In vitro and in vivo myocardial effects of a cyclic AMP phosphodiesterase inhibitor structurally related to natural cardenolides. The myocardial effects of the lactonic deoxybenzoin glucoside, AP 10, an ATPases and cyclic AMP phosphodiesterases inhibitor, were investigated in vitro and in vivo. AP 10 showed marked positive inotropic effects on spontaneously beating frog and mammal isolated hearts. This drug induced a substantial increase in cyclic AMP atrial level comparable to that observed with papaverine in the rat. Its inotropic effects on stimulated rat left atria were moderate and suppressed by reserpine pretreatment, in contrast with papaverine inotropic effects which were not significantly modified. As papaverine (10(-5) M), AP 10 (10(-4) M) shifted to the left the atrial dose-response curve for isoproterenol. The positive inotropic effects of AP 10 were more pronounced at low calcium concentrations. Furthermore, AP 10 prolonged the time course of tension decline in stimulated rat left atria exposed to Ca++ free medium. AP 10 (1 mg/kg) did not induce any in vivo hemodynamic disturbance in both anaesthetized and conscious dogs and significantly improved ventricular automaticity in anaesthetized dogs (0.5 mg/kg). This drug was also compared to quinidine in two in vivo experimental arrhythmias. AP 10 was more effective than quinidine in preventing ouabain-induced arrhythmias in conscious rabbits and electrically-induced atrial fibrillation in conscious dogs. Despite its ATPases inhibiting properties and some structural similarities with cardiac glycosides, AP 10 did not show a typical "digitalis-like" pharmacological profile. It exhibited some of the myocardial features which characterize phosphodiesterase inhibitors as caffeine, papaverine or Ro 7-2956. An interesting particularity of AP 10 action was its capacity to prevent experimental arrhythmias.


The effect of triamterene upon the rat kidney plasma membrane Na-K-ATP-ase activity. Triamterene (2,4,7-triamino-6-phenylpteridine) is a potassium-sparing diuretic whose mechanism of action is not clear. Experiments were performed to study the effect of triamterene upon the activity of Na-K-ATP-ase in the kidney plasma membranes. This enzyme, dissolved within the membrane bilayer, has been considered to be a biochemical vehicle for the active transport of sodium across the cell membrane. Intact and adrenalectomized rats were subjected to a five-day treatment with triamterene in a daily dose of 1.5 mg/100 g body weight. Triamterene was also administered to a group of intact, salt-loaded, rats. The activity of Na-K-ATP-ase in the kidney plasma membranes of intact and adrenalectomized rats treated with triamterene was decreased by 22.4% (p less than 0.05) and 37.2% (p less than 0.05), respectively. The activity of Na-K-ATP-ase in the renal plasma membranes of intact, salt-loaded, rats underwent greater decrease--63% (p less than 0.05). If the decreased activity of Na-K-ATP-ase in the kidney plasma membranes of rats treated with triamterene manifested the diuretic action of triamterene, results obtained in adrenalectomized rats would suggest that triamterene acts directly on the kidney, not via the adrenal glands.


Divergent effects of prostaglandin synthesis inhibitors on pulmonary cyclic 3', 5'-adenosine monophosphate and cyclic 3', 5'-guanosine monophosphate levels in untreated and histamine sensitized mice. Prostaglandin synthesis inhibitors (indomethacin and acetylsalicylic acid) were studied in mice under control conditions and during a period of B. pertussis-induced increased sensitivity to histamine. These compounds were employed to inhibit the generation of prostaglandins and thus allow for analysis of prostaglandin participation in the heightened accumulation of pulmonary cyclic nucleotides in pertussis-sensitized mice. The results show that the two non-steroid antiinflammatory agents studied caused a reduction in basal cyclic GMP levels in pulmonary tissue of mice. Cyclic AMP levels were unaltered. Histamine raised cyclic  GMP levels in sensitized mice even in the presence of cyclo-oxygenase inhibition, but these rises never exceeded basal levels in mice that had not received cyclo-oxygenase inhibitors. It can be concluded that prostaglandin synthesis inhibitors suppress the cyclic GMP system.


Adenylyl cyclase deficient cr-1 (Crisp) mutant of Neurospora crassa: cyclic AMP-dependent nutritional deficiencies. The inability to synthesize cyclic AMP drastically affects the nutritional metabolism of Neurospora crassa. The adenylyl cyclase-less mutant cr-1 (crisp) did not utilize several carbon sources, including glycerol, mannitol, arabinose, and casaminoacids. However, in glucose or acetate it grew as well as the wild type. The following evidence suggested that these nutritional deficiencies were a direct result of the cr-1 mutation: (i), in crosses to wild type they segregated together with the crisp morphological marker; (ii), cyclic AMP added to the cr-1 mutant growth medium overcame the nutritional deficiencies; (iii), the cyclic AMP effect was specific for the crisp mutant, for it was not observed with the wild type, nor with a spontaneous glycerol-utilizing cr-1 strain.


Cellular proliferation, cellular death and atherosclerosis. The multipotential smooth muscle cell (SMC) is the predominant cell in arterial media and intima, and the major cell type involved in proliferative lesions. Studies using a precursor of DNA, namely [3H] thymidine, and autoradiography have shown that proliferation of SMC is an important and early response to atherogenic stimuli, such as cholesterol feeding, surgically induced hypertension or endothelial injury. Cultures of aortic SMC offer excellent in vitro models to study the reactivity of these cells to recognized or suspected risk factors. Pure SMC cultures are obtained by placing small fragments of aortic media in a defined culture medium and their response evaluated by thymidine incorporation and/or increase in size of the outgrowing cell colony. Factors essential for adequate growth include normal serum constitutents, including the lipoproteins and a platelet derived factor. Replacing the normal serum with dietarily induced hyperlipemic serum results in greatly increased proliferation. The serum fraction largely responsible for this phenomenon is the low density lipoprotein. Simultaneous addition of high density lipoproteins partly suppress this reaction. Serum from diabetic or hypertensive--but normolipemic--animals similarly stimulates these cells to increased proliferation.


Adult rhabdomyoma of the larynx.

Adult rhabdomyoma of the larynx. A case of rhabdomyoma of the larynx in a 76-year-old woman patient is reported. The tumor was localized on the left vocal cord. This case is, so far described, the seventh one of adult rhadbomyoma of the larynx. The differential histological and histochemical diagnosis with granular cell myoblastoma is discussed and tabulated. Both tumors can easily be confused. In accordance with previously reported cases no evidence of recurrence after more than two years could be observed.


Marek's disease in chickens: correlation of Marek's disease with nuclear-inclusion formation in feather-follicle epithelium. The dynamics of nuclear-inclusion (NI) formation in feather-follicle epithelium of chickens inoculated with Marek's disease virus (with or without prior immunization with turkey herpesvirus) could be divided into two patterns: 1) transient NI formation at the initial stage postchallenge; and 2) persistent NI formation. Incidence of Marek's disease was closely correlated with the dynamics of NI formation. Active NI formation recurred in chickens showing pattern 2 and was closely related to the incidence of nerve lesions.


Pathogenicity for baby chicks of the G-4260 strain of the picornavirus "avian nephritis virus". The pathogenicity of the G-4260 strain of picornavirus for day-old chicks was studied by intraperitoneal inoculation. No clinical signs were observed. A mild yellowish-tan discoloration of the kidneys was noticed in necropsy 7 to 21 days after inoculation. Mean body weight was significantly lower (P less than 0.01) in inoculated groups than in control groups 7 days after inoculation. In a chronological study on the distribution of the virus in organs, the virus was recovered from various organs, exclusive of the brain and trachea. The virus titer was higher in the kidneys, jejunum, rectum, and bursa of Fabricius than in any other organ. Fluorescent antigens were seen predominantly in the epithelia of the renal tubules.


Pathological changes in chicks inoculated with the picornavirus "avian nephritis virus". One-day-old chicks were inoculated intraperitoneally with a newly isolated picornavirus. The inoculated chicks showed no clinical signs until 28 days postinoculation (PI), but discoloration of the kidneys was recognized from 7 to 21 days PI at autopsy. Histologically, focal lesions were observed in the cortex of the kidneys from 3 to 21 days PI. The lesions were characterized by interstitial lymphocytic infiltration and degeneration of epithelial cells of the proximal convoluted tubules. The degenerated cells contained acidophilic granules in their cytoplasm. Electron-microscope examination of the cytoplasm revealed electron-dense amorphous areas, phagosomal areas with viral particles, and isolated crystal arrays of the virus particles, 23 to 30 nm in size. Granular antigen was also detected by fluorescent-antibody technique in the cells.


Experimental infection of broiler and Leghorn chickens with virulent and avirulent isolates of hemorrhagic enteritis virus. The effects of virulent and avirulent isolates of hemorrhagic enteritis virus were studied in Leghorn and broiler chickens. The viruses caused subclinical infections in both strains of birds. The avirulent isolate produced enlarged spleens, inclusion bodies, and antibody in all inoculated Leghorns. In broilers the avirulent virus produced infection in only half of the inoculated birds. Inclusion bodies were widely dispersed in the spleens of both types of birds. The virulent virus produced infection in all inoculated birds of both strains. Inclusion bodies were numerous in the spleens of Leghorn birds and were widely scattered in the spleens of broilers.


Studies on interferon induction by infectious bursal disease virus (IBDV). II. Interferon production in White Leghorn chickens infected with an attenuated or pathogenic isolant of IBDV. Infectious bursal disease virus (IBDV) isolants that differed in virulence for chickens, were compared as to: 1) induction of interferon in serum and tissues; and 2) stimulation of IBDV serum antibody. Specific-pathogen-free chickens were infected at one day and four weeks of age by the subcutaneous and intranasal routes of inoculation. The pathogenic isolant induced a more generalized interferon response than the attenuated isolant, independent of age or route of inoculation. Pathogenic IBDV stimulated interferon in serum, kidney, lung, thymus, spleen, and bursa of Fabricius. The attenuated virus induced interferon only in the bursa. The serum interferon response was greater following inoculation with pathogenic IBDV than with the attenuated virus. Serum interferon titers peaked 2-3 1/2 days after inoculation. The pathogenic and attenuated viruses stimulated similar IBDV-neutralizing antibody responses, which occurred after peak serum interferon activity.


Low incidence of lymphoid tumors in chickens continuously producing endogenous virus. A flock of 258 male and 243 female chickens of a cross of Regional Poultry Research Laboratory lines 15B and 7(2) were kept in a filtered-air positive-pressure house and observed for tumors from 100 to more than 729 days of age. These birds produced high titers of a subgroup E endogenous virus from the middle of the embryonic incubation period through the end of the experiment. No neoplasms were observed in the males. The females had two neoplasms indistinguishable from lymphoid leukosis and three other neoplasms not involving lymphoid cells. No evidence was found of infection with exogenous lymphoid leukosis viruses, Marek's disease virus, reticuloendotheliosis virus, or adenovirus (isolated on the isolation farm). Inoculation of another sample of this cross with a lymphoid leukosis virus of subgroup A resulted in 88% mortality with neoplasms (mostly lymphoid leukosis) by 167 days of age. The conclusion is that high levels of spontaneously produced endogenous virus do not induce high levels of neoplasms in chickens susceptible to lymphoid leukosis.


