Juvenile nasopharyngeal angiofibroma. An unusual presentation as an oral mass. Although juvenile nasopharyngeal angiofibroma (JNAF) usually presents as a mass in the nasopharynx, the primary manifestation may, in rare instances, occur intraorally. We observed such a case in a 12-year-old boy. The clinical finding of hemorrhage from the nasopharynx or contiguous areas in a male adolescent is an important diagnostic clue which should alert the clinician to the possibility of JNAF as the underlying cause.


Sarcoidosis--1977.

Sarcoidosis--1977. Sarcoidosis is defined as a multisystem disorder characterised by the finding of epithelioid cell granulomas in more than one system. Diagnosis is aided by the use of the Kveim Siltzbach skin test and the development of an "in vitro" Kmif test is discussed. Despite extensive researches the causative agent(s) remains unknown. The granulomas, morphologically, on light and electron microscopy and histochemistry may be indistinguishable from those caused by known agents. Inclusion bodies are also non specific. Central necrosis is rare, and can be usually distinguished from caseation. The close relationship between the monocyte derived, epithelioid cells and lymphocytes is emphasised. Evidence is accumulating that epithelioid cells in sarcoid type granulomas are primarily synthesising rather than phagocytic cells. The products are considered to be mucoglycoproteins and may have both local and systemic actions. Locally it is suggested that the products may be lymphokines which react with associated thymic derived (T) lymphocytes and mononuclear cells and thus play a role in perpetuating the granulomas. Epithelioid cells may also be a source of circulating T lymphocyte function depressants. It has further been suggested that epitheloid cells are the source of the raised angiotensin converting enzyme found in sarcoid sera. Study of epithelioid cell granulomas in sarcoidosis, despite the disappointing lack of evidence of a causative sarcoid agent(s), is thus of considerable interest in furthering knowledge of many diseases characterised by these curious cellular foci.


Partial purification, properties and regulation of inosine 5'phosphate dehydrogenase in normal and malignant rat tissues. IMP dehydrogenase (EC 1.2.1.14) was purified 180-fold from rat liver and from the transplantable rat hepatoma 3924A. The enzymes from the two sources were apparently identical; they exhibited hyperbolic saturation kinetics and an ordered, sequential mechanism, and were subject to inhibition by a number of purine nucleotides. Km values for the substrates, IMP and NAD+, were 12 and 24 micrometer respectively. IMP dehydrogenase activity in a spectrum of rat hepatomas was increased, relative to normal liver, by 2.5--13-fold; these increases correlated with tumour growth rate. Activity in two rat kidney tumours was increased 3-fold relative to that in normal renal cortex; control of activity of this enzyme is apparently altered in neoplastic cells. After partial hepatectomy, IMP dehydrogenase activity began to rise 6 h after operation, reaching a peak of 580% of normal activity by 18 h. Activity in neonatal liver, however, was only slightly higher than that in the adult. Organ-distribution studies showed highest enzyme activities in spleen and thymus. In livers of rats starved for 3 days, where all enzymes, except those involved in gluconeogenesis, showed decreased activity IMP dehydrogenase activity was increased; this change was accompanied by a rise in hepatic GTP concentrations. It is concluded that IMP dehydrogenase is a key enzyme in the regulation of GTP production, and thus involved in regulation of nucleic acid biosynthesis. The increased activity of IMP dehydrogenase in liver of starved rats may be related to the requirements for GTP for gluconeogenesis.


Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. 1. Cathepsin B, a tissue (lysosomal) proteinase, and two humoral proteinases, plasmin and kallikrein, activate the latent collagenase ('procollagenase') which is released by mouse bone explants in culture. Other lysosomal proteinases (carboxypeptidase B, cathepsin C and D) and thrombin did not activate the procollagenase. Dialysis of the culture fluids against 3M-NaSCN at 4 degrees C and, for some culture fluids, prolonged preincubation at 25 degrees C also caused the activation of procollagenase. 2. In all these cases, activation of procollagenase involved at least two successive steps: the activation of an endogenous latent activator present in the culture fluids and the activation of procollagenase itself. 3. An assay method was developed for the endogenous activator. Human serum, bovine serum albumin, casein and cysteine inhibited the endogenous activator at concentrations that did not influence the collagenase activity. N-Ethylmaleimide and 4-hydroxy-mercuribenzoate stimulated the endogenous activator, but iodoacetate had no effect. 4. It is proposed that cathepsin B, kallikrein and plasmin may play a role in the physiological activation of latent collagenase and thus initiate degradation of collagen in vivo. This may occur whatever the molecular nature of procollagenase (zymogen or enzyme-inhibitor complex) might be.


Hypolipidemic activity of in vitro inhibitors of hepatic and intestinal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase. A number of agents including a series of 1,3-bis (substituted phenoxy)-2-propanones were screened in vitro for their ability to inhibit hepatic and intestinal microsomal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase. Effective inhibitors reduced in vivo hepatic and intestinal glycerolipid production and with one exception also lowered serum triglyceride levels, suggesting that agents which inhibit potential rate-limiting steps of glycerolipid biosynthesis may be effective hypolipidemic agents. Two compounds, 1-methyl-4-piperidyl bis (p-chlorophenoxy) acetate (Sah 42-348) and 1,3-bis (p-methylphenoxy)-2-propanone were the best inhibitors of glycerolipid biosynthesis and lipid-lowering agents. The lipid-altering effects of both drugs were compared to chlorophenoxyisobutyrate during high fructose intake in rats. Each agent reduced fructose induced glycerolipid biosynthesis and serum triglyceride levels to similar degrees.


Dilute blood clot lysis time and electrophoretic lipoprotein fractions in a population sample of healthy Romanians. Serum total lipids and cholesterol, electrophoretically determined lipoprotein concentrations, serum pseudocholinesterase and dilute blood clot lysis time were determined in 630 healthy subjects (287 men and 343 women) aged 20-60, working in the food industry. A high incidence of over-weight was noted ranging from 22.4% in women aged 20-40 to 58.7% in men aged 41-60. Over-weight subjects presenting higher levels of serum cholesterol, total lipids and of the pre-beta electrophoretic fraction also had a higher pseudo-cholinesterase activity and a more delayed clot lysis time than normal-weight subjects matched as to age and sex. When the material was divided into quintiles for pre-beta- and beta-lipoproteins, a highly significant delay of fibrinolysis was noted in the fourth and fifth quintiles for pre-beta-lipoproteins, but no significant changes of lysis time occurred with increasing concentrations of beta-lipoproteins. Possible explanations of the abovementioned findings are briefly discussed.


Ultrastructural study of avian synovium infected with an arthrotropic reovirus. Three-week-old chicks were inoculated via the foot pad with the avian reovirus (strain WVU 2937) that has been proved to be the causative agent in avian viral arthritis. The initial stages of the avian reovirus infection in the synovium of the hock joint were studied by transmission electron microscopy to shed light on the early virus-host relationship of an arthrotropic virus and synovial tissue. At 48 hours postinoculation (PI), coated, partially coated, and uncoated virus particles were seen in a dense lysosome-like inclusion in the cytoplasm of subsynovial fibroblasts. Virus replication was demonstrated in fibroblasts of the subsynovium 4 days PI. Infiltration of leukocytes into the area of the virus replication was noted at the time of virus replication (4 days PI). By the second week of the infection (11 days PI), the subsynovium was heavily infiltrated with lymphocytes and plasma cells, and proliferative changes had occurred in the synovial lining cells.


Effect of lipoprotein on in vitro synthesis of DNA in aortic tissue. (1)Using both an explant system from swine thoracic aorta and an aortic smooth muscle cell culture system, we have investigated the effect of lipoproteins on the synthesis of DNA in the absence of serum or serum derivatives. (2)Chemical and morphological data from both systems confirm that (a) neither VLDL, LDL nor HDL account for any appreciable part of the DNA synthesis activity of whole serum. (b) There is no difference in activity between lipoprotein fractions derived from either normocholesterolemic or hypercholesterolemic serum. (c) The activity resident in whole serum is present largely in the pelleted serum protein fractions and in the soluble resideu. (3) The data suggest that smooth muscle cell proliferation results from the interaction of lipoproteins with other factor(s) in serum.


Intercellular glycoproteins and low density lipoprotein binding to fibroblasts. The interaction of low density lipoprotein (LDL) with solubilized subunits of two purified noncollagenous glycoproteins (A and G) of cartilage matrix have been studied in solution using Sepharose chromatography and at the cell surface using fibroblast monolayers. In the presence of A or G, [125I]-LDL forms aggregates of varying size. After pre-incubation with A or G, under conditions which form highly aggregrated complexes, there is an increase in the binding of LDL to fibroblasts. Mixing with A under conditions which form smaller complexes produced no increase in binding to fibroblasts. It is suggested that interactions of this type may be involved in the pathogenesis of atherosclerosis.


Predictable changes in low density lipoprotein composition after acute myocardial infarction. Acute changes in low density lipoprotein cholesterol levels may be due to both a change in the number of LDL particles/ml of plasma and an alteration in the amount of cholesterol per LDL particle. Since LDL cholesterol levels are known to alter abruptly after myocardial infarction, the composition of LDL was determined in nine patients who suffered an uncomplicated transmural myocardial infarction. In six of these, LDL cholesterol levels fell whereas in three LDL cholesterol rose during the first nine days in hospital. The contents of B protein, free cholesterol, phospholipid, cholesterol ester and triglyceride in LDL were determined in the initial sample and the subsequent sample showing the greatest changes in LDL cholesterol level. The proportion of the LDL molecule contributed by B protein, free cholesterol and phospholipid did not differ significantly between the two samples. In contrast, when LDL cholesterol fell, the decrease in the proportion of cholesterol ester was disproportionately greater than in triglyceride. The opposite was observed when LDL cholesterol rose. This inverse relation between changes in LDL cholesterol ester and triglyceride could be expressed by Y = -1.02 X -0.17 (r = -0.94). These data are consistent with a pseudomicellar model of LDL in which the surface components are present in fixed amounts but the interior shell of cholesterol ester and triglyceride varies in an inverse relation depending on the absolute LDL concentration.


Pharmacokinetics of pivmecillinam.

