3) were higher than that on lactate (8.6). The molar growth yield on lactate was increased to 15.5 or 19.8 by the addition of fumarate or nitrate, respectively, to the growth medium, and the molar growth yield on citrate was increased to 25.3 by addition of nitrate. Active growth on pyruvate was only observed in the presence of nitrate, and the molar growth yield was 25.5. From fermentation balances and fermentation systems similar YATP values (g dry wt bacteria/mole ATP) were calculated for all substrates or mixtures of substrates assuming that one mole of ATP is generated at the electron transport from pyruvate, NADH and NADPH to nitrate or fumarate whereas ATP is not produced in the electron transport from lactate to fumarate or nitrate, and, therefore, this assumption was considered to reflect the actual situation. The mean YATP value at a doubling time of 1 h was 16.5 g dry wt bacteria/mole ATP for growth without an added hydrogen acceptor, 14.4 for growth with fumarate, and 14.2 for growth with nitrate.


Virus production with a newly developed microcarrier system. Primary cell cultures as well as established lines have been grown on a recently developed microcarrier configuration that overcomes the problem of toxicity attendant on earlier developments in this technology. Virus yields from these cells propagated on the new microcarriers have been measured. Microcarrier-grown cells, when compared to roller-bottle-grown cells, gave virus yields on a per-cell basis that varied from slightly greater with the Sindbis virus-Chinese hamster ovary cells and polio-WI-38 combinations to approximately one-third with Moloney murine leukemia virus-Cl-1 mouse cells and vesicular stomatitis virus-chicken embryo fibroblasts. Yields ranged from 8.0 X 10(7) to 3.6 X 10(8) cells per 100-ml microcarrier culture and from 3.7 X 10(7) to 4.1 X 20(8) cells per roller-bottle culture. Secondary chicken embryo fibroblast yields were approximately four times as great in microcarrier cultures as in standard roller-bottle cultures, per unit volume of medium consumed. In spite of the reduced virus yields per cell seen in some instances, the greater cellular productivity of microcarrier cultures appears to hold great promise for large-scale virus production. Optimizing microcarrier conditions for specific cell-virus systems should result in improved yields.


Increase in arginine and citrulline production by 6-azauracil-resistant mutants of Bacillus subtilis. In the arginine producer AHr-5, an L-arginine hydroxamate-resistant mutant of Bacillus subtilis, accumulation of N8-acetyl-L-ornithine increased as the level of L-arginine accumulation increased in the medium containing L-glutamic acid. Ornithine carbamoyltransferase of this strain was genetically derepressed. These results suggested that carbamoylphosphate might be deficient in vivo. With the intention to increase endogenous carbamoylphosphate, pyrimidine analogs inhibiting growth were selected and the mutants resistant to these compounds were derived from the AHr-5 mutant. Of the resistant mutants derived, the 6-azauracil-resistant mutant AAr-9 produced 28 mg of L-arginine per ml, which corresponded to more than twofold the amount produced by the parent strain. Derivation of an arginine-requiring mutant from the double-resistant mutant AAr-9 provides a new advantageous method for the production of L-citrulline. The increase in arginine and citrulline production is discussed.


Development of poliovirus having increased resistance to chlorine inactivation. A laboratory strain of poliovirus (LSc) became progressively more resistant to chlorine inactivation during a series of repeated sublethal exposures to the halogen.


Ultrastructure of cutaneous cellular infiltrates in scleroderma. Electron microscopy of the skin was performed in ten patients with systemic and four with localized scleroderma. The following three groups of cells were identified: (1) mature lymphocytes, T lymphoblasts, immature plasma cells, and plasma cells; (2) fibroblasts, fibrocytes, and fibroblast-like cells; and (3) macrophages, undifferentiated mesenchymal cells, and monocytes. Inthose specimens with mononuclear cell infiltrates, the most common cells were lymphocytic-types, macrophages, and fibroblasts with well developed rough endoplasmic reticulum. In the specimens at the fibrotic stage, fibroblasts and histiocytic-type cells predominated. This study suggests that cellular and humoral immunity may play a role in the pathophysiology of scleroderma.