An evaluation of methods for eradication of avian leukosis virus from a commercial breeder flock. Two trials were conducted to determine whether lymphoid leukosis virus (LLV) could be eradicated from chicken breeder stocks in one generation. Dams were selected as potentially virus-free parents on the basis of negative tests for virus in progeny embryos (trial 1) or in vaginal-cloacal swabs (VCS) (trial 2) of the dams. In trial 1, 8 of 12 groups of chickens hatched from selected breeders remained free of LLV infection through 36 weeks of life. In trial 2, VCS appeared to be more efficient in detecting possible shedder dams, and only 1 of 72 groups of chickens showed evidence of infection at 14 weeks after hatching. Within that positive group, a single chicken was shown to be the possible cause of the infection. The results show that eradication of LLV can be accomplished in one generation by: 1) virological examination of dams for shedding; 2) elimination of the shedder dams; and 3) small-group rearing of the progeny chicks.


An enzyme-linked immunosorbent assay for detecting avian leukosis-sarcoma viruses. Immunoglobulins from antiserum raised against chromatographically purified avian myeloblastosis virus (AMV) group-specific (gs) antigens were used in enzyme-linked immunosorbent assay (ELISA). Readily discernible color was produced with 2--3 ng of AMV protein in microplate wells coated with 4 micrograms of salt-precipitated immunoglobulins. When a biological assay, i.e., phenotypic mixing (PM), was the criterion for the infectious status of specimens, the ELISA consistently identified a greater percentage of virus-positive specimens than direct complement-fixation (DCF) tests. Over 95% concordance was obtained between the ELISA and PM bioassays when meconia and whole-blood samples were tested. Moreover, three DCF(-) egg albumens from one virus shedder hen were positive by the direct ELISA. Complete agreement was found between a biological assay for endogenous virus and the ELISA when blood and albumens from inbred chickens were tested. The ELISA is a rapid and convenient alternative to the DCF test for identifying infected chickens in eradication programs, because virus-rich sources such as meconia and blood that are unsuitable for DCF can be tested directly.


A clinicopathologic study on patients suffering from "chronic dysentery". Fifty adult patients with the self diagnosis of "chronic dysentery" were studied. Their faeces were examined microscopically; they were sigmoidoscoped and their rectal mucosa were examined histologically. Most of them had irritable bowel syndrome. Their sigmoidoscopic appearances were normal and the histology showed only mild increase in the numbers of round cells in the lamina propria. This was regarded as normal for the local population. Ten patients showed cysts of Entamoeba histolytica in the faeces. This was thought to be unrelated to the symptoms. Only four patients had sigmoidoscopic as well as histologic evidence of moderate to severe proctocolitis. One of them was proven to be a case of amoebic colitis. These findings have been discussed.


In vitro isolation, propagation, and characterization of duck hepatitis virus type III. The in vitro isolation, propagation, and characterization of duck hepatitis virus Type III (DHV-III), is described. This virus, which is serologically distinct from the classical (Type I) DHV, replicated in liver and kidney cell cultures of duck origin. Replication was limited in chicken and quail kidney and duck embryo fibroblast cultures. It did not replicate in a variety of other cell cultures of avian or mammalian origin. The virus was grown successfully in embryonating eggs of ducks, but not of chickens. DHV-III passed through a 50-nm membrane filter, was stable at pH 3.0 and resisted treatment with 5% chloroform. Virus growth was not inhibited by treatment with 5-iodo-2-deoxyuridine. Electron-microscope examination revealed crystalline arrays in the cytoplasm; virus particles had cubic symmetry, and were about 30 nm in diameter. By these properties, this virus can be classified as a member of the picornavirus group.


Occurrence of atypical fowlpox in poultry farms in Kenya. Atypical fowlpox occurred in several poultry farms in Kenya. On two occasions layers had their eyes closed and egg production dropped. Fowlpox virus was isolated from lesions on the inner surfaces of the closed eyelids. Other chickens had lesions covered by yellow caseous necrotic material in the mouth, around the epiglottis, and in the trachea and choanae. Typical proliferative cutaneous lesions were observed in birds of all ages in other flocks examined. Fowlpox virus was recovered from both cutaneous and diphtheritic lesions. The infected chorioallantoic membranes had focal hyperplastic lesions containing pink-staining intracytoplasmic inclusion bodies in most cells. Transmission studies showed that the virus was highly virulent to susceptible chickens.


A typology of the gnathostome adenohypophysis with some emphasis on its gonadotropic function. Recent publications show that the average gnathostome adenohypophysis consists of four parts and contains six morphological cell types. Histophysiological and immunocytochemical data prove the secretion of one or two gonadotropins by one type of basophils that in numerous species in characterized by the presence of large globules besides secretory vesicles. The existence of a second type of gonadotropin secreting cells remains doubtful. Thyrotropin is produced by a separate type of basophilic cells, prolactin by erythrosinophils of the rostral pars distalis, and somatotropin by orangeophils of the proximal pars distalis. At rostral and caudal places of contact with the neurohypophysis, cells are concentrated that may be lead-haematoxylin-positive, and produce a protein consisting of peptides with hormonal and opiate activities. Among the hormones secreted by these cells, situated in the pars distalis and the pars intermedia, are corticotropin and melanotropin respectively. The factors that cause the differentiation of the primordium of the adenohypophysis are almost entirely unknown.


Isolation of Pacheco's disease herpesvirus in Texas. Pacheco's disease herpesvirus was determined to be the agent responsible for the death of about 200 psittacine birds comprising five species. Clinical signs, necropsy lesions, and virus isolation and identification methods are described.


The nature of the hydroxyapatite-binding site in salivary acidic proline-rich proteins. Protein A and C, which are major components of the acidic proline-rich proteins in human saliva, were digested, before or after adsorption to hydroxyapatite, with alkaline phosphatase, trypsin, thermolysin and  a proteinase preparation from salivary sediment. The results demonstrate that the binding site is located in the proline-poor N-terminal part of the protein, possibly between residues 3 and 25. Phosphoserine is necessary for maximal adsorption of the proteins to hydroxyapatite. When proteins A and C are adsorbed to hydroxyapatite before proteolytic digestion there is a protection of some of the susceptible bonds in the N-terminal part of the proteins and a gradual removal of the proline-rich C-terminal part. Thermolysin can cleave susceptible bonds in the part of the protein that remains bound to hydroxyapatite, but at least some of the resulting peptides are retained on the mineral. Since the ability of the proteins to inhibit hydroxyapatite formation and to bind calcium is located in the N-terminal proline-poor part, it is possible that these activities are retained after proteolytic digestion of the adsorbed proteins.


Isolation and partial characterization of high-density lipoprotein HDL1 from rat plasma by gradient centrifugation. The lipoproteins isolated from rat plasma by flotation in the density range 1.019-1.063 g/ml were further characterized. Using rate zonal ultracentrifugation, we isolated two lipoproteins in almost equal proportions from this density range. Similar isolations may be accomplished with density gradients in a swinging-bucket rotor. On isopycnic-density-gradient ultracentrifugation one component banded at rho = 1.031 g/ml and the other at rho = 1.054 g/ml. More that 98% of the apoprotein of the lighter component was B protein, and hence this particle is LD (low-density) lipoprotein. Of the apoproteins of the rho = 1.054 g/ml particles, designated lipoprotein HDL1, over 60% was arginine-rich peptide, and the remainder was A-I, A-IV and C peptides. The molecular weight of these lipoproteins determined by agarose column chromatography was 2.36 x 10(6) for LD lipoprotein and 1.30 x 10(6) for lipoprotein HDL1. On electron microscopy the radius of LD lipoprotein was 14.0 nm and that of lipoprotein HDL1 was 10.0 nm, in contrast with molecular radii of 10.4 nm and 8.4 nm respectively determined from the gel-permeation-chromatography data. The lipid and phospholipid composition of both particles was determined. Lipoprotein HDL1 was notable for both the concentration of its esterified cholesterol, which was similar to that of LD lipoprotein, and the low triacylglycerol content, resembling that of HD lipoprotein. The possible origin of lipoprotein HDL1 is discussed.


Synthesis and degradation of NAD in guinea pig cardiac muscle: I. Dependence upon the extracellular concentration of nicotinamide and nicotinic acid. The NAD concentration as well as the 14C-incorporation in NAD and the disappearance of 14C-NAD were studied in spontaneously beating atria of guinea pigs at high and low concentrations of the precursors nicotinamide or nicotinic acid. Atria were incubated in Krebs-Henseleit solution containing 15 mM glucose and the appropriate precursors at 30 degrees C. The control NAD concentration (33 nMol/100 mg w.w.) remained unchanged during a 24-h-incubation time. -20 mM 14C-nicotinamide increased the total NAD about three-fold (90 nMol/100 mg w.w.) after an incubation period of 24 h, with positive effects on the performance. The incorporation rate in 14C-NAD was calculated to be 43.7 nMol/100 mg w.w. . 24 h. The ADPR moiety for the NAD synthesis stemmed from an endogenous pool. Between 5 and 20 mM nicotinamide the increase in the NAD concentration followed an apparent Michaelis-Menten kinetics with a Km of 6.1 mM nicotinamide and a Vmax of 70.92 nMol NAD/100 mg w.w. . 24 h. This can be explained as a new synthesis of NAD by a high concentration of nictoinamide and also by a decreased degradation of NAD, due to inhibition of the glycohydrolase by the high concentration of nicotinamide. The ratio of incorporation and disappearance of 14C-NAD during the 8th and 16th h incubation period was 2:1. After pre-incubation with 20 mM nicotinamide for an 8-h period the NAD concentration decreased to normal values after incubation for 8 h in a nicotinamide free medium. -20 mM 14C-nicotinic acid did not change the total NAD level and no significant incorporation in 14C-NAD could be detected, whereas negative effects on the performance occurred. -10 muM 14C-nicotinamide showed a slight increase in the total NAD concentration (39.7 nMol/100 mg w.w.) and in the 14C-incorporation (4.8 nMol/100 mg w.w.) within 24 h. -10 muM 14C-nicotinic acid seemed here to be the better precursor in this concentration. The NAD concentration increased to 49.8 nMol/100 mg w.w. after a 16 h incubation period and the incorporation in 14C-NAD was 12.1 nMol/100 mg w.w. after an incubation time of 24 h. As consequences of the observed different influences of each precursor on NAD turnover and NAD concentration the pathways of NAD synthesis and degradation must be studied. The importance of an increased NAD level for the energy metabolism of the cardiac muscle under aerobic and anaerobic conditions is discussed.


