Effect of dietary cyclopropene fatty acids on the octadecenoates of individual lipid classes of rat liver and hepatoma. The effect of dietary cyclopropene fatty acids on the concentration of octadecenoate chain positional isomers in individual lipid classes of normal liver, host liver, and hepatoma 7288CTC has been determined. The data revealed the following: (a) Saturated and monoene fatty acid percentages of liver phosphatidylcholines and phosphatidylethanolamines were not affected, but the percentage of saturated fatty acids of the triglycerides and cholesteryl esters was increased while the monoene percentages decreased. (b) Oleate to vaccenate percentage ratios, previously shown to be characteristic of individual lipid classes, were completely disrupted. (c) Oleate concentrations of the two major liver phospholipids were elevated, and vaccenate levels were dramatically reduced. (d) Cyclopropene fatty acids appear to inhibit monoene elongation. (e) The elevated concentrations of oleate indicate that an alternate route of oleate biosynthesis must exist if the delta9 desaturation is inhibited by cyclopropene fatty acids as reported previously. (f) In contrast to liver, oleate and vaccenate concentrations in hepatoma were not affected by the dietary cyclopropene fatty acids.


delta9 Desaturase activity in normal mouse liver and hepatoma SS1K. The activity of delta9 desaturase was determined in the microsomal fraction of normal mouse liver and hepatoma SS1K in the presence of the 105,000 x g supernatant. Neither hepatic nor hepatoma soluble fractions were able to modify the low desaturating capacity. Two enzymes from the microsomal electron transport chain associated with delta9 desaturase, namely NADH-cytochrom b5 reductase and NADH-cytochrom C reductase were also measured. The results indicate that the low delta9 desaturase activity in hepatoma SS1K could be related to the reduced amount of desaturase.


Bone infections involving anaerobic bacteria. Over 700 cases of anaerobic osteomyelitis have been reported in the literature. Nonetheless, most reviews of osteomyelitis have paid little attention to the potential role of anaerobes in bone infections. There have, as yet, been no prospective studies of osteomyelitis utlizing optimal anaerobic transport and culture techniques. In a retrospective study of osteomyelitis at Wadsworth VA Hospital from 1973--1975, 39 percent of 58 patients with osteomyelitis had an infection involving anaerobes. Anaerobes were isolated from 81 percent of 27 patients whose specimens were cultured anaerobically. Anaerobes were isolated from nine of ten samples of bone. Anaerobic bacteria were part of a mixed flora involving facultative bacteria in all but two cases. All of the patients with anaerobic infection had non-hematogenous osteomyelitis. Non-hematogenous disease comprises 80--90 percent of the osteomyelitis seen in adults. Our experience at Wadsworth VA Hospital and a review of the literature lead us to believe that anaerobes play a much larger role in osteomyelitis than has been appreciated previously. Infections of the calvarium, mastoid, mandible, maxilla and the extremities are most likely to involve anaerobes. Predisposing conditions include paranasal sinusitis, otitis media, periodontal disease, trauma, peripheral vascular disease, peripheral neuropathy and/or chronic osteomyelitis. The presence of a foul odor is a valuable clinical clue to the presence of anaerobes. Bacteroides, fusobacteria and anaerobic cocci have been reported with almost equal frequency from anaerobic bone infections. While Bacteroides fragilis is the most common anaerobe isolated in infections of other organ systems, it does not appear to be a common pathogen in anaerobic bone infections. The role of anaerobes in osteomyelitis is not yet resolved. They have been isolated in pure culture from infected bone, and under those circumstances are clearly pathogenic. Anaerobes are found more frequently as part of a mixed flora with facultative streptococci, gram-negative bacilli, and less often with S. aureus. In this setting it is unclear which organism or organisms are the primary invaders, or whether there is a synergistic mechanism of infection. The reliability of sinus drainage cultures also remains to be determined. Our retrospective study suggests that certain anaerobes isolated from sinus drainage are not present in infected bone. Cultures of bone or an abscess adjacent to bone would be expected to give more reliable data. The majority of anaerobes other than B. fragilis are susceptible to levels of penicillin achievable with parenteral administration of the antibiotic. Anaerobic pathogens should be sought in the situations noted above. We feel that parenteral penicillin should be part of the initial antibiotic regimen in patients with suspected or documented anaerobic bone infection...


Blood amine acid levels in patients with insulin excess (functioning insulinoma) and insulin deficiency (diabetic ketosis). Blood amino acid concentrations were determined in the postabsorptive state in nine patients with insulin excess (functioning insulinomas), nine juvenile-type diabetics with insulin deficiency (diabetic ketosis due to insulin withdrawal), six juvenile diabetics in moderate metabolic control, and five healthy control subjects. Blood branched-chain amino acid (BCAA) levels were elevated in diabetic ketosis and decreased in patients with insulinomas. Blood concentrations of BCAA were significantly correlated to blood glucose levels, and in diabetics they were also correlated to blood ketone bodies, serum free fatty acids, and glycerol levels. These data indicate an inverse relationship between circulating effective insulin levels and blood BCAA concentrations. It is suggested that blood levels of BCAA might represent an indicator of insulin-dependent alterations of protein metabolism.


Alterations in rat renal cortical and medullary guanosine 3'5'-monophosphate accumulation by oxygen- and calcium-dependent and -independent mechanisms: evidence for a calcium-independent action of oxygen in renal inner medulla. Factors influencing guanosine 3'5'-monophosphate (cGMP) metabolism were examined in slices of rat renal cortex, outer medulla, and inner medulla. In the presence of extracellular Ca2+ and O2, a gradation of steady-state cGMP levels was evident among the tissues (inner medulla greater than outer medulla greater than cortex). Carbamylcholine, bradykinin, histamine, and the divalent cation ionophore A23187 significantly increased cGMP in each tissue. The cGMP-stimulating action of these agents was reversibly abolished by exclusion of either Ca2+ or O2. The influence of Ca2+ and O2 on expression of effects of carbamylcholine and related cGMP agonists was interdependent in each region of the kidney, since both were required for expression of agonist action. By contrast, nitrite, nitroprusside, NH2OH, and nitrosoguanidine increased cGMP in the presence or absence of Ca2+ or O2. Thus, at least two distinct mechanisms for altering cGMP accumulation are operative or expressible in each region of the kidney: one that requires and one that does not require the presence of extracellular Ca2+ and O2. Results also suggested a role for transmembrane transport of Ca2+ in the maintenance of basal cGMP and in the expression of the responses to Ca2+-dependent agonists in renal cortex, outer and inner medulla. Thus, verapamil, which can block such transport, lowered basal cGMP and abolished these responses while ionophore A23187 enhanced cGMP in cortex and medulla only in the presence of Ca2+. The interrelationship of Ca2+ and O2 in control of basal cGMP levels clearly differed in cortex compared to inner medulla. In cortex, Ca2+ and/or O2 deprivation produced quantitatively similar reductions in cGMP. Moreover, expression of the action of O2 to increase cortical cGMP required Ca2+. Thus, O2 effects on cGMP in cortex were closely coupled with or mediated through Ca2+. By contrast, in inner medulla, O2 deprivation resulted in more pronounced reduction in basal cGMP than did Ca2+-deprivation, and O2 significantly increased inner medullary cGMP in the absence of extracellular Ca2+...


Immunological studies of heat-labile virus inhibitors. I. Specificity of absorption onto sensitive viruses and specific response after virus infections. Heat-labile virus inhibitor (HLI) in normal sera of various mammalian species capable of neutralizing variola (VRV) and Newcastle disease viruses (NDV) was studied immunologically. After sucrose density gradient centrifugation of guinea pig serum, the HLI activity against VRV and that against NDV were both demonstrated in the same region sedimenting fastor than IgM. Absorption with partially purified VRV or NDV removed the HLI activity on the homologous virus but not that on the other. Prior saturation of virions with specific antibody blocked the absorption of HLI, suggesting a specific competition for binding site (s) between specific antibody and HLI. The HLI level against variola virus was checked in connection with immunization with vaccinia virus. In human primary vaccination, the HLI level rose sharply within 4 weeks after vaccination, turning to decline gradually to settle at a level higher than that of the conventional neutralizing antibody (NA). In cases of human revaccination, a sharp rise of HLI started 4 days after vaccination and reached the highest level within 7 days, preceding the rise of conventional NA level which occurred about 3 days later. Three rabbits with negative HLI activity prior to vaccinia immunization obtained an HLI activity within 2 weeks, which showed a sharp rise up to 6-8 weeks. One rabbit with a positive prior HLI activity also showed a sharp rise of the HLI activity after immunization. In all rabbits the final HLI level was identical with that of conventional NA. Groups of guinea pigs were immunized with either VRV or NDV. Rises of the HLI level after immunization were observed in all animals, the activity being restricted to the homologous virus used in the immunization. Complement requiring NA was detected during the course of immunization but its behavior was different from that of HLI. The above observations were interpreted to suggest a ubiquitous presence of HLI as a specific reactive agent and its role at an earliest stage of immune response.


A survey of rotavirus associated with gastroenteritis in Aboriginal children in Western Australia. In a year-long survey which was carried out between April, 1975, and March, 1976, faecal specimens from Aboriginal and some non-Aboriginal children who suffered from gastroenteritis were examined by electron microscopy for rotavirus, and also tested for bacteria and parasites. The children were under six years of age and came from all parts of Western Australia, except Perth. Rotaviruses, "astroviruses" and adenoviruses were detected as well as the usual potentially pathogenic bacteria and parasites. Two peaks of rotavirus incidence were found during the year in specimens from Kalgoorlie, but only one peak occurred in Derby. Rotavirus was somewhat more frequently seen in non-Aboriginal than Aboriginal children.


