On the perception of some geometric properties of rotating three dimensional objects. Various observations and conjectures have been made about how we perceive three dimensional objects under monocular viewing conditions; in particular, when such objects are rotating. In this paper these proposals are reviewed and reinterpreted in the light of geometric properties of objects and their projections. Some results are also presented which support the conclusion that the visual system, in reconstructing the object from its projections, requires a fixed time to establish the objects curvature and torsion parameters. In the perceptual reconstruction process these parameters assume positive or negative values, and this equivocation is related to a form of the adjacency principle involving central projections and "perceptual geodesics".


The response of a spatially distributed neuron to white noise current injection. The depolarization of passive nerve cylinder or dendritic tree in the equivalent cylinder representation is assumed to satisfy the cable equation. We consider in detail the effects of white noise current injection at a given location for the case of sealed end boundary conditions and for an initial resting state. The depolarization at a point is a Gaussian random process but is not Markovian. Expression (infinite series) are obtained for the expectation, variance, spatial and temporal covariances of the depolarization. We examine the steady state expectation and variance and investigate how these are approached in time over the whole neuronal surface. We consider the relative contributions of various terms in the series for the expectation and variance of the depolarization at x = 0 (soma, trigger zone, recording electrode) for various positions of the input process. It is found that different numbers of terms must be taken to obtain a reasonable approximation depending on whether the stimulus is at proximal, central or distal parts of the dendritic tree. We consider briefly the interspike time problem and see in an approximate way how spatial effects are important in determining the mean time between impulses.


[Lipid regulation of carbohydrate transport system in Mycoplasma]. Cultivation of Acholeplasma laidlawii cells in media containing unsaturated fatty acids results in changes of the physiological state of the membrane lipid bilayer due to preferable incorporation of an unsaturated fatty acid into lipids. The lipids are capable to regulate the transport activity since the transport rates for glucose, 3-O-methyl-C-glucose, glucerol and erythritol change considerably when the cells are cultivated in media containing different unsaturated fatty acids. The transport activity is also affected by the length of the carbon chain, the degree of the fatty acid saturation and the presence of cholesterol. At the same time the activation energy of the transport activity also changes, which suggests that the regulation by lipids (presumably local changes of the physical properties of lipid domen) is involved in the process of the carrier association with the substrate and/or in translocation of this complex through the membrane.


[Proteinases in growth and spore formation of Bacillus thuringiensis]. Some serine proteases and leucine aminopeptidases were detected inside and outside the cells during the analysis of three crystalline and two acrystalline strains of Bac. thuringiensis var. galleriae. The data obtained on the protease formation during growth and sporulation and the level of their activity are indicative of intracellular proteases involvement in spore- and crystal formation. The enzymes isolated from the culture medium do not probably take part in these processes. The intracellular enzymes may account for the different crystal protein composition of various strains due to limited proteolysis of crystal proteins in the course of biosynthesis.


[Bacterial membrane proteins. Properties of Micrococcus lysodeikticus NADH dehydrogenase]. NADH dehydrogenase was isolated from M. lysodeikticus membranes with FAD as a prosthetic group. It was found the enzyme molecular weight is about 140000 in 0,01 M phosphate buffer, pH 7,4 in 1% Triton X-100. The enzyme molecules are dimers consisting of two subunits with molecular weight of 70000. The content of alpha-helical regions is 30%, that of beta-forms is 13%. The protein globule is cross-linked with the disulfide bonds and has hydrophobic regions on its surface.


[Primary structure of abnormal E-like hemoglobin]. An E-like abnormal hemoglobin was detected in a hematological patient and one of the members of her family. The composition of blood hemolyzates was characterized using acetate cellulose electrophoresis. The abnormal beta-chain was isolated by ion-exchange chromatography of total globin on CM-cellulose. Using peptide mapping of the abnormal beta-chain trypsin hydrolysates, it was shown that the amino acid substitution occurs in peptide beta T3. The amino acid analysis and determination of the abnormal fragment C-terminal amino acid allowed to establish the locus and type of this substitution. The first case of hemoglobin E(alpha 2 beta 2 26Glu leads to Lys) identification on the territory of the USSR is reported.


[Inhibition of succinate and NADH oxidases of submitochondrial particles by iron chelators and sulfhydryl reagents]. The inhibition of succinate- and NADH-oxidase activities of submitochondrial particles by 4,7-diphenyl-1,10-phenantroline was studied. The inhibition was shown to increase when the particles were pretreated with SH-reagents. The treatment of submitochondrial particles with ethanol in the presence of 1,10-phenantroline resulted in a complete inactivation of succinate oxidase and succinate: tetramethyl-n-phenyldiamine reductase; the succinate PMS reductase activity was only partially inhibited after such treatment. It is concluded that tetramethyl-n-phenyldiamine and phenazine metasulfate react with different sites of the succinate dehydrogenase complex. The changes in the properties of submitochondrial particles after ethanol--phenantroline treatment are apparently due to the effect of non-polar solvent rather than to the extraction of non-haem iron.


[Decarboxylation of malonyl-CoA and biosynthesis of mevalonic acid in rat liver]. Biosynthesis of mevalonic acid (MVA), total formation of 14CO2 from [1,3-14C]malonyl-CoA and the activity of malonyl-CoA decarboxylase in subcellular fractions of rat liver were studied. The dependence of the rate of MVA biosynthesis on malonyl-CoA concentration was found to be linear both in 140,000 g supernatant and solubilized microsomal fractions. It was shown that in a composite system (140,000 g supernatant fraction added to washed microsomes, 10 : 1) the optimal concentration ratio for the substrates of MVA biosynthesis (malonyl-CoA and acetyl-CoA) is 1 to 2. In the absence of acetyl-CoA decarboxylation of [1,3-14C]malonyl-CoA was prevalent. In all subcellular fractions studied decarboxylation of [1,3-14C]malonyl-CoA prevailed over its incorporation into MVA, total non-saponified lipid fraction and fatty acids. The degree of malonyl-CoA, decarboxylation was not correlated with the rate of its incorporation into MVA, i. e. the increase in the 14CO2 formation was not accompanied by stimulation of [1,3-14C]malonyl-CoA incorporation either into MVA or into total non-saponified lipid fractions. The incorporation of [1-14C]acetyl-CoA into MVA under the same conditions was considerably lower than that of [1,3-14C]malonyl-CoA. In all subcellular fractions under study the activity of malonyl-CoA decarboxylase was found. The experimental data suggest that a remarkable part of malonyl-CoA is incorporated into MVA without preliminary decarboxylation. A possible role of malonyl-CoA decarboxylase as an enzyme which protects the cell against accumulation of malonyl-CoA and its immediate metabolites -- malonate and methylmalonyl-CoA is disucssed.


[Changes in DNA methylation in alfalfa plants infected with Cuscuta and tissue differences in DNA methylation of the parasite plants]. The tissue-specific differences in the 5-methylcytosine (m5C) content in total DNA of the parasite plant Cuscuta reflexa have been found: DNA from apical parts of the plant is less methylated (m5C = 4,2 mol %) as compared to the DNA from haustoria and posthaustorial regions (m5C = 5,4 mol %). The base compositions of total DNA preparations from C. reflexa grown on various hosts are similar. The m5C amount in stem DNA of the alfalfa plant infected with C. reflexa is by approximately 25% higher than that in the non-infected plant DNA. The GC content in alfalfa DNA does not change as a result of infection. Thus, the parasite induces the hypermethylation of DNA in the host plant. It is assumed that the changes in DNA methylation induced by the parasite plant may play a regulatory role and may cause changes in transcription and replication of host DNA.


[Mechanisms of liver transketolase activation in B1-deficient rats after administration of thiamine]. Gel filtration and equilibrium dialysis demonstrated that the hyaloplasmic fraction of the liver of B1-deficient rats does not practically bind C-TDP in vitro. An addition of the excess of non-labelled coenzyme does not increase the transketolase activity. The data obtained suggest that transketolase activation in the hyaloplasmic fraction of the liver of B1-deficient rats after administration of thiamine in vivo is due to stimulation of the additional synthesis of the enzyme protein rather than to the saturation of the free apoenzyme with newly-formed TDP. In vivo and in vitro studies suggest that the hyaloplasmic fraction of the liver of B1-deficient rats contains no free apoenzyme of transketolase.


[Effects of organic solvent vapors on the protochlorophyllic complex from etiolated leaves. Conditions for reversible and irreversible destruction]. The spectral properties and the ability of etyolated leaves pigments treated with organic solvent vapours (OS) for phototransformations were studied by measuring low temperature fluorescence spectra (-196 degrees C). Under the effects of OS the fluorescence at 655 nm was gradually decreased and that at 630--640 nm was increased. The effects of OS depended on the partial pressure of OS. The ability of the pigments for phototransformations was decreased with an increase in fluorescence at 630 nm. The emission maximum of fluorescence of the pigment formed in the light was shifted by 10--18 nm towards the shortwave region. Partial reversibility of the destroying effects of diethyl ester was found. A removal of the ester vapours resulted in a relative increase of fluorescence in the etyolated leaves at 640--645 nm and a decrease of the amount of "photo-inactive" pigment. The maximum of fluorescence of the pigment formed in the light was shifted towards the long-wave region (approximately 5 nm) as compared to the leaves irradiated in the presence of the ester. Partial functional reconstitution indicates that at least part of the pigment molecules are able to form a protochlorophyllide (protochlorophyll) -- protein complex, similar to the native one.


[Activities of dehydrogenases of the pentose phosphate pathway and transketolase in transplanted mouse hepatomas with different growth rates and in organs of tumor carriers]. The activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and transketolase were studied in the cytoplasmic fractions of transplanted mouse hepatomas differing in their growth rates, and in the liver, spleen and cortical layer of kidneys of tumour carriers and normal mice. It was shown that transplantation of hepatomas changes the activity of the pentose phosphate pathway enzymes in tumour carrier tissues unaffected by neoplasm. Deviations from normalcy were mainly similar to those observed in the hepatomas. The changes in the enzymatic activities were especially well-pronounced in the mice having rapidly growing hepatomas. This may be due to a generalized effect of the tumour on the organism, which is concurrent with malignancy.