Abnormal blood-group-Ss-active sialoglycoproteins in the membrane of Miltenberger class III, IV and V human erythrocytes. 1. We have studied the inherited changes occurring in the sialoglycoproteins of membranes from erythrocytes of type Miltenberger Class III (Mi.III), Miltenberger Class IV (Mi.IV) and Miltenberger Class V (Mi.V) by using sodium dodecyl sulphate/polyacrylamide gel electrophoresis and lactoperoxidase radioiodination. 2. Mi.III erythrocytes lack the normal blood-group-Ss-active sialoglycoprotein but contain an unusual s-active sialoglycoprotein of higher apparent molecular weight. A similar abnormal S-active sialoglycoprotein appears to occur in Mi.IV erythrocytes. 3. The Mi.V condition is associated with the hemizygous absence of both the normal blood-group-MN-active sialoglycoprotein and the normal Ss-active sialoglycorprotein. However, a new sialoglycoprotein component is present in these cells that has properties characteristic of both the MN-active and Ss-active sialoglycoproteins. 4. Our results suggest that the new sialoglycorportein present in Mi.V erythrocytes is a hybrid of the normal MN sialoglycoprotein and an s-active sialoglycoprotein that has properties similar to the s-active sialoglycoprotein found in Mi.III erythrocytes. We suggest that the unusual Mi.V sialoglycoprotein is derived from chromosomal misalignment with unequal crossing-over between the genes for the MN- and Ss-active sialoglycoproteins in a manner similar to that which gives rise to haemoglobin Lepore. 5. Further studies of S-s-erythrocytes confirm that these cells lack normal Ss-active sialoglycoprotein, but contain an unusual component that shows some of the properties of the normal Ss-active sialoglycoprotein. 6. Analysis of erythrocytes of type Mk/Mi.III confirms that, in addition to the known hemizygous lack of the MN-active sialoglycoprotein, the Mk condition is also associated with a loss of the Ss-active sialoglycoprotein. 7. In order to facilitate discussion of the complex changes that occur in these variant erythrocytes, a new unified nomenclature is used for the erythrocyte sialoglycoproteins.


Partial purification and characterization of chick-embryo prolyl 3-hydroxylase. Prolyl 3-hydroxylase was purified up to about 5000-fold from an (NH4)2SO4 fraction of chick-embryo extract by a procedure consisting of affinity chromatography on denatured collagen linked to agarose, elution with ethylene glycol and gel filtration. The molecular weight of the purified enzyme is about 160000 by gel filtration The enzyme is probably a glycoprotein, since (a) its activity is inhibited by concanavalin A, and (b) the enzyme is bound to columns of this lectin coupled to agarose and can be eluted with a buffer containing methyl alpha-D-mannoside. The Km values for Fe2+, 2-oxoglutarate, O2 and ascorbate in the prolyl 3-hydroxylase reaction were found to be very similar to those previously reported for these co-substrates in the prolyl 4-hydroxylase and lysyl hydroxylase reactions.


Spectroscopic forms of carbonmonoxi-cytochrome oxidase. A systematic study of the errors of low-temperature recording of kinetics of the cytochrome oxidase-CO reaction had identified the classic devitrification process of Keilin & Hartree [(1950) Nature (London)165, 504-505]. The methodology described here minimizes this effect, and the computation methods afford appropriate ways of detecting a residual effect. Thus it has been possible to identify that absorption difference spectra and kinetics of the reaction of fully reduced or half-reduced cytochrome oxidase with CO indicate only one spectroscopic form of the respective carbonmonoxi-cytochrome oxidase.


Reversal of part of the aldehyde dehydrogenase reaction pathway during the hydrolysis of an ester. An aldehyde dehydrogenase from rabbit liver, a homogeneous protein on three distinct polyacrylamide-gel systems, has an associated 4-nitrophenyl esterase activity. At pH 7.0 in the presence of 80 micrometer-NADH and 800 micrometer-4-nitrophenyl acetate the enzyme produces NAD+ and a stoicheiometric amount of an aldehyde, as well as hydrolysing the ester. On this and other evidence it is proposed that ester hydrolysis occurs at the usual active site of the enzyme.


Relationship between activity of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase and secretion of very-low-density-lipoprotein cholesterol by the isolated perfused liver and in the intact rat. The hepatic output of triacylglycerol and cholesterol from very-low-density lipoprotein (VLD lipoprotein), and the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase were compared in the isolated perfused rat-liver preparation and in the intact rat. The output of triacylglycerol and cholesterol from VLD lipoprotein by the perfused liver was stimulated by oleate concomitant with stimulation of hepatic microsomal hydroxymethylglutaryl-coenzyme A reductase activity. In the intact animal treated with Triton WR-1339, the magnitude of secretion of triacylglycerol and cholesterol from VLD lipoprotein coincided with the diurnal rhythm of hepatic hydroxymethylglutaryl-coenzyme A reductase activity, which was maximal at 24:00 h and minimal at 12:00 h. These observations suggest that the stimulation of the reductase and of the secretion of cholesterol from VLD lipoprotein by non-esterified fatty acids, as observed with the isolated perfused rat liver preparation in vitro, may also be an important physiological mechanism in vivo. Hepatic cholesterogenesis may be stimulated under conditions conductive to the secretion of the VLD lipoprotein, the primary transport form for triacylglycerol in the postabsorptive state.


Increase in liver nuclear tri-iodothyronine receptors associated with increased deoxyribonucleic acid by long-term administration of tri-iodothyronine in thyroidectomized rats. The effect of long-term administration of small amounts of tri-iodothyronine was examined on the nuclear tri-iodothyronine receptors in rat liver. The maximal binding capacity (C(max.)) and association constant (K(a)) of the receptors were determined in thyroidectomized rats given vehicle alone (group A), 2mug of tri-iodothyronine/100g body wt. (group B) or 7mug of tri-iodothyronine/100g body wt. (group C) for 2 weeks. Scatchard analyses with correction for the amount of endogenous tri-iodothyronine revealed that C(max.) values per g of liver were increased to 1.5 and 2.7 times the control value in groups B and C respectively. Since concentrations of DNA per g of liver were significantly increased in the two groups of hormone-treated rats, C(max.) values per mg of DNA were nearly the same in group B, but still increased significantly in group C compared with group A. K(a) values remained unchanged in all three groups of animals. Mitochondrial alpha-glycerophosphate dehydrogenase activity was 9.6 and 28.7 times as high in groups B and C, respectively, as in group A. Concentrations of endogenous tri-iodothyronine bound to non-histone protein were substantially increased in groups B and C, although concentrations of serum tri-iodothyronine remained rather low. The results obtained indicate that the long-term administration of tri-iodothyronine in small doses induces an increase in the nuclear receptors associated with increased DNA with and without accompanying a relative increase in the receptor concentration in thyroidectomized rats. Also the hormonal effect is closely related to the total number of the nuclear receptors and the concentrations of nuclear tri-iodothyronine bound to the receptors rather than the serum tri-iodothyronine concentrations.


Metabolism of cholecalciferol in land snails. 1. Radioactively labelled cholecalciferol was injected into the land snails Levantina hiersolyma and Theba pisana. Three metabolites (C, D and E), more polar than cholecalciferol, were found. 2. Metabolite C was found to be identical with 25-hydroxycholecalciferol. On injection of 25-hydroxy[26,27-3H]cholecalciferol, metabolite E was predominantly formed. Metabolite D was predominantly formed from cholecalciferol. Metabolites D and E differ from any known cholecalciferol metabolites. 3. The intestine was found to be the tissue capable of carrying out the transformation of 25-hydroxycholecalciferol into metabolite E. 4. 25-Hydroxycholecalciferol and metabolite E were localized in the digestive gland of the snail, the tissue responsible for the absorption of Ca2+ and its storage. Metabolite D was not localized in any specific tissue.


The mechanism of action of lutropin on regulator protein(s) involved in Leydig-cell steroidogenesis. The dependence on lutropin of the synthesis of a proposed short-half-life protein regulator involved in Leydig-cell steroidogenesis was investigated. This was carried out by determining the effect of the protein-synthesis inhibitor cycloheximide, added before and during incubations with lutropin (and/or dibutyryl cyclic AMP), on the rate of testosterone production in suspensions of purified Leydig cells from adult rat testes. The Leydig cells were preincubated in Eagle's medium for 2.5h followed by 30min incubation with and without cycloheximide. The inhibitor was removed by washing the cells and then lutropin was added and testosterone concentrations were determined after incubation of the cells at 32 degrees C. No significant effect of cycloheximide pretreatment on lutropin-stimulated steroidogenesis was found during 60min incubation. This was in contrast with the complete inhibiting effect of cycloheximide when it was added with the lutropin. The pretreatment experiments with cycloheximide were repeated in the presence of dibutyryl cyclic AMP and elipten phosphate (to inhibit cholesterol side-chain cleavage) followed by incubation with lutropin. After 5, 10, 20 and 60min of incubation, testosterone concentrations were 61+/-3, 46+/-3, 27+/-4 and 18+/-4% lower than in the cells pretreated without cycloheximide respectively (means+/-s.e.m., n=4-6). In the cells not pretreated with cycloheximide and in the absence of lutropin, testosterone production increased from 1.36+/-0.5 to 36.5+/-1.0ng/10(6) cells during 20min of incubation, after which no further increase occurred. Pretreatment of the cells with cycloheximide decreased these testosterone concentrations by 65, 46, 42 and 36% in the 5, 10, 20 and 60min incubations respectively (mean values, n=2-4). It is apparent from these results that inhibition of steroidogenesis only occurs if protein synthesis is inhibited in the presence of lutropin or cyclic AMP. A new hypothesis is put forward to explain these findings: it is proposed that lutropin affects the stability of a precursor of a regulator protein by converting it from a stable (inactive) to an unstable (active) form with a short half-life.


Inhibition of pulmonary prostaglandin metabolism by exposure of animals to oxygen or nitrogen dioxide. The effects of exposure of animals to 100% O2 and NO2 on the rate of prostaglandin metabolism by lung and kidney were studied in vitro. Exposure of guinea pigs to 100% O2 for 48 h inhibited the metabolism of prostaglandin F2 alpha by both NAD+- and NADP+-dependent prostaglandin dehydrogenase in lung, but had no effect on the metabolism in kidney. Succinate dehydrogenase, but not glucose 6-phosphate dehydrogenase, in guinea-pig lung was inhibited by exposure to 100% O2. Exposure to 46 p.p.m. but not 16 or 29 p.p.m. NO2 for 6 h inhibited guinea-pig lung prostaglandin dehydrogenase in vitro. The inhibition of pulmonary prostaglandin dehydrogenase by exposure to 100% O2 or to 49 p.p.m. NO2 was dependent on the duration of exposure, but returned to control values within 7 days after cessation of the exposure. The pulmonary transport system responsible for removing circulating prostaglandins from the blood was not affected by exposure to 100% O2 as measured by using the isolated perfused lung. Kinetic analysis of the inhibition of pulmonary prostaglandin dehydrogenase activity in guinea pig exposed to 100% O2 showed non-competitive inhibition with respect to both prostaglandin F2 alpha and NAD+, which suggests destruction or inactivation of the enzyme. Pulmonary prostaglandin dehydrogenase appears to be inhibited by exposure to oxidant gases, which may lead to elevated prostaglandin concentrations in the lungs or in the systemic circulation.