[Treatment of hyperlipoproteinemia type IIa with a "prudent" diet and clofibrate (author's transl)]. 14 previously untreated patients with hyperlipoproteinemia type IIa according to Fredrickson underwent a controlled clinical trial. The study was designed to clarify the effects of clofibrate on the bloodlipids. All patients were willing to cooperate. After leaving their usual dietary habits all of them were given for seven to ten days a "prudent" diet. This diet was rich in vitamins; it had a low caloric-content. 20% of the calories consisted of proteins, 35% of carbohydrates (sweets were omitted) and about 45% of fats with a PS-factor of about 2.2. After the initial dietary treatment all patients were given twice daily for 14 days 500 mg clofibrate. During the use of the "prudent" diet the serum-cholesterol-levels decreased in average with 14.8%. Compared to the values at the beginning of the trial the difference was statistically highly significant. The average-values of triglycerides, phosphatides and the relative percentage of HDL, LDL and VLDL remained unchanged. After the patients received clofibrate there was an additional decrease of the serum-cholesterol-values of 14.8%. The total decrease of the cholesterol-levels compared to the initial values amounted to 27.4%. Furthermore, there was a reduction of the phosphatids in the serum of 14.1% compared to the initial value and of 9.9% compared to the value after dietary treatment alone. Under the combined effects of a "prudent" diet with clofibrate the HDL increased significantly. It can be assumed that clofibrate reduces the serum-cholesterol-levels in cases of hyperlipoproteinemia by decreasing the LDL-fraction, which is rich in cholesterol, and by increasing the HDL-fraction.


[Intestinal yersiniosis: 25 cases of infections with Yersinia pseudotuberculosis and Yersinia enterocolitica (author's transl)]. Yersinia infections in 16 adults and 9 children are reported. 15 cases were caused by Yersinia pseudotuberculosis, 8 of them were proved by serological findings. In 4 cases the infection by Yersinia pseudotuberculosis was likely, in 3 other cases possible only. Real infections caused by serotype IV are demonstrated too. Furthermore there were 10 cases caused by Yersinia enterocolitica, 3 of them were proved by bacterial, the other ones by serological findings. Both germs caused identical symptoms: fever (80%), abdominal pains (56%), diarrhoea (52%), erythema nodosum (44%), arthritis (40%), vomiting (16%), weight loss (16%), lymphoma (12%) and others. In children 50% of erythema nodosum was produced by intestinal yersiniosis. The beginning with gastroenteritis and fever mostly was followed by a second phase with returning fever, abdominal pains, erythema nodosum and/or arthritis. Antibiotic therapy had a definite effect only in the first phase of gastroenteritis and in the two possibly relapsing cases. In two of 5 patients with long standing arthritis the HL-AB 27 was present.


Hepatocellular carcinoma in a young woman with prolonged exposure to oral contraceptives. A case of hepatocellular carcinoma in a young female is presented in which the apparent etiology was the use of oral contraceptives for 5 1/2 years. Sequential therapeutic trials with intraarterial 5-fluorouracil, intraarterial adriamycin, and intravenous 1,3 bis[2-chloroethyl]-1-nitrosourea (BCNU) were unsuccesful. The adverse effects of oral contraceptives on the structure and function of hepatic tissue are reviewed.


[Reactions of the submandibular salivary gland caused by sialography. Experimental research in dogs]. In order to ascertain the damaging effects on the glandular parenchyma and excretory system of the major salivary glands of sialography using iodate contrast media in an oily vehicle, experiments have been carried out on a group of dogs. Among other compounds, Lipiodol UF and Urovison were used, the former oil-based and the latter water-based. Histological slides of the injected gland made three and four weeks afterwards showed in one animal only the presence of a periductal infiltrate and an intracanalicular formation of hyaline thrombotic type that was not easy to interpret. Lipiodol UF was employed in this case. Comparing these results with the literature, it is concluded that Lipiodol is an irritant, especially if it passes beyond the salivary excretory tree, but this is not enough to have it banned absolutely. Contraindications are reported and the need for correct technique stressed.


Biosynthesis of mitochondrial membrane proteins: co-ordination with special reference to cytochrome c oxidase. This paper reviews mechanisms by which the rate of synthesis of subunits of mitochondrial inner membrane protein complexes and the assembly of these subunits are co-ordinated. Current models are evaluated and critically discussed in the light of some recent evidences. The focus is on the incorporation of cytoplasmically-synthesized cytochrome c oxidase subunits in the development of a newer model, which introduces some twists into a combination of several current ideas. A mechanism which governs both organized assembly and the co-ordination of rates of polypeptide synthesis is illustrated and the principles of the model are applied to the elucidation of some odd features of certain mutants. The possibilities that mitochondrial ATPase and cytochrome c reductase may also be synthesized and assembled according to this model are discussed.


Steady-state study of horse-liver ADH: detection of two kinetically heterogeneous components. New theoretical considerations and a new approximation strategy were applied to the kinetic analysis of the experimental relationship between the reaction velocity in the steady state and the concentrations of ethanol and NAD. It could be shown that horse-liver ADH consists of two kinetically heterogeneous components.


[Study of the conformational mobility of globular proteins by pulse methods of NMR]. The protein spin-echo decay and recovery of longitudinal magnetization were studied in seven globular proteins: cytochrome C, ribonuclease, lysozyme, DNA, hemoglobin, serum albumin and gamma-globulin in D2O solutions. For comparison the Tobacco mosaic virus (TMV) protons in D2O solutions were also investigated. The spin-echo decay of all 7 proteins can be separated into three components: a slowly decaying component with an amplitude of about 10% of the amplitude of the total signal, intermediately and fastly decaying components, the two latter being comparable in amplitudes. Longitudinal relaxation is more simple in character. The value of T2 of the protons responsible for the fastly decaying components in linearly dependent on the molecular weight of the protein, a fact indicating that the regions of the proteins with a "rigid" structure can be responsible for this component. The intermediate component, whose contribution increases with temperature, was ascribed to the mobile regions of the protein, and the slowly decaying component to the mobile protein side chains. Weak dependence of T1 on the protein molecular weight and some other obtained data give additional evidence for the presence of motion within macromolecules. The peculiarities of this motion is in good correspondence with the notion about the existence of the segmental motion of the polypeptide chain (conformational mobility of the protein). In contrast to proteins the spin-echo decay of TMV lacked the slow component and the "solid" echo signal was observed which indicates the existence of a "rigid" structure in the macromolecules of the virus.


[Spin label study of the surface of lipid bilayers]. The surface of liposomes and natural membranes has been studied by the method of "spin label--spin probe". Various nitroxyl radicals have been attached to membranes either dueto covalent binding with NH2-groups of phosphatidylethanolamine or due to hydrophobic interactions. Addition of paramagnetics of different charge signs (potassium ferricyanide and dibenzenechromium iodide) to spin labeled membranes results in a decrease of the EPR line intensity without marked broadening. Since the paramagnetic is attached to the membrane surface near the label it broadens the label's EPR spectrum so that it can not be observed. In this case one can observe only the spectrum of labels which have no paramagnetics in the vicinity, the nitroxyl part of radicals being inaccessible to direct paramagnetic impacts. The constants of binding of paramagnetics to the membrane surface have been determined from these experiments. All results (including the assymetry of label rotation) can be explained most simply by assuming that the polar lipid groups are oriented parallel to the membranes surface.


Comparative mutagenicity of alkylsulfate and alkanesulfonate derivatives in Chinese hamster ovary cells. Mutation induction and cell killing produced by selected alkylsulfates and alkanesulfonates have been quantitated using the Chinese hamster ovary/hypoxanthine--guanine phosphoribosyl transferase (CHO/HGPRT) system. Dose--response relationships of cytotoxicity and mutagenicity are presented for two alkylsulfates [dimethylsulfate (DMS), diethylsulfate (DES)] and three alkyl alkanesulfonates [methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), and isopropyl methanesulfonate (iPMS)]. Under the experimental conditions employed, cytotoxicity decreased with the size of the alkyl group. DMS was more toxic than DES, and MMS was more toxic than EMS and iPMS. All agents produced linear dose--response of mutation induction: DMS was more mutagenic than DES, and MMS was more mutagenic than EMS and iPMS based on mutants induced per unit mutagen concentration. However, the following relative mutagenic potency was observed when comparisons were made at 10% survival: DES greater than DMS; EMS greater than MMS greater than iPMS.


[Tryptophanyl tRNA synthetase: isolation and characteristics of the tryptophanyl-enzyme]. The catalytic groups, involved in aminoacyl-tRNA formation remain unknown. The isolation and identification of an active covalent complex between the enzyme and substrate is an essential step in understanding the reaction mechanism. We identified and isolated the covalent complex of tryptophanyl-tRNA synthetase (EC 6.1.1.2) and tryptophane which was able to aminoacylate the tRNATrp in the absence of ATP. In beef pancreas tryptophanyl-tRNA synthetase preparations, isolated by the previously described method, a tightly bound tryptophan was revealed which could not be removed by charcoal treatment, by gel-filtration and by replacement with the excess of typtamine, a competitive inhibitor of tryptophane. This tightly bound tryptophane is able to exchange rapidly and specifically with radioactive tryptophane allowing to obtain [14C]tryptophane-tryptophanyl-tRNA synthetase complex. After the reaction of this complex with NH2OH at neutral pH tryptophanyl hydroxamate is formed proving the activated state of the tryptophane in the initial complex with the enzyme. No nucleotide impurites were noticed in the enzyme preparation; the complex is stable at denaturation. A conclusion is made that the tryptophanyl-tRNA synthetase isolated by our method is a tryptophanyl-enzyme. The tryptophanyl residue could be specifically transferred to tRNATrp in the absence of other substrates of the reaction, the efficiency of the transfer does not exceed 25%. The content of the covalently bound tryptophane never exceeds 1 mole per mole of the dimeric enzyme. The total content of tryptophane in the forms of tryptophanyl-enzyme and tryptophanyl adenylate enzyme complex equals 2 moles per mole of the enzyme. The tryptophanyl-enzyme is destroyed during incubation with AMP or with pyrophosphate. The role of the tryptophanyl-enzyme as a possible intermediate in the course of aminoacylation of tRNATrp is discussed.


