Deletion mutants of simian virus 40 defective in biosynthesis of late viral mRNA. Deletion mutants of simian virus 40 defective in late gene functions have been examined for genetic elements that control the biosynthesis of the viral mRNAs. Mutant-specific RNA from infected cells was identified by CH3Hg/(OH)/agarose gel electrophoresis and mapped by the nuclease S1 technique. Altered RNA species, shortened by a size equivalent to the deletion region, can be detected in cells infected with these mutants lacking sequences within the body RNA segments. On the other hand, mutants that lack the 5'-end of the body sequences (a splice junction) fail to accumulate the respective shortened RNA species. In particular, mutant dl-2301 whose deletion includes both the leader and body splice junctions plus the intervening sequences, exhibits a polar effect on a distal gene. Whereas the late region of dl-2301 can be transcribed normally, the mutant defect appears to be associated with little or no accumulation of the mutant-specific late RNA in the infected cells. These results suggest that splice junctions or the intervening sequences, or both, in the viral genome are control signals for post-transcriptional processing of the viral RNA.


Nucleotide sequence of the BK virus DNA segment encoding small t antigen. The nucleotide sequence from 0.64 to 0.53 map units in the BK virus genome coding for the small t protein has been determined. There is only one open reading frame that can code for a polypeptide of 172 amino acids, the putative small t protein. Beyond this segment, multiple termination codons are present in all three reading frames. There is considerable nucleotide and amino acid sequence homology between this region of BK virus and the analogous region of simian virus 40, especially in the proximal portion from 0.64 to 0.60 map units which is most likely common to the small t and large T BK virus proteins. A comparison of the conserved sequences within the early papovavirus genes both confirms the evolutionary relationship between these viruses and suggests the amino acid composition of the regions required for T antigen functions.


Synthesis and assembly of membrane glycoproteins: presence of leader peptide in nonglycosylated precursor of membrane glycoprotein of vesicular stomatitis virus. Translation of mRNA encoding vesicular stomatitis virus envelope glycoprotein G by as membrane-free ribosomal extract obtained from HeLa cells yielded a nonglycosylated protein (G1 (Mr 63,000). In the presence of added microsomal membranes, G1 was converted to the glycosylated protein (G2 (Mr 67,000) which is inserted in the membrane vesicles as a transmembrane protein. Labeling with methionine donated by wheat germ initiator tRNA1Met showed that G1 but not G2 contains methionine in the NH2-terminal position. Determination of the NH2-terminal sequence of G1, G2, and G showed that a leader peptide of 16 amino acids is present in G1 but absent from the glycosylated proteins G2 and G. This leader peptide contains at least 62% hydrophobic amino acids and is removed presumably during insertion of G1 into the membrane.


Structure of poly(adenosine diphosphate ribose): identification of 2'-[1''-ribosyl-2''-(or 3''-)(1'''-ribosyl)]adenosine-5',5'',5'''-tris(phosphate) as a branch linkage. Poly([14C]adenosine diphosphate ribose) was synthesized from [14C]NAD+ with calf thymus nuclei. The fraction containing poly(adenosine diphosphate ribose) eluted with 0.22--0.40 M phosphate buffer (pH 6.8) from a hydroxylapatite column, was completely hydrolyzed with venom phosphodiesterase, and was separated by DEAE-Sephadex A-25 column chromatography in 7 M urea. A new compound, which constituted 2% of the products from poly(adenosine diphosphate ribose), was found in addition to the expected products--i.e., 5'-AMP, 2'-(1''-ribosyl)adenosine-5',5''-bis(phosphate), and its derivatives. This compound was identified as 2'-[1''-ribosyl 2''-(or 3''-)(1'''-ribosyl)]adenosine-5',5'',5'''-tris(phosphate). The existence of this compound is evidence of a branching structure of poly(adenosine diphosphate ribose), which was previously thought to be a linear molecule. The content of this compound suggests that the frequency of branching is about 1 per 20--30 adenosine diphosphate ribose residues of high molecular weight poly(adenosine diphosphate ribose).


Opiates and enkephalins inhibit synthesis of gangliosides and membrane glycoproteins in mouse neuroblastoma cell line N4TG1. When mouse neuroblastoma clonal cell line N4TG1 cells were cultured in the presence of opiates or enkephalins, in the range 10(-6)-10(-10) M for 24 hr, a dose-dependent inhibition of the incorporation of [3H]glucosamine and [14C]-galactose into sialoglycosphingolipids and glycoproteins was observed. The gangliosides most affected comigrated in thinlayer chromatographic systems with GM2 (GalNAc[AcNeu]-Gal-Glc-ceramide), GM1 (Gal-GalNAc[AcNeu]Gal-Glc-ceramide), and GDla (AcNeu-Gal-GalNAc[AcNeu]Gal-Glc-ceramide). The effects were stereospecific and naloxone-reversible. Polyacrylamide gel electrophoresis revealed that the synthesis of a large number of membrane glycoproteins was also stereospecifically inhibited. Synthesis of other proteins and glycoproteins, proteoglycans, DNA, and membrane phospholipids and the rate of cell division were not altered in any specific or stereospecific manner. Moreover, clonal cell lines (neuroblastomas and oligodendroglioma) and human skin fibroblasts, which do not possess opiate receptors, did not respond to opiates or enkephalins in a stereospecific manner.


Enzymatic activities associated with a purified simian virus 40 T antigen-related protein. A protein antigenically related to the simian virus (SV 40) A gene product has been purified to near homogeneity from cells infected with the adenovirus-SV 40 hybrid virus Ad2(+)D2 and shown to contain ATPase (ATP phosphohydrolase, EC 3.6.1.3) and protein kinase (ATP:phosphotransferase, EC 2.7.1.37) activity. Both enzymatic activities copurify with the protein through six stages including one gel filtration column, two ion exchange columns, and a heparin affinity column. Analogous fractions from extracts of cells uninfected or infected with adenovirus 2 alone do not contain these enzymatic activities. The D2 hybrid protein resolves into two forms (I and II) during ion exchange chromatography. Form I, the major species (85%) of the D2 hybrid protein, elutes from DEAE-Sephadex in 0.37 M NaCl and is able to catalyze the hydrolysis of ATP to ADP + P(i) at a rate of 3 mumol/hr per mg. The remaining 10-15% of the D2 hybrid protein consists of form II which elutes from DEAE-Sephadex in 0.29 M NaCl and is able to hydrolyze ATP as well as to incorporate phosphorus from ATP into either the D2 hybrid protein itself or other protein acceptors such as phosvitin. Although both forms are able to bind DNA, the ATPase activity of form I cosediments with SV 40 DNA more efficiently than does the protein kinase activity of form II during glycerol gradient centrifugation. The ATPase activity of form I is efficiently inhibited by addition of anti-T gamma globulin to the reaction mixture whereas control gamma globulin has no effect. Similarly, the phosphorylation of the D2 hybrid protein by form II is inhibited by anti-T gamma globulin. By contrast, phosphorylation of phosvitin is specifically inhibited by antibody only when the immune complex is removed from the reaction mixture. Thus, it appears likely that one and possibly two enzymatic activities are carried out by the D2 hybrid protein. These findings are discussed in terms of mechanisms of SV 40 DNA replication and virally induced transformation.


Parvovirus RNA transcripts containing sequences not present in mature mRNA: a method for isolation of putative mRNA precursor sequences. We report here a method of RNA preparation that may enrich for precursor RNA sequences and the results of an investigation of adeno-associated virus (AAV) RNA transcription that used this method. Whole cells were lysed with detergent and high salt and separated into supernatant and pellet (crude chromatin) fractions. These fractions were then separately deproteinized by proteolytic digestion and phenol extractions. DNA was removed from the preparation by two cycles of pancreatic DNase digestion and phenol extraction. Hybridization analyses of the RNA obtained from AAV/adenovirus-infected KB (human) cells revealed some AAV-specific RNA sequences that were not present in the mature 20S mRNA. These additional sequences were contained in AAV RNA molecules present in the pellet fraction, whereas the 20S AAV mRNA accumulated in the supernatant. A species of AAV-specific RNA (about 22S), which was associated only with the pellet fraction and was labeled only after a short pulse, appeared to have a kinetic relationship with the more stable cytoplasmic 20S mRNA. These putative AAV mRNA "precursors" and precursor sequences were not observed previously when conventional methods were used to obtain RNA from either whole cells or isolated nuclei.


Vasoactive intestinal polypeptide: specific binding to rat brain membranes. The binding of radiolabeled vasoactive intestinal polypeptide (VIP) to rat brain membranes was investigated. Specific binding of 125I-labeled VIP was reversible and saturable (Bmax = 2.2 pmol/g of wet tissue). Brain membranes exhibited a high affinity for 125I-labeled VIP (KD = 1 nM) at a single class of noninteracting sites. Binding of 125I-labeled VIP paralleled its immunohistochemical localization, being enriched in cerebral cortex, hippocampus, striatum, and thalamus, with the notable exception of the hypothalamus, which had low levels of binding. The density of sites was greater in synaptosomal fractions relative to mitochondrial or nuclear fractions. Secretin and partial sequences of it and VIP inhibited binding to brain membranes with an order of potency similar to that found in other systems. The findings suggest the existence of a unique new class of brain receptors.


Integration and transcription of mouse mammary tumor virus DNA in rat hepatoma cells. Rat hepatoma cells infected with mouse mammary tumor virus (MMTV) acquire viral DNA that becomes covalently linked to the cell DNA. Using restriction endonucleases and the DNA transfer procedure of Southern [Southern , E.M. (1975) J. Mol. Biol. 98, 503--517], we have studied the sites in cellular DNA into which MMTV DNA inserts. These experiments indicate that: (i) there are many sites in cell DNA into which MMTV DNA integrates; (ii) the junctions between viral and cellular DNA occur within a limited portion of the viral genome, (iii) clones that contain MMTV DNA do not necessarily produce viral RNA; and (iv) the extent of transcription and glucocorticoid responsiveness of MMTV proviruses may be dependent on the site(s) in cell DNA in which the viral DNA resides.