Synthesis of renin substrate by rat liver. The present study attempts to determine if the isolated rat liver is capable of synthesizing renin substrate from 14C-labelled amino acids added in the perfusate. The renin substrate is characterized via reaction with renin, forming a substance that is subsequently identified as proangiotensin. Extensive evaluation of the reaction product is carried out by using molecular-sieve chromatography, countercurrent distribution, reactivity with converting enzyme, radioimmunological technique and bioassay. The results demonstrate that isolated rat liver perfused with artificial salt solution is capable of synthesizing a protein that reacts with renin to form a radioactive substance indistinguishable from proangiotensin.


Phosphorylation of multiple proteins of both ribosomal subunits in rat cerebral cortex in vivo. Effect of adenosine 3':5'-cyclic monophosphate. Investigations were carried out on the phosphorylation of ribosomal proteins in vivo in cerebral cortices of immature rats. Two-dimensional electrophoresis revealed that the cerebral 40S subunit contained at least four ribosomal proteins which were phosphorylated in animals given [32P]orthophosphate intracisternally. These proteins exhibited electrophoretic properties similar to those of the constitutive basic proteins S2, S3a, S5 and S6. The cerebral 60S subunit contained several proteins that were phosphorylated in vivo, including three basic proteins with electrophoretic mobilities similar to those of ribosomal proteins L6, L14 and L19. Four other proteins associated with the 60S subunit that were more acidic were also phosphorylated. Phosphorylated congeners of 40S and 60S ribosomal proteins could often be detected in distinct protein-stained spots on two-dimensional electrophoretograms. The cerebral S6 protein consisted of at least five distinct species in different states of phosphorylation. Administration of N6O-2' dibutyryl cyclic AMP increased the proportion of the more phosphorylated congeners of the S6 protein, but appeared to have little or no effect on phosphorylation of other cerebral ribosomal proteins. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also stimulated S6-protein phosphorylation; N2O2'-dibutyryl cyclic GMP had no effect on this process. These observations indicate that several ribosomal proteins of both subunits are normally phosphorylated in rat cerebral cortex in situ. The results also suggest that selective and specific alterations in the phosphorylation state of the S6 ribosomal protein of the cerebral 40S subunit may accompany the production of cyclic AMP during neural activation.


Transient complexes. A new structural model for the activation of adenylate cyclase by hormone receptors (guanine nucleotides/irradiation inactivation). 1. The irradiation-inactivation procedure was used to study changes in the state of association of the protein components of adenylate cyclase in intact rat liver plasma membranes by measurement of alterations in the target size determined from the catalytic activity of the enzyme. 2. A decrease in target size at 30 degrees C in response to p[NH]ppG (guanosine 5'-[betagamma-imido]triphosphate) or GTP was demonstrated, which we take to reflect the dissociation of a regulatory subunit. The effect of GTP is potentiated by glucagon. This effect is not observed at 0 degrees C. 3. An increase in target size was observed in response to glucagon in the absence of guanine nucleotides, which we take to reflect the association of glucagon receptor with adenylate cyclase. 4. We propose a model for the activation of adenylate cyclase by glucagon in which the binding of the hormone to its receptor causes an initial association of the receptor with the catalytic unit of the enzyme and a regulatory subunit to form a ternary complex. The subsequent activation of the adenylate cyclase results from the dissociation of the ternary complex to leave a free catalytic unit in the activated state. This dissociation requires the binding of a guanine nucleotide to the regulatory subunit. 5. The effects of variation of temperature on the activation of adenylate cyclase by glucagon and guanine nucleotides were examined and are discussed in relation to the irradiation-activation data. 6. The effectiveness of hormones, guanine nucleotides and combinations of hormone and guanine nucleotides as activators of adenylate cyclase in both rat liver and rat fat-cell plasma membranes was studied and the results are discussed in relation to the model proposed, which is also considered in relation to the observations published by other workers.


Salmon calcitonin-induced stimulation of 1 alpha,25-dihydroxycholecalciferol synthesis in rats involving a mechanism independent of adenosine 3':5'-cyclic monophosphate. The effect of natural salmon calcitonin on accumulation in plasma of 1 alpha,25-dihydroxy-[3H]cholecalciferol from 25-hydroxy[3H]cholecalciferol in vivo was investigated in vitamin D-deficient thyroparathyroidectomized rats into which graded doses of the hormone were continuously infused by use of a balance study system. A dose-dependent increase in plasma concentrations of 1 alpha,25-dihydroxy[3H]cholecalciferol was observed with calcitonin infusion for 6--30h at a rate greater than 20 M.R.C. m-units/h. Infusion of parathyrin or cyclic AMP produced a similar stimulation [Horiuchi, Suda, Takahashi, Shimazawa & Ogata (1977) Endocrinoly 101, 969--974], but the maximal effect of calcitonin was additive to that of either parathyrin or cyclic AMP. Furthermore concurrent infusion of theophylline (0.5 mumol/h) did not potentiate the effect of submaximal doses (3 and 20 M.R.C. m-units/h) of calcitonin. Plasma concentrations of calcium showed a decrease with calcitonin infusion for 30h, but those of Pi remained unchanged. These results strongly suggest that the rat kidney is endowed with a calcitonin-sensitive 1 alpha-hydroxylase system that is separate from the parathyrin/cyclic AMP system and is independent of changes in plasma Pi.


Inhibition of the iron-catalysed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine. The peroxidation of membrane phospholipids induced in vitro by ascorbic acid or by dialuric acid (hydroxybarbituric acid) does not occur in the absence of traces of metal ions. Peroxidation induced by adding iron salts to phospholipids can either be promoted or inhibited by the chelators EDTA, diethylenetriaminepenta-acetic acid and bathophenanthrolinesulphonate, depending on the ratio [chelator]/[iron salt]. The iron chelator desferrioxamine inhibits peroxidation at all concentrations tested, and it also inhibits the iron-catalysed formation of hydroxyl radicals (OH.) from superoxide (O2-.). Since desferrioxamine is approved for clinical use, it might prove a valuable tool in the treatment of inflammation, poisoning by autoxidizable molecules and radiation damage.


[Cholera toxin induced epileptogenic focus--special reference to cyclic AMP metabolism and epileptogenic focus (author's transl)]. Epilepsy-like convulsive seizures have been induced by cholera toxin administration into the rat amygdaloid complex. Between the 8th and 48th hr after the administration, rhythmic spike discharges (1--3 spikes/sec) were electroencephalographically observed bilaterally in the amygdaloid complexes, and rats exhibited abnormal behaviors such as running, jumping, tail lifting, rearing, vocalization aggressive behavior, facial twitching and increased salivation. During these stages, high voltage spikes were intermittently observed with generalized convulsive seizures. Duration of the seizure was 1--2 min and the incidence was 0--6 times/hr. At 48 hrs after the administration or thereafter, convulsive seizures disappeared and electroencephalographic abnormalities were gradually normalized. Occasional rhythmic spike discharges, however, were observed more than 168 hrs after the administration. Since autoradiographic observations with 125I-labeled cholera toxin revealed that the injected toxin does not spread out at all from the injected site, the use of this toxin seems to be an ideal procedure to produce micro-epileptogenic foci. Cyclic AMP content as well as adenylate cyclase activity in the ipsilateral amygdaloid complex was significantly increased during preconvulsive and convulsive states. The administration of 5 x 10(-8) moles of dibutyryl cyclic AMP through the cannula implanted into the amygdaloid complex also induced behavioral and electroencephalographic abnormalities similar to those found in the cholera toxin-treated animals. These results suggest that cyclic AMP and/or cyclic AMP dependent neuronal mechanisms may play a significant role in the establishment of epileptogenic focus. Possible use of this animal model for the study of anti-epileptic drugs are also suggested.


Triple hormone-receptor assay: a more accurate predictive tool for the treatment of advanced breast cancer? In a group of 74 patients with advanced metastatic breast cancer, 57% of those with cytoplasmic oestrogen receptor activity in their tumours (REC+) showed a clinical response to endocrine therapy. Of 51 patients whose tumour was assayed for both REC and cytoplasmic progesterone (RPC) activity, 9/12 patients with REC+ RPC+ tumours responded to hormone treatment, whereas only 3/30 patients with REC-RPC-tumours had a clinical response. In a group of 19 patients in whom nuclear oestrogen receptor (REN) was also estimated in the pellets from tumour-tissue homogenates, 5/6 with tumours positive for all 3 receptors showed a clinical response. None of the 9 patients with triply negative tumours responded. Addition of the REN assay appears to reinforce the greater precision of prediction when RPC as well as REC are estimated in breast tumours.


Growth pattern of tumours in mice induced by murine Moloney sarcoma-virus and sarcoma-virus-transformed cells. Transplantation of a Moloney sarcoma-virus (MSV-M)-transformed producer cell line (Sac(+)) induced progressively or regressively growing tumours in mice. Progressive growth always occurred after transplantation of an MSV-M non-producer transformant (Sac(-)), whereas the MSV-M released from the producer cells (Sac virus) always induced tumours which regressed. In contrast to the non-producer, the producer transformant Sac(+) as well as Sac virus induced a strong immune response, detected in vitro by cell- and antibody-mediated cytotoxicity assays, and in vivo by transplantation immunity. Implantation of Sac(-) cells led to solid, under-vascularized tumours, consisting histologically of uniform densely packed tumour cells. Sac-virus-induced tumours, however, were very well vascularized and arose by proliferation of different connective-tissue cells. After transplantation of Sac(+) cells, tumours were found to consist of typical tumour cells morphologically similar to Sac(-) cells intermingled with proliferated connective-tissue cells. Cultivation of tumour fragments from Sac(+) and Sac(-) tumours was followed by outgrowth of transformed tumour cells with the properties of the originally implanted cells. Tumour explant cultures from Sac-virus-induced tumours did not lead to growth of stably transformed cells. Co-culture of mouse embryo fibroblasts (MEF) with Sac(+) cells resulted in overgrowth of the transformed cells. Infection of MEF with Sac virus led to transiently transformed cells. It is concluded that Sac(+) cell tumours will resist the strong immune defence mechanisms they induce and grow progressively, if the inoculated cells are able to build up a solid, poorly vascularized nodule in the tissue. This always happens after implantation of 10(6) cells, but only occasionally when fewer cells are inoculated. Sac-virus-induced tumours will always regress owing to the strong immune response. The regression is furthered by the fact that MSV-M infection rarely if ever leads to a stable transformation.