Sister chromatid exchange studies for monitoring DNA damage and repair capacity after cytostatics in vitro and in lymphocytes of leukaemic patients under cytostatic therapy. The effect of various cytostatic drugs was studied on the frequency of sister chromatid exchanges (SCEs) in vitro and in PHA-stimulated lymphocytes of leukaemic patients under cytostatic therapy. The lymphocyte system is a sensitive one for the detection of DNA damage after administration of cytostatic drugs in vitro. Mitomycin C, busulphan, vincristine, chlorambucil, cytosine arabinoside, cyclophosphamide and lycurim were tested. All except cyclophosphamide induced high frequencies of SCEs in the first mitosis after their administration. The experiments with PHA-stimulated lymphocytes in vivo from patients treated with cytostatics showed that cytosine arabinoside, in combination with thioguanine, did not induce higher frequencies of SCEs, whereas in patients who were treated with cyclophosphamide alone or in combination with other cytostatic drugs, there was a higher incidence of SCEs during treatment. About 10 days after the termination of the treatment the elevated freuqencies of SCEs returned to the initial level. After administration of some mutagens, especially alkylating agents in vivo, the lymphocyte system can be used to assess induced DNA repair by continuously monitoring for SCEs.


[Endogenous DNA synthesis in isolated chromatin]. It was shown that chromatin isolated from the liver of adult rats is an effective cell-free system for studying DNA synthesis without using exogenous enzymes or DNA-template. Both replication synthesis initiated in vivo and unscheduled synthesis activated several fold after gamma-irradiation of isolated chromatin proceed in chromatin preparations. Unscheduled synthesis consists of template-dependent and template-independent synthesis. Template-dependent synthesis proceeds with a maximum rate in the presence of all four deoxynucleoside triphosphates (dNTP). Template-independent synthesis proceeds with an appearable maximum rate in the presence of one dNTP whose incorporation is inhibited by the addition of the rest dNTP. All three DNA synthesis in chromatin are ATP-dependent. Replication synthesis but not the unscheduled one is inhibited by actinomycin D and N-ethylmaleinimide. Repair inhibitor--0.01 M caffeine--suppresses the initiation of unscheduled synthesis, but does not influence its elongation. The incubation conditions of chromatin for unscheduled synthesis are optimalized as for temperature, pH, time of incubation, qualitative ionic composition of the medium, concentration of chromatin, ATP, dNTP, MgCl2, NaCl. Michaelis constants for TTP are equal to 1 mM for template-independent synthesis and 3 mM for template-dependent synthesis. At optimal conditions DNA  of chromatin is lengthened by 8 X 10--3% as the result of template-dependent synthesis and by 1 X 10--3% as the result of template-independent. The transition from nuclei to chromatin as well as the purification of chromatin from nuclear membranes enhance the rate of unscheduled synthesis. On the other hand, addition of nucleoplasm or cell extract to the chromatin does not considerably influence the synthesis. So it is suggested that the enzymes of initiation and elongation of unscheduled DNA synthesis are concentrated in the chromatin. The plausible role of unscheduled synthesis in excision and postreplication repair of eukaryotic DNA is discussed.


[Polarity of the environment as a factor determining DNA conformation]. Polarity of double and ternary water-nonelectrolyte systems at the component ratio, corresponding to a half-transition point of DNA from B to A form was evaluated from ESR spectra of a spin-probe. In all cases examined the isotropic super-fine splitting constant (aN) is the same with an accuracy of 0.05 gauss. Small differences in aN are well correlated with the concentration of the groups which are able to form hydrogen bonds with the nitroxide fragment of the radical. Thus, media polarity is a factor which determines the A--B equilibrium of DNA in solution.


Serum high-density-lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins. To determine the associations between high-density-lipoprotein cholesterol levels and use of oral contraceptives or of noncontraceptive estrogens and progestins we analyzed the serum levels of this lipid in 4978 women, 21 to 62 years of age. In estrogen users, the mean level was 6.7 to 15.1 mg per deciliter above the nonuser level (P less than 0.001), whereas in a group of progestin users it was 15.8 mg per deciliter below (P less than 0.001). In women using combination oral contraceptives, the level varied with the type and dose of the component steroids, in general increasing with increasing dose of estrogen and decreasing with increasing dose or potency of progestin. Thus, the net effect of use of a combination oral contraceptive on high-density-lipoprotein cholesterol depends on its formulation.


Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response. We investigated immunologic mechanisms and the role of complement in the pathogenesis of Argentine hemorrhagic fever, a disease caused by the Junin virus, a member of the arenavirus group. Total serum complement activity was reduced to 68 per cent of control values in patients with severe or moderate disease (P less than 0.001). C2, C3 and C5 values were also low (12 to 60 per cent) during the early acute period of the disease. However, serum C4 content was increased to 160 per cent of the control values in the same patients. Total complement activity returned to normal with clinical and laboratory recovery, at the time of detection of antibodies against Junin virus. C1q reactive material was found in four of 19 cases and no relation to the evolution of the disease could be established. These results suggest that immune complexes are not important in the pathogenesis of Argentine hemorrhagic fever, but that activation of the complement system has a role.


Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule. Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma.


Alterations in the surface properties of cells responsive to nerve growth factor. An initial effect of nerve growth factor on a responsive nerve cell line is to increase intracellular cyclic AMP, which in turn leads to a mobilisation of calcium ions. These events are correlated with structural changes in the plasma membrane, increased cell-substratum adhesion, and neurite outgrowth.


Diethylstilbestrol potentiation of the dopamine-elicited formation of adenosine 3',5'-monophosphate in incubated male rat hypothalamus. Dopamine (DA) stimulates the cAMP-generating system in the male rat hypothalamus only to a very low extent (25% above control). Diethylstilbestrol (DES), a synthetic estrogen, was found to be extremely potent (a 4- and 16-fold stimulation at 20 micron and 100 micron, respectively). Addition of either one to an incubation medium containing varying concentrations of the other resulted in a synergistic response. The potentiation by 20 micron DES of the effect elicited by 100 micron DA was the most remarkable, namely, a 3-fold stimulation of the combined response. A 4- and 7.5-fold stimulation of cAMP accumulation was observed when adenosine (100 micron) or adenosine (100 micron) + DA (100 micron) were present in the incubation medium. Theophylline (0.5 mM), an adenosine antagonist, could effectively reduce this effect, as did adenosine deaminase (10 microgram/ml). Clomiphene (50 micron), an estrogen antagonist, exhibited a marked decrease in DES + DA-elicited cAMP formation. Pimozide (40 micron) had the ability to significantly block the stimulatory effects of DES and DA.


Demonstration in human atrial preparations of alpha-adrenoceptors mediating positive inotropic effects. In isolated, electrically driven right auricular strips of the human heart the inotropic effect of phenylephrine was studied. 1. First, the influence of the driving rate on the tension developed (i.e., the frequency-force relationship) was determined by stimulation of the preparations at 0.1, 0.5, 1, 2 and 3 HZ. The force of contraction was lowest at a stimulation rate of 0.1 HZ (36.9 g/g dry weight). The maximally developed force of contraction observed at frequencies of 0.5, 1 and 2 HZ amounted to about 200 g/g dry weight. The values did not significantly differ from each other. 2. The negative log of the EC50 (-log EC50) for the positive inotropic effect of phenylephrine determined at a frequency of 0.5 and 1.0 HZ amounted to 5.28 +/- 0.08 and 5.34 +/- 0.11, respectively. The alpha-adrenolytic drug phentolamine (3 x 10(-6) M) diminished significantly the -log EC50 to 5.01 +/- 0.04 and 4.89 +/- 0.10, respectively. 3. At a frequency of 1 HZ a shift of the concentration-response curve to the right was observed after treatment with the beta-adrenolytic drug pindolol (3 x 10(-8) M); the -log EC50 of phenylephrine decreased significantly to 4.08 +/- 0.07. 4. From these results it is concluded that alpha-adrenoceptors are present in human atria; they mediate positive inotropic effects and are stimulated by phenylephrine.


Decreased cAMP content of the hypothalamus of genetically hypertensive rats. In genetically hypertensive rats an altered catecholamine content of hypothalamic structures has been reported. In the present study cAMP was estimated in the hypothalamus and cortex of genetically hypertensive rats and compared with normotensive controls of the same strain. It is shown, that the cAMP content of the hypothalamus of the hypertensive animals was decreased to about 60% of control values, whereas there was no difference of the cAMP content in the cortical regions of the same animals. These results indicate an alteration of the adenyl cyclase-cAMP-phosphodiesterase system in hypothalamic structures of genetically hypertensive rats.


Possible role of the proximal convoluted tubules of human kidney in chronic glomerulonephritis. A quantitative electron-microscopic study. The amount of forming pinocytic (coated) microvesicles on the apical plasma membrane of kidney proximal tubule cells was assessed in kidney biopsies of 10 patients suffering from chronic glomerulonephritis. A significant correlation was found between the amount of these vesicles and diurnal proteinuria levels (r = 0.889; p less than 0.01). The possible mechanisms of protein reabsorption via pinocytosis in both normal and pathological conditions are considered.


Susceptibility of human embryonic kidneys in organ culture to herpesvirus hominis. 101 pairs of human embryonic kidneys of 5-12 weeks' gestation were maintained in whole organ culture by our previously described technique, with herpesvirus hominis types1 and 2 added to our regular media. One kidney of each pair served as a control and was exposed to identical culture medium without virus. Cultures were maintained for 24-120 h to study the time sequence of viral infectivity. Organs were then examined for the presence of virus by electron microscopy and histochemical staining. Histological studies of virus-infected kidneys showed either (1) complete organ death or (2) virus localization in undifferentiated cells, plus disorganization of architecture in differentiated areas. Control organs showed normal organization.


[Triple contrast ventriculography using air-lipiodol-dimer]. A mixture of three contrast media - air, Lipiodol and Dimer - was used in ventriculography in order to combine the advantages of each of them. Air is used for topographical localisation, Dimer shows the overall shape of the ventricular system and Lipiodol outlines blocks. This simple and rapid technique provides easily interpretable films, whatever the indication for the ventriculography.