Strand-specific attachment of avidin-spheres to double-stranded poliovirus RNA. Poliovirus-specific double-stranded RNA molecules containing covalently attached protein were coupled with a biotin ester through the protein moiety. Subsequent interaction of the RNA-biotin with avidin attached to electronopaque plastic spheres led to the formation of complexes that were easily visualized in the electron microscope. Avidinspheres were associated only with one end of the RNA-biotin molecules, as seen in the electron microscope. Avidin-sphere attachment to poliovirus double-stranded RNA is strand specific, as shown by molecular hybridization of strand-specific probes to the separated strands of denatured complexes. [3H]DNA complementary to polio virion RNA hybridized exclusively to the strands bearing associated spheres [(+) strands] whereas 125I-labeled virion RNA hybridized predominantly with strands without spheres [(-)strands]. This biotin-avidin labeling technique provides a means for the isolation of full-length poliovirus (-) strands and may provide a general means for isolation of double-stranded polynucleotides containing tightly attached protein.


Contribution of negative cooperativity to the thyrotropin-receptor interaction in normal human thyroid: kinetic evaluation. The kinetics of 125I-labeled thyrotropin (125I-TSH) binding to human thyroid receptors are presented. At pH 6.0, binding was maximal (30--35%) and there was one class of binding sites [Kd = 6.8 X 10(-9) M; binding capacity (Ro) = 57 pmol/mg of protein]. At pH 7.4, Scatchard plots of binding were nonlinear, indicating either a single class of negatively cooperative sites (Kd = 3.7 X 10(-9) M; Ro = 26 pmol/mg of protein) or, alternatively, independent high- (Kd = 5.0 X 10(-10) M; Ro = 3 pmol/mg of protein) and low-affinity (Kd = 1.7 X 10(-8) M; Ro = 26 pmol/mg of protein) binding sites. The role of negative cooperativity was evaluated from the rates of association and dissociation at pH 7.4. The kinetically determined binding constants (Kd = 1.7 X 10(-11) M; Ro = 2 pmol/mg of protein) were more similar to those determined for the high-affinity component than to those predicted from the negative cooperativity model. Dissociation of bound TSH was independent of initial site occupancy over a 40-fold range, corresponding to a 100-fold range of free TSH concentration. The dissociation rate of 125I-TSH was enhanced by unlabeled TSH to a similar degree, irrespective of initial binding site occupancy. Because the negative cooperativity model does not accommodate these data, it is concluded that TSH receptors in human thyroid behave kinetically and at equilibrium as a single class of high-affinity sites up to TSH concentrations well above the physiological range.


Cyclic AMP-dependent ATPase activity of bovine heart protein kinase. The adenosine 3",5"-monophosphate (cAMP)-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) from bovine heart is characterized. That the ATPase activity is intimately associated with the catalytic subunit of the enzyme is suggested by the following: (i) the similar dependences of ATPase and protein kinase activities on cAMP; (ii) the dissociation of ATPase activity from the holoenzyme on addition of cAMP and its co-elution with the catalytic subunit on gel filtration chromatography; (iii) the similarity of the relative effectiveness of divalent metal ions in ATPase and protein kinase catalysis; and (iv) the correspondence of kinetically determined Km(MgATP) and Ki(MgADP) values with thermodynamic dissociation constants determined by equilibrium dialysis. The hydrolysis of ATP is stimulated 10- to 20-fold by cAMP in the holoenzyme. The molar specific activity of the catalytic subunit ATPase is approximately 0.7 min-1 with Km(MgATP) = 5 muM. MgADP is a competitive inhibitor of the reaction with a Ki value of approximately muM. The order of the relative effectiveness of metal ions for both ATPase and peptide kinase activities is Mg2+ greater than Mn2+ greater than Ca2+. A possible interpretation of these observations is that the role that the metal ion plays is more directly manifested in bond-breaking than in bond-forming.


Tumor initiators and promoters in the induction of Epstein-Barr virus. The effect of various tumor initiators and promoters on induction of persisting Epstein-Barr virus (EBV) in different lines of lymphoblastoid cells was analyzed. Neither five polycyclic aromatic hydrocarbons, amongst them potent tumor initiators (e.g., 7,12-dimethylbenz[a]anthracene), nor the potent (ultimate) liver carcinogen N-acetoxy-N-2-acetylamino-fluorene induced EBV. A series of compounds, representing three classes of tumor-promoting diterpene esters (e.g., 12-O-tetradecanoylphorbol-13-acetate), efficiently induced EBV in persistently infected cells. The concentration required for maximal induction ranged between 0.5 and 100 nM. Some nonpromoting diterpenes (phorbol, 4alpha-phorbol-12,13-didecanoate, and ingenol) did not induce EBV. However, the nonpromoters, resiniferatoxin and 12-deoxyphorbol-13-decatrienoate, were effective, whereas anthralin, a tumor promoter, did not induce EBV. In three lines of EBV genome-carrying cells (Raji, NC-37, and RPMI 64-10) only abortive induction was noted, leading exclusively to synthesis of early antigen. In cells of lines with low spontaneous virus release (P3HR-1, B95-8, and QIMR-Wil), upon treatment with tetradecanoylphorbol acetate, approximately 20-40 times more viral DNA was recovered as compared to untreated controls. Viral DNA from tetradeca-noylphorbol acetate-induced cultures revealed the same restriction endonuclease cleavage pattern as viral DNA obtained from noninduced cells. Within 10 days after induction, release of infectious virus increased approximately by one order of magnitude. Prostaglandins, reported to be released after treatment with tumor promoters, were ineffective in virus induction under the conditions tested.


Evidence for role of glycoprotein carbohydrates in membrane transport: specific inhibition by tunicamycin. Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts by tunicamycin or other inhibitors of glycosylation resulted in defective transport of glucose, uridine, and amino acid analogs (alpha-aminoisobutyrate and cycloleucine). The defect in glucose transport is accompanied by decreased glucose metabolism, as determined by rates of CO2 and lactate production. In contrast, tunicamycin treatment did not affect other membrane-associated processes, such as secretion of fibronectin and procollagen, uptake of glucose by passive diffusion, Na+/K+ ATPase and adenylate cyclase activities, or stimulation of adenylate cyclase by prostaglandin and cholera toxin. Two glucose/glycosylation-regulated membrane proteins with apparent subunit molecular weights of 95,000 and 75,000 were induced by tunicamycin treatment. Our results indicate that glycoprotein glycosylation is required for membrane transport.


Immunological evidence for two common precursors to corticotropins, endorphins, and melanotropin in the neurointermediate lobe of the toad pituitary. The biosynthesis of corticotropin (ACTH1--39), beta-endorphin [beta(61--91)-lipotropin] and alpha-melanotropin in the toad intermediate lobe was studied by using immunoprecipitation procedures with antisera specific for these peptides. Intermediate lobes were pulse-incubated with [3H]phenylalanine and then chase-incubated for varying periods; the radioactive proteins were immunoprecipitated. Immunoprecipitates were separated by acidic urea or sodium dodecyl sulfate polyacrylamide gel electrophoresis. Evidence from the pulse-chase and sequential immunoprecipitation studies using antisera to ACTH and beta-endorphin suggests that the toad intermediate lobe synthesizes two common precursors (apparent Mr 32,000 and 29,500) containing both the ACTH and beta-endorphin sequences. These precursors are processed to yield several forms of immunoreactive corticotropin (apparent Mr 23,000, 21,000, 13,000, and 4300), immunoreactive endorphin (apparent Mr 11,700 and 3500), and immunoreactive alpha-melanotropin. The 4300 Mr form of corticotropin and the 11,700 and 3500 Mr forms of endorphins were found to comigrate with synthetic ACTH1--39, beta-lipotropin and beta-endorphin, respectively, on both acidic urea and sodium dodecyl sulfate gels.


Altered pattern of growth and differentiation in human keratinocytes infected by simian virus 40. Human epidermal keratinocytes were infected by simian virus 40 in vitro. The structure of the developing keratinocyte colony reflects the spatial separation of cell division and keratinization in intact skin; thymidine-incorporating cells were primarily localized at the colony periphery whereas nondividing, histologically differentiated cells accumulated in the interior. Viral infection produced a dramatic increase in the size of the proliferative population as, simultaneously, differentiation was reduced in the colony interior. These changes were manifest when simian virus 40 T-antigen synthesis was detectable in only a small percentage of the cells; differentiation became increasingly density dependent as the percentage of T-antigen-positive cells rose over serial passage. The disruption of the normal pattern of growth/differentiation localization coincided with a loss of dependence on serum for growth, but preceded the appearance of other virus-induced properties associated with transformation; i.e., the ability to form colonies in soft agar and independence of growth from fibroblasts.


Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties. Platelets enzymatically convert prostaglandin H(3) (PGH(3)) into thromboxane A(3). Both PGH(2) and thromboxane A(2) aggregate human platelet-rich plasma. In contrast, PGH(3) and thromboxane A(3) do not. PGH(3) and thromboxane A(3) increase platelet cyclic AMP in platelet-rich plasma and thereby: (i) inhibit aggregation by other agonists, (ii) block the ADP-induced release reaction, and (iii) suppress platelet phospholipase-A(2) activity or events leading to its activation. PGI(3) (Delta(17)-prostacyclin; synthesized from PGH(3) by blood vessel enzyme) and PGI(2) (prostacyclin) exert similar effects. Both compounds are potent coronary relaxants that also inhibit aggregation in human platelet-rich plasma and increase platelet adenylate cyclase activity. Radioactive eicosapentaenoate and arachidonate are readily and comparably acylated into platelet phospholipids. In addition, stimulation of prelabeled platelets with thrombin releases comparable amounts of eicosapentaenoate and arachidonate, respectively. Although eicosapentaenoic acid is a relatively poor substrate for platelet cyclooxygenase, it appears to have a high binding affinity and thereby inhibits arachidonic acid conversion by platelet cyclooxygenase and lipoxygenase. It is therefore possible that the triene prostaglandins are potential antithrombotic agents because their precursor fatty acids, as well as their transformation products, PGH(3), thromboxane A(3), and PGI(3), are capable of interfering with aggregation of platelets in platelet-rich plasma.