Pharmacokinetics of pivmecillinam. 1 The plasma concentration/time curves of ampicillin and mecillinam in normal subjects were measured after oral administration of ampicillin (500 mg) and pivmecillinam (400 and 600 mg). 2 Similar plasma concentration/time curves of ampicillin and mecillinam in the starved normal subjects followed oral administration of ampicillin (500 mg) and pivmecillinam (600 mg). 3 The plasma concentration/time curve of mecillinam was measured in the same normal subjects after oral administration of pivmecillinam (400 mg) with a reproducible standardized Lundh test meal. 4 There was no statistically significant difference in the plasma concentration/time curve of mecillinam after pivmecillinam/400 mg) and the meal compared with the plasma concentration/time curve after oral pivmecillinam (400 mg) was given to the same subjects when starved. After administration of pivmecillinam (400 mg) with meal, Tasc was significantly delayed beyond the value obtained when the subjects were starved. 5 The pharmacokinetics of pivmecillinam in coeliac disease are normal. This finding contrasts with previous studies on the pharmacokinetics of another pivaloyloxymethylpenicillin ester, pivampicillin, in this condition.


A comparison of cholestyramine and nicotinic acid in the treatment of familial type II hyperlipoproteinaemia. 1 The effects of cholestyramine and nicotinic acid on plasma lipid concentration have been compared in patients with type IIa hyperlipoproteinaemia. 2 During a 3-month period, cholestyramine resulted in a mean decrease in cholesterol levels of 26%. Triglyceride levels rose in eight of the ten patients during treatment with this drug but in the majority of patients remained within the normal range. 3 During nicotinic acid therapy, cholesterol fell by a mean of 21% and triglyceride by a mean of 23%. 4 The slow release preparation of nicotinic acid used was acceptable to the majority of the patients studied and the results therefore suggest that this drug may be a useful alternative to the more widely used agent, cholestyramine.


Pulsed electron paramagnetic resonance studies of types I and II coper of Rhus vernicifera laccase and porcine ceruloplasmin. Electron spin-echo decay envelopes for types I and II copper of Rhus vernicifera laccase and for type II copper of procine ceruloplasmin have been studied. Nuclear modulation patterns show that imidazole is a ligand for all of them. The linear electric field effect (LEFE) in EPR was studied for type I copper in a laccase preparation from which type II had been removed. The symmetry of the site is near tetrahedral and the magnitude of the LEFE is correlated with the intensity of blue color.


RNA phosphorylation: a polynucleotide kinase function in mouse L cell nuclei. Analysis of [gamma-32P]ATP in vitro labeled nuclear RNA shows transfer of gamma-32P from ATP to form the 5'-terminal monophosphate for large RNA molecules. This finding is an actively transcribing nuclear system capable of guanylation and methylation reactions indicates that polynucleotide kinase activity in the eukaryotic nucleus may be functional in kinase reactions involving RNA. It further suggest a participation in the posttranscriptional modification reactions involved in RNA processing. All four nucleosides were found to act as acceptors at the 5' termini of RNA. It is also shown that both ATP and GTP can serve as donors in the nuclear polynucleotide kinase reaction.


The effect of phosphatidylcholine depletion on biochemical and physical properties of a Neurospora crassa membrane mutant. By using the choline starvation process it is possible to deplete the membranes of Neurospora crassa choline auxotroph chol-1 of phosphatidylcholine, without affecting the viability of germinated spores or whole mycelium. Spin label probes were used to examine the possible dependence of the physical state of cellular lipids on the presence of phosphatidylcholine in the membranes. Increased freedom of rotational motion of lipid soluble probes was regularly detected in choline-starved mycelium. The accumulation of neutral lipids (mostly triglycerides) in bulk form was also observed during the choline starvation process. The experiments with isolated and separated lipid classes indicated that the observed increase in fluidity of lipids in choline-starved mycelium is partly due to the difference in physical properties between bulk lipids and membrane lipids. Spin label probe 2N4 (2-propyl-2,5,5-trimethyloxazolidine-N-oxyl), which can partition at the membrane-water interface, exhibited easier partitioning among membrane lipids of choline-starved mycelium.


The role of enzyme I in the unmasking of an essential thiol of the membrane-bound enzyme II of the phosphoenolpyruvate-glucose phosphotransferase system of Escherichia coli. The membrane-bound component of the phosphotransferase system of Escherichia coli, responsible for the phosphorylative uptake of methyl-alpha-D-glucoside has an essential thiol group which becomes available to inactivation by thiol reagents in the presence of the phosphate-accepting sugar or when phosphoenolpyruvate synthesis is inhibited. The form resistant to the thiol reagent requires not only the absence of sugar and an intact phosphoenolpyruvate generating system, but also an intact system generating phosphorylated Hpr which is impaired by heating of a thermosensitive enzyme I mutant.


Evidence for the presynaptic location of adenylate cyclase and the cyclic AMP-stimulated protein kinase which is bound to synaptic membranes. By comparison of activities measured with either intact or ruptured synaptosomes it was found that half of the cerebral adenylate cyclase is presynaptic while all the membranes bound, cyclic AMP-stimulated protein kinase activity appears to be presynaptic with the cyclic AMP receptor facing inward.


Electron spin resonance investigations of membrane proteins in erythrocytes in muscle diseases. Duchenne and myotonic muscular dystrophy and congenital myotonia. Comparison of electron spin resonance spectra of spin labeled erythrocyte membranes from patients with the dystrophic conditions Duchenne and myotonic muscular dystrophy with those of normal controls suggests that alterations in membrane protein conformation and/or organization are present in these disease states. These protein alterations are not apparent in the non-dystrophic disease congenital myotonia. The results suggest a correlation between changes in the physical state of proteins in membranes with the presence of dystrophy. In addition, the present results from erythrocytes lend support for the concept of a generalized membrane defect in these diseases.


Isolation of non-myelin plasma membranes unique to white matter. A procedure is described for isolating two membrane fractions from rabbit spinal-cord white matter enriched with 5'-nucleotidase, a nonspecific plasma membrane marker, 2',3'-cyclic nucleotide phosphohydrolase, an oligodendroglial plasma membrane marker, and acetylcholinesterase, an axonal plasma membrane marker. While the two membrane fractions exhibited similar enrichments with respect to cyclic nucleotide phosphohydrolase, enrichments of 5'-nucleotidase and acetylcholinesterase were significantly greater in the heavier membrane fraction. Selected enzyme markers for cyto- and mitochondrial membranes were not detected. Moreover, gray matter did not yield homologous membrane fractions in the gradient when subjected to the identical procedure, indicating that the two membrane fractions were unique to white matter. While electronmicroscopic examination revealed that both membrane fractions were comtaminated with myelin, the heavier fraction was least contaminated and exhibited a fair degree of homogeneity with respect to single membrane vesicular profiles. It was concluded that both membrane fractions were enriched with oligodendroglial and axonal plasma membranes, with the heavier fraction containing significantly more axolemma.


Miscibility properties of binary phosphatidylcholine mixtures. A calorimetric study. From data obtained by differential scanning calorimetry phase diagrams were constructed, using a thermodynamically based fitting method. The following binary mixtures of phosphatidylcholines in water were studied: 14:0/14:0-glycerophosphocholine/16:0/16:0-glucerophosphocholine, 14:0/14:0-glycerophosphocholine/18:0/18:0-glycerophosphocholine, 12:0/12:0-glycerophosphocholine/16:0/16:0-glycerophosphocholine, 18:1t/18:1t-glycerophosphocholine/14:0/14:0-glycerophosphocholine and 18:1t/18:1t-glycerophosphocholine/16:0/16:0-glycerophosphocholine. A comparison is made of the present results with those obtained using probe techniques and the differences are discussed.


The preparation and use of pyridoxal [32P]phosphate as a labeling reagent for proteins on the outer surface of membranes. Pyridoxal [32P] phosphate was prepared using [gamma-32P] ATP, pyridoxal, and pyridoxine kinase purified from Escherichia coli B. The pyridoxal [32P] phosphate obtained had a specific activity of at least 1 Ci/mmol. This reagent was used to label intact influenza virus, red blood cells, and both normal and transformed chick embryo fibroblasts. The cell or virus to be labeled was incubated with pyridoxal [32P] phosphate. The Schiff base formed between pyridoxal [32P] phosphate and protein amino groups was reduced with NaBH4. The distribution of pyridoxal [32P] phosphate in cell membrane or virus envelope proteins was visualized by autoradiography of the proteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The labeling of the proteins of both influenza and chick cells appeared to be limited exclusively to those on the external surface of the virus or plasma membrane. With intact red blood cells the major portion of the probe was bound by external proteins, but a small amount of label was found associated with the internal proteins spectrin and hemoglobin.


The separation of human serum high density lipoproteins by hydroxy apatite column chromatography. Evidence for the presence of discrete subfractions. Human serum high density lipoprotein subfractions 2 and 3, isolated by preparative ultracentrifugation after blocking the enzyme phosphatidylcholine: cholesterol acyl transferase, have been subfractionated further by hydroxyapatite column chromatography. From subfraction 2 we reproducibly obtained 5 and from subfraction 3, 6 fractions differing in chemical composition and apolipoprotein content. The fractions eluting at low salt concentrations were composed primarily of apolipoprotein-A polypeptides while those eluting at high salt concentrations consisted primarily of apolipoprotein-C. From all the 11 subfractions only one contained the "arginine-rich" polypeptide. The apolipoprotein-C-containing fractions were richer in triacylglycerol, phospholipids and free cholesterol as compared to the apolipoprotein-A-containing ones. Although small differences of their partial specific volumes existed, the obtained values indicate that all subfractions belonged to the parent density class. The implications of these results to the current view of lipoprotein metabolism are discussed.


Evidence for the glycoprotein nature of kidney renin. The glycoprotein nature of renin isolated from either rabbit or human kidney has been demonstrated by affinity chromatography on concanavalin A-Sepharose. The bulk of rabbit renin activity bound to concanavalin A is released by 20 to 50 mM alpha-methyl-D-mannoside. Adsorption of renin is prevented by periodate oxidation prior to chromatography. Mild acid treatment (pH 2.5) prior to chromatography does not alter the concanavalin A binding profile although the pI values of native rabbit renin (5.1-5.6) are shifted into a broader distribution (4.7-6.4). The molecular weight values of rabbit renin obtained by gel filtration and those from zone centrifugation are identical (37000 +/- 1000), consistent with a low percent of carbohydrate in the glycoprotein. A hydrophobic contribution to the binding of renin by concanavalin A is evident since, in the presence of mM Ca2+ and Mn2+, higher concentrations of alpha-methyl-D-mannoside are required to affect the same release of renin at 23 degrees C compared to that at 4 degrees C. Furthermore, 25% ethylene glycol releases renin in the absence of alpha-methyl-D-mannoside. It is concluded that renin contains a small number of carbohydrate residues in relatively close proximity to a hydrophobic surface which enhances the interaction with concanavalin A.