[Determination of structural differences in DNA by pyrimidine isopliths ratios]. Using a modified Burton procedure, twelve pyrimidine nucleotide isopliths of DNA from five mammalian species (human, rabbit, guinea pig, rat and cattle) were determined. A method is proposed for mathematical estimation of DNA block analysis data, revealing a correlation between the specific DNA primary structure, the systemic status of the organism under investigation and the organism's radiosensitivity. In some cases DNA structural differences as determined by pyrimidine isoplith ratios help to distinguish between families of the same mammalian order. Quantitative isoplith ratios demonstrate that ionizing radiation treatment brings about certain changes in DNA primary structure. Their direction is quite the opposite to the main trend in the changes of DNA structure in the course of biological evolution.


[Effects of alpha-tocopherol derivatives on natural quinone levels in the tissues of vitamin E deficient rats]. The effects of alpha-tocopherol and its derivatives (alpha-tocopherylquinone, its short-chained analog--alpha-tocopheronolactone--and short-chained alpha-tocopherylacetate) on the levels of ubiquinone, its cyclic isomer--ubichromenol--and vitamin E in the liver and heart of vitamin E-deficient rats were studied. After injection of alpha-tocopherol derivatives the levels of ubichromenol and ubiquinone in rat liver and heart were increased, while their ratio was decreased. alpha-Tocopheronolactone was found to exert the strongest action, which is probably due to its direct effect on ubiquinone metabolism in rat tissues.


[Lateral heterogeneity of bacterial membranes]. Isolated membranes of M. lysodeikticus were rapidly frozen and disrupted in a Hughes press. After disruption the fragments were centrifuged at 144000 g for 1 hour and part of the supernatant just above the pellet was subjected to isopycnic centrifugation in a continuous sucrose density gradient. It was found that the material tested was a mixture of fragments differing in their buoyant densities. These fragments also differed in their protein/lipid ratios, cytochrome content and dehydrogenase activities calculated per protein and lipid as well as in proportion of the respiratory chain enzymes. The results obtained are indicative of lateral heterogeneity of the bacterial membrane and the existence of areas in the membrane having high concentration of the respiratory chain enzymes. The latter may suggest that the system of substrate oxidation is segregated in the membrane. It is assumed that there exists in the membrane an exchange of components between different electron-transporting chains operated due to their lateral diffusion.


[Isolation and properties of glucose-6-phosphate dehydrogenase from human cultivated cells]. A new procedure for purification of glucose-6-phosphate dehydrogenase resulting in an electrophoretically homogenous preparation made up of 5.10(8) cells (390 mg of protein) is proposed. The enzyme yield is more than 20%. The molecular weights of a subunit and a native enzyme are 55000 and 220000, respectively. The isoelectric point for the protein lies at 4,8. The kinetics of the enzyme thermal inactivation obey the first order equation with the inactivation rate constant of 6.10(-3) min-1.


Development of a ceramic surface replacement for the hip. An experimental Sialon model. The objective of this study was to investigate the design and fixation advantages of Sialon ceramic surface replacements implanted without acrylic bone cement. The biocompatibility and friction and wear properties of Sialon ceramic were compared with more conventional prosthetic materials such as stainless steel and alumina. A functional load-bearing canine hip surface replacement model was established to test Sialon femoral cups designed for fixation by bone ingrowth. The results of the polyethylene wear tests on highly polished ceramic and stainless steel counterfaces were essentially similar. These laboratory data indicated that the in-vivo polyethylene wear performance on metal or ceramic prosthetic surfaces could be expected to be indistinguishable, i.e. the ceramic/polyethylene combination would not offer any improved wear resistance in-vivo. It was found possible to get bone ingrowth into the macrokeying areas of the ceramic femoral cups but not into the microporous surfaces due to the presence of a fibrous membrane lining their internal surfaces. The biocompatability specimens also appeared to be invested with a fibrous membrane. Further studies are under way to determine the relationship between reaming procedures, micro motion at the interfaces and Sialon biocompatibility.


Tensile strength of bone (bone/porous polyethylene) interface. An average tensile strength of 1.35 kgf/mm2 (1920 psi) was obtained. Comparison of all results with related studies on metallic and ceramic implants indicates the overall superiority of plastics as porous implants for many applications.


Uniform microporous biomaterials prepared by the Relamineform technique. The Replamineform process provides a technique for fabricating microporous ceramic, metal and polymer biomedical implant materials. A range of pore sizes can be made in the same material, thus allowing independent study of the effect of pore size and biomaterial on incorporation of implants. This new family of biomaterials shows promise for helping to determine the optimum characteristics to enhance tissue regeneration.


Evaluation of a commercial, porous stainless steel as a prosthetic implant material. In the course of evaluating various porous materials as candidates for prosthetic devices, a commercial stainless steel (316L) was found which was designed for porous filtration applications. Small bars (approximately to 3mm x 3mm x 20mm) were implanted in dog extremeties for periods of 10 to 15 weeks. The average tensile strength of the bone/(bone/metal) interface was found to be 0.975 kgf/mm2 (1380 psi) with no indication of variation with time of implantation. Scanning electron microscopy (SEM) combined with X-ray energy dispersive (XRED) analysis indicates production of calcified bone in the bone/metal composite. Inherent strength and porosity characteristic combined with biocompatbility indicate that this commercially available meterial is a viable implant candidate for attachment to the skeletal system.


Fatigue - corrosion of endoprosthesis titanium alloys. Commercial total hip prostheses often show certain metallurgical faults (porosities, coarse grains, growth dendrites, carbide networks). In order to investigate more accurately the role played by these different parameters in prostheses failure we performed a large number of systematic corrosion, fatigue and fatigue - corrosion tests on these materials and on commercial total hip prostheses. Ultimate strengthes seem to be reached for cast cobalt alloys, whereas titanium alloys, such as Ta 6 V, present very high fatigue limit under corrosion. Thus, rotative bending fatigue - corrosion tests in biological environment provide values about 50 DaN/mm2. This value, is nevertheless appreciably higher than those obtained with stellites and stainless steel. Titanium alloys, because of their mechanical performances, their weak Young's modulus (11000 DaN/mm2) and their relative lightness (4.5. g/cm3), which are associated with a good biocompatibility, seem very promising for permanent implants realisation.


Interpenetrating polymer networks for biological applications. The use of a sequential polymerization method for preparing interpenetrating polymer networks with biocomatible surfaces has been studied. A hydrogel monomer was made to undergo polymerization with simultaneous cross-link formation, in the presence of a swollen thermoplastic elastomer heterophase block copolymer. On removal of the swelling solvent, an interpenetrating network of the hydrogel and the thermoplastic elastomer was obtained, which absorbed water in the manner of a hydrogel, but had mechanical properties superior to hydrogels. The studies employed a poly(ether-urethane) block copolymer as the thermoplastic elastomer. The materials fabricated included samples in which the interpenetrating polymerization extended throughout the termoplastic elastomer as well as samples in which the interpenetrating polymerization was confined to a region near the surface of the latter.


Pre-coated orthopedic implants with bone cement. A study on the feasibility of implants pre-coated with an acrylic bone cement has been performed. Four types of implants, an actual canine femoral prosthesis, a polished steel rod (0.49 cm dia. x 13 cm long) with and without pre-coating, and a sandblasted steel rod with pre-coating were implanted into canine femurs in vitro and in vivo to evaluate the interfacial shear strengths in addition to the bench test. After serial sectioning the samples in discs, push-out tests were made to evaluate the interfacial strengths of cement-bone-implant. The weakest interfacial shear strength was exhibited by the polished rod/cement interface (0.5 MPa) while the strongest was the "old" and "new" cement interface (23.4 MPa). The bone/cement interfacial strength was in between for in vitro (1.17 MPa) and in vivo (1.68 MPa). The shear strength of rod/cement interface increased substantially by sandblasting (6.84 MPa). The microscopic observation of the interface showed somewhat smaller gaps developed for the pre-coated rod than the uncoated rod due to the shrinkage effect. In addition to the overall increase in interfacial strength, the pre-coating may furthermore reduce the setting temperature, the shrinkage, and the amount of monomer released during operation due to the reduced amount of cement at the time of implantation. The more gradual transmission of load from implant to bone and "auto-centering" of implants during operation by pre-coating, are believed to be advantageous over conventional cement fixation method.


Bone bonding through bioadhesives: present status. Until recently use of adhesives was confined to cases in which glued areas could be pre-treated or at least cleaned. Thus, grease or oil contaminated surfaces could not be joined together by glueing. More recently, some adhesives have been developed which allow previous treatment of greasy surfaces to be avoided. Among these we find epoxy resins, acrylics and polyurethances. These adhesives have been used until now in various industries. We have begun a research program with these products and in aiming to design an adhesive which would enable immediate and strong bone bonding and avoid problems of metallic fixation, this study is a continuation of our previous research. Thus we tested - currently available surgical and dental adhesives - original mixtures developed in our laboratory. Mechanical assays were  performed on bone samples from human femurs in different conditions : dried, cleaned, fresh, or after immersion in physiological solution. They consist essentially of tensile tests on Lhomargy and Zwick's machine wherein the stress is directed perpendicular to the interface. Variations of tensile strength (in h bar) are related to hardening time and to mixture composition. The specimens are joined together either in monolayers or in multilayers. The use of adequate catalysts ensures setting at room temperature. Torsion tests and fatigue tests are carried out concomitantly. Standardized bevel fermoral osteotomies were performed on mice with a dental saw after I.P. Nembutal anesthesia in order to test biological tolerance : - for the control group we study the evolution of bone repair after circumferential wiring - for the animals under test, bones are glued together with one of the proposed adhesives. Radiological and histological studies (using classical Azantrichrome staining after demineralization) are carried out at regular time intervals. In the control animals particular attention is paid to the time course of the formation, constitution and evolution of callus. In the test animals, we can observe callus formation, bone growth into the adhesive material and glue resorption, and look for specific antigenic phenomena. Despite expected improvements, bone glueing remains a challenge and only restricted clinical applications can be proposed.


High strength Co-Cr-Mo alloy by hot isostatic pressing of powder. Currently available cobalt alloy prostheses for total hip applications are fabricated by investment casting techniques. Instances of stem fracture have been reported due to metal fatigue secondary to stem loosening or cement breakdown. A new process has been developed which includes the preparation of ultraclean powder and subsequent consolidation of the powder by hot isostatic pressing. The resultant solid material is characterized by 100 percent density and ultrafine grain size. Prostheses prepared by the new process have the same biocompatibility and corrsion resistance as the conventional cast alloy but higher strength and fatgue resistance.