Transfection of human lymphoblastoid cells with herpes simplex viral DNA. The "calcium/dimethyl sulfoxide shock" method of transfection was adapted for use in human lymphoid cell cultures. One microgram of herpes simplex virus type 1 DNA regularly initiated virus replication in four lymphoblastoid cell lines. Per 10(5) cells exposed to 1 microgram of DNA, 0.5--5 cells formed an infectious center. The minimal infective dose of DNA was approximately 500 ng.


Src Gene product from different strains of avian sarcoma virus: Kinetics and possible mechanism of heat inactivation of protein kinase activity from cells infected by transformation-defective, temperature-sensitive mutant and wild-type virus. Sera from certain rabbits bearing Schmidt-Ruppin strain Rous sarcoma virus (RSV)-induced tumors precipitated p60(src) from chicken cells transformed by the homologous virus as well as by other strains [Prague strain RSV, Bryan high-titer strain RSV, and Bratislava 77 strain of avain sarcoma virus (ASV)], the molecular weights (M(r)s) ranging from 60,000 to 64,000. The p60(src) immunoprecipitated from cells transformed by each of these strains incorporated [gamma-(32)P]ATP into the M(r) 53,000 subunit of IgG, though with differing activities. No such protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) was observed when the following immunoprecipitates were used: from uninfected cells, from untransformed cells infected by Rous-associated virus, or from cells transformed by acute leukosis viruses, avian erythroblastosis virus, or myelocytoma virus 29. The kinase reaction had a pH optimum at pH 5.9 and an apparent K(m) for ATP of 4.9 +/- 2 muM, and was dependent on Mg(2+) (K(b) = 46 +/- 12 mM), for which Ca(2+) was no substitute. The kinase was cyclic AMP independent. In order to test whether the protein kinase reaction is directly catalyzed by p60(src), we compared the in vitro temperature sensitivities of the kinase activities from cells infected by transformation-temperature-sensitive mutant and parental wild-type virus. The first-order rate constant for the inactivation of the kinase from extracts of cells infected by the mutant virus was 2-fold greater than that from cells infected by wild-type virus. This result implicates the protein kinase as an enzymatic activity of the src gene product, the p60(src). Concomitant with the loss of the kinase activity by heat inactivation, p60(src) loses 60-70% of its phosphate content. The kinetics of dephosphorylation exactly parallel those for the inactivation of the kinase activity, suggesting that the p60(src) kinase is itself dependent on phosphorylation for its activity.


Effects of chronic parenteral carbohydrate administration on hepatic drug metabolism in the rat. Effects of chronic parenteral carbohydrate administration on hepatic microsomal enzyme activity were studied in the rat. Intraperitoneal injections of either glucose or fructose (2.88 g daily for 7 days) significantly decreased hepatic cytochrome P-450 content and ethylmorphine N-demethylase and aniline hydroxylase activities. By the 5th day, cytochrome P-450 content decreased to 70-76% and ethylmorphine N-demethylase activity to 66-69% of control values. Aniline hydroxylase activity was not significantly altered until the 7th day, by which time it was 77-79% of control values. In vivo assessment of hepatic drug-metabolizing capacity using antipyrine as a test drug confirmed these decreases observed in vitro. Two major conclusions of these experiments are that such variables as time and dose of carbohydrate administration can affect the magnitude of the changes produced and that each parameter measured exhibited a distinctive pattern of change with time. Chronic carbohydrate administration produced hepatic fatty infiltration and glycogen depletion. Since all groups received identical amounts of specific nutrients, fatty infiltration was probably due to increased lipogenesis with decreased hepatic oxidative metabolism of fat. During these experiments neither hypoinsulinemia nor increased levels of cyclic AMP were observed. The molecular mechanisms responsible for hepatic glycogen depletion and decreased MFO activities remain to be established.


Investigation of the mechanism of decreased sensitivity of the rat seminal vesicle to norepinephrine by lithium. Li+ is reported to reduce sensitivity of alpha-adrenergic receptors to NE. The present investigation was designed to investigate the mechanism of this decreased sensitivity on the rat isolated seminal vesicle. In innervated preparations, 1.35 X 10(-3) M Li+ (i) shifted the concentration-response curves of NE, methoxamine, ACh and BaCl2 to the right and reduced their maximum responses; (ii) antagonized the leftward shift and the enhancement of maximum responses to NE by cocaine (2.9 X 10(-4) M), and (iii) reduced only the maximum responses to KCl. In denervated preparations, 1.35 X 10 (-3) M Li+ shifted the concentration response curve of NE to the left without any change in the maximum responses. The antagonistic effects of Li+ on maximal responses to NE, ACh and KCl observed in innervated preparations were significantly increased in Ca++-free medium. Li+ (1.35 X 10(-3) M) increased NE uptake by the seminal vesicle significantly. It is concluded that decreased sensitivity of the seminal vesicle to NE by Li+ could be due to an increase in the uptake of NE and to a nonspecific postsynaptic spasmolytic action.


Use of dermal grafts to cover implants in breast reconstructions. The use of dermal grafts for the reinforcement of the cover over implants in breast reconstructions after radical mastectomy is illustrated in several cases. By carefully selecting the patients, we feel that this relatively minor procedure may replace the use of local of distant flaps in a good many breast reconstructions.


Imipramine and EEG sleep in children with depressive symptoms. Depression in children is currently an area of considerable controversy, as is the use of potent psychopharmacologic agents in children. Since EEG sleep techniques have proven to be useful in understanding the mechanisms of depression in adults and in predicting their response to antidepressants, a pilot study employing these techniques was undertaken in a population of hospitalized children. The EEG sleep of 12 children with significant depressive symptomatology was first examined after a two-week drug-free period and again approximately three weeks later when an optimum dose of imipramine had been maintained for at least 7 -- 10 days. Changes in sleep continuity, as reflected in increased wakefulness and a decreased sleep efficiency, as well as an increase in Stage 2 and a decrease in Stage 4 sleep, were observed throughout the entire sample. REM suppression was also noted, but tended to be most pronounced in those children who improved on imipramine.


Computed tomographic arteriography of the liver. Computed tomographic arteriography (CTA) of the liver performed during intra-arterial infusion of contrast material improved the detection of hepatic lesions in 10 of 12 patients and was the only method that accurately determined the extent of disease in 6. This technique has significant advantages over conventional hepatic computed tomography with or without intravenous contrast enhancement, or selective hepatic angiography. It is recommended in the evaluation of selected patients, especially when there is a discrepancy between the findings obtained by other methods.


Aberrant jugular bulb presenting as a middle ear mass. Case reports of 3 patients seen with a bluish mass behind the tympanic membrane are presented. The initial diagnosis was probable glomus tumor. In 1 patient, middle ear exploration confirmed the presence of a high-lying jugular bulb. In the other 2, venography demonstrated that the jugular bulb projected superiorly into the middle ear cavity. In all 3, polytomography demonstrated a dehiscence of the bony septum which normally separates the jugular bulb from the hypotympanum. When a bony dehiscence is seen in the absence of destructive changes, a diagnosis of aberrant jugular bulb is strongly suggested.


Computed tomography in the evaluation of hepatocellular carcinoma. Computed tomography (CT) was used to evaluate 47 cases of hepatocellular carcinoma: it was definite in 37, equivocal in 5 and negative in 5 cases. No specific patterns of CT images were recognized. Pre- and postcontrast scans were necessary because several tumors could only be detected on one or the other scan. CT may reveal the exact extent of tumor and show additional tumors in case of multiple lesions. However, false negative results are possible in isodense or very small tumors.


Transcatheter occlusion of the gastroduodenal artery. The gastroduodenal arteries of 7 patients were occluded for treatment of duodenal bleeding in 4, hepatic devascularization in 2, and redistribution of blood flow for intra-arterial chemotherapy in one patient. In 6 patients, occlusion was performed with Gianturco coils, and with Gelfoam in one. No major complication was encountered. This approach was successful in the control of bleeding from peptic ulcers, arteriovenous malformation and invasion of duodenum by retroperitoneal metastatic lymph nodes from carcinoma of the testicle. Occlusion of the gastroduodenal artery was utilized for further dearterialization of hepatic neoplasms. Redistribution of hepatic blood flow was accomplished by the occlusion of the gastroduodenal and replaced right hepatic arteries allowing infusion of chemotherapeutic agents into the entire liver through the left hepatic artery.


Angiography of malignant fibrous histiocytoma of bone. Angiograms of 10 cases of malignant fibrous histiocytoma of bone were reviewed and correlated with surgical and pathological findings. Nine tumors were hypervascular. Seven demonstrated malignant characteristics (laking in one and coarse tumor vessels in 6). Seven tumors displaced adjacent normal vessels. All angiograms accurately delineated soft-tissue masses and cortical breakthrough but intraosseous extent was less clearly defined. Tumor thrombi within draining veins were evident retrospectively in one instance. Angiography in these cases contributed substantially to surgical management.


[The radiological symptomatology of primary malignant neoplasia of the kidney (author's transl)]. The radiological signs characteristic of various forms of renal neoplasia are described and the diagnostic value of different radiological techniques is discussed. A rational procedure for the study of primary tumours of the renal parenchyma is proposed, and several cases are presented by way of illustration.


[Cancer epidemiology and French medical data (author's transl)]. The authors remind: cancerous disease's possibilities of description before any treatment through its topography, its morphology and its clinical medicine; the modalities for taking surgical, actinic, chemical, immunologic therapeutics in account; the technics of the cancerous disease supervision after treatment, from the vital points of view (study of observed and relative survival, and of recovery) and from the carcinologic and fonctionnal points of view. They insist on the possibilities of these languages that go from the simple notation of information to the taking of these sundries modalities in account. The disposable datums in France are schematicly described. They concern: the study of survival from hospitable series; mortality by cancer for the whole of the country. The authors consider that no entry must be undertaken without the purposes, in the same way as the considered modalities for analysis, being precisely fixed. They insist on the notion of information level, of which three levels are schematicly defined, according as descriptive epidemiology or epidemiologic research or clinical research is in question.


[Modern methods for surveillance of communicable disease: general introduction (author's transl)]. Epidemiological surveillance has now become a fully developed discipline, to which several technical specialties contribute. All kinds of new problems resulting from present conditions of life have enlarged the field of surveillance beyond the old concept of morbidity-mortality. This has necessitated the application of new methodology--a stimulating challenge for those who are engaged in epidemiological surveillance.