Determination of the exchange integral in binuclear iron-sulfur clusters in proteins of varying complexity. The coupling constants J between the iron atoms in ferredoxin type iron-sulfur proteins containing binuclear clusters were evaluated by two parallel methods. The temperature dependence of the EPR linewidths and integrated abosrption intensities are both related to the energy of the first excited state. The values of J obtained were: center S-1 in succinate dehydrogenase, 90 cm-1; Rieske's iron-sulfur center, 65 cm-1; adrenodoxin, 270 cm-1. The behavior of iron-sulfur center N-1a in NADH:UQ reductase was also examined; its similarity to that of center S-1 indicates that center N-1a is also a binuclear iron-sulfur center, with J = 90 cm-1. Greater rhombic distortion present in the EPR spectrum of a binuclear cluster was associated with smaller values of J.


Structural changes accompanying the removal of pyridoxal 5'-phosphate from phosphorylase b. The changes in physical properties accompanying the removal of pyridoxal 5'-phosphate from glycogen phosphorylase b have been examined. The apoenzyme retains a high degree of structural rigidity, as determined from the time decay of anisotropy. The bulk of the secondary structure remains intact, although a significant change in circular dichroism indicates some degree of alteration. The mobility of a sulfhydryl-linked spin label increases. The restoration of pyridoxal 5'-phosphate reverses this effect, with indication of interaction between subunits. One or more new binding sites for 1-anilinonaphthalene-8-sulfonate appear for the apoenzyme. The kinetics of the recombination of pyridoxal 5'-phosphate with the apoenzyme, as monitored by difference spectra, indicate a high activation energy for the process. The apoenzyme is a reversibly associating system at 20-30 degrees C, pH 7.0.


The cardiac sarcoplasmic reticulum-glycogenolytic complex. A possible effector site for cyclic AMP. Cardiac sarcoplasmic reticulum-glycogenolytic complex, isolated as a single peak on sucrose density gradient, may function as a "compartmented" effector site for cyclic AMP resulting in modulation of both glycogenolysis and calcium transport. The conversion of phosphorylase b to a is stimulated by ATP and inhibited by protein kinase inhibitor. Cyclic AMP alone stimulated neither phosphorylase b to a conversion nor calcium uptake. An inhibitor of adenylate cyclase depressed both calcium uptake and phosphorylase activation and both functions were subsequently stimulated by micromolar concentrations of cyclic AMP. Endogenous phosphorylation of sarcoplasmic reticulum was also inhibited by adenylate cyclase inhibitor and the inhibition was reversed by cyclic AMP. These results suggest that the sarcoplasmic reticulum of cardiac muscle is an internal effector site for cyclic AMP which may regulate both calcium and metabolism. It appears that cyclic AMP formation in vitro is not the rate-controlling step in the activation sequence.


[Interaction of cytochrome c with bilayer membranes]. Cytochrome c when adsorbed on bilayer phospholipid membrane (BLM) induced an adsorption potential of the order of 50 mv which relaxes gradually. The value and the sign of the adsorption potential depend upon the initial polarisation of the membrane. On the positively charged surface of the membrane (polarisation above 120 mv) the orientation of adsorbing molecules of the protein inverts. Ferri- and ferrocytochrome c have different affinity to phospholipids of BLM. The reduction of protein electrostatically bound to lipid bilayer causes its partial desorption when oxidation results additional adsorption of cytochrome c. Protein does not penetrate through the membrane. Electric conductivity and capacity of BLM are slightly influenced by cytochrome c adsorption. The capacity of BLM formed from an isooctane soluble complex of cytochrome c with phospholipid is less than the capacity of pure lipid bilayers.


[Interrelationship between structural and functional modifications in the membranes of the sarcoplasmic reticulum following lipid peroxidation]. Structural and functional modifications of sarcoplasmic reticulum membranes from skeletal muscles by molecular oxygen was studied. Lipid peroxidation (accumulation of 5-10 nmoles hydroperoxides/mg lipids) results in membrane permeability increase for Ca2+-ions whereas the activity of Ca2+-dependant ATPase preserved unchanged. In the temperature range 5-30 degrees C decrease of solubilization parameter alpha (for nitroxide radical 2,2,6,6-tetramethylpiperidin-1-oxyl) was registered while alpha reached the control values at temperatures higher than 30 degrees C. Further increase in lipoperoxide content (more than 20 nmoles/mg lipids) lead to inhibition of Ca2+dependant ATPase. In this case alpha was lower than in intack membranes in the whole temperature interval investigated. The loss of Ca2+-accumulating capacity is explained on the basis of peroxide clusters formation in lipid bilayer regions of sarcoplasmic membrane. One of the mechanisms of Ca2+-dependant ATPase inhibition after lipid peroxidation is the deficiency of polyunsaturated fatty acyls in microenvironment of the enzyme.


[Factors influencing formation of dinitrosyl complexes of non-heme iron in vitro preparations of mouse liver and yeasts]. Total content of Fenh and its amounts incorporated into paramagnetic dinitrozyl complexes of Fenh (complexes 2.03) which are formed in vitro in homogenates of mouse liver and yeast preparations treated with nitrogen oxide was determined by means of chemical and ESR methods. Formation of the complexes 2.03 in the liver homogenate is limited by the content of easily dyalized weakly bound Fenh, in yeasts--by the content of pair RS-groups. It is suggested that in the liver preparation Fenh incorporated into the complexes 2.03 is determined by the interaction of reduction cytoplasm agents with ferritin. A change in the content of Fenh may affect the appearance and disappearance of the complexes 2.03 in animal tissues in vivo.


[ESR study of the state of manganganese in chloroplasts]. In chloroplasts isolated in tris-HCl buffer in the presence of 0.1 M NaCl or in the absence of salts an asymmetric ESR spectrum of Mn2+ was observed which differs in shape from the ESR spectrum of Mn2+ aquanions usually observed in chloroplasts treated with ultrasonics, reducer, 0.8 M tis-HCl buffer, pH 8. The transition from asymmmetric spectrum to the symetric one takes place in the presence of reducers and in some cases is induced with light. Causes of asymmetry of the ESR spectrum of Mn2+ in chloroplasts are discussed.


[Mechanism of oxidative phosphorylation. III. Relationship between the composition of the mitochondrial incubation medium and functional parameters]. Functional properties of rat brain mitochondria were different in Krebs-Ringer solution as compared to these in the media with mannit. Mitochondria in the presence of cytochrme c increased endogenous respiration essentially after the introduction of mannit into the polarographic cell. It is concluded that mannit metabolised by mitochondria as other non-cell compounds, must not be in the media of incubation of mitochondria, while studying the oxidative phosphorylation mechanism.


[Influence of phospholipids of different natures on the structure of ferricytochrome c]. Influence of the two types of lipid molecules (neutral and acidic phospholipids) on the structure of ferricytochrome c in lipid-protein complexes was studied with the use of circular dichroism and absorption spectroscopy methods. It was found that interaction of ferricytochrome c with acidic phospholipids (cardiolipin and phosphatidylinositols) brings about some changes in the protein conformation, while interaction with neutral phospholipid (phosphatidylcholine plus 10% lauric acid) does not. Some difference in the mode of interaction of different acidic phospholipids with ferricytochrome c was also observed. As evidenced by visual light absorption spectra, cardiolipin induced the disruption of hem--methionine 80 bond in the protein molecule, while phosphatidylinositols do not cause such an effect.


[Oxidation and phosphorylation in rat liver nuclei and nuclear membranes in postnatal development and regeneration after partial hepatectomy]. Specific oxygen consumption by isolated nuclei of liver cells of newborn rats is higher and phosphorylation is lower as compared to adult animals. This is correlated with a higher free cytochrome oxidase activity as determined in the absence of detergents or tetramethyl-p-phenylenediamine. Correspondingly, oxygen consumption by isolated nuclear membranes of rat liver 44 hrs after partial hepatectomy is also increased and the P/O ratio is decreased 2.2-fold as compared to the controls.


[Effect on some pyridine derivatives on the activity of heart NAD glycohydrolase]. Effect of some 3- and 4-substituted pyridines on enzymatic hydrolysis of NAD by rabbit heart muscle NAD-glycohydrolase has been studied. It is shown that some 4-substituted derivatives in contrast with 3-substituted ones produce an inhibitory effect on the enzyme activity. A new efficient inhibitor of rabbit heart muscle NAD-glycohydrolase (I50 = 10(-3) M)--N1-(2-lactyl)-N2-(isonicotinoy)hydrazine, inducing uncompetitive inhibition of hydrolysis of NAD is found. The mechanism of the inhibitory effect of N1-(2-lactyl)-N2-(isonicotinoyl)hydrazine was investigated and the rate equation for enzymatic hydrolysis of NAD in the presence of inhibitor is calculated. It is suggested, that the inhibitory effect of N1-(2-lactyl)-N2-(isonicotinoyl)hydrazine is due to the formation of triple inactive complex inhibitor-enzyme-adenosinediphosphateribose.


[Enzymes of anabolic and catabolic nucleic acid pathways in human hepatomas, in liver of healthy persons, and in liver of patients with cancer of gastrointestinal tract]. The activities of enzymes catalyzing the formation of nucleic acid precursors, nucleoside kinases, as well as of those involved in the degradation of nucleic acids, were studied in nuclei of the liver of healthy persons, human hepatomas and the liver of patients with cancer of gastrointestinal tract. The activities of thymydine kinase and uridine kinase in the human hepatoma nuclear sap were found to increase 40- to 50-fold and 120- to 150-fold, respectively, as compared to those in normal human liver. The activities of DNase and RNase in the fraction of chromatin protein of human hepatomas, on the contrary, decreased almost to zero. As to the liver of patients with cancer of gastrointestinal tract, drastic alterations in the activities of nucleoside kinases and nucleases in the direction characteristic of tumors themselves were observed. This phenomenon is regarded as a manifestation of the systemic effects of the tumor on the host.


[Interaction of ubisemiquinone with the high-potential iron-sulfur center of submitochondrial particle succinate dehydrogenase. EPR study at 240 and 12 degrees K]. The ESR spectra of beef heart submitochondrial particles were measured in the same samples at 240 degrees and 12 degrees K. There is close similarity between the inhibitory action of alpha-thenoyltrifluoroacetone, ethanol and ferricyanide on the non-saturating free radical signal SQ-2 observed at 240 degree K and peak at g=1.99 (and 2.04) which is visible only at very low temperatures. This result strongly supports our previous proposal that both ESR signals are manifestations of the ubisemiquinone complex with the High-Potential Iron-Sulfur protein of succinate dehydrogenase.