[The nature of crystals in plasma cells present in a case of apparently benign biclonal gammapathy]. A 77 years old white man presents, in his blood serum, a moderate gammapathy with 2 monoclonal peaks, IgAk and IgGlambda, and in his urine a little quantity of BJk, without any clinical or radiological manifestation. The sternal bone marrow showed 3-5% plasmacells, mostly containing many needlelike inclusions in the cytoplasm. These inclusions, red-violet at the May-Grünwald-Giemsa, were PAS and Sudan negative; positive at the Danielli reaction (for proteins). The alpha-naphtil-acetate-esterase and the acid phosphatase were present in one outer layer of the inclusions; ATP-ase was absent. At the electron microscopy, the inclusions were localized outside the rough endoplasmic reticulum; they exhibited a crystalline structure and were surrounded by an envelope which reminded the lysosomes. Basing on the morphological pattern, as well as on the presence of some lysosomal enzymes and on the lack of staining of crystals with fluorescinated anti-Ig sera, the hypothesis is stressed of an abnormal lysosomal hyperactivity, possibly leading to crystallization of the enzymatic proteins in the lysosomes.


[Calcitonin, gastrin, parathyroid hormone and the autonomic nervous system]. Stimulation of the beta-adrenergic terminations was employed to determine whether calcitonin-secreting thyroid C cells are derived from the neural crest. Calcitonin secretion was increased, whereas parathormone, insulin and gastrin values were not significantly changed. In addition, administration of a beta-blocking drug before ethanol led to a marked fall in calcitonin with respect to the baseline. Once again, other hormone levels were not affected.


[Behavior of total lipids, cholesterol, lipoproteins and apolipoprotein A in the blood of subjects with acute hepatitis and chronic hepatopathy]. Serum total lipids, lipoprotein cholesterol, apolipoprotein A (Apo A) and liver function parameters have been investigated in patients with acute viral hepatitis and chronic liver disease. Hypertriglyceridaemia, absence of alpha and pre beta bands on the lipoprotein electrophoresis pattern, low level of Apo A, presence of abnormal lipoproteins (beta-VLDL and beta2-LP) were observed in the early phase of acute hepatitis. A positive correlation was found between Apo A and triglyceride bile acids, log total bilirubin, log SGPT. Lipoprotein abnormalities are probably due to low lecitin-cholesterol aciltransferasi activity. The reappearance of alpha lipoprotein and the increase of Apo A are sensitive indices of improvement of liver function. In chronic liver disease the levels of cholesterol and Apo A correlate with changes in the hepatocellular function.


Replacement estrogen therapy for menopausal vasomotor flushes. Comparison of quinestrol and conjugated estrogens. Quinestrol, conjugated estrogens, or placebo was used to treat 156 patients with pernicious vasomotor instability in a prospective, double-blind, randomized, multiinvestigator trial. Vasomotor flushes were severe in approximately 80% of the cases and moderate in 20%, relatively equally distributed among the various drug groups. Both qinestrol and conjugated estrogens were significantly more effective than placebo in relieving vasomotor symptoms (by chi2 analysis, P less than or equal to 0.05). Greatest improvement was seen in the group receiving the higher once weekly quinestrol dosage of 0.2 mg followed by the group on the lower quinestrol dosage of 0.1 mg once weekly and the group on conjugated estrogens, 1.25 mg daily for 21 days on and 7 days off. No significant difference in relief of vasomotor flushes was shown between the active drug groups. No drug-related complications or side reactions of significance occurred. The results indicate that once weekly quinestrol is effective in relieving the vasomotor symptoms of the menopause. Either of two once weekly quinestrol regimens is an effective as conjugated estrogens given daily in a cyclic manner and therefore offers an alternative form of exogenous estrogen therapy.


Relation of herpesvirus hominis type II to carcinoma of the cervix. An animal model for the induction of long-term latency of herpesvirus hominis type II. Proof of latency of herpesvirus hominis type II (HVH-II) following acute vaginocervical infection must be validated if it is to be considered an etiologic factor in carcinoma of the cervix. An animal model is presented which demonstrates acute HVH-II vaginocervical infection. Following the primary acute infection, animals maintained for an equivalent of 60 human years display persistance of the herpesvirus in the pelvic sensory ganglia. Evidence of the specificity of HVH-II as the infectious agent is presented.


Sheep erythrocyte and bluetongue virus antibody responses of spleen cell cultures from mice. The optimum conditions for the culture of cells from dissociated spleens were determined. Routinely, 10(7) cells were seeded per ml of RPMI 1640 medium supplemented with 20% pre-tested foetal calf serum. For the assay of the immune response, cultures were supplemented with 30 muMolar mercaptoethanol. The immune responses to sheep erythrocyte and bluetongue virus antigens were determined by the haemolytic plaque-forming cell assays described by Oellermann (1974) and Oellermann, Carter & Marx (1976a). The optimum sheep erythrocyte antigen concentration was 2 X 10(6) erythrocytes per 10(7) spleen cells and maximum IgM plaque-forming cells were detected after 4 days in culture. Successful stimulation of the immune response to bluetongue virus was achieved in spleen cell cultures from mice previously primed with bluetongue virus. The optimum antigen concentration was 30-40 ng bluetongue virus per 10(7) spleen cells and the maximum plaque-forming cell response was observed after 4 days in culture.


Predicting adult stature without skeletal age and without paternal data. The RWT method for predicting adult stature from childhood variables uses the current recumbent length and weight of the child, the stature of each parent, and the skeletal age of the child as predictor variables. There is only a small increase in the errors of prediction if population mean values are substituted in the prediction equations when the father's stature, the skeletal age of the child, or both these variables are unknown. This modified method is more generally applicable than the original RWT method.


Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion. The triad of aniridia, ambiguous genitalia, and mental retardation (AGR triad) is the characteristic clinical feature of three unrelated patients with previously unreported chromosome 11 short arm interstitial deletions. A Wilms' tumor in one patient establishes one cause for the aniridia-Wilms' tumor association. The genetic heterogeneity of aniridia, the AGR triad, and Wilms' tumor are demonstrated, and Wilms' tumor is indicated to be a neoplastic birth defect which can result from a variety of embryologic insults, some of which may be chromosomal or heritable.


Field dependence and the effect of REM deprivation on thirst. Recently a number of studies have concerned the possible function of rapid eye movement (REM) sleep and the mastery of stress. The present study was designed to explore the possibility that REM sleep might play a function in reducing the potency of a stressful physiological stimulus, thirst, as well as the possibility that such a function might be specific to individuals falling at different points along the field-dependence dimension. While there was no difference between REM deprivation and non-REM awakening nights in subsequent morning thirst, there was a significant interaction between field dependence and night on morning thirst measures for 10 college students. These results are discussed in light of previous work on stylistic differences in dreaming and their possible role in adaptation to stress.


[Whited Addison's disease. Eight cases (author's transl)]. In 8 cases of Addison's disease due to adrenal tuberculosis, the substitutive treatment appeared unnecessary since more than one year. Urinary 17-OHCS were in the normal range but did not rise after ACTH injection except in two cases. In all the cases, plasma ACTH was elevated but lower than in severe adrenal insufficiency, and in the range of those observed in congenital adrenal hyperplasia. The nycthemeral variation of plasma ACTH were maintained. Therefore, an apparently normal basal cortico-adrenal function was obtained by an excessive stimulation by endogenous ACTH. The one year prescription of anti-tuberculosis chimiotherapy to 6 of these patients was possibly responsible for the partial reversal of adrenal insufficiency. However the substutive therapy appears needless in every day life, such a treatment would eventually be necessary during stress conditions.


Testing blood plasma from cattle in leukosos-free herds for antibodies against bovine leukemia virus (BLV). As a prelude to the introduction of serological methods in the Danish leukosis eradication programme, an examination for antibody to Bovine Leukemia Virus (BLV) was carried out in 215 randomly selected leukosis-free herds in three areas where 3 routine haematological screening tests had bee made over a period of 6 years. A gel diffusion test was applied to plasma samples. Of 3319 animals screened, none were found to have detectable levels of antibody to BLV in their plasma. This would seem to indicate that false positive reactions are not a serious problem in connection with this test, and also that herds classified as leukosis-free after a series of haematological herd tests carried out within a period of some years, are in fact free from infection with Bovine Leukemia Virus.


Persistence of infection with infectious bovine rhinotracheitis virus in Danish cattle herds. The later course of IBR virus infections in 11 dairy herds in endemic areas and in an imported beef herd is described. In 2 herds the infection was limited to those animals which developed a genital infection after insemination with semen from an infected AI centre. In two other herds where genital infection was observed clinically a spreading occurred, probably because of carelessness in clinical examinations, although the possibility of an additional spreading by the respiratory route had to be considered, too. In one herd signs of a respiratory disorder were noticed and assumed to have been caused directly by IBR virus. In the other 7 herds a spreading by the respiratory route was evidenced serologically. In some of these herds there were no indications of spreading after the extensive initial spreading, while in others there were single cases of infection later on, in particular in one small herd where the ventilation was inadequate.


RNA:DNA hybrids are more stable than DNA:DNA duplexes in concentrated perchlorate and trichloroacetate solutions. Rates of formation of RNA:DNA hybrids have been measured as a function of temperature and compared to DNA:RNA duplex denaturation temperatures in 4 M sodium perchlorate, 4 M NaClO4-6 M urea, and 3 M rubidium trichloracetate solvents. The usual bell shaped curves of reaction rate versus temperature were observed. The optimal temperatures for the RNA:DNA association reaction are 5 degrees to 12 degrees greater than the Tm's for DNA:DNA denaturation in these solvents, just as in formamide. R-loops of phi80d3ilv DNA with E. coli rRNA can be formed at high efficiency in these solvents.


DNA polymerase alpha is associated with replicating SV40 nucleoprotein complexes. Simian virus 40 (SV40) nucleoprotein complexes were extracted from nuclei of infected monkey cells and fractionated on neutral sucrose density gradients. Complexes which contained replicating SV40 DNA (95S) separated well from those containing closed circular supercoiled viral DNA (75S). DNA polymerase activity was associated with the replicating nucleoprotein complexes but not with the slower sedimenting complexes. This DNA polymerase activity coprecipitated with the nucleoprotein complexes in the presence of MgCl2 and remained associated with the 95S complexes. This DNA polymerase activity has been identified as primarily DNA polymerase alpha on the basis of its sedimentation behavior, optimum salt concentration, and sensitivity to N-ethylmaleimide. DNA polymerase gamma activity was also detected in the complexes, but DNA polymerase beta was not associated with the complexes.