[International influenza surveillance (author's transl)]. Influenza may be considered a convenient model to set up a methodology for surveillance in a country, which can further be extended to other diseases. The solidarity which exists among Directors of National Influenza Centres is one of the reasons for its success. On positive result, and one which is not negligible, has been the stimulating effect which influenza surveillance had on the development of virus laboratories in tropical regions.


[Network for the epidemiological survey of the enteroviruses in sewage (author's transl)]. Poliomyelitis still occurs each year in France: 27 cases in 1973, 21 cases in each of 1974 and 1975, 8 cases in 1976. Because of the risk, a survey of the spread of poliovirus in healthy populations and in sewage was organized by the Ministry of Health according to the departmental note DGS/HP/1st/250, 9-2-73. The Laboratoire d'Epidémiologie Virale of the Laboratoire National de la Santé was in charge of the technical aspects of the survey. A preliminary questionnaire was sent to each D.D.A.S.S. (Direction Départementale de l'Action Sanitaire et Sociale) in order to find out the local possibilities for sampling and preliminary treatment of the sewage samples. In 1974, all the samples were sent to the Laboratoire d'Epidémiologie Virale. Since 1975, samples have been sent to a local virology laboratory when available. The sewage samples were concentrated according to SHUVAL's or LUND's methods depending on the local conditions. Both methods tested in our laboratory were found equally efficient. In order to improve their technical laboratory methods, the virologists collaborating in this survey joined together in a working group "Virus et Eaux". For isolating the enteroviruses, we recommend the inoculation of each concentrated sample into primary monkey kidney cells grown in vials; an overlay of agar is added after inoculation. This plaque method allowed us to isolate several strains from one sample. It was possible to demonstrate that polioviruses differing in serotypes and thermosensitivity might be detectable in the same sample. Few of the isolated polioviruses (11/272) showed the same thermoresistance as did the wild strains. Certain enterovirus serotypes are known to be responsible for epidemics of meningitis and neurological disorders. It was of interest to identify non-poliomyelitic enteroviruses isolated from sewage. The study of enterovirus spread in sewage in comparison with that in healthy children is in progress.


[Experimental investigations of the content of glycogen in the adrenal gland of the rat after application of dexamethasone, ACTH and a combination of both (author's transl)]. The influence of dexamethasone, ACTH and the combination of both on the glycogen content of the rat adrenal gland was studied. Dexamethasone induces a transient increase of the adrenal glycogen content in a time and dose-dependent manner. The application of ACTH has no effect on the glycogen content. Surprisingly, the increase of the glycogen content induced by dexamethasone is completely blocked by the simultaneous application of ACTH.


The integrative role of lecithin:cholesterol acyl transferase in triglyceride clearance. There is evidence that not only lipoprotein lipase (LPL) but also lecithin:cholesterol acyl transferase (LCAT) are involved in the directional flow of triglyceride (TG) from endogenous very low density lipoproteins (VLDL) and chylomicrons as part of a general energy storage pathway. Evidence is given to suggest that LCAT plays an integrative role in this process.


Relationship between plasma lecithin:cholesterol acyltransferase activity and plasma triglyceride concentration in non-pregnant and pregnant Brazilian women. Plasma concentrations of total, esterified and unesterified cholesterol, total phospholipid and triglyceride (TG) and lecithin:cholesterol acyltransferase (LCAT) activity were measured for 28 young non-pregnant women and for 31 young pregnant women from the city of Campina Grande, Brazil. During pregnancy plasma lipid levels and LCAT activity were successively increased and subsequently fell in post-partum samples. For both non-pregnant women and during each trimester of pregnancy and post-partum the activity of LCAT was significantly and positively correlated with the plasma concentrations of each lipid, the highest degree of correlation being found between LCAT and TG. No significant increase in plasma high density lipoprotein cholesterol occurred during pregnancy, and this parameter was not significantly correlated with LCAT activity in either pregnant or non-pregnant women. Instead low density lipoprotein (LDL) cholesterol was significantly increased in pregnancy and was significantly, positively, correlated with LCAT activity in both pregnant and non-pregnant women. The results emphasize the probable importance of LCAT in the metabolism of LDL and triglyceride-rich very low density lipoproteins, and pregnancy may provide a useful model for further studies of the physiological role of LCAT.


Failure of orotic acid to suppress activity of plasma lecithin:cholesterol acyltransferase. There are theoretical reasons for postulating a relationship between turnover of triglyceride-rich lipoproteins and plasma cholesterol esterifying activity, and some experimental evidence exists to support such a hypothesis. Orotic acid has been given to rats to determine whether blocking the hepatic release of very-low-density lipoproteins would also reduce hepatic secretion of lecithin:cholesterol acyltransferase (LCAT). No evidence of such an effect was found. In a single human experiment orotic acid exerted only minimal effects on serum concentrations of lipoproteins, and LCAT activity was apparently unaffected.


Lecithin:cholesterol acyltransferase in partial ileal bypass rats. In cholesterol-fed rats 6 weeks after partial ileal bypass, there was a significant (56%) decrease in serum cholesterol. Also, the concentration of very low density lipoprotein (VLDL) cholesterol was dramatically reduced after operation. However, after the operation, the percentage of high density lipoprotein (HDL) cholesterol was very high, i.e., 45% of the total lipoprotein cholesterol, whereas it was only 25% before operation. The initial rate of lecithin:cholesterol acyltransferase (LCAT), when assayed according to Stokke & Norum, showed an increase from 29 +/- 2 mumole/ml/h for non-operated cholesterol-fed controls to 121 +/- 7 mumole/ml/h after operation (p less than 0.01). After intestinal bypass the extrahepatic triglyceride lipase activity in serum was reduced by 60%, and there was no significant difference in hepatic triglyceride lipase. These observations indicate that in partial ileal bypass, the low serum cholesterol is due to the high HDL cholesterol and the high LCAT activity.


Plasma lecithin:cholesterol acyltransferase activity in hypophysectomized rats. Hypophysectomy in rats induces a decrease in VLDL and HDL and an increase in LDL. To investigate the importance of lecithin:cholesterol acyltransferase (LCAT) for these changes, plasma LCAT activity was determined, both according to the methods of Stokke-Norum and Glomset-Wright. Plasma LCAT activity as assessed by both these methods decreased significantly after hypophysectomy, indicating a reduction in plasma enzyme concentration. Plasma total and free cholesterol increased slightly, while the concentration of cholesteryl esters and triglycerides remained unchanged. Blood sugar and FFA decreased. The osmotic resistance of the red cells was increased, and target cells were seen. There was a decrease in blood haemoglobin and haematocrit. Serum total protein concentration, electrophoresis, and plasma ALAT activity did not change. The observed changes in lipoproteins and LCAT following hypophysectomy can be partly explained by decreased liver secretion of both LCAT and VLDL. Because of the complex relationship between lipoproteins and LCAT, no clear-cut conclusions about the association between decreased HDL and LCAT can be drawn. The precise hormonal mechanisms controlling LCAT activity and lipoprotein metabolism remain to be solved.


Erythrocyte membrane alterations in lecithin:cholesterol acyltransferase deficiency. Structural, compositional, and functional abnormalities were found in the erythrocyte membranes of homozygotes for LCAT deficiency. Similar but less pronounced abnormalities were also present in the heterozygotes for this disorder. Some of the membrane alterations, which included decreased osmotic fragility, changes in phospholipid composition, and membrane sulfydryl group latency, as well as changes in the activity of membrane p-nitrophenylphosphatases and acetylcholinesterase, may be secondary to the changes in plasma lipids. However, since plasma lipids (and LCAT activity) were normal in the hereozygotes, the existence in both the homo- and the heterozygotes of erythrocyte membrane abnormalities unrelated to plasma LCAT activity seems likely.


Familial lecithin:cholesterol acyltransferase deficiency. Further studies on plasma lipoproteins and plasma postheparin lipase activity of a patient with normal renal function. Plasma lipoproteins and postheparin plasma were investigated in a patient with familial LCAT deficiency with normal renal function and without proteinuria. As revealed by gelfiltration the large molecular weight LDL2 was not present, and myelin structures were not found in LDL1 or LDL2 when she was on her ordinary diet. After 60--65% fat diet for one week the large molecular LDL2 was found, but only in low concentration. We have no explanation for the difference in the lipoprotein abnormalities of this patient and others with this disease. There is no major difference in the fat content in the ordinary diet of the Norwegian patients with familial LCAT deficiency, nor has our patient any clinical signs of malabsorption. Furthermore, there was no difference in lipoprotein lipase or hepatic lipase activity in postheparin plasma between our patient and others with the same disease. However, whereas hepatic lipase activity was within the reference values, lipoprotein lipase activity was rather low in all patients investigated. We suggest that impaired VLDL catabolism in plasma, because of LCAT deficiency and low lipoprotein lipase activity, may partly explain the low HDL concentration consistently found in  patients with familial LCAT deficiency.


Lipoproteins in plasma from patients with low LCAT activity due to biliary obstruction. A high density lipoprotein (HDL) fraction, designated cholestatic HDL1, has been isolated by zonal ultracentrifugation from patients with long-standing biliary obstruction. This lipoprotein fraction consists exclusively of disc-shaped particles rich in phospholipid and unesterified cholesterol. The fatty acid composition of the minor cholesteryl ester fraction was characterized by a low content of linoleic acid. Apoprotein E was the dominating protein' component, while only small amounts of apolipoprotein A-I were found. Immunochemical studies of cholestatic HDL1 indicate that a considerable proportion of the particles contained apo E as its only protein constituent. All patients had a markedly reduced endogenous cholesterol-esterifying ability. The finding of apparently primary LpE particles in biliary obstruction may be related to this secondary LCAT deficiency.


Relationship between high density lipoproteins and the rate of in vitro serum cholesterol esterification. The rate of in vitro esterification of serum cholesterol and the concentrations of serum high density lipoprotein cholesterol (HDL-C) were measured in 18 women and 9 men, 74--95 years of age. Subjects in this age group can have HDL-C levels below accepted limits of normal. The subjects were divided into two groups, one with HDL-C less than 40 mg/dl and the other with HDL-C 40 mg/dl or higher. The rate of in vitro serum cholesterol esterification in the former group was 2.00 n. moles/ml/min, significantly higher (p less than 0.02) than 1.62 n. moles/ml/min present in the latter group. There was no correlation between the cholesterol esterification and a protein (s), which can produce an immune gamma globulin that completely inhibits in vitro serum cholesterol esterification. These findings are discussed with reference to the putative relationships between HDL-C and atherosclerosis.