Engineering criteria for biomaterials: some thought on in situ measurements. Several non-destructive techniques now exist which show promise of providing information about implant performance in situ. Surface wave ultrasonics have been used successfully in the laboratory to measure the anisotropic properties of bone. It has also been used clinically to assess rates of fracture healing. Acoustic emission has been used experimentally to investigate bone abnormalities such as microfracture and osteoporosis in vitro. Application of these techniques to clinical studies depends upon the establishment of the appropriate parameters for bone and the various biomaterials used as implants. Surface wave ultrasound may also provide information about tissue ingrowth into porous systems. Acoustic emission can be especially significant in the early detection of implant failure.


Water orientation and motion in phospholipid bilayers: a comparison between 17O- and 2H-NMR. 17O- and 2H-NMR spectra were obtained of a lamellar phase of dipalmitoyl-3sn-phosphatidylcholine (DPL) and D2 17O with water content of 3--15 moles water/mole DPL, in the temperature range 20 to 80 degrees C. In every case, the quadrupole splittings observed for 17O were 6.6 times larger than those for 2H. Therefore the two methods contain in principle the same information, but with less details from 17O. On the other hand, dynamic information is easily obtained from 17O linewidth data and complements the deuterium results.


Rates of deactivation processes of indole derivatives in water-organic solvent mixtures--application to tryptophyl fluorescence of proteins. The fluorescence quantum yield and the fluorescence decay of indole, 3-methylindole, 1-methylindole and N-acetyltryptophanamide have been measured in different water-dioxane mixtures. For the first three derivatives, the fluorescence decays were found independent of the emission wavelength and were analyzed as single exponential functions. In the case of N-methylindole the rate of the non radiative deactivation processes knr increased linearly with the molar fraction of dioxane whereas for indole and scatole the variation of knr was biphasic. This behaviour can be explained by two excited state deactivations of these non N-methylated compounds in water and high water content mixtures; one of these deactivation processes occuring through an hydrogen bond between the N-H group and a water molecule. The rate of non radiative deactivation of N-acetyltryptophanamide was dominated by the internal quenching involving the intramolecular carbonyl. The rate of the radiative deactivation process kF of these four compounds increased linearly with the wavenumber of the fluorescence spectrum maximum. Data relative to the three non N-methylated derivatives fell practically on the same straight line. Data from other works have been gathered in order to check if a similar relation between the intrinsic kF and vF values can exist for the tryptophyl fluorescence emission of proteins.


Thermodynamic analysis of carbon monoxide binding by hemoglobin trout I. Calorimetric measurements at 25 degrees of the differential heat of CO binding by hemoglobin trout I have been examined together with the CO binding isotherms for the protein at 4 degrees and 20 degrees. Simultaneous treatment of these data sets by a statistically rigorous technique permits evaluation of all the thermodynamic parameters for both the Adair and the Monod, Wyman, Changeux (MWC) models. The results show the details of the unusual temperature dependent cooperativity which this hemoglobin exhibits. In the Adair formalism the increasingly favorable free energy change for successive steps of ligand binding are nearly linearly paralleled by increasingly negative enthalpy changes for these steps. This causes the enhanced cooperativity observed as the temperature is decreased. For the MWC case, lowering the temperature increases the stability of the unligated T state relative to the unligated R state since the enthalpy of the T leads to R transition is 29.4 kcal mol-1. Simultaneously, the favorability of ligating R forms relative to T is enhanced since R form ligation is 14.1 kcal (mol CO)-1 more exothermic than that of T. The balance between these opposing effects is to increase ligand binding cooperativity at low temperatures. The predicted temperature dependence of the Hill coefficient for the MWC and Adair models is identical at low and intermediate temperatures, but, interestingly, would show a strong divergence at high temperatures where negative cooperativity is suggested for the Adair case and positive cooperativity for the MWC case.


A model for the behaviour of phosphorylase b. The generation of different binding sites via intermediate enzymatic states. The model given in this paper can be applied to enzymatic systems which have more than two conformational states in equilibrium and which clearly exhibit heterogeneity in the binding of one ligand. The model we propose makes possible quantitative interpretation of our experimental results and of those of many other workers as well. In some cases calorimetric, dialysis and kinetic magnitudes, when plotted against ligand concentration, give multiregional or "stepwise" curves. We suggest that such a behaviour arises because total occupation of one class of binding sites completely moves the enzyme towards a different conformational state in which the affinity for the ligand is greatly increased by the formation of a new class of binding sites. Our calorimetric results for the interaction between some nucleotides and phosphorylase b closely conform to our model.


Thermodynamics of nucleotides binding to phosphorylase b. The effects of several chemical modifications in the AMP molecule on its interaction with phosphorylase b are examined by microcalorimetry, equilibrium dialysis, light scattering and ultracentrifuge experiments. In this work we report the results obtained for eight AMP analogues corresponding to different substituents in the puric base or in the ribose, or to different positions of the phosphate. The thermodynamic properties of the interaction between the phosphorylase b and the above mentioned nucleotides are also reported. The following conclusions were obtained: a) Except for IMP and 2'dIMP all the nucleotides studied clearly show two types of binding sites in the enzyme. b) The interaction of the nucleotide with its weaker affinity binding site is highly dependent upon chemical alterations in the puric base. c) Both the amino group in C(6) and the N(1) of the adenine in the AMP seem to play an important role in the conformational transitions induced by the nucleotide on the enzyme. d) The tetramerization of phosphorylase b in the presence of 10(-2) M AMP and in the conditions of the ultracentrifuge experiments is drastically affected by modifications in the ribose-phosphate part of the AMP molecule.


On the role of the active site helix in papain, an ab initio molecular orbital study. On the system methanethiol/imidazole/formaldehyde (modelling the active site of papain) we performed ab initio self-consistent-field molecular orbital calculations using a rather large basis of Gaussian-type functions. A point charge representation of the long central alpha-helix present in the enzyme, was added in order to establish the influence of the electric field of the helix (which amounts to 10(9) V m-1 in the active site region) on the equilibrium: RSH...Im in equilibrium RS-...ImH+, which is an essential step in a recently proposed mechanism for the catalytic action of papain. Our results show that the helix stabilizes the ion-pair by 15 kcal mole-1 more than the neutral form making the two configurations energetically equivalent and lowers the energy barrier in the reaction path by 8 kcal mole-1, thus shifting the equilibrium considerably towards the ionic situation and increasing the rate of proton transfer by several orders of magnitude. We conclude that "active site" helices, present in many enzymes, play a pertinent role in enzyme catalysis.


Dextran biosynthesis and dextransucrase production by continuous culture of Leuconostoc mesenteroides. Leuconostoc mesenteroides NRRL B-512(F) was grown in continuous culture under conditions of energy-limited growth. The extracellular enzyme dextransucrase (sucrose: 1,6-alpha-D-glucan 6-alpha-glucosyltransferase EC 2.4.1.5), was not detected in glucose- or maltose-limited cultures. Under conditions of sucrose-limited growth, the enzyme activity of the cell-free culture supernatant increased with increasing dilution rate only after the critical concentration of enzyme inducer (sucrose) in the chemostat had been achieved. The appearance of fructose in the effluent of the sucrose-limited chemostat at higher dilution rates indicated that sucrose was being diverted to dextran biosynthesis. The competition between bacteria and extracellular enzyme for the common substrate sucrose represents an inefficiency in the system of enzyme production. Dextransucrase was isolated from the cell-free culture supernatant by ammonium sulfate precipitation and DEAE-cellulose chromatography. The enzyme preparation exhibited both dextran biosynthetic activity and an invertase-like activity. The biosynthetic efficiency was increased by decreasing the temperature from 30 to 10 degrees C. The enzyme was irreversibly denatured by prolonged incubation in the absence of Ca2+.


Lipase synthesis in hydrocarbon fermentation. A study was undertaken to establish conditions and relationships for the production of lipases during hydrocarbon fermentation. A culture of Candida lipolytica was isolated by a kerosene enrichment technique from oil-soaked soil and this microbe was used to study the production of lipase on a kerosene-mineral salts medium. The optimum pH, medium, and temperature for lipase synthesis were established and the properties of the isolated enzyme in terms of its activity and lipid specificity were studied.


Proteolytic denaturation and methods of improving the stability of glucose isomerase preparations. Evidence is provided in support of proteolytic denaturation of free and immobilized preparations of glucose isomerase from a Bacillus species. A number of methods to improve the stability with respect to proteolysis have been tested and their advantages as well as shortcomings are discussed. These methods include hollow-fiber treatment, gel permeation, thermal treatment, and addition of protease inhibitors. The half-life of the free and the cellulose acetate fiber-entrapped preparations of glucose isomerase can be significantly improved. For example, the hollow-fiber treatment can improve the half-life by an order of magnitude.


Theoretical and experimental analysis of a soluble enzyme membrane reactor. Recently enzyme immobilization techniques have been proposed that are mainly founded on the formation of an enzyme-gel layer onto the active surface of an ultrafiltration membrane within an unstirred ultrafiltration cell. If the membrane molecular-weight cutoff is less than the enzyme molecular weight and hence such as to completely prevent enzyme permeation (once the enzyme solution has been charged into the test cell and pressure applied to the system), a time progressive increase in enzyme concentration takes place at the upstream membrane surface that can eventually lead to gelation and hence to enzyme immobilization. However, depending on the total enzyme amount fed, the maximum enzyme concentration achieved in the unsteady state could be less than the gelation level. In this situation, no immobilization occurs and the enzyme still remains in the soluble form although it is practically confined within a limited region immediately upstream the membrane and at fairly high concentrations. In this paper, the experimental conditions that allow gelling to occur are discussed together with a theoretical analysis of the soluble enzyme membrane reactor which is obtained when no gelling takes place. Such a system could be usefully employed in performing kinetic analyses at high enzyme concentration levels that are still in the soluble form.