[Distribution of Cl. perfringens in preserved food and the lecithinase activity of isolated strains]. This is a study of 414 different foodstuff types for Cl. perfringens presence determination. Of the meat products are with the highest contamination - 32 per cent, next ranking seasoning spices ond condiments, and auxiliary materials - 10.9 per cent. In milk, dairy and confectionary products it is isolated in 3.8 per cent of samples, while in tinned foodstuffs - in 1.8 per cent. Lecithinase production of the isolated strains in Kitt-Tarozi bouillon, Following 18-20 hour-long cultivation at 37 degrees C is studied, and dosed within limits ranging from 5 to 100 DMO. In meat food - pork in its own sauce, the development and lecithinase activity of some strains with different doses lecithinase in the enriching bouillon is studied after cultivation of the same at room temperature for 18-20 hours. Under the conditions outlined it is established that the growth of the strains is analogical to that of the bouillon, whilst their lecithinase activity shows a several-fold increase, and is dependent on the individual characteristics of the strains, and on their adaptive properties. The produced quantity of lecithinase does not affect the toxicity of strains upon oral infection of the animals experimented.


[Methods of taking alcohol samples on solid adsorbents]. The effect of silicagel porosity on the adsorptional and desorptional qualities of alcohol is investigated in the course of detecting alcohols in the working environment air. Large porous silicagels, inured at 600 degrees, yield optimal 95 per cent desorption water at sample stay exeeding 2 hrs. A method of taking alcohol samples from the air of the working environment, using 10 cm glass tube filled with two layers silicagel, is developed and introduced in practice.


[Surgical treatment of Wilm's tumours in children (author's transl)]. Introductory data on nephroblastoma occurence in children is followed by a general discussion on the methods of procedure used in treatment of these tumours in the last century. Then the author gives definite indices how to treat the disease surgically. In the description all groups of clinical advancement (promotion) of the neoplasm and the age of children are mentioned. The paper is supplemented by 20 Polish as well as foreign works (bibliographies).


[1 alpha-hydroxyvitamin D3: chemical synthesis and biological effect]. A method for the synthesis of an analog of vitamin D3--1alpha-hydroxy vitamin D3 (1alpha-OH D3) from cholesta-4,6-dien-3beta-ol was developed. Biological activity of this compound in the chick organism was measured. The growth stimulating effect of 1alpha-OH D3 and its effect on bone tissue mineralization and serum biochemical parameters (content of calcium, inorganic phosphorus and activity of alkaline phosphatase) were 4--5 times higher than those of vitamin D3 in low doses (19.5--39 pmole/day). In chicks given 1alpha-OH D3 at doses of 39--195 pmole/day most biochemical parameters reached plateau typical of chicks adequately provided with vitamin D. A peculiar feature of 1alpha-OH D3 was a rapid response of the chick organism to/low doses.  As early as one hour after intramuscular injection of 650 pmole of 1alpha-OH D3 to D-avitaminotic chicks, the content of calcium-bound protein in the intestinal mucosa and active transport of calcium ions in the inverted intestinal sac increased drastically. It was demonstrated that 1alpha-OH D3 showed antirachitic action, when the physiological reaction to vitamin D3 was inhibited by dietary strontium.


Conformationally restricted bicyclic analogs of somatostatin. A model for a biologically active conformation of somatostatin is proposed. This model is based primarily on the biological results obtained with novel bicyclic somatostatin analogs having a covalent bridge replacing the side chains of residues 5 and 10, 6 and 11, and 5 and 12, respectively, rather than on physical measurements on the hormone in solution. The high activity of an analog in which Phe6 and Phe11 are replaced by cystine provides evidence that these phenylalanines stabilize the biologically active conformer through "hydrophobic bonding" but do not directly interact with the receptor. The synthesis of the novel bicyclic analogs of somatostatin and the effects of these on the inhibition of secretion of insulin, glucagon, growth hormone, and gastric acid are described.


Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Treatment of pigeon erythrocyte membranes with cholera toxin and NAD(+) enhanced the GTP stimulation and suppressed the F(-) activation of the adenylate cylase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. In the presence of NAD(+) labeled with (32)P in the AMP moiety the toxin catalyzed the covalent incorporation of radioactivity into membrane proteins with molecular weights (M(r)s) of 200,000, 86,000, and 42,000. Extraction of toxin-treated membranes with Lubrol PX followed by affinity chromatography on a GTP-Sepharose column resulted in a 200-fold purification of the 42,000-M(r) labeled protein and in its complete separation from the other labeled proteins. The fraction containing the purified GTP-binding component from toxin-treated membranes conferred an enhanced GTP-stimulated activity on adenylate cyclase solubilized from nontreated membranes. Likewise, the addition of GTP-binding fraction from nontreated membranes to an enzyme solubilized from toxin-treated membranes restored F(-) stimulation of the adenylate cyclase. The toxin-induced modification of adenylate cyclase and the incorporation of radioactivity into the 42,000-M(r) protein were partially reversed upon incubation with toxin and nicotinamide at pH 6.1. The results indicate that cholera toxin affects the adenylate cyclase system by catalyzing an ADP-ribosylation of the 42,000-M(r) component bearing the guanyl nucleotide regulatory site.


Epinephrine-induced elevation of guanosine 3':5'-cyclic monophosphate in isolated fat cells of rat. The effects of epinephrine (as low as 0.1 muM) on guanosine 3':5'-cyclic monophosphate (cGMP) and adenosine 3':5'-cyclic monophosphate (cAMP) in isolated fat cells were examined. Epinephrine increased both cGMP and cAMP levels, with the elevation of cAMP preceding the rise of cGMP. Maximal elevation was obtained with 1 muM epinephrine for each nucleotide. The increase in content of cGMP and cAMP due to epinephrine was completely blocked by a beta-adrenergic antagonist (5 muM propranolol). Phentolamine (10-100 muM), an alpha-adrenergic antagonist, enhanced the response to epinephrine resulting in elevation of cAMP levels, whereas a high concentration (100 muM) of phentolamine suppressed the elevation of cGMP. The ability of epinephrine to increase cGMP and cAMP levels was markedly diminished by "feedback regulator" partially purified from the incubation mixtures of isolated fat cells exposed to epinephrine [Ho, R.J. & Sutherland, E. W. (1971) J. Biol. Chem. 246, 6822-6827], whereas an increase in cGMP, but not cAMP, levels was observed in isolated fat cells incubated with "feedback regulator" alone (without epinephrine). These observations suggest the possibility that the epinephrine-induced elevation of cGMP levels in isolated fat cells might be mediated by an increase in formation of intracellular "feedback regulator" due to an elevation of cAMP by epinephrine.


The "sarcoma-specific" region of Moloney murine sarcoma virus 124. Labeled, purified 30S RNA from Moloney murine sarcoma virus was annealed to an excess of Moloney murine leukemia virus complementary DNA. Upon treatment of the resulting DNA.RNA hybrids with RNase H followed by sucrose gradient sedimentation, and undigested 18S RNA molecule was recovered. This RNA molecule was shown to represent the "sarcoma-specific" region of the virus. The unintegrated linear DNA provirus of murine sarcoma virus 124 was isolated from newly infected cells and a physical map of the sarcoma-specific region was obtained. First, unintegrated full-length linear proviral DNA molecules were cleaved by several restriction endonucleases. The reciprocal position and orientation with respect to the viral RNA of the resulting fragments were established. The location of the sarcoma-specific region was determined by competition-hybridization with 125I-labeled viral genomic RNAs and proviral DNA fragments. A 1500-base-pair fragment was obtained by cleavage with HindIII + Bgl II. This fragment mapped between 750 and 2250 base pairs from the right end of the proviral DNA (corresponding th the 3' terminus of the viral RNA) and contained the whole set of the sarcoma-specific information. This murine sarcoma virus proviral restriction fragment is approximately of the same size and map position as the isolated 18S sarcoma-specific RNA.


Amino-terminal amino acid sequence of the major structural polypeptides of avian retroviruses: sequence homology between reticuloendotheliosis virus p30 and p30s of mammalian retroviruses. The major structural polypeptides, p30 of reticuloendotheliosis virus (REV) (strain T) and p27 of avian sarcoma virus B77, have been compared with regard to amino acid composition. NH2-terminal amino acid sequence, and immunological crossreactions. The amino acid composition of the two polypeptides is distinct, and a comparison of the first 30 NH2-terminal amino acids of REV p30 with that for the first 25 of B77 p27 yields only three homologous residues. In competition radioimmunoassays the polypeptides show no crossreactivity. A comparison of the amino acid composition and NH2-terminal amino acid sequence of REV p30 with those reported for several mammalian retrovirus p30s shows remarkable similarities. Both REV and mammalian p30s contain a large number of polar residues in their amino acid composition and show approximately 40% homology in the first 30 NH2-terminal amino acids. No crossreactivity could be observed, however, in competition radioimmunoassays between Rauscher murine leukemia virus p30 and that of REV. The observations reported here suggest a close evolutionary relationship between REV and the mammalian retroviruses.


Inhibition of translation by poliovirus: inactivation of a specific initiation factor. Translation of vesicular stomatitis virus (VSV) mRNA, like host mRNA translation, is inhibited in cells infected with poliovirus. To study the mechanism of poliovirus-induced inhibition of protein synthesis, we prepared extracts from poliovirus-infected and uninfected HeLa cells. Poliovirus mRNA was translated in lysates from both infected and uninfected cells, while VSV mRNA was translated only in the lysate from uninfected cells. Addition of purified translation initiation factors to the extract from infected cells showed that one factor, eIF-4B, could restore VSV mRNA translation in the infected lysate, but did not increase poliovirus mRNA translation. Further experiments involving translation of VSV mRNA in mixed extracts from poliovirus-infected and uninfected cells showed (i) that there was not an excess of an inhibitor of VSV mRNA translation in the infected lysate, but (ii) that an acitivity that caused a slow inactivation of eIF-4B was present in the infected lysate. Inactivation of eIF-4B appears to be the mechanism by which poliovirus infection causes a selective inhibition of translation.