Transfer and equilibration of LCAT-generated cholesteryl esters in human lipoproteins. Non-enzymatic net transport of cholesteryl esters (CE) from HDL to VLDL in exchange for triglycerides has been reported in vitro. Likewise, in vivo observations have been adduced favoring the same process in human subjects and implicating LCAT product lipoproteins as carriers. Exchange of CE among lipoproteins is thought not to occur. In experiments in which LCAT-generated radioactive CE are formed from cholesterol dispersion in plasma, exchange to near equilibrium is observed. To better define this process, a labeling procedure employing lecithin: 3H-unesterified cholesterol single bilayer vesicles was devised. The order of lipoprotein labeling with isotopic CE is HDL greater than VLDL greater than LDL. After 19 hours of incubation, esters reached equilibrium. Control experiments with vesicles treated by purified LCAT showed that this result could not be explained by distribution of discrete ester-rich vesicle products or their binding to lipoproteins. Subfractionation of labeled lipoproteins on agarose columns confirmed completeness of equilibration, except for the HDL subfraction of smallest size, which is incompletely equilibrated. These results indicate that LCAT-generated CE are capable of equilibration among human lipoproteins.


The role of high density lipoproteins in lecithin:cholesterol acyltransferase activity: perspectives from Tangier disease. Lecithin:cholesterol acyltransferase activity and the lipid composition of VLDL and LDL were examined in five patients homozygous for Tangier disease. The following results were obtained: I. The percentage of cholesterol that was esterified was similar in Taniger and control lipoproteins. II. Linoleic acid was the predominant fatty acid constituent of cholesteryl esters in Tangier plasma. III. Molar cholesterol esterification rates in Tangier plasma were reduced; however, fractional rates of cholesterol esterification were equal to or exceeded those of control plasma. IV. In vitro addition of apoprotein A-I and isolated lipoproteins led to a concentration-dependent increase in the initial rates of cholesterol esterification in Tangier plasma. It is concluded that HDL is not an exclusive substrate for the LCAT reaction, and that cholesterol esterification is not impaired in Tangier plasma.


Regional localization of the gene for human phosphoribosylpyrophosphate synthetase on the X chromosome. Sixty-eight independent hybrid clones were isolated after irradiated normal human lymphocytes were fused with Chinese hamster fibroblasts lacking hypoxanthine-guanine phosphoribosyltransferase activity. The cells were grown under selective conditions requiring retention of the X chromosome-linked locus for human hypoxanthine-guanine phosphoribosyltransferase. The frequency and patterns of cotransference of human phosphoribosylpyrophosphate synthetase with the selected marker and with additional X-linked enzymatic markers confirm X linkage of the structural gene for human phosphoribosylpyrophosphate synthetase and support assignment of this gene to a position on the long arm of the X, between the loci for alpha-galactosidase and hypoxanthine-guanine phosphoribosyltransferase.


Thyroid hormone action at the cellular level. A large body of circumstantial evidence suggests that the basic unit of thyroid hormone action is the triiodothyronine nuclear receptor complex. This complex stimulates the formation, directly or indirectly, of a diversity of messenger RNA (mRNA) sequences. A generalized increase in mRNA as well as a disproportionate increase in a limited number of RNA sequences have been demonstrated. Regulation of thyroid hormone effects may be carried out largely at a local cellular level. Highly selective alterations in sensitivity to the triiodothyronine nuclear receptor complex may occur at specific target genes. Metabolic factors and hormones participate in such regulation. In a given tissue, alterations in the total number of receptor sites has not been shown to be useful as an index of thyroid hormone response, and local modulation of the response to the triiodothyronine receptor complex by a variety of factors other than triiodothyronine may be carried out at a postreceptor level.


Polyoma virion and capsid crystal structures. X-ray diffraction shows that complete virus particles and empty capsids crystallize isomorphously. The surface morphology of the protein coat, as revealed by electron microscopy, is the dominant structural feature determining the intensity of x-ray reflections to a resolution of approximately 30 angstroms. The structure and variability of the viral chromatin core can now be analyzed by comparison of electron density maps.


Amino acid sequence homology between histone H5 and murine leukemia virus phosphoprotein p12. The amino terminal acid sequences of several mouse leukemia virus phosphoproteins (p12) show definite homology with the amino terminal conserved region of H5 histones, the phosphorylated nuclear proteins of nucleated erythrocytes. Differences in the amino acid compositions of the two groups of proteins seem to rule out the possibility that they evolved from a single common ancestral gene. The finding of sequence homology between viral p12's and cellular histones, however, is consistent with evolution of retrovirus structural proteins by a process of differentiation from preexisting cellular genes. The conserved primary and secondary structure at the amino terminal region, common to both groups of proteins, may be related to their common function of nucleic acid binding modulated by phosphorylation.


[Contribution to the study of endocrinopathies in black Africans (author's transl)]. For a long time endocrine pathology was unrecognized or even denied to exist in Black Africans, but this is not true. It seems to be recognized more frequently since medicalization has increased. This pathology does not present any particularities. Hyperthyroidism appears frequently, at least in urban areas. A series of 87 personal cases has permitted a review of the principal clinical and biological aspects; myasthenia seems to be particularly important; radical treatment is preferred over prolonged medical treatment which is not within the financial possibilities of our patients. There have been 30 observations of cortico-adrenal anomalies of which 7 known personally. It must be noted that the Black living in his traditional rural environment presents a certain degree of physiological hypocorticism with respect to whites and especially Blacks of higher social standing. Pathological hypocorticism is essentially due to tuberculosis; the melanodermia is evident to an alert observer. Metabolic hypercorticism produces the usual manifestations. Only 9 cases of Sheehan syndrome have been reported (5 personal). In the Black African woman, it appears earlier than in Europe often due to premature nuptiulity and the higher incidence of tachyparity. One is surprised that this syndrome is detected so rarely; it is, without a doubt, often well tolerated during a long period of time therefore goes undetected.


[Early and unusual presentation of temporal arteritis. A report of 7 cases (author's transl)]. The authors report 7 cases of temporal arteritis, proved by biopsy, with unusual early symptoms. They emphasize dental extraction as a possible incitant of the disease. Diagnosis is very often overlooked when local symptoms of involvment of temporal arteries are lacking. Various head and neck pain, fever of unexplained origin, weight loss, when associated with erythrocyte sedimentation rate greater than 50 mm, should convince the physician to biopsy the temporal artery of people over the age of 60. Steroid therapy must begin as soon as diagnosis is made.


[Thrombocytosis and primary bronchial carcinoma. Study about 164 patients with bronchial carcinoma (author's transl)]. This paper is relating the study of 164 patients with primary and proved bronchial carcinoma. A thrombocytosis superior to 400,000/mm3 was observed in 36.6 p. cent of cases. But no statistic relation was found between the histological type of tumor, a biological inflammatory state, the existence of metastasis and thrombocytosis. However thrombocytosis was more frequently observed among anaemic and hyposideremic patients. No significantly changes of paO2 and paCO2 were noted in patients with thrombocytosis. The systematic platelet count could be of an interest in the interpretation of some thoracic radiography.


[The clinical course of late cutaneous porphyria (author's transl)]. Study of the course of 23 patients, with late cutaneous porphyria, after 3 to 8 years. So, we remark: the clear improvement of the majority of the patients, from whom a quarter appear entirely cured, the more satisfactory affects of bleeding and alkali-therapy, the absence of reference with the course of chronic alcoholism the absence of visceral complication of porphyria.


[Fine needle aspiration biopsy in pneumology. 351 punctures]. From 351 transthoracic punctures with a fine needle, the authors determine their method of exam. The cytologic study of the samples permits a positive diagnosis of pulmonary opacity for 60 p. cent to 70 p. cent of the cases. The rentability reaches 89 p. cent for malignant lesions. The complications with the fine needle are very unusual comparatively to the technics allowing a histologic study, although rentability is equal for these two methods.


[Preventive treatment of thromboembolic disease in thoracic surgery (author's transl)]. The aim of the present work is twofold: 1) to find a simple method of diagnosing a genuine risk of post operative thromboembolic disease: the level of platellets and of fibrine, the cephaline-kaolin test, the thromboelastogram and the para-coagulation tests were not considered satisfactory by authors. Only the isotopic detection of venous thrombosis is able to confirm the value of a given preventive treatment; 2) to achieve an effective prevemtive treatment: the pre and post-operative heparin therapy (an adaptation of Kakkar's method) eliminates the clinical accidents, reduces the number of isotopic venous thrombosis, but might increase the incidence of hemorrage.


[Local tolerance of subcutaneous heparin. Double-blind comparison of calcium and sodium heparins (author's transl)]. One hundred and twelve subcutaneous injections of concentrated heparin (25,000 IU/ml), half in sodium heparin and half in calciparine, both with an identical heparin cation, were given in doses varying from 0.2 ml to 0.5 ml by a single operator in a double-blind study to assess the comparative local tolerance of the two heparin salts. The occurrence of bruising at the point of injection, more frequent with sodium heparin than with Calciparine, proved to be the distinguishing factor. Overall after 48 hours, 31 hematomas were observed with the sodium salt versus 20 with calciparine. McNemar's test of comparing matched proportions confirms this result (p = 0.03) and, with the order of the two treatments taken into consideration, J.J. Gart's exact test gives p = 0.0101.


[Surgical treatment of Wolff-Parkinson-White syndrome (author's transl)]. This report relates the surgical experience with 75 patients with WPW. The patients' symptoms were either SVT alone or SVT associated with a pathway with a lethal potential. In some, the Kent pathway caused SVT but did not cause cause pre-excitation. In others, multiple pathways were found. Success has been achieved in 35 of the last 36 patients with freewall pathways treated by surgery. Problems still remain with the posterior septal group. The indications for operation have been broadened to include all patients with significant symptoms.