[Effects of polyene antibiotics and detergents on cell membranes of polyene-sensitive and polyene-resistant strains of Candida albicans]. Various detergents and EPR-probes of 4,4-dimethylspiro[5alpha-androstan-17beta-ol-3,2-(1,3-oxazolidin-3-oxyl)]2CH3OH; 2,2,6,6-tetramethylpalmitoyl-amidopiperidine-1-oxyl and 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinoxyl were used to establish structural differences in the membrane of polyene-sensitive and polyene-resistant strains of C. albicans. It was shown that the type of protein-lipid interactions is modified by the changes in the sterol component of the polyene-resistant strain membranes. This manifests itself in a decrease in sensitivity of membrane alkaline phosphatase for levorin and the detergents, as well as in the alteration of the lipid fluidity pattern of the polyene-resistant strain membranes as compared to the membranes of original culture of C. albicans. Treatment of polyene-sensitive strain membranes with amphotericine B causes more intensive protein-lipid interactions, which is not observed in case of the polyene-resistant strain. It is assumed that C. albicans resistance to polyenes is due to the existence of strong protein-lipid interactions in the membrane coupled with ergosterol substitution by other sterol components.


[Interrelationship between the generation of oxygen anion-radicals and the reduction of artificial acceptors and cytochrome P-450 by NADPH-cytochrome c reductase]. The interaction of NADPH-cytochrome c reductase with oxygen, artificial acceptors and cytochrome P-450 is investigated. It is found that generation of oxygen anion-radicals (O2-), determined from the reaction of adrenaline oxidation into adrenochrome, proceeds independently on the reactions of interaction with artificial "anaerobic" acceptors-cytochrome c, dichlorophenolindophenol. Propylgallate competitively inhibits the reaction of adrenaline oxidation by isolated DADPH-cytochrome c reductase and non-competitively suppress the reaction of cytochrome c reduction. In contrast to the process of electron transfer on cytochrome c, there is a direct correlation between the rate of cytochrome P-450 reduction and the rate of adrenaline oxidation in liver microsomes. Hexobarbital increases V of the adrenaline oxidation reaction and does not affect the Km value, while metirapon, a metabolic inhibitor, decreases the Vmax and does not change Km. On the basis of the data obtained it is suggested that the reactions of NADPH-cytochrome c reductase interaction with oxygen and artificial "anaerobic" acceptors are connected with different redox-states of flavoprotein or with different flavine coenzymes, and that the electron transport on cytochrome P-450 and directly on oxygen takes place in interrelated redox-states of flavoprotein.


Regulation of cyclic nucleotide phosphodiesterase activity in rhesus fetal muscle. In both fetal and adult rhesus muscle, low levels of guanosine 3':5'-monophosphate (cyclic GMP; 0.25--5.0 micrometer) stimulated the adenosine 3':5'-monophosphate (cyclic AMP)-phosphodiesterase (PDE) at low substrate levels; the fetal enzyme was more sensitive than the adult (supernatant and particulate fractions). At high levels of substrate cyclic AMP (25--100 micrometer), hydrolysis was not influenced by either 10 or 20 micrometer cyclic GMP but the fetal and adult series were equally inhibited by 40 micrometer cyclic GMP. In the supernatant fraction cyclic AMP inhibition of cyclic GMP hydrolysis increased with increasing cyclic AMP levels. There was no difference between fetal and adult muscle preparations in percent inhibition; however, in the adult series, the inhibition was noncompetitive whereas in the fetal series the inhibition was competitive. The Ki for cyclic AMP was 40 micrometer for fetal and 100 micrometer for adult cyclic GMP-PDE. The Vmax values for cyclic GMP-PDE and both cyclic AMP-PDE enzymes were higher in the fetal series.


Effect of ethanol and prednisolone on growth rate and adherence of normal and SV 40 transformed hamster fibroblasts. Ethanol decreases the growth rate of normal cells, prednisolone increases it. These factors have no effect on the growth rate of transformed cells. Ethanol increases the detachment and mortality of transformed cells, prednisolone has an inverse effect. Both factors affect neither adherence nor mortality of normal cells.


Electron paramagnetic resonance determination of a low-lying excited state in Chromatium vinosum high-potential iron protein. The temperature dependence of the EPR spectrum of oxidized high-potential iron protein from Chromatium vinosum has been studied. From line width and intensity measurements it is possible to determine the position of the first excited unoccupied state, 160 +/- 10 cm-1 above the ground state orbital.


ESR an optical absorption studies on the copper(II) interaction with small peptides containing aromatic amino acids. The interaction of Cu(II) with di- and tripeptides each containing phenylalanine, tryptophan or histidine in the amino acid chain has been investigated by means of electron spin resonance (ESR) and optical absorption spectroscopy. Cu(II) complexes of dipeptides and tripeptides exhibit different magnetic and optical parameters. Dipeptide complexes have larger gparallel-values and smaller A parallel values than tripeptide complexes. When compared to dipeptide complexes, the d-d band of the central metal ion is blue shifted for tripeptide complexes. There are no significant difference in the behavior of Cu(II) peptide complexes containing phenylalanine or tryptophan. Complexes of histidine containing peptides, however, show modified spectra caused by the participation of the imidazole nitrogen in the coordination to Cu(II). The imidazole nitrogen seems to coordinate in-plane with other coordinating atoms or in an axial position depending on the kind of peptide.


A comparison between Nitrosomas europaea and Thiobacillus novellus on the basis of their oxidation systems of inorganic compounds. Nitrosomonas europaea and Thiobacillus novellus were compared with each other on the basis of the biochemical properties of their inorganic compound-oxidizing systems. Cytochromes c of the two organisms differ considerably from each other; N. europaea cytochrome c-552 belongs to the "bacterial-type"  cytochrome c, while T. nouellus cytochrome c-550 resembles eucaryolic cytochrome c. The specificity of cytochrome oxidase for cytochrome c as the electron donor is different between the two organisms; T novellus oxidase reacts rapidly with cytochromes c of the organisms which seem to be higher than the organisms whose cytochromes c react rapidly with N. europaea oxidase. On the basis of these facts, N. europaea seems to be older organism than T. novellus in terms of evolution.


[Participation of the alpha- and beta-adrenoreactive systems of the brain in the regulation of contractile thermogenesis in the cat]. The influence of intraventricular injections of alpha- and beta-adrenergic substances (mesaton, phentolamine, isadrin, and propranolol) was investigated in cats. It was found that the central alpha-adrenoreceptors were involved in the shivering activating system and beta-adrenoreceptors -- in the inhibitory one.


[Phosphoinositide content in the erythrocyte membranes of rats with spontaneous hypertension]. The values of triphosphoinositides (TPI) and monophosphoinositides (MPI) contents per 1 mg of membrane protein in the erythrocyte hosts of spontaneously hypertensive rats (SHR) constitute 178 and 74%, respectively, of that in the erythrocyte hosts of normotensive rats (NR). The total amount of phosphoinositides in the erythrocyte hosts of NR is more than 120% of the total amount of these lipids, in the erythrocyte hosts of SHR.


[Action of lipases on low-density serum lipoproteins]. It was shown that the action of phospholipase A2 on low density serum lipoproteins (LDL) in the presence of serum albumin led to decrease in the floatation coefficient. Lipase hydrolyzed LDL triglycerides after pretreatment of the latter with phospholipase A2. Due to the action of lipases the LDL residue loses its solubility and the cholesterol-rich precipitate forms. The loss of solubility of lipoproteins treated with lipases and proteinases may occur in vivo, underlying athermao formation, i.e. can thus serve as one of the factors in the pathogenesis of atherosclerosis.


[Study of the effect of cAMP on the mitotic regimen in the esophageal epithelium of tumor-bearing mice]. The mitotic activity and number of DNA-synthesizing cells in the epithelium of the esophagus of the tumour-bearing albino mice were studied for 24 hours after the injection of dibutyryl cyclic 3', 5'-AMP. It was shown that injection of the preparation led to the blocking of cells in the G2-phase of the mitotic cycle, and to prolongation of mitosis during the first hours of the experiment without changing the total number of cells undergoing mitosis in the course of 24 hours.


Stimulation of the hexose monophosphate shunt independent of hydrogen peroxide and superoxide production in rabbit alveolar macrophages during phagocytosis. Phagocytosis and oxidative metabolism of human polymorphonuclear leukocytes (PMN) and rabbit alveolar macrophages (AM) were studied. Human PMN ingested a mean of 12 polyvinyl toluene latex particles (2 micrometer in diameter) per cell. There was stimulation of O2- and H2O2 production, light emission, and activation of the hexose monophosphate shunt during phagocytosis by human PMN. Rabbit AM ingested 51 latex particles (2 micrometer in diameter) per cell. There was no stimulation of the production of O2- and H2O2 or light emission associated with phagocytosis by rabbit AM, while the hexose monophosphate shunt was activated. Similar metabolic changes were obtained in both cell types when opsonized zymosan was used as phagocytic particles. 1-14C-glucoseoxidation was stimulated by H2O2 and methylene blue in both resting human PMN and rabbit AM. It is concluded that activation of the hexose monophosphate shunt in rabbit AM during phagocytosis is independent of O2- and H2O2 production.


Infectious hepatitis (hepatitis A) research in nonhuman primates. A satisfactory animal model has been found for laboratory studies of human hepatitis A-namely, the white-moustached marmoset (Saguinus mystax). With this species it has been possible to perform serum-neutralization tests and to develop immune-adherence and complement-fixation tests demonstrating antigen and antibody to the virus. The recent work in marmosets has also led to determination of the agent's characteristics: it most closely resembles the enteroviruses of the picornavirus family. These advances open the way for development of a routine serologic test for diagnosis of the disease, of a human immune globulin for general use that would be precisely standardized for hepatitis A antibody, and, ultimately, of a vaccine. They also provide bases for epidemiologic studies that could reveal nonspecific measures for the disease's control. In addition, there is indication that marmosets could be used for safety control of the hepatitis B vaccine that has already been developed. An adequate supply of S. mystax-threatened by recent embargoes on their exportation-is essential to continuation of this work. The question of marmoset supply, both in the short term and over the long range, deserves serious review.


The herpesvirus group.

The herpesvirus group. Several agents in the herpesvirus group are known to infect man. They cause a wide variety of conditions, ranging from coldsores to chickenpox and shingles. At the same time a number of the herpesviruses have been linked with malignant diseases in both lower animals and man.


[Effect of hyperoxia on triacylglycerol lipase activity of the rat lung (author's transl)]. An investigation of acid and neutral triacylglycerol lipases in rat lung tissue has been carried out. The effect of high oxygen concentration in the inspired gas mixture on the activities of the two triacylglycerol lipases has been studied. Hyperoxia had a strong inhibitory effect on both enzymes, the degree of inhibition being dependent on the duration of exposure. Dibutyryl-3',5' AMP and NaF restored completely the activities of the inhibited triacylglycerol lipases, while adrenaline and caffeine had no effect. The possible mechanisms of the effects of oxygen on lung triacylglycerol lipases are discussed.