New method of determining kinetic constants for immobilized enzymes in a packet-bed reactor system. A new graphical method of determining the kinetic constants for immobilized-enzyme systems is proposed and illustrated with some examples. The advantages of using this method are that these kinetic constants can be determined accurately and conveniently from the conversion data of a packed-column enzyme-reactor system.


[Creation of steady alterations of motor activity in chick embryos under conditions of controlled experiments]. Steady alterations of motor activity in chick embryos were demonstrated under conditions of a controlled experiment, in production regimens of various directions. During controlled support by electrocutaneous stimulation of threshold amplitudes of the movements, the following characteristic time periods were distinguished: transitional, of steady alterations of motor activity with minimization of the amount of electrostimuli, and of the period of aftereffect. The conclusion is drawn about the united adaptive effect (minimization of biologically adverse influences) provided by the biorhythm of motor activity with directional potentiation of the activity of the components, which are not supported by adverse effects.


[Relationship between hypercapnic and hypoxic stimuli of respiration during muscular activity]. Pulmonary ventilation (V) and alveolar gas composition (PACO2, PAO2) were studied in 12 healthy men who performed gradual muscular work under conditions of controlled hypercapnia, hypoxia, hyperoxia or their combinations. The respiratory response was estimated by absolute values of ventilation at the given PACO2 value and by its rise by 1 mm Hg of increased PACO2 (delta V/delta PACO2) under rest and under transitional and steady-state exercise. The exercise on-switch was accompanied by displacement to the top and an increased slope of the response curve (delta V/delta PACO2) not related to the work load. These changes suggest multiplicative interaction of the neurogenic and hypercapnic drives in the load switch-on. During steady-state exercise an important role of the hypoxic drive was revealed: hypoxemia induced a shift of the delta V/delta PACO2 response curve to a higher level, especially with the great work load. Thus the positive interaction between the hypercapnic and hypoxic respiratory drive augments with muscular exercise.


[Role of increased peripheral vascular resistance in burn shock]. The effect of lethal burn injury on the parameters of hemodynamics and respiration was investigated in intact rabbits and those with disconnected aortal and sinocarotid reflexogenic zones. The rabbits of both groups demonstrated similar changes in cardiac output and total oxygen consumption. Unlike intact animals, the burn in rabbits with disconnected reflexogenic zones did not lead to a marked increase in the peripheral vascular resistance. Accordingly, the systemic arterial blood pressure in them fell to a considerably greater extent than that in the intact animals. The life span of the rabbits exposed to burns was less as compared to the intact ones. A reflex compensatory nature of the increased peripheral vascular resistance in burn shock is suggested.


[Change in the contractile activity of the rabbit myocardium as a result of burn shock of different duration]. Experiments were carried out on the papillary muscles prepared from the rabbit heart 10, 60 or 180 minutes after exposure of the animals to thermal burn. Isometric tension in the changing stimulation frequency of the preparation (the range being 0.1-2.0 Hz) and in post-stimulating potentiation was recorded. It was shown that the disturbance degree of the myocardial contractile activity caused by the burn rose depending on increased shock duration. It was evidenced by the following findings: in all the papillary muscles prepared 3 hours after burn and in 50% of the preparations taken one hour after the injury the "biphasic" dependence frequency power (F-P) peculiar to healthy myocardium changed to "monophasic" one (contraction amplitude progressively decreased on the frequency growing), and poststimulating potentiation, absent in the normal myocardium state, appeared. Within 10-minute shock duration only several preparations revealed poststimulating potentiation, F-P changes being absent. Normal rhythmoinotropic relationships in the myocardium restored under the influence of two-fol increase of (Ca2+)o or under prolonged (3-4 hours) perfusion of the preparation with normal Tyrode's solution. The changes observed in the myocardium rhythmoinotropic relationships produced by the burn shock were similar to those occurred as a result of the calcium canals block by the compound D-600.


[Effect of craniocerebral hypothermic perfusion on the metabolism of ischemic brain]. Intravascular perfusion of the brain by colloid-saline "extracellular" fluid was carried out in 58 experimental dogs against the background of acute hypoxia. Biochemical indices of metabolism in flowing and outflowing brain fluid as well as in the brain tissue were studied. It was shown that under conditions of acute hypoxia normo- and particularly hypothermic intravascular perfusion of the brain by colloid-saline fluid decreases the disturbances of metabolic homeostasis.


[Pancreatic enzyme spectrum in chronic stress]. In acute experiments on white male rats the enzyme spectrum of pancreas homogenate was studied in the process of 30-day adaptation after 3-hour exposure to the muscular loading (compulsory swimming in the water at a temperature of 32 +/- 1 degree C), the heat (overheating at 40-41 degrees C) and the cold (cooling at -3-4 degrees C). It was shown that the initial periods of adaptation to the factors mentioned (2d-12th day) were characterized by a considerable decrease in the activity of all the enzymes under study. With subsequent adaptation of the animal body to these stresses the enzyme activity level recovered to the initial value (18-24th day) and remained more or less stable up to the end of the experiment (30th day). It is suggested that the alteration of the pancreatic enzyme spectrum proceeds with the participation of the hypothalamic-hypophyseal-adrenal systems as a general adaptation syndrome.


[Lipid peroxides and thrombosis].

[Lipid peroxides and thrombosis]. In incubation of rabbit platelets with ADF, adrenalin, serotonin and thrombin the level of hydroxyperoxides serotonin and thrombin the level of hydroxyperoxides serotonin and thrombin the level of hydroxyperoxides they show, determined with respect to malonic dialdehyde, rises simultaneously with the enhancement of aggregation activity. Still higher level of malonic dialdehyde can be found in platelets of the animals with thrombosis of pulmonary vessels. The studies performed demonstrate that accumulation of malonic dialdehyde in platelets involves an initial stage of the thromboti process development. This finding can be used in the diagnosis of early stages of intravascular thrombogenesis.


[Study of bromthymol blue-prealbumin in the blood serum of rats under hyperbaric oxygenation]. Three-fold increase of BTB-prealbumin (Rm 1.0) in rat serum following fierse convulsions under hyperbaric oxygenation (6 ati, 30-35 min) has been proved by disc electrophoresis. Glial S100-protein and 7-fold increase in the all-organ component of brain BTB-prealbumin were found by immunochemistry to appear in the serum of experimental rats. The consequences of disorders in the blood-brain barrier for non-specific, all-organ proteins and potentialities of protein output from the brain into the blood similarly to neurophysins under hyperbaric oxygenation are discussed.


[Characteristics of the energy of electrostatic interaction of the formed elements of blood in experimental myocardial ischemia]. The diffusion and z-potentials of red cells of the blood outflowing from the zone of myocardial ischemia through the branch of the large cardiac vein were studied during acute period of experimental myocardial infarction. This enabled one to calculate the energy of electrostatic repulsion (EER) between blood constituents and to identify the factors exerting a significant effect on this value in acute experimental myocardial infarction induced in 20 dogs by ligation of the anterior interventricular branch of the left coronary artery. It was shown that the energetic state of the double electric lesion is the leading factor in the changed EER and in manifestation of the aggregation activity by the blood constituents. It was noted that the energetic potentials of red cells of the blood collected from the zone of myocardial ischemia show a statistically significant reduction.


[Role of lipid peroxidation and alpha-tocopherol in the conductivity of model membranes from phospholipids of the liver of rats with burns]. The membrane conductivity for K+ and Ca+2 ions was studied on bilayer phospholipid membranes formed by phospholipids extracted from the rat liver 1 hour, 1, 3, 7, and 15 days after burning. A pronounced increase in the membrane conductivity was noted. The most potent effects were seen by the 1t, 3d and 7th day of the experiment and the conductivity value varied depending on the medium pH. The process was accompanied by lipid peroxidation increase. Intraperitoneal administration of alpha-tocopherol at 1 mg/kg dose immediately after burning, followed by injections on the 3d, 7th and 12th day, normalized the characteristics studied. Bilayer membranes formed by healthy rat liver phospholipids previously added with an appropriate amount of methyl oleate or cumylhydroperoxide demonstrated higher conductivity as compared to the normal.


[Effect of ornid on the regulation of cerebrovascular circulation]. An investigation of ornid, using radioisotopic, electromagnetic and resistographic methods, has shown the drug to diminish cerebral circulation and to abolish completely the constriction of the brain vessels induced by stimulation of the sympathetic and somatic nerves. Ornid prevented the development of experimental disturbances of the cerebral circulation of adrenergic nature.


[Course of acute myocardial ischemia in dogs depending on the pharmacological background]. In acute myocardial ischemia of dogs glycogen is mobilized most completely and its break down products are utilized most efficaciously after administration of izatin rather than after gamma-hydroxybutyric acid (GABA) and guthymin. Izatin potentiates a beneficial effect of GABA on myocardial energy efficiency.


[Quantitative determination of lysozyme in the blood serum]. A method, based on the lysozyme ability to selective sorption on chitin followed by reversible enzyme-substrate complex formation, is suggested for quantitative determination of lysozyme in blood serum. The technique offers no difficulty in application, requires no expensive equipment and therefore can be used in clinical practice.


[Effect of methotrexate on the expression of alloantigens in the population of murine lymph node cells]. The effect of methotrexate given intraperitoneally to (CBA X C57BL/6j) F1 mice on the expression of alloantigens in the lymphatic node cell population was investigated. For this purpose cells from intact or methotrexate-treated F1 mice were injected into the foot-pad of CBA mice. The reaction was estimated as an increase of the regional popliteal lymphatic node in comparison with contralateral (intact) one. The injection of methotrexate in doses of 50 and 75 mg/kg significantly increased the alloantigenicity of the F1 mouse lymphatic node cell population.


[State of the erythrocyte surface (echinocytosis) in experimental carcinogenesis]. Characteristic red cell deformation, echinocytosis peculiar to mammary tumour susceptible C3H mice, were revealed by a comparative study of erythrocytes in animals with a different natural resistance to spontaneous carcinogenesis. 58.6% of spiny red cells was found at the early latent period (at the age of 3-4 months) and reached 91.1% at the late latent period (at the age of 11-12 months). In the blood of intact C57BL/6 mice resistant to mammary carcinogenesis, at the same ages the echinocyte count ranged from 16.0 to 18.7%. The tumour growth (spontaneous tumour in C3H mice and transplantable Ehrlich adenocarcinoma in C57BL/6 mice was accompanied by an increase in the echynocyte count and in the expression of echinocytosis (up to 96.6 and 65.3%, respectively). Possible pathogenetic mechanisms of echinocytosis in carcinogenesis are discussed.