[Bi-tissular malignant tumors of the lung. 2 cases]. Two new cases of multiple components pulmonary carcinoma are described: a pneumoblastoma and a epitheliosarcoma. Differenciating clinical features and nosological problems are recelled, allowing to discuss the classification of these two observations.


[Paraneoplastic syndromes in carcinoma of the kidney (author's transl)]. The authors present a group of patients with renal carcinoma in whom there were paraneoplastic signs such as fever, liver failure, hypertension and polycythemia. They noted, moreover, the most important clinical aspects, evaluating the incidence of these signs in relation to the course and diagnosis. They discuss also the frequency of presentation of each of these paraneoplastic manifestations, commenting on the various theories which have been suggested to explain them.


[Second malignacies complicating Hodgkin's disease. 1 case]. It is reported a case of long-term Hodgkin's disease treated with several courses of radiotherapy and chemotherapy and complicated with acute myeloblastic leukemia. Authors discuss the responsability of treatment immunosuppression, viral infections, levamizole and genetic factor.


[Acute ulcerative colitis associated with cytomegalic inclusion virus in a non-immunodepressed patient (author's transl)]. A new case of acute ulcerative colitis associated with cytomegalic inclusion virus within the colonic wall is reported. Some unusual features are discussed, such as the absent defect in cellular or humoral immunity, the location of the lesion which were limited to the sigmoid colon, and the fatal outcome of the disease. The possible pathogenic relationship between cytomegalic infection and acute a chronic ulcerative colitis are reviewed.


[The treatment of acute myeloblastic leukemia in the elderly patients (author's transl)]. Thirty eight patients over 60 years with acute myeloblastic leukemia are studied. 16 p. cent (3 out 19) of the patients 60--69 year-old and 42 p. cent (8 out 19) over 70 died before any treatment or effective chemotherapy. Among the patients who received and effective chemotherapy, 48 p. cent responded and 7 complete remissions were obtained. The rate of responders is lower in oldest patients; nevertheless when a response whether complete or partial is observed, the survival of responders is dramatically improved. This invites to treat with effective chemotherapies every patients suffering from acute myeloblastic leukemia in the elderly. However, the comfort and the quality of survival must not be omitted.


[A useful addition to the cyto-diagnosis of hemorraegic pleural fluids: the histological examination of the clot (author's transl)]. As an addition to classical cytology, the authors propose this histological examination of the clot, which is frequently observed in pleural fluids. This clot is taken before any centrifugation which might alter the former cellular groups. This method has been undertaken on 98 cases out of 196. Only 61 clots were prepared according to the histological technique, out of which 24 were positive. The only criteria taken under consideration were the histioid, trabecular or glandular groups. This technique enables the authors to a precise diagnosis in about one third of the suspicious cases and, besides, to discover a few positive cases which had escaped the routine technique.


[Hospitalisation at home of children seen in a pediatric outpatients (author's transl)]. The authors relate their experience of hospitalisation at home of 74 children selected in a pediatric outpatients over a period of 5 years. They show the advantages of this method of care which are much greater than the few disadvantages and regret that it is not used more often.


Obstruction of the abdominal aorta by a primary retroperitoneal tumor. An angiographically demonstrated case of total occlusion of the abdominal aorta by a malignant retroperitoneal tumor is presented. Surgical exploration revealed a diffuse tumor of the retroperitoneum involving the wall and lumen of the abdominal aorta and vena cava, respectively. Histologic and ultrastructural evaluation of the tumor established a diagnosis of malignant fibrous histiocytoma. Total occlusion of the abdominal aorta thus represents another angiographic finding in retroperitoneal tumors.


Ultrasonography in trophoblastic disease. Five cases of trophoblastic disease evaluated by gray scale ultrasonography were reviewed. The ultrasonographic findings of trophoblastic disease are discussed and illustrated. Theca-lutein cyst is reported to be associated with high levels of human chorionic gonadotropin (HCG). From our limited study, there was no correlation between theca-lutein cyst formation or size and the HCG titers of the patients at the time of examination. Molar evacuation must be followed in correlation with abdominal ultrasound and frequent monitoring of HCG levels.


Antibody to hepatitis B surface antigen is not cytotoxic to antigen-secreting hepatocytes. A continuously growing cell line which produces hepatitis B surface antigen was grown in the presence of antibody to the surface antigen. Antibody from animal and human sources was used. Neither growth rate nor cell morphology was affected and the cells did not inactivate the antibody over a 4-day incubation period. The surface antigen produced was specifically neutralized. These results suggest that hepatic injury occurring in response to hepatitis B virus infection is not mediated by humoral immunity to the surface antigen.


"Blue bodies" in a case of cryptogenic fibrosing alveolitis (desquamative type) an ultra-structural study. A patient with cryptogenic fibrosing alveolitis, with both mural and desquamative features, had two lung biopsies at the times of coronary artery surgery. These lung specimens were studied, using light and electron microscopy, with immunofluorescence techniques and electron microanalysis. In addition to the typical changes of cryptogenic fibrosing alveolitis previously reported, we found "blue-staining bodies" within alveolar macrophages and giant cells. These bodies were 15--25 micrometer in diameter with an iron rich outer rim and core of connective tissue mucin--possibly chondroitin sulphate or dermatan sulphate. It seems unlikely that these "blue bodies" were due to fibreglass dust to which the patients had had a trivial exposure, but their exact nature and significance remains unclear.


[Vaccination using an inactivated vaccine on a pig-breeding farm infected with the virus causing Aujeszky's disease (author's transl)]. When Aujeszky's disease was detected on a large pig-breeding farm, all normal sows and boars were vaccinated with an ethyl-ethylene-imine (EEI) vaccine produced in the Bundesforschungsanstalt für Viruskrankheiten der Tiere (Federal Research Institute for Viruses Diseases in Animals) in Tübbingen, Western Germany. The vaccine contained DEAE dextran as an adjuvant. The vaccine was inoculated twice by intramuscular route at a three weeks' interval, 5 ml. being inoculated at one time. Hyperimmune serum was inoculated in young pigs. In addition, hygienic procedures were adopted, consisting in disinfection and isolation. The disease was successfully controlled within eight weeks. Sows which developed Aujeszky's disease showed hardly any symptoms suggesting lesions of the central nervous system. Pulmonary lesions were the outstanding clinical feature. The semen quality of the affected male swine had markedly deteriorated. This was resorted to normal, however, within from five to ten weeks. The incidence of abortion and piglet mortality were low. In view of the results of virological and serological studies, it was concluded that the persistence of this strain of virus (causing Aujeszky's disease) was very slight.


The 1977 outbreak of bluetongue in Cyprus. Bluetongue outbreaks, ranging from isolated cases to widespread infections, have occurred in Cyprus in about half of the years since 1924. Serious outbreaks occurred in 1924, 1939, 1943, 1946, 1951, and 1965. Most cases occurred in September, October, November and December. The last outbreak prior to 1977 was in 1969. Virus types isolated in the past were types 3 and 4. In 1977 the outbreak was serious, affecting 13.1 per cent of 27,837 in-contact sheep; these were scattered in 303 flocks of 65 villages throughout the Government-controlled area. The virus type isolated was type 4. Culicoides were involved in bluetongue transmission in the island.


Possible histologic markers for early and late stages of breast cancer. The degree of productive fibrosis, amount of lymphoid infiltrate and nuclear grade have been studied in 492 consecutive cases of duct-infiltrating breast cancer. It has been found that highly significant relationships exist between these morphologic parameters of breast cancer: lymphoid infiltrate is directly related to nuclear anaplasia and antagonized by productive fibrosis; conversely, productive fibrosis is inversely related to nuclear anaplasia and antagonized by lymphoid infiltrate. Significant inverse relationships between productive fibrosis and lymphoid infiltrate persist in tumors that have the same nuclear grade. It is suggested that lymphoid infiltrate and productive fibrosis are suitable candidates as morphologic markers to estimate the age of breast cancer, while the nuclear grade is a suitable tool to identify subgroups with different behaviour in the NOS (not otherwise specified) category of breast cancer.


Studies on intrarenal prostaglandins. Effect of unilateral renal artery constriction on lipid droplets in the medullary interstitial cells of the 'opposite' kidney in rabbits. The unilateral renal artery in rabbits was constricted, and lipid droplet count in the medullary interstitial cells of the 'opposite' kidney was performed 1 week after surgery. Lipid droplet count in hypertensive rabbits was less than that in both nonhypertensive and normal rabbits and was inversely proportional to the mean blood pressure. Lipid droplet count was significantly correlated with the juxtaglomerular granulation index and the sodium content in the inner medulla. The present results suggest that, in the opposite kidney of rabbits hypertensive due to unilateral constriction of the renal artery, the enhanced release of prostaglandins and the washout of solute in the renal medulla may be induced as a response to increased perfusion pressure and elevated circulating angiotensin.


[Effect of dichloroethane on the hydroxylating and conjugating activity of the membranes of the cytoplasmic network of liver tissue]. The hydroxylating and conjugating activities of the cytoplasmic network membranes in the rat liver tissues were studied as affected by dichloroethane. Administration of this substance decreases the monooxygenase and uridine diphosphate glucuronyl transferase activities in the tissue under study. The reduced content of cytochrome P450 is the earliest index of a decrease in the hydroxylating activity of the liver tissue. This fall in the hydroxylating and conjugating activity in the cytoplasmic network membranes of the liver tissues testifies to the fact that the intensity of the metabolism and detoxication of certain foreign substances in this organ under the effect of dichlorethane is reduced.


[Biological characteristics of the plaque variants of the swine vesicular disease virus]. The Swine Vesicular Disease virus yields a heterogenic plaque population consisting of large round plaques of 8-10 mm, small uniform plaques with slightly indented contours, measuring 1-3 mm, and single plaques of transient form and size. The reisolates of the large (Lpf) plaques give a population that is similar to the initial virus, while the cloning of the small (Mpf) plaques leads to a homogenic population of such plaques. In vivo, the virus of the large plaques manifests enhanced virulence for swine. On the other hand, the selected small-plaque variant is apathogenic, which makes it possible to produce a live avirulent vaccine.