SV40 T-antigen expression in acute non-lymphocytic leukaemia. Susceptibility to SV40 virus infection has been suggested as an in vitro marker of predisposition to leukaemia and possibly other cancers in man. To evaluate this relationship, sporadic as well as familial cases of acute non-lymphocytic leukaemia were tested. Among skin fibroblast lines from 22 patients without family history of leukaemia, eight had values above the 95% confidence limit for the normal control population. In four leukaemia-prone families, elevated T-antigen expression was found in all four patients tested and in three-quarters of 36 blood relatives. In addition, elevated values were found in two of three cases of acute myelogenous leukaemia associated with constitutional cytogenetic anomalies, and in all three cases with preleukaemic haematologic disorders. Since SV40 T-antigen expression was elevated in most persons prone to acute non-lymphocytic leukaemia, as well as over one-third of sporadic cases, heritable risk factors may be involved in both groups.


Characterization of simian virus 40 transcriptional intermediates in infected CV1 cell nuclei. Simian Virus (SV40) transcriptional intermediates (T.I.) were isolated from infected cell nuclei incubated in vitro in the presence of the four ribonucleoside triphosphates. The nascent mRNA strands in the viral DNA-RNA hybrid molecules were hydrogen bonded to their template by 200-250 nucleotides on the average, as judged from the extent of their RNase resistance and the aspect of T.I. under electron microscope after treatment with 50 per cent formamide. The RNA polymerase involved (RNA polymerase II) synthesized up to full length transcripts at a rate of approximately 150 nucleotides/min. at 25 degrees C. Each SV40 infected cell was found to contain about 200 active T.I. molecules at the peak of late transcription. The DNA in the T.I. molecules was exclusively form I DNA only in cell infected with the tsA30 mutant of SV40 that had been transferred to non-permissive temperature in order to arrest DNA replication, but both form I DNA and molecules behaving as replicative intermediates (R.I.) in wild type infected cells.


Effects of cyanogenic agents on reproduction and neonatal development in rats. A diet consisting of 50% gari (a form of cassava meal) was found to cause no significant biochemical and haematological changes in adult female rats. Although this diet caused a significant increase in their serum thiocyanate levels, there was no corresponding significant increase in the weight of their thyroid glands. The offspring of these rats had significantly lower birth weights and brain weights and never attained the same adult weights as those of the controls. Adult female rats fed a diet consisting entirely of raw cassava had significantly reduced haematological and biochemical indices. This diet also caused an increased incidence of cannibalism and a significant reduction in the frequency of pregnancy, the average number of the litter and the birth weights among these rats. In addition there was an increased incidence of neonatal deaths among the offspring which also had poor development, reduced brain weights and an increased tendency towards biting their litter-mates. Adult female rats fed diets containing 5 and 10 g cyanide/100 g laboratory diet survived for more than 3 months but never became pregnant. They developed enlarged thyroid glands and tumours of the large intestine. The relevance of these findings to the areas of the world where cyanogenic glycosides form the staple diet is discussed.


Development of phosphoenolpyruvate carboxykinase ferroactivator in fetal and young rats and guinea pigs. The development of ferroactivator, a protein that permits Fe2+ to activate the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, was compared to that of the carboxykinase in rat and guinea pig fetuses and neonates. Significant ferroactivator was present in the liver of the fetal rat and in the liver and kidney of the fetal guinea pig in the last half of gestation. The development of ferroactivator does not parallel that of the carboxykinase which does not attain maximal levels until after birth. Thus, the ferroactivator cannot be rate limiting for neonatal gluconeogenesis. It was found, unexpectedly, that the carboxykinase was increased during suckling in the guinea pig.


Increase of neutrophil alkaline phosphatase in the mothers of leukemic children. A comparative study of the polymorphonuclear neutrophiles of 62 parents of children suffering from acute leukemia and of 110 couples with normal children revealed a marked increased of Neutrophil Alkaline Phosphatase (p less than 0.05) in the mothers of the leukemic children. The other parameters (periodic acid Schiff and myeloperoxidase) were unchanged.


Collagen metabolism in the liver of normal and carbon tetrachloride treated rats. A significant increase in the activity of prolyl hydroxylase, in the relative collagen synthesis and in the hydroxyproline content was observed in the liver of rats treated for five weeks with CCl4 when compared to control liver. Five weeks after the suspension of the treatment, the activity of prolyl hydroxylase and the relative collagen synthesis returned to normal, but the hydroxyproline content of the liver of the CCl4-treated animals remained significantly higher than that of the controls. These findings suggest that an impairment in the mechanisms responsible for the resorption of the scar tissue could account for the accumulation of collagen within the parenchyma in liver fibrosis.


Recent developments in the estimation of trace toxic substances in food. A survey has been made of about 120 papers appearing in the food literature in which mass spectrometry has been employed to measure toxic contaminant levels. The areas covered are, mycotoxins, nitrosamines, polyhalogenated hydrocarbons and other industrial contaminants. All the essential analytical details have been collected and the limitations of the present day methods are discussed. The reader may conclude that sometimes there is a lack of essential information and that a more standard reporting procedure for quantitative assays is needed.


Studies on the control of respiration and behaviour during development in ewe-reared lambs. Radiotelemetric recordings have been made in a series of newborn lambs with implanted electrodes and transducers and an external back-pack transmitter. Cardiac, respiratory and behavioural data have been gathered. These data have been analysed firstly with respect to age. The cardiac and respiratory data have then been related to both sleep state and age. An unexpected rise in both heart and respiratory rates was found after birth and marked differences were obvious in respiratory control in REM and non-REM sleep states.


Excitability and NADH fluorescence of spontaneously active portal veins in relation to glucose withdrawal. The effect of glucose withdrawal upon mechanical activity and the redox level of pyridine nucleotides and flavoproteins was investigated in isolated rat portal veins under aerobic conditions. A decrease of extracellular glucose concentration correlated with contractile activity. During acetylcholine-induced tetanic contractions. NADH and flavoproteins were oxydized only in vessels supplied with glucose. The myogenic activity was restituted when glucose was added after withdrawal parallel with a reduction of NAD and flavoproteins. The results suggest that glucose, besides its effect on the energy metabolism, has an influence on the excitability of smooth muscle cells of rat portal veins.


Effect of adenosine on adrenergic neurotransmission in the superfused rat portal vein. This study examined the effect of exogenously applied adenosine on the release of 3H-norepinephrine from the field-stimulated, superfused rat portal vein. Adenosine was found to inhibit the field-stimulated release of 3H-norepinephrine in a dose-dependent manner in 50- to 1,000-microM concentrations. The effect was reversed when adenosine was washed out. The inhibitory effects of adenosine were antagonized by theophylline (10-4 M) which by itself showed a slight enhancement of stimulated 3H-norepinephrine release. ATP was found to inhibit 3H-norepinephrine release at the same concentration as adenosine while inosine was inactive. When adenosine was tested in the presence of the muscarinic and alpha-adrenergic blocking agents atropine and phenoxybenzamine along with indomethacin, a prostaglandin synthesis inhibitor, its inhibotory effect on the stimulated release of 3H-norepinephrine persisted. It is concluded that adenosine and/or ATP can modulate the nerve-stimulated induced release of norepinephrine presumably by an action on the adrenergic nerve terminals.


[The activity of cytochrome oxidase in the normal cerebral cortex and after destructive and irritating lesions. Histochemical research]. Production of an epileptogenic focus by cobalt-gelatin implantation in the cerebral cortex of the rat determines a local increase of cytochrome oxidase activity in neurones and probably a decrease of its activity in neuroglia. This variation of oxidative metabolism is not characteristic of the "epileptic neuron" since it takes also place after non irritative lesions, though remaining less conspicuous and less extensive.


[Comparative study of anti EBV antibodies in non-Hodgkin's lymphomams and angio-immunoblastic lymphadenopathies (author's transl)]. Antibody titers to Epstein-Barr virus (EBV)--related antigens (viral capsid antigen : VCA; early antigen : EA; and EBV associated nuclear antigen : EBNA) were determined in the sera of 86 patients and 150 matched control subjects. The patients belonged to four histological groups : diffuse and nodular non-hodgkin's lymphomas angio-immunoblastic lymphadenopathies and apparented syndroms. The incidence of antibodies to other herpes-viruses (cytomégalovirus, herpes simplex virus, and varicella zoster virus) was compared. There was a significantly higher incidence of anti VCA and anti EA titers in some patients, not associated with an increase in titres of antibodies to other herpes viruses.


[Epidemiology of carcinoma of the cervix (author's transl)]. In order to explain why modes of sexual life influence the incidence of cervical carcinoma, several factors have been claimed to be involved. There is no solid basis for the hypothesis that sperm may be mutagenic. By contrast, epidemiological studies showed that partners whose life is not sedentary bring back home to their wives an increased risk of cervical carcinoma. The infectious factor does not seem to be associated with syphilis but may well be represented by herpes genitalis virus (Herpes Simplex type 2 virus). Women with cervical carcinoma show a variety of immunes reactions to this virus, and these reactions are statistically less frequent in control groups. In the laboratory, mouse and hamster cells have been transformed into cancerous cells by means of herpes simplex virus type 2.


Temperature and inhibitory junctional transmission in guinea-pig ileum. The effects of temperature on the inhibitory junctional potential (i.j.p.) and the electrotonic potential, recorded in the circular smooth muscle of the guinea-pig ileum, were studied with intracellular microelectrodes. The amplitude and time course of the i.j.p. were both dependent on the ambient temperature, the i.j.p. becoming smaller and more prolonged as the temperature was lowered. In contrast, the electrotonic potential was not much affected by temperature. The atropine-resistant 'late' depolarization was also dependent on temperature. These results are consistent with the mechanism of release, of the nonadrenergic noncholinergic inhibitory transmitter, being sensitive to temperature and with the inhibitory conductance change, underlying the i.j.p., being long compared to the membrane time constant of the circular smooth muscle.


Prevalence of nine different micro-organisms in the female genital tract. A comparison between women from a venereal disease clinic and from a health control department. In a study of the prevalence of nine different micro-organisms in the female genital tract in a Swedish population, significantly higher isolation rates occurred among women attending a venereal disease clinic than among those attending a gynaecological health control department. The prevalence of Candida albicans, however, was similar in different groups, individual susceptibility being the most important factor. Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma hominis occurred concomitantly with Neisseria gonorrhoeae, indicating a similar epidemiology for all these agents. Younger patients seemed to have an increased susceptibility to C. trachomatis whereas older patients had an increased susceptibility to T. vaginalis.