[Effect of age, castration and pregnancy on carcinogenesis, induced by 1,2-dimethylhydrazine, in CBA mice]. Subcutaneous injection of 1,2-dimethylhydrazine into female CBA mice once a week resulted in the development of tumours of the colon, anal region, uterus and liver. In 12-13-month-old mice treated with DMH an earlier appearance (week 8) of uterine sarcomas and more rapid increase in the incidence of tumours of the anal region were noted as compared to 3-month-old mice. In pregnant females treated with DMH a statistically significant decrease in the uterine sarcoma incidence was observed (10.3% versus 48.3% in nonpregnant). Pregnancy exerted no effect on the incidence of tumours at other sites. Castration did not affect the time of appearance and the incidence of tumours of any site.


[Resistance of BCG-vaccinated body to tumor growth after administration of cyclophosphamide and desensitization]. It was shown that tumor growth is intensifying as a result of tumor cell implantation not only in early sensitization of BCG-vaccinated organism (see previously published data) but at the later period as well. Cyclophosphan removed this effect whereas desensitization carried out against the background of cyclophosphan action restored it. The data on the relationship between tuberculin allergy and the state of immunological defence reactions of the body suggest the possibility of stimulation of tumor growth as well as of its inhibition.


[Conditions controlling the development of distant intercellular interactions during ultraviolet radiation]. The study is concerned with ascertaining the role of UV radiation in distant intercellular interactions (DII) and the conditions resulting in "MIRROR" CYTOPATHIC EFFECT ("M" CPE). It has been found that the UV radiation-induced extreme state of the cells in a radiant culture produces distantly in an intact detector culture, which has only an optic contact with it, the cytopathic effect (CPE) as a repercussion of a specificity of morphological manifestations imprinted in the affected culture. UV preparadiation of the detector cells aids in manifestation of the "mirror" CPE.


[Mitotic indices of bone marrow cells and their correlative relationships in dogs]. It was shown that mitotic indices of erythroblasts, basophilic and polychromatophilic normoblasts, myeloblasts, promyelocytes and myelocytes decline depending on the degree of cell differentiation and are quantitatively expressed by the ratio 4:2:1. The feedback between the value of mitotic indices and the number of cells which is expressed by power dependence was identified.


[Changes in platelet aggregation and fibrinolytic activity of blood in healthy persons during the 23-day physical cycle]. The blood of 100 health humans aged 18 to 40 years was analysed. The aggregation of platelets and blood fibrinolytic activity were shown to change within 23-day physical cycle according to Swoboda and Fliess. In the negative phase the platelets count, their aggregation, desaggregation process and blood fibrinolytic activity were higher than in the positive one. No substantial differences in platelets aggregation and blood fibrinolytic activity were found during the positive and negative phases of the emotional or intellectual cycles.


[ultrastructure of rosette-forming cells in the wall of intestinal allotransplant]. The development of a specific rosette-formation was observed following total allotransplantation in the small intestine wall. The rosettes were formed from the central lymphocyte or neutrophil and adjucent plasmatic cells. The formation of plasmatic rosettes (P-rosettes) is considered as a possible index of the graft reaction versus the host.


[Distribution of the bone marrow cells in the skeleton of mice]. The data on the content of nucleated bone marrow cells in 17 skeletal portions of the hybrid F1 (CBA X C57B1) laboratory mice weighing 18-21 g are presented. The bone marrow content in the bones of the spine, head, inferior limb, pelvis, upper limb, sternum and ribs constituted 33.7; 19.6; 17.6; 11.9; 8.2 and 9.0% of the total amount, respectively. The epxerimental results are compared with the literature data.


[Effect of maternal hypoxia on the neurogenesis of the cerebral cortex of rat progeny (autoradiographic study)]. Rats with 15-day pregnancy were exposed to two-hour hypoxia corresponding to 8,000 m altitude. On the 18th day of pregnancy they were administered thymidine-3H three times. Quantitative autoradiographic studies were performed on brain cortex neurons of 30-day rat progeny. The animals who had sustained intrauterine hypoxia were shown to have obviously higher number of labeled neurons in IId, IIId and Vth layers of the sensomotor area than controls. Differences in the label intensity were also revealed. It is suggested that maternal hypoxia may delay differentiation and maturation of the brain cortex neurons in the progeny.


[Effect of acetylcholine on the mast cells of the dura mater]. The effects of various doses (100 mg/kg, 200 mg/kg and 500 mg/kg) of acetylcholine on the mast cells of the dura mater was studied in white rats by electron microscopy and the Falck fluorescent method. The qualitative and quantitative differences were found in the processes of accumulation and removal of monoamines depending on the drug dosage. The data obtained allow to suggest the stimulating effect of acetylcholine on monoamine secretion.


[Method of preparation of the microspecimens of intestinal villi]. In order to get significant microscopic pictures a method is proposed for embedding in paraffin and preparing precisely planed serial sections of some intestinal villi isolated from the enterobioptate mucosa fixed with 12% neutral formalin under the control of binocular magnifier. The method ensures an adequate evaluation of different forms the whole of villi or in micropreparations.


[Characteristics of impedance properties of metal bioelectrodes]. Dependence of interelectrode impedance on the metal type, electrode area of processing its working surface and current frequency was investigated. A series of 15 materials according to their impedance characteristics were obtained and a relationship between a sequence of preparations of heavy metals according to the density of albuminates they produced was established. It was demonstrated, that electrode difference in impedance of extreme members of the series was considerable in the zone of low frequency and was insignificant in the zone above 10-50 Khz.


[Use of the television analysing system in the studies on microcirculation]. In the experiments on anesthetized rats the television analysing system (LEITZ-TAS) was used for evaluation of quantitative structure-functional characteristics of microcirculation under intravital conditions and the development of microvessel network, for measuring geometric parameters of microvessels and blood flow change in them, as well as to define the degree and spreading of the disturbances in the vessel wall permeability.


The effectiveness of rubidazone in hairy cell leukemia (leukemic reticuloendotheliosis). Two patients with hairy cell leukemia treated with the anthracycline antibiotic rubidazone are presented. One achieved a complete remission and the other a good partial hematologic and bone marrow remission. Neither has relapsed (at 20 and 13 mo, respectively), and neither has been retreated. Intensive supportive measures were required during the prolonged myelosuppression that followed treatment. The relative youth of the patients (ages 24 and 39 yr) may have contributed to their ability to survive until normal marrow recovered. Chemotherapy should not be employed in the initial management of hairy cell leukemia. However, if life-threatening granulocytopenia and thrombocytopenia occur secondary to bone marrow replacement by leukemic cells, and improvement does not occur using alternative methods of therapy, consideration could be given to chemotherapy with rubidazone. Facilities for intensive supportive care should be available.


Treatment of hairy cell leukemia (leukemic reticuloendotheliosis) II. Chlorambucil therapy in postsplenectomy patients with progressive disease. Four postsplenectomy patients with progressive hairy cell leukemia were treated with daily low doses of an alkylating agent (chlorambucil, 4 mg). An objective response, measured by improvement in blood counts in four patients as well as decreased bone marrow involvement on core biopsy in three patients, could be documented within 6 mo. It is important to identify the postsplenectomy patient with progressive disease as early as possible in order to initiate low-dose single agent chemotherapy and have the time necessary to effect an objective response.


Paroxysmal nocturnal hemoglobinuria associated with infectious mononucleosis. A previously healthy 16-yr-old girl was found to have pancytopenia, low reticulocyte count, a cellular bone marrow, and a negative Coombs test, all coincident with clinical and laboratory evidence of infectious mononucleosis. Symptoms and signs of infectious mononucleosis subsided, but pancytopenia and hemolytic anemia persisted. Sucrose hemolysis and acid hemolysis tests supported a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). After 18 mo, the platelet count is normal, but leukopenia and hemolytic anemia continue. The development of PNH in this patient suggests it may have resulted from an effect of infectious mononucleosis.


The protective effect of intraperitoneal splenic autotransplants in mice exposed to an aerosolized suspension of type III Streptococcus pneumoniae. Splenosis has been shown to occur after traumatic injury to the spleen. It is postulated that this is the mechanism for the low incidence of bacterial infection in this group of patients when compared to those who undergo splenectomy for other reasons. Therefore, we studied the effect of exposure to an aerosolized suspension of type III Streptococcus pneumoniae on splenectomized mice who had either all or half of their splenic tissue cut up and reimplanted into the abdominal cavity 8 wk prior to bacterial exposure. It was determined that the mortality experience of these two groups of mice was similar to each other and no different from the sham control group, although all three groups had a statistically significant lower mortality experience than the splenectomized control group. This study demonstrates that splenosis in mice can protect against aerosolized bacterial infection.


Mononuclear cell tissue factor: cell of origin and requirements for activation. Human mononuclear leukocytes generate the procoagulant material tissue factor (TF) following stimulation by endotoxin, mitogens, or antigens in vitro. We have examined tissue-factor generation by mononuclear cell subpopulations prepared in a variety of ways in order to determine the cell of origin of mononuclear cell TF and the conditions necessary for maximal in vitro TF generation. We have also examined the relationship between in vitro TF generation and in vivo or in vitro measures of delayed hypersensitivity in response to identical antigen stimulation. Our results demonstrate that the monocyte is responsible for the bulk of mononuclear cell TF generation in vitro and that adhesion alone is not sufficient stimulation for significant.