Purification of the fusion protein of Sendai virus: analysis of the NH2-terminal sequence generated during precursor activation. The two glycoproteins of Sendai virus, the hemagglutinin-neuraminidase and the fusion protein (F), were separated and purified by affinity chromatography on a Lens culinaris lectin-Sepharose column. F was shown to consist of two disulfide-bonded glycopolypeptide chains, F1 and F2, of molecular weights 51,000 and 11,000, each of which contained 15% carbohydrate by weight. Amino-terminal sequence analysis showed that F2 was blocked and that the hydrophobic sequence NH2-Phe-Phe-Gly-Ala-Val-Ile-Gly-Ile-Ile-Ala-Leu-Gly-Pro-Ala-Thr- was at the amino terminus of F1. This sequence shows identity at six positions with the hydrophobic amino-terminal sequence of the smaller glycopolypeptide chain, HA2, of the hemagglutinin of influenza virus. Both F1 and HA2 are formed by proteolytic cleavage of precursor glycoproteins (Fo, Sendai virus; HAo, influenza virus). Since these cleavages confer infectivity upon both Sendai and influenza viruses and the ability to induce cell-to-cell fusion upon Sendai virus, the hydrophobic NH2-terminal sequences on F1 and HA2 may play a role in fusion of viral and host-cell membranes.


Assay for early cytoplasmic effects of the src gene product of Rous sarcoma virus. When microinjected into normal fibroblasts, cytoplasmic extracts of cells transformed by Rous sarcoma virus caused dissolution of microfilament bundles. This activity was not found in extracts of normal cells. The maximum effect was seen within 30 min of injection, and the activity could still be measured after a 10-fold dilution of the cytoplasmic extracts (14 mg/ml original protein concentration). The activity was trypsin sensitive and was destroyed by boiling, but was not RNase sensitive. Protein synthesis was not required for the disruption of actin-containing stress fibers by the injected activity. Microinjected cytoplasts prepared from normal 3T3 cells also showed dissolution of microfilament bundles, indicating that the cell nucleus was not required for expression of activity. Extracts made from fibroblasts transformed by Rous sarcoma virus having a temperature-sensitive mutation in the src gene were also temperature sensitive in the microinjection assay. Thus, the activity of extracts from cells infected with src mutant virus, but not from cells infected with wild-type virus, was destroyed either by in vitro incubation of the extract at the nonpermissive temperature before injection or by incubation of recipient cells at the nonpermissive temperature after injection. We conclude that the microinjection assay can detect a cytoplasmic activity coded for by the src gene of Rous sarcoma virus and that an early direct or indirect target of the src gene product is the cytoskeleton and cell motility system. This result is discussed in relation to the hypothesis that submembranous arrays of microfilaments, microtubules, and their associated proteins interact with cell surface receptors to form a surface modulating assembly that functions as a key regulator of cell growth.


Direct evidence for 6-fold symmetry of the herpesvirus hexon capsomere. Rotational power spectrum analysis of scanning transmission electron micrographs of negatively stained herpesvirus capsids has given direct evidence for the 6-fold symmetry of the herpesvirus hexon capsomere. Individual hexons have been analyzed in situ without interference from other parts of the capsid because only one level of the capsid was in focus in the micrograph. This study found hexons to have 6-fold symmetry. The majority of the mass of each hexon subunit was seen to lie on a line connecting the centers of adjacent capsomeres. This agrees with analysis of conventional micrographs of capsid fragments, which are also presented, as well as with biochemical data and theoretical expectations.


Vasoactive intestinal peptide: a potent stimulator of adenosine 3':5'-cyclic monophosphate accumulation in gut carcinoma cell lines in culture. Vasoactive intestinal peptide (VIP) is a potent and efficient stimulator of adenosine 3':5'-cyclic monophosphate (cAMP) accumulation in a human colon carcinoma cell line, HT 29. cAMP accumulation is sensitive to a concentration of VIP as low as 3x10(-12) M. Maximum VIP-induced cAMP levels were observed with 10(-9) M VIP and are about 200 times above the basal levels. Half-maximum cAMP production was obtained at 3x10(-10) M VIP. (125)I-Labeled VIP was found to bind to HT 29 cells; this binding was competitively inhibited by concentrations of unlabeled VIP between 10(-10) and 10(-7) M. Half-maximum inhibition of binding was observed with 2x10(-9) M VIP. Secretin also stimulated cAMP accumulation in HT 29 cells, but its effectiveness was 1/1000 that of VIP. The other peptides tested at 10(-7) M, such as insulin, glucagon, bovine pancreatic polypeptide, somatostatin, octapeptide of cholecystokinin, neurotensin, and substance P, did not stimulate cAMP accumulation. Prostaglandin E(1) and catecholamines stimulated cAMP production but were 1/2.3 and 1/5.5 as efficient as VIP, respectively. Another malignant cell line from the gut, the human rectal tumor cell line HRT 18, is also sensitive to VIP. In HRT 18 cells, VIP stimulated cAMP accumulation with a maximal effect at 10(-8) M; half-maximum stimulation was observed at about 10(-9) M. These results demonstrate the presence of VIP receptors in two malignant human intestinal cell lines (HT 29 and HRT 18) in culture and provide a model for studying the action of VIP on cell proliferation.


beta-Lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant beta-endorphin. beta-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly, obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with beta-lipotropin and beta-endorphin coeluted with 125I-labeled human beta-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human beta-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of beta-endorphin and decreased concentrations of beta-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma beta-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of beta-endorphin were detectable. These data indicate the lack of significant amounts of beta-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of beta-lipotropin to beta-endorphin.


Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs. Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.


Cell fusion induced by scrapie and Creutzfeldt-Jakob virus-infected brain preparations. Cell fusion was induced by brain extracts containing the scrapie virus and the virus of Creutzfeldt-Jakob disease. The assay involved quantitation of colony-forming ability in a double selection system, strandardized against fusion induced by Sendai virus. Correlation between the logarithm of virus dilution and the hybrid colony number gave similar curves for scrapie virus and Sendai virus. Fusion induction may explain some aspects of pathogenesis in these diseases and provide a potential in vitro assay.


In vitro isolation of stable rat sarcoma viruses. A Sprague-Dawley (SD-1) rat embryo culture, at low passage level, released an endogenous ecotropic type C virus (SD-RaLV) and after about 20 further passages it underwent spontaneous transformation. The SD-RaLV, released from the transformed cells, did not cause rapid transformation of other rat embryo cells. However, when the transformed cells were repeatedly cocultivated with three different chemically transformed and serially transplanted rat tumor cell lines (sarcoma, carcinoma, and hepatoma), rapidly fibroblast-transforming "sarcoma" viruses (RaSV) were recovered after each attempt. RaSV was not recovered from one of these tumor cell lines before transplantation, nor could focus-forming virus be rescued from these same tumor cells by cocultivation with other cells releasing heterologous type C viruses. Foci were induced on normal rat kidney and several other rat embryo cell strains within 7-15 days and both productive and nonproductive NRK clones were derived. The productive clones were positive for rat specific p30 antigen and the RaSVs released were serially transmitted to other rat embryo cells. RaSV genome was rescued from the nonproductive clones by superinfection with SD-RaLV, wild rat type C virus, and several heterologous type C viruses. These observations appear to represent naturally occurring transformation-specific (src) genes being recovered in vitro in the form of stable "sarcoma" viruses. These viruses differ from the Kirsten and Harvey strains of murine sarcoma virus in that they apparently contain no MuLV sequences and are of purely rat origin.


Ultrastructural localization of gamma-aminobutyric acid receptors in the mammalian central nervous system by means of [3H]muscimol binding. This study utilizes tritiated muscimol binding and electron microscope autoradiography (Ilford L4 emulsion and phenidone development) to localize gamma-aminobutyric acid (GABA) receptor sites in the cerebellum of the rat. In the cerebellar cortex, silver grains were associated with somata and dendrites of basket and stellate cells in the molecular layer, with somata and primary and secondary dendritic shafts of Purkinje cells, axons and terminals of basket cells in the pinceau or basket, initial axonal segments and myelinated axons of Purkinje cells, and dendrites of granule and Golgi cells in the granular layer, and with somata and dendritic shafts of large and small cells in the cerebellar nuclei. These data correspond well to the light-microscope-autoradiographic observations in the cerebellum previously reported [Chan-Palay, V. (1978) Proc. Natl. Acad. Sci. 75, 1024-1028]. Label over GABA receptor sites can be localized to the plasma membranes between pre- and postsynaptic elements at synaptic junctions, of which 88.9% of the samples are axodendritic and the remaining 11.1% are axosomatic. GABA receptor sites are also found along axonal membranes of the GABA-containing basket cell within the basket surrounding Purkinje cells, where true axo-axonal synapses are rare. It is speculated that GABA receptors in the basket may suggest a possibility of the basis for synchronization, either self-inhibition or facilitation within the basket formation, or presynaptic suppression of inhibitory action of basket cell on Purkinje cell.


alpha-Bungarotoxin blocks nicotinic transmission in the avian ciliary ganglion. alpha-Bungarotoxin binds to nicotinic receptors in skeletal muscle, blocking neuromuscular transmission. Because this toxin has recently been shown to bind to chicken ciliary ganglia, an attempt has been made to determine whether it also blocks nicotinic transmission in this ganglion, alpha-Bungarotoxin (1 micrometer) completely blocked nicotinic transmission in both the ciliary and choroid neurons of chicken and pigeon ciliary ganglia. The effect of the toxin could be partially reversed by prolonged washing (2--8 hr). Incubation of ganglia with d-tubocurarine (0.1 mM) prior to the addition of alpha-bungarotoxin significantly decreased the duration of the washout period necessary to restore transmission. These results suggest that d-tubocurarine and alpha-bungarotoxin are interacting with the same receptor. Under similar conditions, alpha-bungarotoxin did not block nicotinic transmission in the rat superior cervical ganglion, in agreement with previous reports. The avian ciliary ganglion is the only vertebrate autonomic ganglion in which both alpha-bungarotoxin binding and alpha-bungarotoxin blockade of transmission have been shown to occur. This ganglion therefore provides a model system for using alpha-bungarotoxin to study neuronal nicotinic receptors.