[Immunocytologic analysis, in rat hypothalamus, of neurons producing peptides related to endorphin, ACTH, MSH and beta-LPH. Comparison with other peptidergic and monoaminergic neurons]. In rat hypothalamus intraventricularly injected with colchicine, the same neurons of the ventral region are stained with I.S. against alpha and beta-endorphin, (1-24) and (17-39) ACTH, alpha and beta-MSH, and beta-LPH. They are distinct from those producing LH-RH, somatostatin, neurophysin, and dopamine. These results suggest that the same neurons elaborate peptides identical with or immunologically related to endorphins, ACTH, alpha-MSH and beta-LPH, probably issued from a common precursor.


[Evidence for the production of a fusion factor during in vitro infection of sheep choroid plexus cells by visna virus]. One of the most important early events during the infection of sheep choroïd plexus cells in culture by Visna virus is the synthesis by these cells of a fusion factor distinct from the virus. The cell fusion activity of this factor does not seem transmissible. It promotes cell shape changes and a migration of the nucleus towards the cell wall.


[Comparative adrenergic activity in the Long Evans and Sprague Dawley rat]. Sprague Dawley rats show a more pronounced reactivity of their alpha and beta receptors than Long Evans rats after an infusion of noradrenaline.


Multiunit activity in the mesencephalic reticular formation and septal area of freely moving newborn rat. A surgical technique to implant stereotaxically fixed probes for recording multiunit activity /MUA/ from the mesencephalic reticular formation and septal area of freely moving 6--12 hr old newborn rat is described. In both brain areas the spontaneous firing of neuron populations showed close correlation with the stages of wakefulness and sleep cycle.


Virus detection in soils: a comparison of four recovery methods. Among nine eluents tested, 0.5% (w/v) isoelectric casein at pH 9.0 and 0.5% (w/v) non-fat dry milk (pH 9.0) were the most efficient in eluting poliovirus type 1 (Sabin) from Eustis fine sand. However, no significant difference was found between the overall (elution followed by concentration) virus recoveries by non-fat dry milk, isoelectric casein, beef extract, and glycine-EDTA methods. High overall recovery (75%) of low input (200 PFU) of viruses from 100 g of soil was achieved by the isoelectric casein method. It was found that the recovery efficiency of this method was not significantly affected by the soil type, following examination of four Florida soils. The mean overall recovery for the four soils was 50%. For other enteroviruses, the overall recovery for coxsackie B3 was 88% but was significantly lower (23%) for echovirus 4. Examination of the efficiency of the casein method under field conditions showed that it was possible to recovery low poliovirus numbers from soil (0.9-1.3 PFU/g soil).


Hibernation: an opioid-dependent state?

Hibernation: an opioid-dependent state? Hibernation reduces substantially the heart rate of hamsters as well as the respiratory rate, the body temperature and the arousal level. The heart rate is reversed dramatically by the injection of low doses of Naloxone and in some cases the hamster arouses prematurely from hibernation. The effect is not due to the pain of the injection because saline injections do not produce such changes. The effect requires a pre-existing state of hibernation because Naloxone has no cardioacceleratory or arousal effect in non-hibernating hamsters that have had their heart rate and body temperature decreased substantially during hypothermia. These results suggest that endogenous opioids may contribute specifically to the state of hibernation. Moreover, a physiological role may exist for an anti-opioid system in the promotion of arousal from hibernation.


Extramammary Paget's disease.

Extramammary Paget's disease. In a 74-year-old man extramammary Paget's disease of the scrotal and perianal areas masqueraded as tinea cruris and chronic dermatitis for 7 years before it was diagnosed. Topical therapy with 1% 5-fluorouracil cream resulted in clinical improvement but not histologic clearing.


Serological survey for Aujeszky's disease in native sows of Canada. A serological survey was initiated to uncover subclinical foci of infection with pseudorabies virus. A total of 2819 serum samples, collected from sows during February to November 1977, were found negative for antibodies to pseudorabies virus.


Treatment of grade III and IV astrocytomas with BCNU alone and in combination with VM-26 following surgery and radiation therapy. Twenty-one patients with grade III or IV astrocytomas were assigned randomly to receive either BCNU alone or BCNU and VM-26 after surgery and radiation therapy. Patients surviving radiation therapy and receiving single-agent chemotherapy had a median survival of 14 months while those receiving combination chemotherapy had a median survival of 22 months (P greater than 0.05). None of the patients who failed BCNU-only therapy responded to VM-26. Performance status was not affected by either regimen. Computerized tomographic scanning of the brain was useful only in confirming tumor progression. Two patients died from BCNU-related interstitial pulmonary fibrosis.


Tamoxifen-induced tumor stimulation and withdrawal response. A postmenopausal breast cancer patient with a measurable lung metastasis was treated with tamoxifen. The tumor doubling time of the pulmonary lesion was 140 days during spontaneous growth and 52 days during tamoxifen therapy, an almost threefold increase in tumor growth rate. This stimulation persisted fro 1 month after discontinuation of tamoxifen and was followed thereafter by a withdrawal regression lasting greater than 6 months. Awareness of the possible tumor growth enhancement with tamoxifen is of importance especially in view of its prolonged activity. Hormone withdrawal regression may occur following tamoxifen therapy, and a sufficient time interval should therefore elapse between cessation of tamoxifen and initiation of other therapeutic modalities.


Therapy for hepatocellular cancer with intrahepatic arterial adriamycin and 5-fluorouracil combined with whole-liver irradiation: a Northern California Oncology Group Study. Thirteen patients with hepatocellular cancer were treated with intrahepatic arterial Adriamycin and 5-fluorouracil combined with whole-liver irradiation. Six patients (46%) had an objective regression and five (38%) had stable disease. Symptomatic improvement was noted in 81% of the patients. The minimum median survival time was 5.0 months for those patients who responded. Toxicity was acceptable. This is an effective combination for the treatment of this especially aggressive and intractable form of cancer.


Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide in advanced adenocarcinoma and large cell carcinoma of the lung. Thirty-six patients with advanced carcinoma of the lung (30 with adenocarcinoma and six with large cell carcinoma) were treated with a combination of mitomycin C, Adriamycin, and cyclophosphamide (MAC) in a phase II study. Seven partial remissions were observed in adenocarcinomas, while none were seen in large cell carcinomas. The survival of patients in remission was clearly prolonged (P less than 0.01), with responders living a median of at least 39 weeks compared to 17 weeks for nonresponders. The combination was well-tolerated with moderate anorexia, nausea, vomiting, and alopecia. Myelosuppression was manageable but was more pronounced in previously chemotherapeutically treated patients. MAC offers a reasonable response rate in patients with adenocarcinoma of the lung with significant prolongation of survival; however, there was no significant advantage when compared to mitomycin C used as a single agent.


Treatment of small cell bronchogenic carcinoma with VM-26. VM-26 is active in small cell bronchogenic carcinoma even in patients resistant to previous chemotherapy. The overall response rate was 28%, with a response rate of 29% in patients resistant to previous chemotherapy. This response rate is similar to that obtained with other single agents including Adriamycin, vincristine, cyclophosphamide, and procarbazine. The mild subjective and objective toxic effects of the drug make it a potentially useful agent in the treatment of this tumor.


Functional significance of interrenal cell zonation in the adrenal gland of the duck (Anas platyrhynchos). Slices of whole adrenal gland tissue, incubated in vitro in the presence of ACTH for 1 h and 2 h produced corticosterone and aldosterone in constant ratio (16:1). Tangential slices taken from the region immediately below the connective tissue capsule and slices taken from deeper regions of the gland consisted primarily of cells conforming to the distinct structural characteristics of the subcapsular zone (SCZ) and inner zone (IZ) tissues respectively. When samples were incubated in the presence of ACTH for 1 h and 2 h, the interrenal cells of the SCZ produced relatively more aldosterone than cells taken from the IZ of the gland. The corticosterone: aldosterone ratio for the IZ after 1 h (68:1) and after 2 h (102:1) were ten times greater than the ratios for the SCZ after 1 h (7:1) and after 2 h (10:1). The SCZ slices were not more than 60 cells thick and consisted of cells arranged in cords. These cells contained irregular nuclei, mitochondria with shelf-like cristae and a moderate abundance of smooth endoplasmic reticulum. In contrast, the production of large amounts of corticosterone by the cells of the IZ was associated with tissue containing more vascular space than the SCZ and the cells contained large round nuclei surrounded by an abundance of smooth endoplasmic reticulum and the mitochondria had tubular rather than shelf-like cristae.


Neurons of the rat hypothalamus reactive with antisera against endorphins, ACTH, MSH and beta-LPH. In rat brains intraventricularly injected with colchicine, the same discrete neurons of the arcuate and ventromedial nuclei can be stained with antisera against alpha- and beta-endorphins, (1-24)ACTH, (17-39)ACTH, alpha- and beta-MSH, and beta-LPH, as demonstrated by comparative studies in consecutive serial sections. These neurons are strongly reactive with anti-(17-39)ACTH, anti-beta-endorphin, anti-alpha-MSH and anti-beta-MSH, and more faintly stained with anti-alpha-endorphin, anti-beta-LPH and anti-(1-24)ACTH. Exceptionally, neurons reactive with anti-(17-39)ACTH and anti-beta-endorphin are poorly stained or completely negative with anti-alpha-MSH and anti-beta-MSH. Immunoreactive fibers end in the lateral median eminence and in the arcuate nucleus proper, or form ascending pathways along the third ventricle. Comparative studies with other antisera or with the Falck and Hillarp technique show that these neurons differ from the elements producing LH-RH, somatostatin, neurophysin, oxytocin, vasopressin and dopamine. These results suggest that the same neurons of the rat hypothalamus synthesize several neuropeptides identical with or immunologically related to endorphins, ACTH, alpha-MSH and beta-LPH, probably arising from a common precursor molecule similar to that found in the corticotropic cells of the pituitary. These neuropeptides of a common cellular and molecular origin might be involved in basic processes of the central nervous system as neurotramsmitters or neuromodulators.


Ultrastructural localization of immunoreactive corticotropin, beta-lipotropin, alpha- and beta-endorphin in cells of the human fetal anterior pituitary. Cells immunoreactive with anti-alpha-(17-39) ACTH, beta-(1-24) corticotropin, beta-LPH, alpha- and beta-EP were identified in the human fetal anterior pituitary at the ultrastructural level using the peroxidase-antiperoxidase complex method on ultrathin sections. Only one definite cell type was revealed by all these antisera. All granules of each individual immunostained cell reacted regardless of the antiserum used. The immunostained cells occurred in groups and were sometimes located in the wall of the follicle-like structures commonly observed in the fetal anterior pituitary. The cells revealed two main aspects: 1) The largest elements were rich in organelles, and their numerous secretory granules showed significantly variations in size (250-500 nm in diameter), electron density of their content and stain-deposit intensity. The ergastoplasm, consisting of irregular tubules, was poorly developed. In the vicinity of the conspicuous Golgi apparatus, organelles related to the GERL complex were commonly observed. Multivesicular bodies were frequent. Some of these cells showed bundles of microfilaments (60 nm in thickness). 2) The smaller cells had an electron-lucent hyaloplasm with sparse organelles; they contained fewer granules and never showed microfilaments. The immunocytological results are consistent with the synthesis of a molecule similar to pro-opiocortin by this type of endocrine cell in human fetuses. Morphological evidence for the maturation process of this precursor and for the secretory activity of these cells and its possible regulation is presented and discussed.