Partial purification of thrombopoietin from the plasma of thrombocytopenic rabbits. Partially purified thrombopoiesis-stimulating activity was prepared from the plasma of thrombocytopenic rabbits using ammonium sulfate precipitation and DEAE cellulose, Sephadex, and carboxymethyl cellulose chromatography. The protein fraction precipitated by an ammonium sulfate saturation of 60%-80%, previously shown to contain thrombopoiesis-stimulating activity, was used as starting material. Column chromatography was carried out at room temperature at pH 5.6. Under these conditions, thrombopoiesis-stimulating activity (thrombopoietin) was retained by DEAE cellulose (0/03 M citrate-phosphate buffer) and carboxymethyl cellulose (0/003 M citrate-phosphate buffer), and eluted with 0.4 M NaCl. Thrombopoietin was retarded by Sephadex G-100; the ratio of the elution volume to the void volume was 1.32:1. Immunoelectrophoretic analysis of partially purified thrombopoietin indicated that following removal of most of the albumin by DEAE chromatography, only proteins with the mobilities of beta-globulins and albumin and traces of other anodally migrating proteins were detectable in the fractions that contained thrombopoiesis-stimulating activity. Thrombopoietin was not dialyzable and was stable from at least pH 5.6 to 7.5. It was approximately 1000-fold purified following sequential chromatography with DEAE and carboxymethyl cellulose. Although the three fractions described reproducibly stimulated thrombopoiesis, as measured by increased levels of selenomethionine-75Se (75SeM) in the circulating platelets, platelet counts did not increase.


Decrease of the major high molecular weight surface glycoprotein of human granulocytes in monosomy-7 associated with defective chemotaxis. By use of the galactose/NaB3H4 surface labeling technique followed by polyacrylamide slab gel electrophoresis, it is shown that the major labeled surface glycoprotein (GP130) of normal human blood granulocytes is markedly reduced in granulocytes from three patients with a chromosomal abnormality in all or most bone marrow mitoses. The abnormality consisted of monosomy-7 in two and deletion of the distal half of the long arm of chromosome-7 in the third. The granulocytes from these patients showed reduced chemotaxis. These results suggest that the expression of GP130, as well as the chemotactic ability of the cells, are at least in part controlled by one or several genes on chromosome-7. The GP130 protein may be involved in normal granulocyte chemotaxis.


Characteristics of human mononuclear phagocytes. In this study human mononuclear phagocytes from the bone marrow (promonocytes and monocytes), peripheral blood monocytes, and tissue macrophages from the skin and the peritoneal cavity were studied with respect to their morphological, cytochemical, and functional characteristics, cell surface receptors, and 3H-thymidine incorporation in vitro. The results show similarities between mononuclear phagocytes of the three body compartments with respect to esterase staining, the presence of peroxidase-positive granules, the presence of IgG and C receptors, and pinocytic and phagocytic activity. Promonocytes are the most immature mononuclear phagocytes identified in human bone marrow, and since about 80% of these cells incorporate 3H-thymidine, they are actively dividing cells. Monocytes, whether in bone marrow or the peripheral blood, and both skin and peritoneal macrophages label minimally with 3H-thymidine and thus are nondividing cells. Since the characteristics of mononuclear phagocytes in man and mouse do not diverge greatly, it is probable that the cell sequence based on in vitro and in vivo 3H-thymidine labeling studies in the mouse holds for man as well. The successive stages of development of the human mononuclear phagocyte cell line will then be as follows: monoblasts (not yet characterized in man) divide to form promonocytes, and these cells in turn divide and give rise to monocytes that do not divide further; they leave the bone marrow, circulate in the peripheral blood, and finally become macrophages in the various tissues.


Drug-induced agranulocytosis: in vitro evidence for immune suppression of granulopoiesis and a cross-reacting lymphocyte antibody. Two patients with agranulocytosis associated with diphenylhydantoin (DPH) therapy and clinical data suggesting suppression of granulopoiesis were investigated using in vitro culture techniques for committed granulocyte/macrophage precursors. Addition of DPH to cultures containing the patients' sera resulted in significant suppression of colony growth. Extensive studies on the acute serum from one patient revealed the drug-dependent inhibitory activity to be nondialyzable, resistant to chloroform extraction, heat stable, active in the presence of heat-inactivated fetal bovine serum, active against autologous as well as allogeneic cells, and absent from convalescent sera. Drug-dependent bone marrow colony-suppressing activity was removed by absorption on an antiimmunoglobulin-Sepharose column but not by IgG-Sepharose. The serum show non-drug dependent suppression of oxygen consumption by normal polymorphonuclear leukocytes engaged in phagocytosis and also showed evidence of ability to opsonize these cells. When the serum was incubated with mitogen-stimulated lymphocytes, suppression of 3H-thymidine uptake by autologous but not allogeneic cells was noted. Similarly, the serum suppressed short-term 3H-thymidine uptake by autologous but not allogeneic bone marrow. Absorption of the patients' sera with allogeneic polymorphonuclear leukocytes, autologous polymorphonuclear leukocytes, or autologous lymphocytes removed the drug-dependent inhibitory activity, but absorption with allogeneic lymphocytes did not. These data are most consistent with the presence of a noncomplement dependent antibody capable of suppressing granulopoiesis, mediating peripheral destruction of polymorphonuclear leukocytes, and cross-reacting with a lymphocyte antigen of limited population distribution.


Monoclonal immunoglobulin rescue from a patient with chronic lymphocytic leukemia and autoimmune hemolytic anemia. In order to test whether autoimmune hemolytic anemia in a patient with chronic lymphocytic leukemia was due to autoantibody production by the neoplastic clone, somatic cell hybrids were constructed between the patient's leukemic cells and a mouse myeloma line. Light-chain-restricted human immunoglobulin was secreted by 4 of 11 of the established hybrid lines. No binding of this immunoglobulin to red cell surface antigens could be detected. Thus, we conclude that the autoantibody in this patient represented a concomitant reactive response and was not the product of the malignant clone of B cells.


Lipopolysaccharide responsiveness of malignant lymphoid cells in a patient with hairy cell leukemia. The malignant cells in a patient with hairy cell leukemia responded most evidently to lipopolysaccharide (LPS) in in vitro culture for 3 1/2 days when the conventional tritiated thymidine uptake method was used. Since the malignant cells from patients with several other forms of leukemia and the peripheral blood mononuclear cells from healthy individuals did not show a comparable degree of responsiveness to LPS, we could exclude the possibility that this response was due to effects on contaminating normal mononuclear cells or to the nonspecific conditioning effect through LPS-affected contaminating normal monocytes. Morphological changes were observed with photo- and electronmicroscopy. It is likely that the hairy cells from the patient did respond to LPS, and whether or not this phenomenon may be confined to this type of lymphoid leukemia is not being investigated.


Clonal growth of metastatic carcinoma of bronchus in bone marrow culture. Bone marrow cells from a 35-yr-old male with small cell anaplastic carcinoma of the bronchus and bone marrow metastases were cultured in semisolid agar. Numerous small clones grew in the cultures, with a similar gross appearance to clones produced by cell from a proportion of patients with acute myeloid leukemia. Examination of the cells from these clones by electron microscopy revealed marked differences between these cells and cells grown in cultures from normal and acute myeloid leukemia marrow. This suggests that metastatic cells of the anaplastic carcinoma of the bronchus grew in clones in the agar culture system.


The role of sodium and potassium ions in the contractile response and development of tachyphylaxis to angiotensin II on vascular smooth muscle. The role of sodium and potassium ions, and the possible involvement of the membrane sodium pump has been studied in the development of a contractile response to, and the development of tachyphylaxis to, angiotensin II. It is suggested that a membrane depolarization may have a role in the mechanism of the contractile response to angiotensin II, as responses of the rabbit aorta to angiotensin II were selectively inhibited in K-free medium. Acute or chronic increases in medium sodium, however, did not influence the response of the rabbit aorta to angiotensin II. On the rat aorta increased medium sodium concentrations potentiated the response to angiotensin II and inhibited the development of tachyphylaxis. Membrane depolarization or hyperpolarization does not appear to be part of the mechanism of development of tachyphylaxis to angiotensin II on the rat aorta, as response to both NE and angiotensin II were inhibited equally by exposure of the rat aorta to K-free medium, i.e., nonspecific desensitization occurred, as opposed to the specific desensitization which defines tachyphylaxis.


L-ascorbic acid: effects on aortic glycosaminoglycan 35S incorporation in rabbit-induced atherogenesis. The effects of L-ascorbic acid on 35S-incorporation into thoracic aorta glycosaminoglycans and upon aorta cholesterol levels were determined in hypercholesterolemic rabbits. No significant difference was observed in serum free or esterified cholesterol levels between animals receiving L-ascorbic acid supplementation or saline while maintained on a cholesterol diet (0.5%). A 15-fold higher serum cholesterol was observed in animals on the cholesterol diet to those animals which received a normal rabbit (Purina) diet. L-Ascorbic acid increased sulfated glycosaminoglycans concentrations in hypercholesterolemic rabbits which paralleled lower tissue free and esterified cholesterol levels. The 35S-specific activity of glycosaminoglycans in hypercholesterolemic animals receiving saline was much greater than in those animals receiving L-ascorbic acid. This suggests that L-ascorbic acid plays a role in the maintenance of adequate levels of aortic sulfated glycosaminoglycans. This then is a suggested biochemical mechanism of L-ascorbic acids interaction in the atherogenic process.


Action potential generation in reaggregates of rat aortic smooth muscle cells in primary culture. Cultured vascular smooth muscle cells were prepared from adult rat aortas. The cells were dispersed by collagenase/elastase, and allowed to reaggregate into small spheres (50-200 micron in diameter) by plating on to cellophane. These primary cultures were incubated for 5-14 days, and then impaled with microelectrodes. The mean resting potential was -55 mV, and the mean input resistance was 9.0 M omega. The cells were quiescent, electrically and mechanically, and electrical stimulation usually did not elicit responses. However, addition of Ba++ (1 mM) or tetraehtylammonium ion (TEA; 5-15 mM) induced excitability (with accompanying contractions), either as spontaneous action potentials or by allowing responses to electrical stimulation. The cells became partially depolarized (e.g., to -36 mV) by these agents, and the input resistance increased. The frequency of spontaneous firing of the Ba++-induced spikes was affected by polarizing current pulses, as expected for pacemaker behavior. Elevation of Ca++ in the bathing solution increased the amplitude (overshoot) of the action potentials, and the spikes were blocked by verapamil (10(-5) M). Electron microscopy showed that the reaggregates consisted of a tight packing of elongated small-diameter cells, some of which exhibited thick and thin myofilaments and 'dense bodies'; many cells possessed surface caveolae. The results of this study demonstrate that reaggregates of arterial smooth muscle in primary culture can maintain functional and morphological characteristics of intact arterial smooth muscle, and therefore provide a useful preparation for the study of vascular smooth muscle function and control.