[Properties of 3':5'-AMP- and 3':5'-GMP-phosphodiesterases in the retina]. The activity of 3':5'-AMP and 3':5'-GMP phosphodiesterase was determined in retina of some animals. In all cases the enzymic activity with the presence of 3':5'-GMP is higher than with utilization of 3':5'-AMP. About 60% of the enzyme activity with 3':5' GMP as a substrate is lost in the process of obtaining the outer segments extracted from the bovine retina. The enzyme activity was completely detected with 3':5' AMP as a substrate. The both enzymes are equally extracted from the photoreceptory membranes by a weak ionic buffer. Differences are found in the stability of 3':5'-AMP and 3':5-GMP-phosphodiesterase during storage. The form of the enzyme splitting 3':5'-GMP is more unstable.


[Micromethod of determining the complement-binding properties of commercial series of the foot-and-mouth disease virus]. Investigations were carried out to establish the possibility of using a micromethod of the complement-fixation test to determine the complement-fixing properties of productional series of the foot-and-mouth disease virus. It was found that the micromethod referred to is an economically profitable and practically simple one. It is readily applicable requiring no particular apparatuses and equipment, is specific, and can successfully be used instead of the routinely employed CFT method. The micromethod suggested is economical, requiring minimal amounts (0.025 cu.c7) of the components taking part.


Giant cell tumor of bone. Variations in patterns of appearance of different cell types. Eleven benign giant cell tumors of bone were studied in the electron microscope, and the fine structural localization of acid phosphatase was elucidated. Three distinct cell types are always present in these tumors: stromal cells type 1; stromal cells type 2; and multinucleated giant cells. Small mononuclear cells may also occur, but are not likely to be actively participating in the neoplastic process. The range of variability in the fine structure of the different cell types constituting this tumor has been established. Variations in appearances include: a) presence of nuclear pseudoinclusions in stromal cells type 1 and multinucleated giant cells; b) aberrations in the structure of the rough surfaced endoplasmic reticulum in the same cell types; c) occurrence of ruffled borders, ectoplasmic layers and cytoplasmic labyrinths containing acid phosphatase in the giant cells. Some giant cells show evidence of marked phagocytic activity and contain large and numerous residual bodies carrying acid phosphatase. The significance of the interrelations between the different cell types are discussed and the possible role of stromal cells type 2 in immunological mechanisms directed against the tumor cells are mentioned.


Pituitary adenoma, primary parathyroid hyperplasia and papillary (non-medullary) thyroid carcinoma. A case of multiple endocrine neoplasia (MEN). An acidophilic pituitary adenoma associated with primary nodular parathyroid hyperplasia and a small papillary thyroid carcinoma was discovered at the autopsy of a 44 year old female acromegalic. The thyroid carcinoma showed evidence of lymphatic spread. Several etiopathogenetic mechanisms for the non-medullary thyroid carcinomata associated with Multiple Endocrine Neoplasia (MEN) have been postulated, since the follicular epithelium of the thyroid does not belong to the neural ectoderm derivates unlike the C-cells of the thyroid, the adenohypophysis and probably the parathyroid glands. Apart from genetic influence, or coincidence, one has to rule out carcinogenic exposure or hormonal influence. Clinically speaking, one should always consider whether malignant thyroid disease coexists with hyperplastic or neoplastic parathyroid tissue.


[Proliferation of hamster embryo fibroblast cultures infected with the herpes simplex virus]. In the HEF system in logarythmic and stationary phases of the culture growth the type-2 herpes simplex virus serves as a stimulator of proliferative processes in the cell (there is an increase of the labelled cells index, mitotic index and the intensity of labelling). The capacity of herpes virus not to suppress the cell DNA synthesis, as infestious viruses do, but to stimulate poliferative abilities of the cell indicates a presumable potential oncogenicity of this virus.


[Inhibitory effect of cerebrospinal fluid on the activity of sodium-, potassium-ATPase in animal brain synaptic membranes]. Liquor cerebrospinalis, obtained from patients with various diseases, inhibited Na, K-ATPase from rat and bovine synaptic membranes and did not influence on the activity of Mg-ATPase. The inhibition was independent on the type of disease. The inhibitory effect of liquor cerebrospinalis disappeared after dyalisis of it against Krebs-Ringer solution. Liquor cerebrospinalis appears to contain an endogenous inhibitor of synaptic Na,K-ATPase, which controls the enzymatic activity in vivo.


[Three decades' experience in the treatment of bronchogenic carcinoma by pulmonary resection (author's transl)]. A review of the development of thoracic surgery is followed by a description of the results obtained by us in the surgical treatment of bronchogenic carcinoma from the difficult beginnings in 1947 up to the present day. The diagnostic investigations, indications for operation and the operative risks are discussed on the basis of 1532 pulmonary resections. The subsequent fate of this patients is known to us almost without exception over a period of three decades. Diagrams show the ten-year survival rates. The importance of early diagnosis and the priority of surgical treatment are two basic conclusions which still hold true today.


[The role of the adenohypophysis in connection with changes in the thyroid caused by old age (author's transl)]. The findings indicate that changes caused by old age in the mechanism of the TSH action on the thyroid occur in the phases which are connected with the storage of adenosine triphosphate. That leads one to assume that changes caused by old age in the thyroid responsiveness to the action of TSH are probably conditioned by the following phenomena: 1. the decrease in the receptors "pro tropes" hormone and/or the disturbance of the correlations between TSH and the receptor 2. disturbance of the activity of the adenylocyclase 3. the phospho-diesterase activation.


Cooperative pathway induction of T lymphocyte mitogen stimulation. Isolated peritoneal mouse macrophages pretreated with the mitogenic enzyme combination neuraminidase (EC 3.2.1.18) plus galactose oxidase (EC 1.1.3.9.) (NAGO), or with NaIO4, stimulate macrophage-depleted lymphocytes mitogenically by a macrophage-derived signal, different from the originally used mitogen. Polyethylene glycol (PEG) treatment of the cultures, although itself nonmitogenic, strongly enhances the mitogenic response of the lymphocytes. Under culture conditions the macrophage-derived signal is transmitted to lymphocytes by direct cell contact, a finding which explains the need of a critical cell density for T lymphocyte stimulation. In the absence of macrophages, lysates from mitogen-preteated macrophages stimulate column-purified lymphocytes in the presence of PEG. Our results indicate that mitogenic activation of lymphocytes is mediated through two sequential triggering events, induction (by mitogen treatment) of a macrophage-derived signal and commitment (by nonmitogenic PEG treatment) of lymphocytes to react to the signal. Reconstitution of the mitogenic response can be achieved by a sequential induction of both these events.


Depressed prostaglandin release from peritoneal cells induced by a T cell adjuvant, lentinan. PGE and PGF release from peritoneal exudate cells was studied in mice after injection with two beta (1-3) glucans, the antitumor active lentinan and the inactive pachyman, 4 days after injection of both polysaccharides, the spontaneous and phagocytosis-induced PGE and PGF release was markedly suppressed. However, only the immunopotentiator lentinan induced peritoneal exudate cells which exhibited a longer lasting diminished PG release. The data suggest that the T cell adjuvant lentinan may potentiate cellular immune responses by reducing synthesis of immune suppressive prostaglandins from peritoneal exudate cells.


[Spasm of the adductor muscles, pre-dislocation and dislocations of the hip joints in children and adolescents with cerebral palsy. Clinical observations on aetiology, pathogenesis, therapy and rehabilitation. Part I: The effect of open myotenotomy of the gracilis muscle and of the long and short adductor muscles in connection with total extrapelvine resection of the obturator nerve, on the hip joints and static function (author's transl)]. Spasm and contraction of the adductor muscles involve, on the one hand, danger in respect of the development of a dislocation of the hip, and are a serious impediment to a walking ability on the other. Hence, surgery is often necessary. The article reports on the results of consequent weakening of the adductor muscles as a result of open myotenotomy in association with complete extrapelvine resection of the obturator nerve. 27 patients were subjected to surgery--in most cases bilaterally--at an age between 2 years and 5 months and 18 years, with a follow-up period of up to 15 years. The study does not include patients with spastic dislocation of the hip in whom this method was applied on the non-dislocated side and on the dislocated side in combination with iliopsoas tenotomy. This method makes it possible to achieve regression of existing defective positions of the hip joints. In a few cases, the valgus position of the neck of the femur was corrected to some extent. In two patients it was not possible to prevent the progress of a developing dislocation of the hip. These results show that, whereas the adductor muscles represent an essential factor for the occurrence of a spastic dislocation of the hip, other forces are most probably also involved. In the majority of cases, results were favourable in respect of the static function, although in some cases the success became evident after several years only, especially in mentally retarded patients and in apathetic individuals. Important for therapeutic success is the follow-up. The principles of its therapy are thoroughly discussed. Surgery is indicated only in special cases. Indications must be observed very strictly, since the risk of excessive weakening of the adductor muscles should not be underestimated.


[Suicide risk and care of suicide attempters]. Starting from the notion of suicidal risk and a critique of its usage, it is possible to distinguish groups whose suicidal risk is particularly high. The suicidal group-composed of persons who have already attempted to commit suicide once-is in this paper the subject of general considerations as well as personal research. The latter shows that it is still difficult to detect those persons who are about to commit suicide and that tell-tale signs-be they clinical or resulting from tests-are still not very reliable. The difficulties encountered by secondary prevention are made obvious by two pieces of research done on the taking in charge of suicide-prone persons in a university general hospital. the timely recognition of the pre-suicidal syndrome and of the self-denial syndrome is very important for suicide prevention. Self-depreciation, and consequently the narcissistic blow is, as are the aggression phenomena, one of the psychological cores which lead to an act of suicide. Medical attitudes concerning the suicidal person are analyzed, and the difficulty in the psychotherapeutic relationship is stressed. Pratical considerations on the psychotherapeutic approach to the suicidal person close up the article.


Comparison of Fusobacterium sp. versus Bacteroides sp. in the monoxenic cultivation of E. histolytica. By means of the performed studies it was established that 6 Fusobacteria strains enhanced the growth of E. histolytica while 4 Bacteroides strains did not possess this property.


[Electron microscopic study of several features of spore formation in type B Clostridium perfringens]. The authors carried out electron microscopy of the thin sections of Cl. perfringens, type B (strain No. 89). Material of middle electron density was revealed on the cell wall surface from the first hours of the culture growing; the cytoplasm displayed both rod-like incorporations with transverse striations, and phage particles. Different spore formation disturbances were revealed in the strain under study. In the majority of cells spore formation was blocked at the III--V stage. Besides, there were pseudospores, whereas mature spores were rarely encountered, and even those which did occur, were at the stage of growing.