Ultrastructure of pinealocytes of the cotton rat, Sigmodon hispidus. Fine structural features of pinealocytes of cotton rats (Sigmodon hispidus) were examined. Golgi complexes, mitochondria, endoplasmic reticulum and polysomes are usual organelles seen in the perikaryonal cytoplasm of pinealocytes. Many non-granulated vesicles (40 to 80 nm in diameter) and a few granulated vesicles (about 100 nm in diameter) are associated with the Golgi cisternae. Occasionally, the cisternae contain granular materials. The perikaryonal cytoplasm of pinealocytes is characterized by the presence of inclusion bodies. These bodies are usually round in shape, not bounded by a limiting membrane and composed of fine granular or filamentous materials of high electron-opacity, which are similar in appearance to the substance seen in the nucleolonema. Pinealocyte processes, filled with abundant non-granulated vesicles and some granulated vesicles, are mainly found within the parenchyma and occasionally in perivascular spaces.


Polarity of three-dimensional structures derived from isolated hog thyroid cells in primary culture. When cultured in polystyrene dishes subjected to previous treatment and supplied with a serum-containing medium, hog thyroid cells form monolayers displaying dome-like arrangements after three to four days. Cells involved in formation of "domes" are morphologically polarized; the apical microvilli of these cells point toward the culture medium. When the tissue is cultured in untreated polystyrene dishes, thyroid cells remain in suspension; their aggregates swell progressively and form hollow spheres encompassed by a single layer of cells. The polarity of the cells forming such spheres is inverse in comparison to the condition characteristic of the intact thyroid gland. When culture medium is supplemented with TSH, PGE1, PGE2 or dBC, structures resembling true follicles are formed in both types of cultures. Gelatin, added to suspension cultures, is also capable of promoting follicle formation. Cultured thyroid cells regularly form an epithelial layer as a result of the interaction of cellular processes. However, the polarization of this layer depends on culture conditions. Thus, structures with either a normal follicle-like polarization of their cells or showing an inverted type of polarization can be obtained.


[Neuronal activity specific to paradoxical sleep in the bulbar reticular formation in the unrestrained cat]. Single units were recorded in the bulbar reticular formation (BRF) of unrestrained, freely behaving Cats. In the ventromedial part of the BRF (n. reticularis magnocellularis, Mc) corresponding to the "bulbar inhibitory center", we have found a cluster of cells showing tonic activation highly selective to paradoxical sleep (PS). Furthermore, we have confirmed the presence of the same type of cells in the dorsomedial part of the BRF which corresponds to the medial part of the n. reticularis parvocellularis (Pc). The functional significance of these two groups of cells is discussed in terms of the postural atonia and the atonia of jaw closer muscles observed during PS.


Active and inactive renin in normal human plasma. Comparison between acid activation and cryoactivation. Inactive renin in human plasma is converted to active renin in vitro by acid activation or by cryoactivation. Renin activity was measured at pH 5.5 and renin concentration at pH 7.4. The plasma renin activity before and after cryo-treatment is termed active (APRA) and total (TPRA) plasma renin activity; the plasma renin concentration before and after acid treatment active (APRC) and total (TPRC) plasma renin concentration. In this study we demonstrated that in normal subjects the proportion of active to total renin after cryo-treatment averaged 61%, which was significantly (p less than 0.001) higher than the mean percentage active renin of 34 found with the acid activation procedure. Plasma angiotensin II correlated significantly with APRA, TPRA, TPRC and plasma angiotensin I (PA I), but not with inactive renin, which suggests that inactive renin does not produce angiotensin II in vivo. Cold treatment after acid activation and acid treatment after cryoactivation did not provoke a significant change in the measured renin concentration. Our data support the view that acidification of the plasma activates more than does cryo-treatment, and that inactive renin does not contribute to plasma angiotensin II.


[Coprologic diagnosis of amebiasis : the rectocolitis cell trap and the value of cultures]. The authors give the differential characters of dysenteric amoebae and cells observed in the feaces of patients affected by recto-colitis. In this purpose, they recall the usefullness of cultures for both the presence and the possibility of determination of the Amoebae. In short, they deplore the misappreciation of these advantages.


Values of APO-1 and APO-B in humans according to age and sex. Two series of 100 subjects each, males and females, have been studied for the determination of plasma values of apo-A1, the major peptide of HDL, and of apo-B, the major peptide of LDL. To minimize a possible influence of variations in plasma lipid levels, two series of subjects were selected with very similar mean values of plasma cholesterol and triglyceride. Despite this criterion of selection apo-A1 was significantly lower in males (127 +/- 18 mg/l) than in females (137 +/- 15 mg/l) while the reverse was true for apo-B (99 +/- 16 mg/l in males vs. 91 +/- mg/l in females). Both apo-B and apo-A1 showed a tendency to increase with advancing age with the greatest increase for apo-A1 (in both sexes) and for apo-B (only in males) from the 3rd to the 4th decade of age.


Determination of cholesterol and phospholipid concentrations in high-density lipoproteins by heparin-manganese chloride precipitation. Cholesterol as well as phospholipids in high-density lipoproteins (HDL) have been measured in 60 serum samples after heparin-manganese chloride precipitation of the apolipoprotein B containing lipoproteins. The values obtained correlated well with values from ultracentrifugal separation (slope 1.11 for cholesterol, 0.92 for phospholipids). Furthermore, there was a significant correlation between the low-density lipoprotein (LDL) cholesterol estimated by the formula of Friedewald et al. and the ultracentrifugally separated LDL cholesterol (slope 1.02). By the additional determination of HDL phospholipids with a precipitation procedure, further information about the "antiatherogenic" is easily available.


Evaluation of functional thymic hormones in Arabian horses with severe combined immunodeficiency. Arabian horses with severe combined immunodeficiency disease (SCID) were evaluated for thymic hormone activities using thymic extracts and sera. Extracts prepared from thymus of SCID horses were able to increase the number of spleen cells responding to sheep red blood cells in irradiated, bone marrow-reconstituted mice. In addition, ultrafiltrates prepared from sera of these immunodeficient horses, which contained material with molecular weight of less than 50,000 Daltons could (a) induce a population of human bone marrow precursor cells to differentiate into cells bearing SRBC receptors and form spontaneous E-rosettes, a characteristic of T lymphocytes, and (b) stimulate cyclic adenosine monophosphate (AMP) synthesis in mouse thymocytes. Based on in vivo and in vitro effects, it was concluded that the defect of these Arabian horses with severe combined immunodeficiency disease did not involve a complete thymic hormone inadequacy.


Lymphocyte activation induced by Trichinella spiralis infection reflected as spontaneous DNA synthesis in vitro. Spleen cells from mice, infected with Trichinella spiralis, were cultured in micro and macrocultures without stimulatory agents. As controls, various polyclonal T and B cell activators were used. During the course of the infection the cells exhibited an increased spontaneous DNA synthesis compared to the cells from uninfected controls. It was also found that the relative proportion of theta and Ig-positive cells and macrophages was not significantly affected by the infection. To characterize the in vivo stimulated cells one week after infection various techniques were used. Autoradiography combined with immunofluorescence revealed that virtually all labelled cells were Ig-negative. Removal of macrophages by silica powder decreased the spontaneous DNA synthesis but not to the level of the controls. Spleen cells from infected nude mice did not show any increased spontaneous DNA synthesis, whereas the effluent cells obtained after separation on Ig-complexed columns still showed an enhanced spontaneous DNA synthesis. These results indicate that T. spiralis infection causes a macrophage dependent activation of T cells which in vitro is detectable as spontaneous DNA synthesis.


Effects of clofibrate on plasma lipids and high-density lipoprotein levels in renal allograft recipients. Thirteen successfully transplanted renal patients with normal and elevated plasma lipids were treated as out-patients for two-month intervals with placebo and clofibrate (2 g/day) and whole plasma and lipoprotein triglyceride and cholesterol concentrations were measured. With clofibrate treatment, plasma triglyceride (194 +/- 11 to 157 +/- 10 mg/100 ml; P less than .01) and cholesterol (242 +/- 8 to 212 +/- 8 mg/100 ml; P less than .002) concentrations both decreased significantly despite the continued administration of stable immunosuppressive doses of prednisolone. While the absolute changes in cholesterol in the low and high-density lipoprotein classes varied considerably following clofibrate administration, the ratio of cholesterol in the low and high-density lipoproteins fell from 3.8 to 3.3. This theoretically beneficial anti-atherogenic effect was significant (P less than .01) in male allograft recipients only. These findings indicate that clofibrate treatment favorably influences the cardiovascular risk posed by both qualitative and quantitative disturbances in lipoprotein transport following successful renal allografting.


Emotional responses to subcortical electrical stimulation in psychiatric patients. Subcortical electrical stimulation was applied to the prospective surgical target area during 158 stereotactic operations in 135 psychiatric patients. The following target areas were studied: rostral cingulum below and in front of the genu of the corpus callosum (52 cases) genu (46) cingululum just above the genu (11) middle cingulum (6) anterior internal capsule (33) subcaudate region, 'substantia innominata' (10 cases). Forty-seven per cent of the cases reacted to stimulation with subjective emotional sensory responses. Stimulation of differ targets had significantly different results. Responses were obtained most frequently from the cingulum and genu, and least frequently from the anterior capsule and subcaudate regions. Stimulation of the rostral cingulum often caused 'negative' responses, i.e. an increase in or the appearance of anxiety and tension (11/15 cases). The opposite was true of the adjacent genu of the corpus callosum; on stimulation of this structure anxiety and tension disappeared or diminished (18/19 cases). Schizophrenic patients experienced such 'positive' responses significantly more often than non-schizophrenics. In non-anesthetized patients autonomic reactions were very rare.


Distinction between benign and malignant type of Parkinson's disease. Clinical data demonstrate that there is a significant difference between at least two types of idiopathic Parkinsonian patients; a benign type of Parkinson's disease and a malignant type. They can be distinguished by the time course of a disability-score, independent of the duration of the disease. The benign cases respond very well to L-Dopa (Madopar) treatment and show a long lasting (7 years) drop in the disability, whereas the improvement of disability in the malignant cases is much smaller and lasts for about one year, followed by an increase of disability. The duration of the disease is 12,5 +/- 0,4 years in the benign type but only 4,0 +/- 0,3 years in the malignant type. Akinetic crises, off-phases, hyperkinetic crises and toxic deliria after Madopar treatment can be observed later in the benign than in the malignant cases. These results suggest that the degeneration of the dopaminergic nigrostriatal system occurs much more rapidly in malignant cases than in benign cases of Parkinson's disease.