Effect of isoprenaline and phenylephrine on the adenosine 3',5'-monophosphate content and mechanical activity of cold-stored and fresh taenia caecum from the guinea-pig. 1. Cold storage treatment of the guinea-pig taenia caecum had a greater inhibitory effect on the isoprenaline-induced relaxation than that induced by phenylephrine. Prolonged cold storage (12-14 days) almost abolished the effect of isoprenaline but only reduced the phenylephrine effect. The ED50 of cyclic adenosine 3',5'-monophosphate (cyclic AMP) that elicited muscle relaxation was not altered by the prolonged cold storage. 2. After cold storage treatment, tissue cyclic AMP content was decreased; however, isoprenaline still caused a dose-dependent increase in the cyclic AMP level. The threshold dose of isoprenaline for cyclic AMP accumulation was the same in fresh and cold-stored preparations. 3. In the fresh preparation, the onset of the isoprenaline (10(-6)M)-induced relaxation preceded the increase in tissue cyclic AMP. 4. Isoprenaline, phenylephrine, adrenaline and noradrenaline at doses (ED50) sufficient to induce muscle relaxation did not always increase the cyclic AMP level. 5. Similarly, the responses to papaverine and nitroglycerine were not accompanied by an increase in cyclic AMP. 6. The adenylate cyclase and phosphodiesterase (low and high Km) activities of taenia caecum were not attenuated by the prolonged cold storage. 7. Propranolol inhibited both the isoprenaline-induced relazation and cyclic AMP accumulation; however, the pA2 values were significantly different for the two events. 8. Based on these results, both the relaxation and cyclic AMP accumulation caused by isoprenaline are mediated by activation of beta-adrenoceptors but are independent phenomena.


The effect of angiotensin I converting enzyme inhibitor (SQ 20881) on the release of prostaglandins by rabbit kidney, in vivo. 1. Prostaglandin E- and F-like material has been estimated in renal venous blood of the left kidney of anaesthetized rabbits following renal nerve section. Prostaglandins were estimated by bioassay following solvent extraction and column chromatography. 2. Electrical stimulation of the renal nerves of the left kidney to reduce renal blood flow by approximately 15% for 15 min resulted in a significant increase in the concentration of prostaglandin E-like material in the renal venous blood. The peak values were normally seen either in the last 5 min of the stimulation period or in the first 5 min after the end of the stimulation period. The concentration of prostaglandin F-like material was not significantly altered. 3. Similar reduction of renal blood flow of the left kidney by renal artery constriction also resulted in a significant increase in the concentration of prostaglandin E- but not F-like material in renal venous blood. The timing and magnitude of the response was comparable with that observed with renal nerve stimuation. 4. The effect of an angiotensin I converting enzyme inhibitor, SQ 20881, on the response to both renal nerve stimulation and renal artery constriction has been studied. The administration of the drug did not significantly reduce the release of prostaglandins from the denervated kidneys, however, the increase in prostaglandin E-like material, in response to both stimuli, was abolished. 5. The results suggest that the increase in prostaglandin E-like material released from the kidney in response to low frequency stimulation or to modest reductions in renal blood flow is dependent on the release of renin and that the effect is mediated by the formation of angiotensin II and not angiotensin I.


A computer assisted comparison of 99Tcm-methylene-diphosphonate and 99Tcm-pyrophosphate bone imaging. A total of 350 patient studies were carried out using clinical trials' batches of the Technetium (MDP) agent for bone scintigraphy (The Radiochemical Centre), and a commercially available Technetium pyrophosphate agent (CIS). The bone seeking properties of 99Tcm Sn-methylene-diphosphonate (MDP) and 99Tcm Sn-pyrophosphate (PYP) were evaluated by their comparative uptake in compact bone, cancellous bone and soft tissue using a region-of-interest technique. From these data uptake ratios were computed in order to correlate the values with (a) the amount of 99Tcm-MDP injected, (b) the time after injection and (c) the age of patients examined. All ratios derived with 99Tcm-MDP were superior to those using 99Tcm-PYP and were not dependent on the amount of 99Tcm-MDP injected. Uptake ratios determined for 99Tcm-MDP (1.5 h to 2.5 h after injection) were found to be higher than those for 99Tcm-PYP 2.5 to 3.5 h after injection. Soft tissue accumulation of 99Tcm-MDP, visible on scintiphotos, occurred only in 26% of cases but with 99Tcm-PYP, in 75% out of all cases studied. A decrease of cancellous bone/compact bone ratios with increasing age of the patients was found with both radiopharmaceuticals. This is most probably correlated with a diminished mass and/or surface of the cancellous bone in the elderly patient.


Neuronal circuitry in the basal septum and preoptic area of the rat. Extracellular action potentials of spontaneously active units were studied in the basal septum and medial preoptic area (SPOA). Units responded in a similar way during stimulation of the amygdala, the reticular formation, the medial geniculate nucleus or the ventral hippocampus. The initial response was either short latency (6--35 msec) excitation or inhibition, the latter being predominant. A percentage of neurones (14.5%) did not respond. Only one response did not have an inhibitory component and responses have been further classified on the basis of the presence or absence of a postinhibitory excitation, and its rhythmicity. Single neurones tended to respond in a similar way to stimulation of different sites. Long inhibition (100--400 msec) is often preceded by excitation and may be a recurrent mechanism whilst short inhibition (18--55 msec) may be a 'direct' mechamism. Long inhibition  may be mediated by GABA as it is weakened by intravenous bicuculline whilst short inhibition was not affected. A small amplitude barrage of action potentials at the onset of inhibition was suggested to be generated by inhibitory interneurones within the SPOA. Rhythmic postinhibitory excitatory responses suggest transmission of activity from stimulation sites to the SPOA via the thalamus. A hypothesis for local neuronal circuitry of spontaneously active neurones in the SPOA was proposed.


Activity of neurons in the region of the substantia nigra during feeding in the monkey. The activity of single neurons in the region of the substantia nigra of the monkey was recorded during feeding to investigate their function in ingestive behavior. It was observed that some neurons in the substantia nigra and the adjacent tegmentum altered their activity during feeding, in relation to mouth movements. The activity of these neurons was related to mouth movements in that the responses of the units were similar when the monkeys drank fluids with different tastes as long as the same movements were made, in that equally good responses could be obtained when the monkey moved his mouth to non-food objects, and in that in some units opposite responses were obtained when ipsilateral as compared with contralateral mouth movements were made. It was also shown that the responses of these units associated with mouth movements were similar when the monkeys were hungry and when they were satiated. These findings suggest that the activity of some neurons in the region of the substantia nigra is related to the execution of movements which may be involved in feeding, and that the activity of these neurons is not related to the initiation of feeding. Self-stimulation through the recording microelectrodes could be obtained just dorsal to the substantia nigra, but the neural basis of this self-stimulation is not known.


Role of norepinephrine in the release of prolactin induced by suckling and estrogen. Release of prolactin from the anterior pituitary can be induced by a variety of neuronal and hormonal stimuli, including suckling and estrogen. To determine whether noradrenergic neurons in the central nervous system mediate the response to either of these stimuli, norepinephrine synthesis was inhibited by diethyldithiocarbamate (DDC; 50 mg/kg). When administered to suckled, lactating rats, DDC had no effect on suckling-induced increase in plasma prolactin. The drug also had no effect on prolactin levels in ovariectomized rats. However, when DDC was administered to ovariectomized rats treated with estrogen to increase plasma prolactin levels, there was a fall in plasma prolactin levels which correlated with a decrease in hypothalamic norepinephrine synthesis. It is proposed that estrogen increases noradrenergic neuron activity which in turn increases prolactin release from the pituitary.


Autoradiographic localization of opiate receptors in rat brain. III. The telencephalon. Opiate receptor distribution, determined by the autoradiographic localization of stereospecific [3H]diprenorphine binding sites, was examined in the telencephalon. Areas showing very dense or dense localization of receptors included parts of the presubiculum and amygdala, patchy areas in the caudate-putamen and accumbens, the subfornical organ, the interstriatal nucleus of the striae terminalis and the anterior olfactory nucleus, pars externa. Lower densities were found in other parts of the hippocampal formation, the deeper part of the cerebral cortex, the entopeduncular nucleus, globus pallidus, nucleus triangularis septi and nucleus paratenialis. The significance of these findings is discussed in terms of the biochemical and physiological actions of opiates.


[Study of a virilizing adrenal cortical tumor. Analysis of urinary steroids by gas-liquid chromatography and mass spectrometry]. The C19 and C21 urinary steroids from a virilizing adrenal tumour with high levels of plasma 17alpha-progesterone and its urinary metabolites have been identified and quantitated by gas chromatography and mass spectrometry of sephadex fractions of the total urinary extract. Of the fifty five identified steroids thirteen were new compounds or known compounds not found before in such a case. The actiology of the apparent 21-steroid hydroxylase deficiency is discussed at the light of these analytical results and of the hormonogenesis enzymatic induction of the tumour biopsy.


Effects of Solanum malacoxylon extract on rachitic chicks. Comparative study with vitamin D3. A comparative study of the effects of vitamin D3 and of a partially purified extract of Solanum malacoxylon has been carried out in rachitic chicks. Vitamin D3 and Solanum malacoxylon increased intestinal calcium absorption and serum calcium levels. They normalized the bone water and ash content. Vitamin D3 produced an increase of serum phosphate while Solanum malacoxylon further decreased the already low phosphate values. Vitamin D3 significantly increased the body weight increment of rachitic chicks, but Solanum malacoxylon did not. It appears that Solanum malacoxylon duplicates certain actions of vitamin D but lacks its phosphate-regulating and growth-promoting actions.


Effect of neomycin and ionophore A23189 on ATP levels and turnover of polyphosphoinositides in human erythrocytes. The relationship of polyphosphoinositide metabolism to erythrocyte ATP levels was examined. Turnover of polyphosphoinositides was not closely dependent on ATP as it is reported to be in yeast. Neomycin increased 32P incorporation into diphosphoinositide and to a lesser extent into triphosphoinositide without affecting intracellular ATP. Treatment of intact cells with ionophore A23187 resulted in a decrease of at least 80% in polyphosphoinositide levels which followed a decrease in cellular ATP and an increase in phosphatidate. The results indicate that polyphosphoinositide turnover does not regulate energy charge in the erythrocyte. However some of the events which follow treatment of erythrocytes with metabolic inhibitors or calcium and ionophore may be related to the accompanying decrease in polyphosphoinositide levels.