[Effect of small doses of diphtheria exotoxin on cell cultures]. High diphtheria exotoxin concentrations induced irreversible injuries to all the cultures under study (L, HeLa, spcv pzM). However, its final titres in the mentioned cells differed. HeLa and pzM cells, being highly sensitive, can be recommended for titration of dipheria exotoxin, instead of the expensive guinea pig tests. Low (subtoxic) doses produced cytoproliferative action and caused changes of the cell properties.


[Action of cyclic adenosine monophosphate on the spleen antibody--forming cells of rabbits immunized with Escherichia coli]. Cyclic adenosine monophosphate (cAMP) parenterally injected to rabbits (immunized intraperitoneally with thymus-independent antigen of killed E. coli 0127/545) during January--April inhibited production of antibody-forming cells (AFC) in the spleen of these animals, and during May--June it increased the AFC count. Both the stimulating and inhibitory effect of cAMP was associated with the administration of the same doses of 25--250 microgram/kg. The nature of the cAMP effect on the production of the AFC depends on the initial immune response level. At the maximum immune response and in the absence of the dose-effect dependence cAMP inhibited the antibody formation, but when the immunological reaction was below the maximal level and in the presence of the dose-effect relationship cAMP increased the AFC production.


[Clinical immunological characteristics of herpes zoster]. Changes of antibody formation of 96 patients with various clinical forms of herpes zoster were traced by indirect hemagglutination inhibition test. Four variants of the immunological response were distinguished; clinical characteristics of each of these groups is presented. The initial antibody level failed to determine the severity of the course of the disease in herpes zoster.


[Comparative study of the smallpox vaccines from B-51, EM-63 and L-IVP in a controlled epidemiological experiment. II. The characteristiics of the immunogenicity of the smallpox vaccines]. Immunogenicity of smallpox vaccines prepared of EM-63, L-IVP, and B-51 strains was studied under conditions of strict controlled epidemiological trial. Skin reactions to revaccination and vaccines antigenic activity indices were detemined in the persons vaccinated. Changes in the virus-neutralizing and antibodies suppressing hemagglutination was the same in persons vaccinated with any of the preparations tested. The maximal virus-neutralizing antibodies level was determined 1 month after the vaccination and persisted without any essential changes for one year. The titre of hemagglutination inhibiting antibodies also reached the maximum in one month, but diminished gradually by the end of one year after the vaccination. There were found no significant differences in the antigenic activity of the vaccines. The vaccines studied also displayed no difference in the number and character of skin reactions to revaccination. In comparing the antibodies level and the character of skin reactions to revaccination it was found that the titres of hemagglutination inhibiting antibodies and virus-neutralizing antibodies of 1:40 and over were in the great majority of cases determined in the blood sera of the vaccinated persons with the immediate and negative reactions to revaccination, i. e. in those with intensive postvaccinal immunity.


[Nonspecific means of increasing the sensitivity of the passive hemagglutination reaction]. The effect of some methods of preliminary treatment of erythrocytes on the PHAT depended on the sensitin náture and the method of erythrocyte load. In case of erythrocyte load with nonprotein and immunoglobulin sensitins without any conjugating agents the simulating effect of heating and periodate treatment was caused not by increase of stable sensitin binding, but by the reduction of physico-chemical resistance of erythrocytes. This effect of erythrocyte treatment permitted to increase the sensitivity of the antibodies and antigens determination. In loading the erythrocytes with the aid of conjugating agents and in sensitization with protein antigens after Boyden no stimuating effect of the treatment was noted.


[Course of the hypertensive syndrome in spongioblastoma multiforme]. Of 140 patients with brain tumors of a supratentorial localization, in 50 cases a multiform spongioblastoma was established; it was verified either by a surgical operation, or during section. Three variants of the hypertensive syndrome were distinguished: tumorous, pseudovascular, pseudoinflammatory. The morphological brain studies determined an expressed vascular and cellular reaction to the malignant tumorous process. In a pseudoinflammatory clinical variant inflammatory changes were more expressed, while in pseudovascular--vascular changes. An atypical clinical development of multiform spongioblastoma is determined by the localization of the tumor, its histological structure, infiltrating growth and intoxication stemming from the tumor.


[Study of muscle excitability in response to currents of different duration in the diagnosis of nerve injuries]. The "strength-duration" curve was studied in 154 patients in different periods after injury to the median nerve, ulnar nerve or both nerves. The most probable mean values of strength (U) in changes of the duration (t) of the current 1--6, 7--11 months and more than 12 months after injury were obtained by means of the equation U=a0 + a1t +a2t2 by the least squares method. It was established that the excitability of muscles diminishes continuously but persists more than 15 years after total anatomical interruption of the nerve. Absence of electroexcitability of the forearm muscles as a result of ischemia is not a contraindication for nerve suturation. Suturation of the nerve leads to restoration of sensibility and active contractions of the hand muscles. The deviations in the "strength-duration" curve are signs of partial injury to the nerve. It was found that the more the number of deviations in the "strength-duration" curve and the more its left part on the side of the injury resembles the curve recorded from the symmetrical healthy muscle, the more rapidly is the nerve conduction restored and the more rapidly it improves after nonoperative treatment.


Kinetic studies of the interaction of uranyl ions with inorganic pyrophosphatase from baker's yeast. Kinetic measurements were performed to test the effect of uranyl ions on the enzymatic hydrolysis of pyrophosphate. A strong inhibition of the enzyme was found. From a Dixon-plot an inhibition competitive to the substrate magnesium pyrophosphate and an inhibitory constant of Ki = 3 . 10(-7) M was deduced.


Varicose veins in congenital angiodysplasias. Three cases of Klippel--Trenaunay--Weber's syndrome are presented. The syndrome is characterized by cutaneous hemangioma, hypertrophy of an extremity and varicose veins. It is combined with angiodysplasias, either in the form of aplasia/hypoplasia of deep veins and/or in the form of arteriovenous shunts. The varicose veins will frequently be the dominant symptom, and it is emphasized that surgical treatment should not be instituted until the patient has been examined angiographically, with both phlebography and arteriography. The methods and the classification are discussed and the possibilities of treatment are outlined.


Tissue culture studies on human pituitary tumours: long term release of anterior pituitary hormones into the culture medium. A study was undertaken to determine the length of time that human pituitary tumours are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions and to study the spectrum of hormone release by functioning and "non-functioning" pituitary neoplasms. Fragments from the pituitary tumours of 10 patients in the following categories: 1 Cushing's disease, 2 with amenorrhoea-galactorrhoea, 3 with acromegaly, and 4 with "non-functioning" pituitary tumours and from 2 normal human anterior pituitary glands were placed in primary culture immediately after surgery. The in vitro release of human growth hormone (hGH), prolactin (Prl), thyrotrophin (TSH), adrenocorticotrophin (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was measured by specific radioimmunoassays at the end of each week in culture. Hormone release was surveyed from 6 weeks to 6 months depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data. In the initial week of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumours (1 amenorrhoea-galactorrhoea and 3 acromegaly) in concentrations up to 100 ng/ml of medium while 5 of the 6 hormones were readily detectable in the media from 2 additional tumour samples (Cushing's disease and 1 "non-functioning" pituitary tumour). The media of the remaining 4 tumours contained at least 3 of the 6 hormones (1 amenorrhoea-galactorrhoea and 3 "non-functioning" pituitary tumours). After 6 months in culture, the 6 hormones were readily detectable in at least 1 of the 5 surviving cultures and hGH (up to 800 ng/ml) and LH were each detectable in the media from 2 cultures. Although most of the hormone concentrations in the media decreased with length of time in culture, there were 2 exceptions. First in the media from 5 of the 12 cultures from both controls and tumours, Prl concentrations increased after 50 to 80 days culture. This increase usually lasted for several weeks before Prl levels again began to decline. The second unusual finding occurred in a tumour from a patient with acromegaly in the media of which hGH levels rose from 60 ng/ml to 800 ng/ml between days 125 and 174. These findings of prolonged hormone release in vitro give promise of future usefulness of tissue culture methods for study of polypeptide hormone releasing mechanisms and long-term production of human anterior pituitary hormones for use in research and possible therapy.


17-Hydroxyprogesterone in the cosyntropin test: results in normal and hirsute women and in mild congenital adrenal hyperplasia. The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.


17 alpha-Hydroxylase deficiency. A combination of hydroxylation defect and reversible blockade in aldosterone biosynthesis. We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17 alpha-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days. Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17 alpha-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone. We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2.


Response of plasma non-conjugated oestradiol to manipulated adrenal function by ACTH and dexamethasone. The present study is concerned with the regulation of free plasma oestradiol in relation to maternal adrenal function during late human pregnancy. Blood was collected in 9 patients at short time intervals of 30 min from 17 h to 3 h. In order to exclude endogenous ACTH-secretion 5 patients received 12 mg dexamethasone over 48 h. Between 20 h and 2 h 0.25 mg ACTH1-24 (Synacthen) was infused into the subjects. Non-conjugated oestradiol was determined by radioimmunoassay and total plasma cortisol by protein binding method. During the application of ACTH free oestradiol increased from 21.3 +/- 5.7 to 25.5 +/- 7.1 ng/ml (P less than 0.025) in the patients without dexamethasone. The increase was moderately correlated to rising cortisol (r = 0.58, P less than 0.001). Plasma oestradiol reached its maximum level after 90 min, followed by a tendency to decline despite persisting stimulation of maternal adrenals. The patients receiving dexamethasone exhibited during ACTH-infusion a rise of oestradiol from 3.8 +/- 1.9 to 7.8 +/- 3.1 ng/ml (P less than 0.001). Increasing oestradiol was strongly correlated to plasma cortisol (r = 0.67, P less than 0.001). The phenomenon of earlier declining oestradiol levels did not occur. These results suggest that maternal adrenals predominantly regulate the formation of free oestradiol. Plasma cortisol indicating maternal precursor production balances the increase of oestradiol by suppressing foetal precursor supply.