Transferring load to flesh: part IX. Cushion stiffness effects. Stresses developed within flesh in contact with a cushion are examined analytically. Compressive, tensile, and shear stresses within flesh in proximity to a bone are given as a function of cushion stiffness (major parameter) and the overall Poisson's ratio of flesh (minor parameter). It is shown that an individual already sitting on a soft cushion receives relatively minor benefit when a still softer cushion is substituted. This result follows from the fairly flat (saturated) trend of both shear and tensile stress with respect to cushion stiffness, once the soft cushion domain (less than 10 PSI) is entered. Only flesh normal stress (compression) responds significantly to incremental changes of stiffness within the soft cushion range; reducing the cushion stiffness 50 percent will typically reduce local compressive stress by roughly 20 percent. While such a gain is real, it is also modest.


Locomotion assistance through cane impulse. The extent of locomotion assistance gained through cane usage by those with hip disorders is assayed. Employing as a standard the propulsive impulse delivered by each lower limb of a healthy young male, the cane is shown to supply about one-fifth the equivalent impulse, aside from other possible benefits. Full test values are given for nine handicapped subjects.


[Motivation factors for smoking in adolescents]. The study reports on the motivations of tobacco consumption in various populations of youths in North-Switzerland. A questionnaire obtained from 1436 school-children in the Cantons of Zurich and St. Gall indicated that 9% of the boys and 3% of the girls have tried their first "curiosity-cigarette" before age 6. Among 400 female students of nursing there were 32% smokers, and one of four was smoking more than 20 cigarettes per day. In boarding schools the smoking habits varied according to pedagogic influences. Boys from farming families originating from East-Switzerland were smoking at a rate of 23% between ages 17-21. Girls of similar origin and age were smoking in 14% of the cases. Apprentices of the same age working in the metal industry of the city of Zurich were smoking in 55%, boys from High Schools in 30% of the cases. There were 17% of abstinents from alcohol among non-smokers as compared to 2% among smokers representing a significant difference. In High School-students from Berne there were 23% of smokers as compared to 3% of non-smokers with previous experience with hard drugs. The results of a Health Education Program conducted during three years as a longterm intervention demonstrated that tobacco consumption was significantly reduced in test groups as compared to controls.


[Health education: prevention of smoking]. With the aim of primary prevention, the Health Education Service of Geneva organizes in all schools since 1970, an information campaign against the dangers of smoking! The objectives of this preventive action are to render the pupils conscient of the dangers of smoking, to draw their attention on the lures of advertisement and to permit them to make a personal opinion on the subject. This information is given in primary and secondary schools by the teachers who receive the necessary audio-visual equipment from the Health Education Service. In the higher degrees, this information is integrated in a regular health teaching program. All future teachers also receive an "anti-smoking" information given by doctors of our Department. We hope that this form of objective and scientific instruction in schools will minimise the effects of publicity, making the young people aware of the risks they encounter.


Effectiveness of measures against smoking. The objective of a program to control cigarette smoking is to reduce illness and early mortality. This requires a) reducing the taking up of smoking, b) increasing the giving up of smoking, c) reducing the dosage of harmful substances received by the smoker, and d) protecting the non-smoker. Such a program requires both an educational effort and a management approach. The success of past educational efforts has changed the nature of current efforts from an emphasis on persuading people to stop smoking to an emphasis on encouraging those who have been unsuccessful to try again, to assist them, and to use dosage reduction as an alternative to quitting. Managerial efforts most promising are the gradual reduction of harmful substances in the smoke, economic disincentives, and limitations of smoking in public places, thereby protecting both the smoker and the non-smoker.


[The effect of tobacco and alcohol on pregnancy course and child development]. Smoking during pregnancy may cause small-for-date babies, severeness and frequency depending on the number of cigarettes per day. Regular and heavy smoking appearently increases perinatal mortality. A similar correlation and additionally an increased rate of newborns with major abnormalities was observed when the father regularly smoked 10 and more cigarettes per day, even then when the mother was a non-smoker. The mechanism involved is unclear. Based upon present information one may favour the view that smoking of the father impairs spermiogenesis rather than "passive" smoking of the mother. Regular intake of liquor by the mother is well correlated with a shortened duration of pregnancy--that means an increased rate of abortion and prematurity. The consequences and responsibilities in the frame of family planning and prenatal care are discussed. The results referred to were attained mainly by a prospective study "Course of pregnancy and child development" supported by the German Research Foundation (Deutsche Forschungsgemeinschaft).


[Fetal alcohol syndrome].

[Fetal alcohol syndrome]. The author presents cases of dysmorphic children born to alcoholic mothers to illustrate his discussion of the "fetal alcohol syndrome". The fact that this malformative syndrome has not been recognized before 1968 is amazing, particularly if one considers the high frequency of alcohol addiction and the relative specificity of the birth defects making up the syndrome. Newborns from severely alcoholic mothers are small for date, microcephalic, and they have abnormal facial features, as well as an increased frequency of other malformations (heart, genitalia, extremities). Neurological and mental deficiencies are recognized early in most of these children. Central nervous system anomalies are beginning to be described by the neuropathologists, which correspond to these clinical findings.


[Association of tobacco and alcohol in cancer]. Heavy drinking and heavy smoking are often associated; the effects of either alcohol and tobacco on human cancer can not be easily disentangled. Appropriate adjustments need to be made to pinpoint the role of either factor. Both smoking and drinking play a role in cancer of the buccal cavity, pharynx and oesophagus; they seem to multiply their effects. Cancer of the larynx is also related to both alcohol and tobacco, but the role of alcohol appears only when exposure to tobacco is also present. While tobacco smoke is known to contain carcinogens, the mechanisms by which alcohol provoke cancer remain obscure; it may act by facilitating the penetration of carcinogens in the mucosa-carcinogens might be present in some alcoholic beverages; a direct action of ethanol can not be excluded. Epidemiological evidence is clear enough, however, to predict a substantial drop of incidence of buccal, pharyngeal, oesophageal and laryngeal cancers if alcohol and tobacco consumption could be reduced.


[Pathobiochemistry of alcoholism].

[Pathobiochemistry of alcoholism]. Liver alcohol dehydrogenase (ADH) represents the main enzyme of normal alcohol metabolism. Total activity of this enzyme varies largely due to the occurrence of isoenzymes and of genetic polymorphisms. One genetic variant, called "atypical", is characterized by a higher specific activity. In carriers of this variant enzyme an initially faster rate of ethanol metabolism leads to higher blood acetaldehyde levels. Acetaldehyde, as a toxic intermediary metabolite, causes tachycardia, nausea and flushing of the face. A high frequency for "atypical" ADH is observed in mongolid races and consequently a hypersensitivity to alcohol is often observed in Orientals. Hence, certain genetically determined enzyme patterns may represent an aversive factor with regard to alcohol consumption. In Caucasians the phenotypes with "atypical" ADH are less frequent. However, in individuals with the "atypical" variant regular intake of alcohol may lead to an increased organotoxicity due to acetaldehyde.


[Early recognition and diagnosis of alcoholism]. The starting point is a discussion of the definition of alcoholism in its various aspects: somatic, psychic and social sequelae, loss of control, amount of alcohol consumption. The clinical approach is oriented on target symptoms ("Leitsymptome") followed by a search for details of symptoms of alcoholism. Diagnostic tests for alcoholism and their problems are discussed. Examples of these tests are described, especially the Munich Alcoholism-Test (MALT).


[Alcoholism and driving ability].

[Alcoholism and driving ability]. Utilizing reports of expert opinions issued by the Unit of Traffic Medicine and Psychology, Institute of Forensic Medicine, Geneva (908 cases between 1965 and 1977), the authors evaluate the different levels of estimates on driving ability in chronic alcoholics (46 cases). Diagnosis of chronic alcoholism is sometimes difficult. It is necessary that the medical experts get in touch with the family physician and with the neighbourhood of the patient reported. The authors demonstrate that the conclusions of these reports frequently include restrictions regarding limited driving permission or a limitation to a permit for a learner's drivers license.


[Intoxication at the wheel].

[Intoxication at the wheel]. A large body of experimental and statistical evidence demonstrates that even mild alcohol intoxication with blood alcohol concentrations above 0,5% is associated with a significantly increase in the susceptibility for an accident. The lowering of the critical concentration limit is indicated from a medical, social-political and economical point of view.


[Drinking behavior in Switzerland].

[Drinking behavior in Switzerland]. The results of a broad survey of drinking behaviour in Switzerland are reported. It is based on a questionnaire considered to be representative obtained from 1500 residents of Switzerland between 15 and 74 years of age. The study confirms previous findings that, similar as in other countries, alcohol consumption in Switzerland is distributed in the population as a logarithmic curve. The results demonstrate that the alcohol consumed in amounts which are considered to be dangerous to health (daily consumption of pure alcohol: 80 grams and more) was found to be 30% of total consumption in German and French Switzerland, and 47% in Italian Switzerland respectively. In contrast to other countries there is no predominance of particular beverages, but there are some clear-cut preferences for certain beverages in certain areas within the country. The study further demonstrates that in areas with higher average consumption a higher percentage of heavy consumers is found; this is particularly the case for French and Italian Switzerland. Moreover, a higher average consumption is associated with an increase in mortality rates from alcohol-related cirrhosis of the liver. The relationship between regional average consumption and mortality rates from cirrhosis indicates not a linear, but an exponential increase of the latter with rising consumption. It was found that the following social-demographic variables are significantly associated with the prevalence to drinking: sex, age, income and education.


[Medico-psycho-social rehabilitation of alcoholics: a multidisciplinary approach]. In heavy problem drinkers with loss of control and severe disruptive behavioral disorders, the general practitioner cannot offer a comprehensive program coping with all the disturbed parameters: those of the individual, the family, the friends, the working and leisure time environment. In these situations a multidisciplinary team approach is very helpful. A close collaboration between physician, nurse, social worker and psychologist enables the team to implement the comprehensive program in a more efficient way and with the active participation of the patient, his family and social environment. In this paper the author deals with the inner structure of the team model. Today there is a shifting from the traditional "paternalistic team model" (i.e. medical leadership) toward a more democratic team structure as a result of emancipatory pressures from the social work profession. The author presents a critical view of extreme emancipatory tendencies aiming at abolishing the disease concept of alcoholism and the team members professional identity as well as the role differences between therapist and client. The professional rehabilitation model is compared with the Alcoholics Anonymous self help model, and possibilities and limits of an interdisciplinary cooperation between the two approaches are stressed.