Fructose-1,6-diphosphatase activity in brown adipose tissue of the developing rat. An enzyme activity capable of converting fructose-1,6-diphosphate to fructose-6-phosphate was demonstrated to present in crude tissue extracts from brown adipose tissue of the rat. Mg2+ was essential for the expression of activity. EDTA (0.5 mM) increased the activity by 30%. Fructose-1,6-diphosphate in concentrations of 1 and 10 mM inhibits activity by 30% and 60% respectively. A 65% inhibition was observed  in  the presence of 0.2 micrometer 5' AMP. The activity of the enzyme was measured in rat brown adipose tissue at different stages of development. It rises sharply between day 2 and day 6 and continues to increase reaching a maximum between 6 and 11 days. Thereafter the activity gradually declines to values observed prenatally. The normal developmental rise in activity could be prevented by chemical sympathectomy on day 2. This procedure had no effect when carried out on day 9. There was a significant increase in enzyme activity after cold adaptation. The possible physiological significance of this enzyme in brown adipose tissue is discussed.


Affinity chromatography of myosin, heavy meromyosin, and heavy meromyosin subfragment one on F-actin columns stabilized by phalloidin. A method of affinity chromatography based on the trapping of actin filaments within agarose gel beads is described. This method can be used for the purification of myosin and its active proteolytic subfragments, as well as for studies on the interaction between actin and these proteins. Actin columns stabilized by phalloidin bind myosin, heavy meromyosin (HMM), and heavy meromyosin subfragment 1 (HMM-S1) specifically and reversibly. The effect of pyrophosphate and KCl on the dissociation of actomyosin, acto-HMM, or acto-HMM-S1 complex is reported. We also describe the single-step purification of myosin from a crude rabbit psoas muscle extract.


Insulin-like effects of fluoroacetate on lipolysis and lipogenesis in adipose tissue. Hormone-stimulated lipolysis in adipose tissue was inhibited by fluoroacetate and there was a concomitant decrease in both the basal and hormone-stimulated cyclic AMP levels. Adenylate cyclase (EC 4.6.1.1) activity in membrane preparations was inhibited by fluoroacetate. There was no influence of fluoroacetate on the low Km cyclic AMP phosphodiesterase (EC 3.1.4.17) activity. The rate of glucose conversion to fatty acids was increased when adipose tissue was incubated in the presence of fluoroacetate. The outputs of pyruvate and lactate into the incubation medium were decreased at this time, suggesting decreased tissue pyruvate levels and a site of activation of lipogenesis distal to pyruvate formation. Pyruvate dehydrogenase (EC 1.2.4.1) activity was increased twofold in adipose tissue incubated in the presence of fluoroacetate. This was attributed to a fluoroacetate-induced inhibition of pyruvate dehydrogenase kinase, the enzyme responsible for inactivating the pyruvate dehydrogenase complex. Glucose transport was increased to a small but significant degree by fluoroacetate. In addition, both the tissue content of citrate and its release into the incubation medium were increased, suggesting that fluoroacetate resulted in an inhibition of aconitase (EC 4.2.1.3). The tissue ATP content was unchanged. Because the antilipolytic and lipogenic effects of fluoroacetate parallel those of insulin, they may share a common mechanism.


The reactivity to N-ethyl maleimide of the subunits of cytochrome oxidase. Beef heart cytochrome oxidase (EC 1.9.3.1) prepared in this laboratory consistently presents 10 Coomassie blue staining zones on SDS-polyacrylamide gel electrophoresis. At pH 7.0 only two of these polypeptides (III and VIa) are labelled by radioactive N-ethyl maleimide (NEM). The labelling of VIa is variable and correlates with activity of particular oxidase preparations. When cytochrome oxidase is isolated from alkylated membranes, either mitochrondria or electron transport particles, polypeptide VIa is found not to be labelled; polypeptide III is more strongly labelled than when isolated oxidase is alkylated, and label now appears in polypeptide I which is not alkylated upon treatment of isolated oxidase with NEM.


Characterization of the local and systemic virus neutralizing activity in swine vaccinated with a porcine enterovirus. The virus neutralizing substance in the gastrointestinal tract of swine vaccinated in different ways with porcine enterovirus strain T80 was characterized by tests for enhancement and absorption of virus neutralizing activity by class specific antiporcine Ig antisera. The gastrointestinal virus neutralizing activity of piglets which were vaccinated with live virus orally resided predominantly in the IgA class, although some activity was present also in the IgM and IgG classes. The serum virus neutralizing activity of this group was present in all three classes but primarily in the IgG class. The IgA in the serum of this group was presumably of gut origin. However, in piglets vaccinated with live virus intramuscularly, with formaldehyde-inactivated virus orally or intramuscularly or with ethylenimine-inactivated virus by both oral and subcutaneous routes, both serum and gastrointestinal virus neutralizing activity were attributable predominantly to antibodies of the IgG and IgM classes. None possessed serum IgA. There was evidence also for the presence of Ig fragments in some gastrointestinal extracts.


The protective effect of two porcine enterovirus vaccines in swine. Piglets vaccinated with a single oral dose of live porcine enterovirus strain T80 were protected to a highly significant degree against an oral challenge dose of 140 plaque forming units of T80 virus, in comparison with nonvaccinated controls, in terms of serum antibody response, titres and distribution of virus in the gastrointestinal tract contents and tissues and duration of virus excretion in the feces. Piglets vaccinated with multiple doses of adjuvanted, PE60-concentrated ethylenimine-inactivated virus administered both orally and subcutaneously showed only a slight degree of protection against the same challenge dose, despite the fact that they possessed high serum antibody titres at the time of challenge. Piglets vaccinated orally with live virus showed a degree of protection even against a challenge dose of 10(7.41) plaque forming units of T80 virus in terms of titres and distribution of virus in the gastrointestinal tract and duration of excretion of virus in the feces. Protection in the piglets dosed orally with live virus appeared to be attributable to the presence of relatively high levels of virus neutralizing antibody of the IgA class in the gastrointestinal tract.


Bovine lymphosarcoma in twin calves.

Bovine lymphosarcoma in twin calves. Lymphosarcoma in twin female calves, apparently the first to be observed in Canada, is reported here. Peripheral blood and cultured mononuclear cells of one of the calves showed aneuploidy of the chromosomes. No hematological or serological evidence of bovine leukemia virus infection was observed in the other members of the herd. Bovine leukemia virus infection of the leukemic cells could not be detected by electron microscopy or by tissue culture procedures. There is a need to clarify the relationship of the calf form of the disease to the adult form of enzootic bovine leukosis.


Isolation of a new porcine enterovirus in the United States. A cytopathogenic virus isolated from an Iowa farm pig with diarrhea was identified as a member of Group 5 of the porcine enteroviruses. Clinical signs observed in other pigs in the herd were diarrhea, debilitation and gauntness. Morbidity and mortality rates were approximately 50% and 3% respectively.A Group 5 porcine enterovirus had not been previously isolated in North America according to the Western Hemisphere Committee on Animal Virus Characterization.


Depression of glutamate-mediated synaptic transmission by benzyl alcohol. The data obtained from this study suggest that the nonionizable anesthetic benzyl alcohol has two prominent actions on GABA- and glutamate-mediated synaptic transmission at the lobster neuromuscular junction. They are as follows: (1) depression of the excitatory end-plate potential and the postsynaptic membrane response to applied glutamate, and (2) a hyperpolarization of the postsynaptic resting membrane potential associated with a decrease in effective membrane resistance. No change in amplitude of the inhibitory end-plate potential or inhibitory reversal potential was seen. Excitatory miniature end-plate potential frequency was also unaffected. The depression of excitatory synaptic transmission appears to be due to a decreased responsiveness of the postsynaptic receptor-ionophore complex.


Cannabinoid effects on adenylate cyclase and phosphodiesterase activities of mouse brain. The experiments presented in this paper examine the mechanisms underlying the ability of cannabinoids to alter the in vivo levels of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in mouse brain. It was found that changes in cyclic AMP levels are a composite result of direct actions of cannabinoids on adenylate cyclase (EC 4.6.1.1) activity and indirect actions involving the potentiation or inhibition of biogenic amine induced activity of adenylate cyclase. Furthermore, the long-term intraperitoneal administration of 1-(--)-delta-tetrahydrocannabinol to mice produced a form of phosphodiesterase (EC 3.1.4.17) in the brain whose activity is not stimulated by Ca2+, although its basal specific activity is similar to that of control animals. In vitro, the presence of the cannabinoids caused no significant changes in activity of brain PDE at the concentrations tested. Some correlations are presented which imply that many of the observed behavioral and physiological actions of the cannabinoids in mammalian organisms may be mediated via cyclic AMP mechanisms.


Virus detection on grapes.

Virus detection on grapes. Grapes inoculated with poliovirus 1 and coxsackievirus B5 were washed with water, 0.5% polyehtylene glycol, or phosphate-buffered saline with 1% serum. These washes were equally efficient at removing virus but much of the virus in the water was noninfectious until treated with 0.5% polyethylene glycol.


Treatment of trophoblastic neoplasia at the Cancer Control Agency of British Columbia. Over a period of 29 years 30 patients with gestational trophoblastic neoplasia were referred to the Cancer Control Agency of British Columbia. Five patients had benign disease and required no further treatment after having had dilatation and curettage. The remaining 25 patients were treated with methotrexate or hysterectomy, or both. Actuarial survival rates were 96.4% at 1 year and 90.6% at 5 years. There was a high correlation between malignancy and high titres of human chorionic gonadotropin (HCG). All cases of hydatidiform mole must be followed closely by means of estimations of HCG titre.


Criteria of complete remission from trophoblastic neoplasia with the use of human chorionic gonadotropin (HCG) excretion pattern as a parameter. The excretion pattern of human chorionic gonadotropin (hCG) or luteinizing hormone (LH) was observed in the urine of 77 patients with trophoblastic neoplasia, 109 with complete remission from trophoblastic neoplasia, and 94 with no trophoblastic neoplasia, when the anti-beta-subunit hCG system radioimmunoassay (anti-beta-subunit RIA), which specifically measured hCG was used. The sensitivity of anti-beta-subunit RIA was limited to urinary hCG 16 mIL/ml from the specificity of the anti-beta-subunit serum. Luteinizing hormone in the urine of patients with complete remission and in normal menstrual, postmenopausal, and castrated women was less than 16 mIU/ml in most cases. The excretion pattern of urinary hCG in the patients undergoing treatment for trophoblastic neoplasia was more clearly comprehended with the anti-beta-subunit RIA as compared with the anti-hCH RIA. The criteria for judgment of complete remission were that the hCG value dropped to less than 16 mIU/ml and that cellular response was not observed at least in the last two courses.