Affinity labeling of a cell surface receptor for epidermal growth factor. The membrane receptor for epidermal growth factor (EGF) on 3T3 cells has been identified and specifically labeled radiochemically using a photoreactive derivative of EGF. Photoreactive EGF, labeled with 125I, was incubated with 3T3 cells and then photolyzed in situ to generate a nitrene capable of reacting with a wide variety of chemical bonds. Analysis of the system by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed, besides the band of EGF, only 1 other major radioactive band which migrated at approximately 190,000 daltons. This band was absent when a nonresponsive and nonbinding variant of 3T3 was used. A direct proportionality between binding activity and crosslinked complex formation was demonstrated using a variety of binding conditions. The crosslinked complex in intact cells is accessible to the action of a macromolecule like trypsin at 4 degrees, suggesting a cell surface location for this complex. Upon incubation of cells at 37 degrees, radioactivity from previously formed EGF-receptor crosslinked complex is converted by cellular action to 3 forms of mol wt less than or equal to 58,000 daltons. These are not accessible to trypsin action upon intact cells.


Effect of haemagglutinating virus of Japan on the potassium compartmentation and the membrane potential of human erythrocytes. HVJ induces release of potassium and changes in membrane potential of certain types of cells. These changes are quite dependent on incubation temperature and are inhibited by the addition of con A to cell suspensions prior to the addition of viruses.


Reduction mammaplasty with discovery of occult breast carcinoma in twins: case reports. A pair of twins is presented in whom breast carcinomas were found. A reduction mammaplasty in the first twin uncovered an occult intraductal carcinoma. Subcutaneous mastectomies were then done in both twins for identical, mirror-image lesions, The first twin subsequently required a radical mastectomy on the involved side.


Burn syndactyly.

Burn syndactyly. When the entire digital web space has been destroyed by burn scarring and there is a contracture of the volar aspect of the web as well as the dorsum, Z-plasties and skin grafts alone seldom produce a satisfactory web space. During the past 3 years, for the release of 46 contracted web spaces in 20 burned patients, we have turned a rectangular flap from the dorsal surface of the web through into an inverted-T incision in the palm. The adjacent sides of the defects have been skin grafted. In all these patients, we obtained satisfactory release of the contracture and restoration of the web space.


Cholangiographic abnormalities in patients with inflammatory bowel disease. Twenty patients with inflammatory bowel disease, abnormal liver function tests and abnormal endoscopic retrograde cholangiograms were found to have a spectrum of abnormalities affecting the intra- and extrahepatic biliary trees. The intrahepatic systems were abnormal in all patients and demonstrated ductal stenosis, ectasia, decreased arborization and major duct obstruction. The extrahepatic systems were abnormal in 75 percent of cases with stenosis, diverticula formation and mural irregularity being the most frequent abnormalities. The value of endoscopic retrograde cholangiography in this patient group is to exclude extrahepatic obstruction, establish a nonoperative diagnosis, and assist in determining the method of treatment.


Dose-time relationships and the local control of small cell carcinoma of the lung. Since 1971, 66 patients with small cell carcinoma of the lung--32 with limited and 34 with disseminated disease--have received irradiation to the primary tumor. There were 20 local failures, 90% of which were apparent within 30 weeks of the start of irradiation. Patients were treated with local irradiation only (32), irradiation plus combination chemotherapy (25), or local plus total body irradiation (9). With local irradiation alone, tumor control increased with increasing biologic dose. When chemotherapy or total body irradiation was added, doses of irradiation that were otherwise insufficient for local control proved to be effective.


Endotracheal irradiation of adenoid cystic carcinoma of the trachea. Management of advanced or recurrent primary tracheal neoplasms has been restricted to palliative external beam irradiation. A patient with recurrent adenoid cystic carcinoma of the trachea was recently treated again by combined external irradiation and endotracheal brachytherapy with iridium 192 sources; the results were dramatic without significant normal tissue toxicity. This endotracheal brachytherapy technique might be applied to tracheal tumors of different histology or more limited extent.


The air meniscus sign in sclerosing hemangioma of the lung. The air meniscus sign occurs in a number of lung conditions, including infection, benign and malignant tumors, and hematoma. Sclerosing hemangioma does not appear to have been implicated previously in this connection. Two such cases are described. Possible mechanisms of air meniscus formation and its diagnostic value in sclerosing hemangioma are discussed.


The Klippel-Trenaunay syndrome: clinical and radiological aspects. Klippel-Trenaunay syndrome (KTS) is characterized by port-wine hemangiomas, deep venous system abnormalities, superficial varicosities, and bony and soft-tissue hypertrophy. When associated with an arteriovenous fistula, it has been termed Klippel-Trenaunay-Parkes-Weber syndrome. It is imperative that both the radiologist and surgeon be aware of this entity, as incomplete evaluation and inappropriate surgery may be devastating. Radiological workup includes phlebography, angiography, and conventional radiography of the involved extremities. Surgery should be performed only to relieve deep venous obstruction (if present) or to correct inequality in the lengths of legs. Removal of superficial varicosities is contraindicated because it will worsen existing symptoms. Five cases of KTS are presented and the literature reviewed.


[Cellular hypersensitivity in the infection of mice by Junin virus. I. Passive transfer]. The data presented confirm previous evidence of delayed hypersensitivity in mice following infection with Junin virus. Adaptive transfer of sensitized cells from adult mice which had received 5 Junin virus injections into preinfected newborn mice shortened their survival by 72 hours. It was clear, however, that the development of the immunological mechanism in adult mice occurred under certain conditions. This evidence was confirmed by the observations that the induction of cell-mediated immunity and the response of sensitized lymphocytes to viral antigens appeared to be related to multiple injections of the virus. On the other hand, the sensitized cells were present in adult mice by day 9 and vanished 60 days after the infection. These results revealed the difference between the lymphoid cells from adult mice in the early and the late stages of immunity. The implications of these results in the development of the fatal neurological disease induced by the Junin virus in newborn mice are discussed.


[Cellular hypersensitivity in the infection of mice by Junin virus. III. Experience with Cr51 an antitheta serum]. Several aspects of the appearance and development of delayed hypersensitivity in mice infected with Junin virus are described. The results obtained showed that the development of the immunological mechanisms occurs irrespective of age. Spleen cells of donor mice inoculated with one i.p. dose of Junin virus had a poor cytotoxic activity, as demonstrated by 51Cr release and adoptive immunity procedures. Spleen cells treated with anti-theta serum and complement did not strikingly affect the development of Junin virus disease in mice. This demonstrated the capacity of T lymphocytes to influence the course of the viral infection of newborn mice adoptively transferred with immune spleen cells. No difference were detected in the virus titer in the brains of transferred and control animals, this fact suggests that immune T lymphocytes are not involved in Junín virus clearance.


Aldosterone regulation in anephric patients. The response of plasma aldosterone to hemodialysis, 3 h orthostatism, K-loading and angiotensin II and ACTH infusions has been studied. Hemodialysis, orthostatism and angiotensin II infusion do not modify aldosterone levels. By the contrary ACTH and potassium originate a significant increase in plasma aldosterone. They seem to be the main aldosterone secretion regulators in the absence of renin production.


Acetylcholinesterase from Wistar rat brain. Acetylcholinesterase (E.C.3.1.1.7) was partially purified from rat brains stored in toluene. Extraction was performed using buffers containing non-ionic tensoactive detergents. Some properties of the enzyme were affected by the use of different activity measurement methods, such as the short-time radiometric or the long-time colorimetric method. There were two zones of maximum activity in the range pH 7.5-8.0 and 8.0-8.6, respectively. There seems to be a histidine residue in the enzyme that participates in the catalytic process. Thermal denuration presented first order kinetics and different thermodynamic parameters were obtained on using different incubation periods. On using the short-time activity measurement method there was activation at high substrate concentration, but with the long time method there was a marked inhibition produced by excess of substrate. However, if the enzyme was extracted from fresh rat brain, toluene untreated, these differences dissapeared. Gel filtration and disc electrophoresis showed the presence of multiple and interconvertible forms of the enzyme.


[Effect of ACTH administration on liberation of testosterone by the Leydig cell (author's transl)]. The possible rôle of the Leydig cells ithe changes of testosterone levels induced by ACTH administration is studied. 14 male Wistar rats weighing about 300 g were separated in two groups. One was treated with I mU.I./100 g/day of ACTH i.m. for 6 days and the other with saline solution as control Rats, testes and adrenal glands were weighed and plasma testosterone levels were measured. The Leydig cells dispersed collagenase was inbubated for 120 min at 37 degrees C in the presence and in the absence of 10 mU.I. of HCG. The weight of adrenal glands in the treated rats was greater than in the control group. Treated rats had lower plasma values than the controls. Testosterone secretion by the Leydig cells, in basal situation and after stimulation with HCG, was lower in the treated group. Leydig cells of untreated rats were incubated with 12.5, 6.2, 3.1, 1.5 mU.I. of ACTH and supplemented with 2.5 pU.I. of HCG. No difference in testosterone secretion in either groups was observed.


[The E.E.G. and E.M.G. findings in sudanophilic leucodystrophy (author's transl)]. Four patients with infantile familial sudanophilic leucodystrophy confirmed histologically and biochemically were investigated by E.E.G. and E.M.G. The E.E.G. showed a severe, non-specific slow wave abnormality, of moderate voltage and disorganized in 2 cases, with some critical' tonic' discharge. E.M.G. study was normal in relaxed muscle; peripheral nerve stimulation, however, revealed marked slowing of motor conduction velocities favouring a segmental demyelinisation process, which was ultimately confirmed histologically. This study underlines the value of investigation of infantile encephalopathies.


Lack of tumor-promoting ability of certain environmental chemicals in a two-stage mouse skin tumorigenesis assay. The food antioxidants butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) were tested as tumor promoters on CD1 female mice initiated with 7, 12-dimethylbenz(a)anthracene (DMBA). At a dose of 1 mg twice weekly they did not promote skin tumors. Nor did they produce tumors when tested as a complete carcinogen without DMBA initiation. The polychlorinated biphenyl Aroclor 1254 (PCB) and the polybrominated biphenyl Firemaster-6 (PBB) were also tested for their ability to promote skin tumors; at a 100 microgram dose twice weekly they were inactive. The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a dose of 0.1 microgram twice weekly did not promote skin tumors in DMBA-initiated mice. TCDD, PCB, and PBB did not promote spontaneous tumors. None of the compounds at the dosages tested significantly increased the intrafollicular epidermis, nor did they appear to be chronically toxic to the test animals. These results indicate that dosage may be an important factor in promotion, since several of the tested compounds are known to be promoters in pulmonary and hepatic systems.