A peculiar brain scan pattern in necrotizing leukoencephalopathy after treatment for CNS-leukaemia. Two patients with CNS-leukaemia who developed a leukoencephalopathy after cranial irradiation and methotrexate administration are described. Conventional brain scanning with 99m TC-pertechnetate showed a peculiar pattern which suggested the presence of radio-activity within enlarged ventricles, but were later interpreted as accumulation in the periventricular white matter. The brainscan pattern correlated well with the neuropathological findings in the case where autopsy was performed. This brain scan pattern is for unknown reasons only rarely mentioned in literature. It seems a useful tool in diagnostic procedures in similar patients.


Primary intracranial malignant lymphomas a fine structural cytochemical and CSF immunological study. Cytochemical and electron microscopical studies in six cases of primary intracranial malignant lymphomas, four of which were diagnosed by biopsy, confirmed their ultrastructural identity with extraneural malignant lymphomas classified as immunoblastomas and immunocytomas. Demonstration of transformation of 'blast-like' cells (immunoblasts) toward rough E. R. developing cells in all these tumours argue for the B-dell origin of these types of cerebral lymphomas, previously referred to as reticulum cell sarcomas/microgliomas. CSF studies showed increased levels of B cells with surface IgG in two cases of immunoblastoma, and increased IgG levels with light chains in two cases each immunoblastoma and of pleomorphic immunocytoma, while one case of immunoblastoma showed a normal T cell to B cell ratio with increased monoclonal and surface, IgM suggesting some morphological and immunological heterogeneity of these lymphomas.


Auditory brainstem evoked responses in brainstem compression due to posterior fossa tumors. Five patients with unilateral posterior fossa tumors were investigated with Auditory Brainstem Evoked Responses (B.E.R.). The B.E.R., recorded from the ear ipsilateral to the tumor, were consistent with a lesion of the acoustic nerve or the cochlear nuclei in all patients. The contralaterally evoked responses in four patients with large tumors and radiological signs of brainstem compression showed normal latencies and amplitudes of the first three waves, while waves IV and V were definitely abnormal with respect to amplitudes and latencies. (The 4th patient had a normal wave IV and a delayed, small wave V). In one patient with a relatively small acoustic neurinoma the contralateral B.E.R. were normal. It is concluded that the upper pontine and lower midbrain level, presumed sites of generation of wave IV and V of the B.E.R., are more susceptible to brainstem compression due to unilateral posterior fossa tumors, than the lower parts of the brainstem.


Collateral circulation and stealmechanisms in innominate and subclavian artery obstruction. Various types of collateral circulation and of intra- and extracerebral stealmechanisms have been described during the past two decades. The object of this short report is to discuss the clinical-angiographic data of two patients with extracranial cerebro-vascular occlusion, also in relation with current literature. Two case histories are described. The first showed a double extracerebral steal plus intracerebral interhemispheric steal, due to innominate artery obstruction. The second had only a external vertebral collateral circulation due to proximal subclavian occlusion. The factors which precipitate collateral circulation to steal are discussed.


Extracranial CSF shunting for infantile non tumoral hydrocephalus--a retrospective analysis of 360 cases. A series of 360 consecutive extracranial CSF shunts performed between June 1960 and June 1976 for infantile non tumoral hydrocephalus is reviewed. The surgical methods used, the reasons for re-operation, the time distribution of post-operative complications, the causes of death and the long term results are analysed and discussed for each of the four groups: tetraventricular communicating hydrocephalus, triventricular hydrocephalus, obstructive hydrocephalus with a ventriculo-cisternal block and post-meningocele or post-myelomeningocele hydrocephalus.


Ascorbic acid deficiency and hypertrophic osteodystrophy in the dog: a rebuttal. Plasma ascorbic acid (PAA) in normal Labrador Retriever dogs less than one year of age averaged 1.22 +/- 0.05 mg/dl (x +/- sem) and was significantly higher than the value of 0.89 +/- 0.03, for Labrador Retrievers two years of age and older. No significant diurnal variation in PAA was observed. Oral or intravenous administration of 0.5 or 1.0 g of ascorbic acid (AA) elevated PAA for less than 8 hours. Injection of ACTH caused a significant decline in PAA for the initial 2 days, with variable results thereafter. Labrador Retriever puppies fed a ration high in protein, energy and calcium developed the typical skeletal diseases of overnutrition, including hypertrophic osteodystrophy (HOD). The addition or oral AA (0.5 g twice daily) had no ameliorating effect on the skeletal lesions. Instead AA supplementation resulted in relatively higher serum calcium values which, presumably by enhanced hypercalcitoninism, decreased bone resorption. Thus, AA treatment of dogs with HOD is contraindicated, as it can only aggravate the osseous lesions of HOD. The decreased PAA reported in dogs with HOD is interpreted to be the result of stress from pain.


Evaluation of sodium stibogluconate in the treatment of cutaneous leishmaniasis in Syria. A series of 31 patients presenting with skin lesions with positive smears for leishmania parasites were treated with sodium stibogluconate (each ml of injection containing the equivalent of 100 mg pentavalent antimony). The drug was administered either intramuscularly at a dosage of 6 ml daily for at least 10 days or infiltrated around the lesion (maximum 2 ml per lesion) at weekly intervals for 3 to 4 consecutive weeks. Twenty-four (77%) of the patients were assessed as showing a successful response, with parasites absent from the smear and the lesions healing at the end of treatment. Poor results, however, were reported in 5 of the 16 patients treated solely by infiltration. Follow-up of a few patients at 3 months showed that the healing process was prompt and little disfiguration was produced, lesions on the trunk tending to heal more quickly than those on the face.


Vitamin D-resistant rickets. A prototype of nutritional management of a genetic disorder. The discovery of the vitamin D endocrine system has opened up many possibilities in our understanding of metabolic bone disease. Of particular importance is the fact that we can now manage certain genetic disorders resulting in vitamin D-resistant rickets or vitamin D-resistant hypocalcemia with the new active hormonal forms of vitamin D and with intelligent dietary management to provide for correction of the mineral difficulty. Thus, in the case of vitamin D dependency, replacement need only be with the missing hormone, 1,25-(OH)2D3. On the other hand, familial hypophosphatemia requires adjustment of the plasma phosphorus by frequent administration of oral phosphate and the adjustment of intestinal calcium absorption by 1,25-(OH)2D3. Renal failure patients require the adjustment of plasma phosphorus concentration and parathyroid hormone status, and the administration of the missing hormone 1,25-(OH)2D3. Hypoparathyroid patients require oral calcium plus 1,25-(OH)2D3, and premature infants require administration of the 1,25-(OH)2D3 because the immature kidneys and immature parathyroid glands fail to produce the required amount of this hormone. Other vitamin D-resistant rachitic conditions cannot be discussed here for lack of space and for lack of information. Undoubtedly, such patients as those having rickets secondary to renal tubular acidosis and rickets secondary to hepatic disorders will eventually come under effecti dietary and hormonal management. In this sense, the vitamin D endocrine system and vitamin D-resistant rickets can serve as a prototype of management of a genetic disorder by dietary means.


Assessing the need for follow-up: the relationship of prognosis to posthospitalization adjustment. Parents of children (N-64) hospitalized at a psychiatric hospital between the years 1971 and 1976 rated their child's adjustment in a number of behavioral areas. Problems in school, making friends, acting age-appropriately, and handling aggression were reported to be the major sources of difficulty for 40% of the former patients. No statistical relationship was found between clinicians' prognosis at discharge and children's post-hospitalization adjustment. The authors discuss some of the variables that mitigate against accurate outcome prediction and argue for the integration of an organized follow-up program into their treatment program.


Some unusual complications of myelography and lumbosacral radiculography. In 570 patients an examination of the subarachnoideal space was performed. In 77 of them oily contrast media, in 93 oxygen and in the remaining 400 patients different water-soluble contrast media were used, including Conray 60, Dimer X and Amipaque. Neurotoxic spinal complications occurred in 12 of the 400 patients investigated with hydrosoluble agents (i.e. in 3%). In one of them after investigation with Dimer X, intense cramps in the lower extremities caused a fracture of the femoral neck within a few hours after the investigation. In another patient, investigated with Amipaque, a psychotic reaction with amentia and paranoid symptoms developed, which disappeared completely after 4 days.


Cyclic nucleotides and ethanol tolerance and dependence. Acute ethanol administration decreases cyclic AMP levels in brains of some animal strains. The ethanol-induced decrease of cyclic GMP levels cannot be blocked by intraventricular infusion of calcium but it can be prevented by pretreatment with pyrazole. Although cyclic AMP levels in the cerebral cortex change reciprocally after acute ethanol administration and during withdrawal, the increase observed during withdrawal is probably secondary to some withdrawal processes. Ethanol decreases cerebellar GABA levels only in rats which are stressed prior to sacrifice. Chronic intraventricular infusion of calcium increased the intensity of an acoustic startle response during ethanol withdrawal while EGTA infusion delayed the development of tolerance to the hypothermic effect of ethanol. The ratio of cyclic GMP to GABA levels is postulated to be important for expression of the withdrawal syndrome.


Fructose-1,6-diphosphatase and glucose-6-phosphatase in newborn rats with intrauterine growth retardation. The activities of two gluconeogenic enzymes, glucose-6-phosphatase and fructose-1,6-diphosphatase were examined in the normal and intrauterine growth retarded (IUGR) rat during the first 5 days of life. The fructose-1,6-diphosphatase activity, 1.54 +/- 0.10 mumol/min/g liver (means +/- SEM) in control and 1.47 +/- 0.20 in the IUGR rats, increased in both groups on days 2--4 but remained significantly lower in the IUGR rats through day 4 (4.53 +/- 0.6 mumol/min/g liver in control and 3.09 +/- 0.22 mumul/min/g liver in the IUGR rats, P less than 0.01). The glucose-6-phosphatase activity increased similarly in both groups. The weight of the IUGR rats remained lower through the third postnatal day (6.47 +/- 0.42 compared to 8.64 +/- 0.27 g in control rats). Blood glucose concentrations at birth were 117 +/- 11 mg/dl in control rats and 73 +/- 11 mg/dl in the IUGR rats (P less than 0.01). Although the glucose concentrations increased in both groups on days 2--4, the IUGR rats maintained relatively lower levels (P less than 0.01). The results indicate that IUGR fetal rats do not have augmented gluconeogenesis in spite of hypoglycemia. In addition, effective gluconeogenesis in the neonatal period appears to be delayed.