Immunotherapy with autologous white cell infusions ("lymphocytes") in the treatment of recurrrent glioblastoma multiforme: a preliminary report. Autologous leukocytes (10(7) to 10(9)), obtained with the Haemonetic's Leukaphoresis apparatus, were inoculated directly into recurrent glioblastoma tumors via indwelling catheters or by direct intratumoral injection through existing craniotomy openings. The rational use for autologous leukocyte (lymphocyte) infusions was based on in vitro autologous lymphocyte cytotoxicity to glioblastoma cells in the absence of serum inhibitory factors. Seven of 17 patients treated had life expectancy under 1 month; all patients had received definitive surgery, and all but two received radiation, nitrosourea chemotherapy and/or dexamethasone, and showed evidence of clinically recurrent disease. Following autologous leukocyte infusion (lymphocyte/granulocyte ratio 1:1), eight patients sustained clinical improvement and were alive up to 17 months later. No neurotoxicity ascribable to the procedure has been observed. One patient, who was comatose at the time of single leukocyte infusion, returned to full activity and lived for 17 months without an increase in tumor mass by brain scan. These results suggest that infusions of autologous leukocytes (lymphocyte-monocytes) directly into glioblastoma may be a viable additional treatment for glioblastoma and certainly warrants further evaluation.


Experiment with 659 consecutive lymphograms in children. Between 1963 and January 30, 1975, 659 children under 16 years of age were referred for bipedal lymphography at the Institut Gustave-Roussy. Approximately one-third were under 5 years of age. The vast majority had documented malignant disease. Successful bilateral lymphatic cannulation and lymph nodd opacification were accomplished in 86.7% of all children. Another 11.6% had successful unilateral lymphograms, which usually provided sufficient information to be considered as diagnostic stldies. In only 1.7% of all children was the study unsuccessful bilaterally. Lymphatic cannulation failure rates progressively decreased as the child increased in age. There were five "allergic" reactions (0.75%), one of which was considered life-threatening, and one instance (0.15%) of a transient neurological deficit. No permanent sequelae or deaths were attributed to the lymphogram.


Cervical carcinoma with adenoid cystic pattern: a light and electron microscopic study. Three cases of cervical carcinoma with an adenoid cystic pattern were studied by light and electron microscopy. All were found to be compatible with the histologic picture of adenoid cystic carcinoma in other body sites. Although there was some variability in the pattern among the tumors, areas of each exhibited a cribriform appearance characterized by small cells with sparse cytoplasm arranged around cystic gland-like lumina. Only one tumor displayed cylindromatous formations similar to those described by Billroth. Two of the tumors were associated with foci of squamous cell carcinoma while the third contained areas suggestive of such a component. Electron microscopic examination showed varied morphology of the cysts, manifested by true glandlike lumina, extracellular spaces containing replicated basement membrane or enclosed stroma. In view of the observed diversity in the light and electron microscopic morphology of adenoid cystic carcinomas of the cervix, it is apparent that this tumor is not a distinct histologic entity. Accordingly, it is recommended that the terminology "cervical carcinoma with adenoid cystic pattern" be utilized.


Carcinoma in situ of the breast.

Carcinoma in situ of the breast. A series of 87 cases of carcinoma in situ of the breast was reviewed. IN 49 CASes in which lobular carcinoma in situ was shown on biopsy, three patients were found to have invasive carcinoma in the subsequently done mastectomy. All three of these cases were in a group of 14 patients shown in have bilateral lobular carcinoma in situ on biopsy. In a group of 38 patients with intraductal carcinoma on biopsy, seven were found to have invasive carcinoma in the mastectomy that was subsequently done. Lymph node metastases were found in one patient in the lobular group and four patients in the intraductal group. Three patients in the intraductal group died of cancer. None in the lobular group has died of cancer.


Intranuclear tubular structures observed in the cells of an alveolar cell carcinoma of the lung. Intranuclear tubular structures observed in the cells of an alveolar cell carcinoma of the lung are described. The structures were composed of membraneous tubules, measured about 60 nm in diameter, and had an electron-dense central core. These unusual structures were seen in the nuclei of neoplastic cells (Type II pneumocytes). The nature of the tubular structures remains unsolved, but morphologic characteristics and associated grnaulomatous reaction in the stroma imply the possibility of an unknown virus-like infection.


Basosquamous (transitional cloacogenic) carcinoma of the sigmoid colon. A case of basosquamous or so-called transitional cloacogenic carcinoma of the sigmoid colon, which arose above the pelvic brim at the peritoneal reflection, is reported. We were not able to find a report of this histologic type of tumor arising this far from the pectinate line of the anus, which is the most common primary site of this neoplasm. Possibilities as to the histogenesis of this tumor at this site are stated. The neoplasm also produced parathyroid hormone (PTH) and also possibly adrenal corticotrophic hormone (ACTH), which had not been previously reported for this specific neoplasm.


Clinicopathologic features of encapsulated hepatocellular carcinoma: a study of 26 cases. The clinicopathologic features of 26 cases of hepatocellular carcinoma (HCC) surrounded by a grossly distinct capsule-like fibrous tissue were studied. The frequency of this type was 10.3% among autopsy cases of HCC. The mean age of the patients was 64.1 years, which was significantly older compared with that of 143 cases of nonencapsulated HCC. Hepatitis-B surface antigen in serum was positive in 18.7% of the cases studied, the positivity rate being lower than that of HCC in general. Histologically, the tumor was relatively well differentiated and the capsule was the product of slow expanding growth. Intravenous tumor invasion was less frequent compared with other types of HCC. Clinically, celiac angiography proves to be a most useful diagnostic method; a thick capsule may be demonstrated as a thin radiolucent rim around the mass. The clinical course from the early stage is protracted and, if detected early, this type of HCC may be removed surgically.


Adenoid cystic carcinoma of the larynx: a report of four cases and a review of the literature. Adenoid cystic carcinoma (cylindroma) is a well-recognized tumor that is frequently encountered in the major salivary glands, the lacrimal glands and in the minor salivary glands of the oral cavity and upper respiratory tract. Only 60 cases of adenoid cystic carcinoma have been described arising in the larynx. Four new cases are reported and the literature is reviewed. In the larynx, these tumors arise almost exclusively in the subglottic and supraglottic regions--areas having large numbers of seromucinous glands of the minor salivary gland type. These malignant tumors, whether occurring in the larynx or elsewhere, tend to grow quite slowly with prolonged non-specific symptomatology and protracted clinical course. Despite their slow growth, in a majority of cases, they eventually lead to the death of the patient.


Oncocytoma of the lung.

Oncocytoma of the lung. A tumor diagnosed as an oncocytoma was removed from the lower right lung of a 22-year-old patient. Specimens from the formalin fixed tumor were studied by light microscopy and by electron microscopy. Large numbers of mitochondria were observed in all the tumor cells at the ultrastructural level despite many artefacts due to fixation. The presence of two tumor cell types "typical" oncocytes and "condensed" oncocytes were demonstrated by electron microscopy. This appears to be the second pulmonary oncocytoma in which mitochondrial hyperplaxia has been demonstrated. The tumor was similar to previously reported cases of salivary gland oncocytomas.


Antibody responses in normal infants and in infants receiving chemotherapy for congenital neuroblastoma. Three infants with congenital neuroblastoma received a primary series of diptheria-pertassis-tetanus (DPT) immunizations during and after courses of chemotherapy with immunosuppressive medications. Serum IgG, IgA and IgM levels and antidiphthria and antitetanus antibody responses were measured and compared with those of normal infants of similar age. Protective levels of antibody were achieved by the study patients as well as by the control group. These results support the view that children with malignancies who are receiving chemotherapy should not be denied immunization with inactivated vaccines.


Preliminary clinical results from U.S. fast neutron teletherapy studies. Over 700 patients with cancer have been treated with fast neutron beams since 1972 in three U.S. programs at the M.D. Anderson-TAMVEC (Houston and College Station, Texas), University of Washington (Seattle, Washington), and MANTA (Naval Research Laboratory, Washington, D.C.). Clinical applications are about to start at the Fermilab (Batavia, Illinois) and Cleveland Clinic-NASA (Cleveland, Ohio). To date, studies have included: 1) effects of different treatment patterns and doses; 2) responses of several tumor types at many anatomic sites; and 3) acute and long-term normal tissue tolerances. Responses of several cancers, such as extensive epidermoid carcinoma of the cervix and "fixed" metastatic cervical adenopathy, have been encouraging. In patients with glioblastoma multiforme, good tumor responses have not lengthened survival compared with the following conventional radiation therapy. Both local tumor control and "cure" have been compromised by the inclusion of patients with very extensive cancers. In general, treatment has been well tolerated. These preliminary studies provide the basis for planned clinical trials.


Breast carcinoma following radiotherapy of metastatic Wilm's tumor. A 22-year-old women developed breast cancer 15 years after radiotherapy to the lung for metastatic Wilms tumor. Her 32-year-old mother died of bilateral breast cancer, suggesting a genetic predisposition to radiogenic cancer. Recent improvements in the survival of children with certain cancers necessitate long-term surveillance for iatrogenic neoplasia, particularly when familial susceptibility is evident.


Histopathological study of the first Medical Research Council Nephroblastoma Trial. A histological analysis of the tumors from the first Medical Research Council (M.R.C.) Nephroblastoma Trial was carried out. Material from 104 out of the 111 concluded cases was suitable for assessment. The degree of tubular differentiation and the presence or absence of glomeruli, cysts and papillary structures were correlated with clinical stage and survival. A significant association was found with regard to tubular differentiation. Papillary structures appeared to be important, but the number of cases was small. The presence of either glomeruli or cysts was not a statistically significant feature as regards prognosis.


Hemostatic factors in primary hepatocellular cancer. Detailed coagulation studies were performed in a group of 19 patients with primary hepatocellular cancer (PHC) and the results were compared statistically with the findings in 19 control subjects. Various funcitonal and immunochemical methods were employed in determining the possible presence of functional or structural coagulant protein abnormalities. The patient group was characterized by prolonged prothrombin  times, partial thromboplastin times, and Reptilase times, increased levels of fibrinogen, factor VIII, and factor VIII-related antigen, moderately devreased levels of factor V, factor IX, factor X, antithrombin III, and plasminogen, and reduced levels of factor II and factor VII. Functional, immunochemical, and biochemical analysis failed to detect the presence of acquired protein abnormalities. These findings indicate that hemostatic changes in primary hepatocellular cancer are nonspecific in character. Severe alterations in the plasma levels of one or more of these hemostatic factors may occur.


HBAg-positive chronic liver disease associated with cirrhosis and hepatocellular carcinoma in the Senoi. Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer.