[Alcoholism in the young].

[Alcoholism in the young]. The ideas on alcoholism have somehow changed during these last years. In the past, ideas were axed mainly on the individual causes of alcoholism; today we are more interested on the sociocultural factors. Statistics prove, on the other hand, that there is a considerable increase of alcoholism by the youth. Young people begin earlier ordinary consumption of alcohol, or take alcohol with drugs, or replace hard drugs by alcohol. It is very urgent to study this new phenomenon, and to think about new structures, in order to take care of the victims of this new pathology.


[Sociocultural requirements for alcohol and tobacco education measures]. If behaviour changes are taken as a criteria for the effectiveness of alcohol and tobacco education, the results of evaluation research are not encouraging. The unefficiency of alcohol and tobacco education is considered to be caused on the one hand by a too limited concept of education applied to teaching programmes. On the other hand a number of antagonisms between educators and pupils result from not taking into consideration sociocultural facts. At the outset, these antagonisms bring about the failure of measures for alcohol and tobacco education. A number of postulates to overcome the contradictions between educational aims and the expectations of pupils are discussed.


[Evaluation of measures to reduce cigarette consumption in Switzerland]. Policy instruments were examined to reduce cigarette consumption in Switzerland. The results can be summarised in two points: a) Tax increases and anti-smoking publicity (health education) are effective measures to reduce cigarette smoking. The effect is especially pronounced when both instruments are combined. b) The effect of a ban on advertising could not be examined for Switzerland due to lack of data. Results of studies abroad lead to the assumption that cigarette consumption can be influenced more by the tobacco tax and anti-smoking publicity than by a ban on advertising. This is by no means to say that such a ban would have no effect.


[Tobacco, mortality and morbidity of atherosclerotic cardiovascular diseases--a prospective study in Paris]. In the Paris Prospective Study, after a 6,5 year follow-up, mortality and atherosclerotic disease incidence are studied according to the tobacco consumption measured at entry among 7746 middle-aged men in the same administrative group. Mortality is 3 times higher among smokers; the excess mortality of smokers concerns particularly cancers, especially cancers of the upper part of the digestive tube or lung cancers and coronary heart disease. The incidences of leg atherosclerosis and of hard coronary diseases increase very much with the quantity smoked and inhaled. The cigarette consumption is linked with the development of coronary diseases independently of other risk factors; it is taken into account in a five risk factor combination which gives the best estimation of individual risk of future disease. The theoretical effects of the reduction of cigarette consumption on the individual risk or on the incidence of coronary diseases are given. A multifactorial prevention with a small reduction of the level of several risk factors might reduce that incidence in the population.


[Smoking and mortality in Swiss physicians: results of an 18-year survey]. A prospective mortality study of tobacco smoking of Swiss physicians is reported over a period of 18 years (1955-1973). The mortality rate increases with the intensity of the daily smoking quantity, going till to the double of non-smokers. This elevation is not seen in late smokers. Contrary to the habits of English doctors, who smoke mostly cigarettes, in Switzerland the death rates of cigars (mostly Stumpen) and pipe smokers are as much elevated as for cigarette smokers. In intensive smokers the mortality reached for all 3 the same rate (2,4-2,6). Under the various causes of death lung cancer was only seen in smokers (92,5% intensive smokers). Heart infarctions death has in smokers the highest rate in the age of 35-54 years, going back till 75 years where the death rate is nearly the same as in non-smokers. The passover in mortality of the intensive smokers in full activity of life is documentated by the statistic of Swiss Doctors. Therefore it is a positive factor that in the last 18 years the number of cigarette-smokers in physicians declined from 37% to 21% and the number of past-smokers has gone up from 17 to 38%, but the number of only cigars and pipesmokers is always the same.


[Passive smoking].

[Passive smoking]. Passive smoking is the involuntary inspiration of smoky indoor air. Based on the information available today, it may be assumed that passive smoking normally is no health hazard as far as the classical smoker's diseases (lung cancer, myocardial infarct, etc.) are concerned. Nevertheless, it is probable that irritations caused by tobacco smoke have an unfavorable influence on the health of small children and that of already sick persons. The main problem of passive smoking is annoyance due to odor and irritations of eyes and respiratory organs. Our investigations in a climatic chamber with healthy subjects show that air pollution caused by tobacco smoke as indicated by 5 ppm CO leads to marked eye irritations--objectively as well as subjectively--in 15 to 20% of the subjects. This corresponds to smoking 10 cigarettes per hour in a small room with an air ventilation rate of four times per hour. If air pollution caused by tobacco smoke lies below the level of 2 ppm CO, irritations and annoyance for healthy persons are regarded as low and tolerable. This corresponds to about four cigarettes per hour under the same circumstances.


Comparison of the effects of a benzotriazinium iodide and quinidine on guinea-pig heart. 1 The actions of 2-n-propyl-4-p-tolylamino-1,2,3-benzotriazinium iodide (TnPBI) and quinidine were compared on guinea-pig heart preparations. 2 Quinidine had negative inotropic and chronotropic effects on guinea-pig isolated atria and on Langendorff hearts: TnPBI had negative inotropic and chronotropic effects on Langendorff hearts, but showed a positive inotropic effect on isolated atria at low dose levels. 3 Both quinidine and TnPBI increased the effective refractory period of guinea-pig atrial preparations. 4 The effects of TnPBI on transmembrane action potentials indicated a mixed class I and class III action according to the classification of Vaughan Williams (1970). 5 These effects are discussed in relation to the antiarrhythmic actions of TnPBI.


Effects of delta 9-tetrahydrocannabinol, 2.4-dinitrophenol and pentolinium tartrate on behavioural thermoregulation in mice. 1 A new apparatus in which mice are allowed to shuttle between the warm and cool parts of a continuous oval tunnel has been designed for the measurement of drug effects on behavioural thermoregulation.2 The length of time that untreated mice spent in the warmer part of the apparatus (tunnel wall temperature 38 degrees C) was found to be inversely related to the temperature of the cooler part (wall temperature 18 degrees , 24 degrees or 30 degrees C).3 Mice treated with 2,4-dinitrophenol at a dose known to be hyperthermic at an ambient temperature of 32 degrees C (20 mg/kg s.c.) spent an increased length of time in the cooler part of the apparatus (wall temperature 18 degrees C) and did not exhibit any change in rectal temperature.4 Mice treated with pentolinium tartrate at a dose known to be hypothermic at room temperature (5.0 mg/kg i.v.) spent a decreased length of time in the cooler part of the apparatus (wall temperature 24 degrees C) and did not exhibit any change in rectal temperature.5 It is concluded from the above results that the apparatus can be used to measure drug effects on behavioural thermoregulation.6 In experiments of 30 min duration, mice treated with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) at doses known to be hypothermic and to lower oxygen consumption at room temperature (20 mg/kg i.p. or 2.0 mg/kg i.v.) spent a longer time in the warmer part of the apparatus between 15 and 30 min after injection. Rectal temperatures measured 30 min after injection were only slightly less than those of control mice. In these experiments the wall temperature of the cool tunnel was 24 degrees C.7 In experiments of 15 min duration, mice treated with Delta(9)-THC (20 mg/kg) and then placed in the apparatus spent more time in the cooler part of the apparatus (wall temperature 24 degrees C) and exhibited a large fall in rectal temperature.8 It is concluded that immediately after injection of Delta(9)-THC the mice do not attempt to oppose drug-induced falls in deep body temperature by moving into a warm environment and that only later do the animals demonstrate a preference for a warm environment.


An effect of haloperidol on the increased food and water intake induced in rabbits by 2-deoxy-D-glucose. Rabbits treated with 2-deoxy-D-glucose (2DG) (300 mg/kg) show an increased intake of food and water. Pretreatment with haloperidol (1 mg/kg) abolishes the increase in water intake but does not prevent the increase in food intake.


Cardiovascular effects of hypertonic sodium chloride solutions when injected into the liquor space of anaesthetized cats. 1 In cats anaesthetized with chloralose, hyper- and hypotonic solutions were injected into the cisterna magna (in 0.5 ml) or into a lateral cerebral ventricle (in 0.2 to 0.3 ml), with aqueduct cannulated to prevent the injected solution from entering the subarachnoid space, and the effects on blood pressure and heart rate were examined. 2 Cisternal injections of hyper- and hypotonic solutions of NaCl (0.51 M and 0.05 M), glucose (1.03 M and 0.10 M), or sucrose (1.02 M and 0.10 M), as well as distilled water produced a rise in arterial blood pressure with tachycardias. Isotonic solutions of NaCl, glucose or sucrose were ineffective. 3 Ventricular injections of the hypertonic NaCl solution, also produced a pressor response with tachycardia effects when injected in this way. 4 The pressor responses and the tachycardias occurred after bilateral vagotomy and resulted from a sympathetic discharge which, on cisternal injection, originated from structures reached from the subarachnoid space, and on ventricular injection, from structures in the ventricular walls, probably in the hypothalamus. 5 The stimuli responsible for the discharge, were, on cisternal injection, the changes in osmolarity and on ventricular injection, the sodium ions.


The effects of location, experiences with the civil disturbances and religion on death anxiety and manifest anxiety in a sample of Northern Ireland university students. A total of 315 Northern Ireland university students were compared to 302 Republic of Ireland university students in terms of death anxiety, manifest anxiety, and perception of dangerousness of aspects of their environment and attitudes toward the civil disturbances in Northern Ireland. Also using these variables in the Northern Ireland sample, Protestants were compared to Catholics, those having had experiences with the disturbances were compared to those not having had such experiences, and those living in nominally dangerous areas of Belfast were compared to those living in nominally safer areas of Belfast. Students living in Northern Ireland had higher death anxiety and stronger fears than students living in the Republic. Those having had experiences with the civil violence had higher manifest anxiety and stronger fears than those not having has such experiences. Persons living in safe environments thought the disturbances to be more serious than those living in more dangerous environments, a result which is discussed in terms of the media and cognitive dissonance. Finally, an argument is made that the influence of religious denomination is an overemphasized variable in the understanding of the civil disturbances.