Influence of bile acids and free fatty acids on physicochemical properties of LP-X. In this study it is demonstrated, that incubation of both, bile acids and free fatty acids with LP-X, the abnormal plasmalipoprotein found in patients suffering from cholestasis or LCAT-deficiency, results in striking alterations of the physico-chemical and immunological properties of LP-X: 1. The cathodic mobility in agar is changed into an anodic mairation of the material. 2. The unique appearance of LP-X on electronmicrographs is altered by the incubation revealing fingerprint like structures. 3. The albumin portion of LP-X becomes immunologically detectable. 4. Bile salts cause marked changes in the hydrated density of the material as determined by zonal ultracentrifugation. 5. In vitro incubation of LP-X with postheparin plasma causes a complete disappearance of LP-X as judged by its typical migration on agar electrophoresis. All these alterations can be prevented or reversed by the addition of albumin in appropriate concentrations. These findinga are important in the light of studies designed to investigate the catabolic action of plasma lipolytic enzymes on LP-X, as well as for follow up studies of LP-X concentrations during the course of disease.


Hydrogen sulfide: effects on avian respiratory control and intrapulmonary CO2 receptors. The respiratory response to acute inhalation of hydrogen sulfide (H2S) and the response of pulmonary CO2 receptors to this gas were studied in male White Leghorn chickens. Inhaling low concentrations of H2S (0.05%) for 30 min had no effect on ventilation, but respiratory frequency and tidal volume became irregular and variable in birds that inhaled 0.2% and 0.3% H2S for that period. All birds that inhaled 0.4% H2S died within 15 min. H2S, presented in the gas stream of unidirectionally ventilated birds, caused an increase in the discharge frequency of intrapulmonary CO2 receptors and an increase in the amplitude of sternal movements. Because an increase in the discharge of these receptors normally inhibits the central respiratory neurons and may lead to apnea, it is clear that H2S also has actions that increase the output from these central neurons. The possibility that H2S affects the intrapulmonary CO2 receptors by inhibiting carbonic anhydrase in them is discussed.


Harvesting of granulocytes for transfusion therapy by haemonetics 30. Yield, morphology and in vitro functions of collected granulocytes. By means of a Haemonetics 30 blood cell separator white blood cells (WBC) were collected for transfusion purposes from 21 normal unstimulated donors. Citrated Hydroxyethyl Starch (HES) was used as anticoagulant. A mean yield of 1.13 x 10(10) WBC was obtained in 2 1/2-3 h. Half of the collected WBC were PMN cells containing a few per cent band forms, the other half lymphocytes and monocytes (12%). No shift in the distribution of WBC was found during the leucapheresis. Light and electron microscopy did not reveal any damage or changes in the structure of the processed granulocytes. The Trypan blue exclusion test showed 99% vital cells. In vitro assessment of the chemotactic and bactericidal activity of the collected granulocytes showed normal function. Also the content of myeloperoxidase was within normal range.


[Changes in the monosynaptic reflex during wakefulness and sleep of children with cerebral paralysis]. Changes of the H reflex during sleep were studied in 13 children with cerebral palsy (8 with spastic tetraplegia, 2 with a mixed form of cerebral palsy without spasticity, 3 with hypotonic diplegia or tetraplegia). These modifications were compared with those of 5 normal children of the same age. During repeated night recordings, responses in the calf muscle elicited by electrical stimuli to the posterior tibial nerve were studied at the same time as the EEG, EOG and EMG of the mental muscles. The results show that:--in normal children the max H reflex progressively decreases in amplitude from wakefulness to REM sleep; -- in spastic patients there is only a slight decrease in the H reflex in NREM sleep and no significant change in REM sleep; the amplitude of the H reflex is always greater than that in the control group; -- in the dystonic and hypotonic group the results obtained are similar to those of the control group. From these results one may draw the conclusion that in spastic patients as opposed to the control, dystonic and hypotonic groups, normal balance between the function of supraspinal systems regulating the amplitude of the spinal reflexes is alterated probably through the scarce functionality of the supraspinal inhibitory structures.


Demonstration of electrophoretically restricted virus-specific antibodies in serum and cerebrospinal fluid by imprint electroimmunofixation. A sensitive technique for the electrophoretic characterization of virus-specific antibodies is described. Electrophoretically separated Ig is allowed to diffuse into a virus-antigen containing gel. The antibodies bound to viral antigen are then demonstrated by 125I-labelled rabbit antihuman Ig and autoradiography. Electrophoretically restricted antibodies against measles, rubella, mumps or herpes simplex viruses were demonstrated in some normal sera. The antibody patterns of normal cerebrospinal fluids (CSF) closely resembled those of the matching sera. A selective increase of oligoclonal antibodies was demonstrated in CSF from patients with infection of the central nervous system (CNS) caused by any of the four viruses. We propose that the method may be used to demonstrate local synthesis in the CNS of antibodies against viral or other antigens.


[Primary hyperparthyroidism. Analysis of 152 patients with special reference to acute life threatening complications (acute hyperparathyroidism)]. The findings of 152 patients with proven primary hyperparathyroidism are reportedmthe purpose of the analysis was to find difference between the various clinical manifestations of the disease. Furthermore the occurrence of acute hyperparathyroid crisis in our series as well as in the literature are described. 65.8% of the patients were females, 34.2% were males. The leading symptom in 98 patients (group I) were kidney stones and in 23 patients (group II) cystic bone disease. Both manifestations of the disease occurred in only 7 patients (group III) and no symptoms related to the kidneys or to the bones occurred in 24 patients (group IV). Because of the difference of the clinical manifestations the additional data were analyzed for each group separately and compared with each other. There was no difference in the mean serum calcium levels for all four groups, however, patients of group I were on the average younger, the duration of the disease was longer and the weight of the parathyroid adenoma was lower compared to the other three groups, Data are presented regarding calcium excretion, phosphate clearance and tubular reabsorption of phosphate for each group. At operation single or multiple adenoma formation was present in 133 patients, whereas diffuse hyperplasia was found in 17 and carcinoma in 2 other patients. 46 of the adenomas were found in an atypical anatomical localisation. This observation is responsible for the many unsuccessful or second explorations of the neck; The weight of the adenomas varied between 0.1 and 23.5 g. The most difficult diagnosis was that of diffuse hyperplasia. The sucess of the surgical intervention was usually established in over 80% of the cases within 24 to 48 hours after the operation with a significant fall of serum calcium. There ist still no definite explanation for the variability of the clinical manifestations of primary hyperparathyroidism. Parathyroid hormone determinations on larger numbers of patients are not yet published. The assumption, that different hormones or peptide fragments are reposible for the different action on bone and kidney is discussed; In our series of 152 patients acute hyperparathyroid crisis occurred eight times. Our findings are compared to the other well documented cases in the literature. Main symptoms were nausea, vomiting, abdominal pain and different states of cerebral dysfunction. Most of the patients had calcium levels over 16 mg/100 ml. Partial renal insufficiency with elevated blood urea and phosphate retention was found in over 50% of the cases. Overall mortality of all cases with acute parathyroid crisis is 52.5%. The pathogenesis of acute hyperparathyroidism and the implications of high calcium levels are discussed. According to our own experience hypercalcenia can be controlled with an intensive therapeutic program and emergency operation for acute parathyroid crisis is no longer necessary.


Heavy metals in tissues of stranded short-finned pilot whales. Selected tissues from four short-finned pilot whales that stranded at Cumberland Island National Seashore were analyzed for total cadmium, mercury and selenium by neutron activation. Cadmium reached a maximum mean wet weight concentration of 31.4 ppm in the kidney tissues. Maximum mean wet weight concentrations of mercury, 230.0 ppm, and selenium, 44.2 ppm, were found in the liver tissues. The lowest concentration of each metal was found in the blubber. Postmortem examination showed that the whales had no food in their stomachs. The whales must have been utilizing metabolic reserves, contaminated with residual concentrations of heavy metals, prior to beaching. This utilization of reserves probably resulted in the high concentrations of cadmium, mercury and selenium found in the liver and kidney tissues. Since the heavy metal concentrations were three to four times greater in the stranded whales, as compared to apparently healthy whales of the same species, it is suggested that heavy metal toxicosis may have been a factor contributing to this particular stranding.


Toxic gases from fires.

Toxic gases from fires. The major lethal factors in uncontrolled fires are toxic gases, heat, and oxygen deficiency. The predominant toxic gas is carbon monoxide, which is readily generated from the combusion of wood and other cellulosic materials. Increasing use of a variety of synthetic polymers has stimulated interest in screening tests to evaluated the toxicity of polymeric materials when thermally decomposed. As yet, this country lacks a standardized fire toxicity test protocol.


Commissural transmission: maturational changes in humans. Latency differences between ipsilateral and contralateral somatosensory evoked potentials show maturational trends in keeing with the myelogenic timetable and development of the corpus callosum. The distribution and modality-specific projection of early ipsilateral activity suggests an origin in the contralateral posterior-parietal area.


beta-Adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity. The density but not the affinity of beta-adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol. Exposing rats to light for 12 hours increased the binding of this radioligand in 3-month-old but not in 24-month-old rats. The reduced responsiveness to catecholamines seen in aging may be due to a decrease in the number of beta-adrenergic receptors which, in turn, may be caused by an impaired capacity of receptors in aged animals to adapt to changes in adrenergic neuronal input.


Investigation of electron tunneling between cytochrome c peroxidase and cytochrome c. The nature of electron transfer between the bound complex cytochrome c and cytochrome c peroxidase has been investigated. Experimental verification of the predicted charge-transfer band provides evidence of electron tunneling as the mechanism of transfer between these molecules in solution at room temperature. The measured transfer distance is congruent to 7 angstroms between heme edges, which results in a distance of congruent to 15 to 20 angstroms between iron atoms.