Direct immunochemical detection of prostaglandin-E and cyclic nucleotides in human malignant tumors. Immunofluorescent localization of prostaglandin-E (PGE), cyclic AMP (CAMP), and cyclic GMP (cGMP) was studied in tumor tissues from 40 patients with a variety of solid tumors. Representative normal tissues served as controls. Rabbit antisera specific for PGE or the cyclic nucleotides were used, and the reactions observed were correlated with the degree and type of lymphocytic reaction at the tumor margins. Strong PGE immunofluorescence was detected in tumor cells in 27 of 42 malignancies; by contrast nine of 13 normal tissues showed weak PGE reactions, cAMP was detected in 30 of the 42 malignancies; cGMP was noted in only seven of the 42 malignant tissues and in none of the normal tissues studied. The most common malignant tumor profile (17/42) was that of positive PGE and cAMP and negative cGMP staining. Tumors showing strong staining with anti-PGE or cAMP demonstrated a distinct trend towards heavier lymphocytic infiltration with a predominance of T cells at their margins, although this association did not reach statistical significance in the present material.


Comparative epidemiology of carcinoid and oat-cell tumors of the lung. Oat-cell carcinoma and bronchial carcinoid share histologic features with the Kultschitzky cell, and this argues for a common origin from the Kultschitzky cell for these tumors. In this view, the carcinoid represents the less malignant form and the oat-cell carcinoma the highly malignant adenocarcinoma of the colon, the epidemiologies of the benign and malignant forms of tumor arising from the same precursor are similar. However, the epidemiology of carcinoid tumor and that of oat-cell carcinoma are different. Although the ectopic production of hormones links the two kinds of tumor, it is also seen in other histologic types of lung carcinoma. Lung carcinoids occur in the genetic disorder of multiple endocrine adenomatosis, suggesting a genetic etiology for at least some carcinoids. This contrasts with the exogenous etiologic agents of cigarette smoking, occupational exposure, and urban domicile for oat-cell carcinoma. All these strong differences between lung carcinoid and oat-cell carcinoma indicate a markedly different process of carcinogenesis, which casts doubt on the hypothesis of a common cell precursor.


Multiple infiltrating glomus tumors in children. Two children with  multiple infiltrating glomus tumors of the lower extremities presented in infancy with clinical and, in one, radiological, signs of varicose veins. Surgical therapy was followed by multiple recurrences, a phenomenon attributable to the infiltrative properties of the tumor. This variant of multiple glomus tumor may be congenital and is probably hamartomatous in nature.


Nine year follow-up of a case of benign liver cell adenoma related to oral contraceptives. The case of a 26-year-old women on oral contraceptives who developed a benign liver cell adenoma that was successfully resected is reported. She continued on her oral medication and developed a recurrence 3 years later. On her second laparotomy, the liver tumor was merely biopsied and not removed. Oral contraceptive use was continued for an additional 3 years and then stopped. The tumor has regressed and is no longer palpable or diagnosable. The patient continues to be well 9 years following her first surgical procedure.


Benign liver-cell adenoma associated with long-term administration of an androgenic-anabolic steroid (methandienone). A 19-year-old man with paroxysmal nocturnal hemoglobinuria treated for 3 years with Methandienone was admitted to the hospital with hemoperitoneum due to the rupture of an hepatic tumor. Histology revealed that it was a benign liver cell adenoma, with a pathologic appearance and mode of clinical presentation closely resembling those of cases observed to develop in association to contraceptive steroids.


Multiple hepatic adenomas and a hepatocellular carcinoma in a man on oral methyl testosterone for eleven years. Numerous small hepatic adenomas and hepatocellular carcinoma developed in a man after 11 years of methyl testosterone ingestion. The man presented with an acute surgical abdomen and a large filling defect in the liver. Laparotomy disclosed hemoperitoneum and a large hepatic hematoma. Focal hemorrhagic infarction in the excised right liver lobe involved both adenomas and normal parenchyma. Review of the English literature reveals no other case of both a benign and a malignant hepatocellular neoplasm associated with anabolic steroid therapy. Hemorrhagic benign liver tumor must be considered in the differential diagnosis in both female and male patients on hormone therapy who present with acute abdominal pain.


Experimental carcinogenesis: induction of multiple tumors by viruses. Many viruses are able to cause the development of tumors when inoculated into suitable vertebrate hosts. Among them, polyoma virus can induce tumors in several mammalian species: not only many different kinds of tumor, but a large number of tumors within a single individual. Tissue culture studies employing cells from mice and hamsters, as well as observations of the manner of tumor development following polyoma virus injection in these species in vivo, suggest that some, or all, of the tumors so induced are multiple primaries. Because of the availability of mice of different genetic constitutions, the relative ease with which mouse cells from both normal and malignant tissue can cultivate in vitro, the known responses of mice to many carcinogenic agents, as well as the availability of transplantable, metastasizing mouse tumors, it is believed the polyoma virus/mouse host system would provide a highly suitable model in which an experimental approach to the elucidation of mechanisms for the origin of multiple tumors would be possible.


Multiple primary tumors in domestic animals: a preliminary view with particular emphasis on tumors in dogs. Cattle, horses, cats, and dogs with microscopically confirmed multiple primary tumors were reported to the Veterinary Medical Data Program, a system to collect, store and retrieve veterinary clinical information. Of 2611 tumors diagnosed prior to, concurrent with, or subsequent to other tumors during the period studied, 2361 were in 1062 dogs and 250 were in 120 other animals in all other species categories. The 604 multiple primary malignancies (two or more malignant tumors in one animal) were similarly distributed, by species, with 512 in dogs and 92 in all other species combined. The total number of multiple tumors reported in dogs closely approximated a theoretic model of random distribution, but several site-pairs of tumors seemed to occur excessively; one pair (mammary tumors and tumors of internal female organs) might parallel a similar excessive occurrence in women, suggesting a possible spontaneous tumor model for the latter.


The epidemiology of oral cavity, pharyngeal and esophageal cancer outside of North America and Western Europe. Geographical variations in the incidence of oral cavity, pharyngeal, and esophageal cancer were studied, with special reference to rates in countries outside of the United States and Western Europe. Although reporting techniques differ greatly and comparisons must be made with caution, significant variations are evident. Tracing such differences often reveals possible etiologic factor for these forms of cancer. The roles are discussed of known environmental carcinogens, such as N-nitroso compounds, polycyclic aromatic hydrocarbons, and such cultural habits as smoking or chewing tobacco, excessive consumption of alcoholic beverages, as well as other possible factors in the etiology of these cancer types.


Patterns of second malignant neoplasms in children. A search of the records of 10 pediatric oncology centers revealed 102 children with more than one malignant neoplasm. In this group of 102 patients, all pediatric cancers were seen as initial lesions, but Wilms' tumor and retinoblastoma were over-represented and leukemia and brain tumors underrepresented. Survival variation as well as tumor susceptibility may be responsible for this disproportion. Osteosarcomas and chondrosarcomas were the most frequent second malignant neoplasms (SMN). Embryonal tumors were rare as SMN and adult-type tumors (carcinomas) appeared at earlier than expected ages, whether arising after irradiation or not related to that form of therapy. Radiation was associated with 69 SMN, genetic disease accounted for 27 SMN and both conditions were noted in 15 SMN. In the group of 21 patients for whom neither radiation nor a known genetic disorder could be implicated, there were three with colon carcinoma and glioma and five with leukemia or lymphoma and glioma. These combinations may reflect new tissue-specific hereditary cancer syndromes.


In vivo initiated rat liver carcinogenesis studied in vitro; formation of alcoholic hyaline-type bodies. Epithelial liver cells isolated from rats after oral diethylnitrosamine administration were established in culture. When propagated in vitro for 2--3 months, over half the cells contained acentric nuclei and large juxtanuclear inclusions resembling the hyaline deposits (Mallory bodies) in cirrhotic livers of alcoholics. The morphological changes and disarrayed filaments in these bodies were retained on serial passages for many months. Cells inoculated into nude mice or newborn rats produced carcinomas from which cells with these abnormalities were reestablished in continuous culture.


Solubilisation of Epstein-Barr virus (EBV)-associated nuclear antigen from Raji cells and chromatin by treatment with various molarities of NaCl. The solubilisation of Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) by treatment with various molarities of NaCl was investigated using the 125I--IgG absorption assay. Ninety percent of the antigenic activity detected using the 125I--IgG absorption assay was insoluble at 0.15 M NaCl. It could be rendered soluble by treatment with 2.0 M NaCl, but reprecipitated upon return to 0.15 M NaCl. EBNA was partially extracted from Raji chromatin by treatment with 0.35 M NaCl. The efficiency of extraction was increased by homogenisation in 2.0 M NaCl followed by dialysis to 0.35 M NaCl. The data demonstrate the close association of EBNA with Raji chromatin and suggest that it may be a chromatin-associated non-histone protein.


Effects of selenium on azo dye hepatocarcinogenesis. Groups of male Sprague--Dawley rats were maintained on three regimens: I. basal diet plus 0.05% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), II. same as I plus 6 ppm selenium (Na2SeO3) in the drinking water, and III. same as I plus 6 ppm selenium added to the diet in the form of a high selenium yeast. The 3'-MeDAB was incorporated in the diet for 8 weeks and then removed. The selenium supplements in Groups II and III were continued for an additional 4 weeks. At sacrifice the liver tumor incidence from was ascertained as the ratio of animals with tumors/total number of surviving animals per group. Selenium reduced the incidence  from 92% (11/12) in the Group I control, to 46% (7/15) in Group II and to 64% (9/14) in Group III.


Differences between the structural dynamics of plasma membranes of normal hamster lymphocytes and lymphoid cells neoplastically transformed by simian virus 40 as revealed by laser Raman spectroscopy. The Raman spectra of highly purified plasma membranes from SV40-transformed GD248 lymphocytes have been compared with the spectra of the membranes of normal cells over the spectral region 100 cm-1 to 3010 cm-1. Striking differences between the two membrane categories were observed in the thermal response of the CH-stretching and acoustical regions. Analysis of CH-stretching shows that the membranes of normal cells exhibit a thermal transition centered at 7 degrees and approximately 5 degrees wide. The membranes of GD248 cells, in contrast, show a lipid transition centered at -5 degrees and 12-18 degrees wide. Analysis of the acoustical region yields equivalent results. The membrane proteins of normal membranes undergo a large thermotropic transition, starting at 39 degrees (sample temperatures), whereas this transition begins at 23 degrees with GD248 plasma membranes. The results suggest the possibility that SV40-specific membrane proteins may modify the collective thermotropic behavior of both normal membrane proteins and membrane lipids.