[Murine hematopoietic stem cells after acute and chronic administration of vincristine]. The effects of vincristine on bone marrow hemopoietic stem cells were studied in mice. After the administration of a single dose of the drug there is a sharp decline in the content of CFUs. When the drug is given in small, weekly doses for 16 weeks, after an initial drop, the stem cell content rises at a normal level where it remains, although with wide oscillations. On the whole the effects of vincristine on b.m. CFUs are comparable with that observed after vinblastine administration.


[Histochemical and ultrastructural studies of the innervation of the lymph-vessel and blood-vessel wall. 1. Adrenergic innervation]. The adrenergic innervation of the lymph vascular wall was studied by means of the Falck fluorescence histochemical tecnique and electron microscopy with Tranzer and Richards' histochemical tecnique. The lymph vessels wall, compared with that of blood vessels, shows very few adrenergic nerve fibers located in the adventitia outside the smooth muscle cells. The possible role of the nervous system in the motor control of the lymph vessels is discussed.


[Histochemical and ultrastructural studies of the innervation of the lymph-vessel and blood-vessel wall. II. Cholinergic innervation]. Using the Acetylcholinesterase (AChE) tecnique applied to light and electron microscopy, was observed that the lymph vascular wall shows very few and inconstant AChE-positive fibers. The cholinergic fibers run prevalently longitudinal in the perivascular connective tissue, only brief segments show a loose network. The results are discussed and compared with blood vessels innervation.


[Effects of passive movement of the arm on respiration in humans]. Cyclic passive movements of the right arm at 1Hz induce an increase in pulmonary ventilation in man. This results from an increase in frequency of the respiratory cycles, mainly due to a shortening of the expiratory phase, and from an increase of the instantaneous flow. The delay between the beginning of the arm movements and the onset of the increase in flow is about 450msec.


Respiratory ventilation during muscular contraction in man. Brief contraction of arm muscles affects respiratory ventilation either by increasing respiratory frequency or by increasing the instantaneous flow. Both these changes occur at a time subsequent to muscle contraction and can be attributed to a reflex mechanism originating from the muscles.


[Preliminary observations on the ultrastructure of the human laryngeal glands: the secreting cells]. The secretory portions of human laryngeal glands consist of seromucous and mucous cells. Seromucous cells contain granules either homogeneously dense or endowed with a bipartite structure, consisting of a clear peripheral halo and a central dense portion. In any case, however, they exhibit a morphological appearance different from that observed in seromucous granules of salivary glands. Mucous cells vary considerably according to the functional state.


[Some cytological aspects of the epithelium of the striated ducts in the human parotid and submaxillary glands]. Some cytological features peculiar to striated ducts epithelium of normal parotid and submaxillary glands were investigated by transmission electron microscopy. Interspersed among the clear cells, which comprise the great majority, dark cells have been encountered. Large lipoid bodies with histochemical reactions typical of lipofuscins were also observed. In three case only, polysome-lamella complexes consisting of concentric lamellar cylinders alternating with layers of polysomes were noted. This study indicates that some ultrastructural features, previously attributed to inflammatory diseases, may also occur in normal salivary glands.


Electromagnetic properties of biological solutions. - II. Methodological considerations on microwave spectroscopy of human sera. A wide-band analysis is proposed about the behaviour of the dielectric constant of human sera, using a proper mathematical model. Each serum is identified by two parameters. There is a good agreement between theoretical and experimental data.


CSF electrophoresis: an adaptation using cellogel RS for identification of protein banding. A CSF electrophoresis on a particular gelatinized cellulose acetate (Cellogel RS) has been tested. The method allows the routine separation of many protein fractions in concentrated CSF in a very brief time and affords the recognition and quantification of oligoclonal banding, that is of extreme importance in the diagnosis of some neuropathies as multiple sclerosis.


[Spectral properties of perselenosulfide]. The riductive scission of a diselenide (selenocystamine) produced by disulfide gives the perselenosulfide, a new compound. Its formation kinetics, carried out a several pH values, were recorded spectrophotometrically at 375 nm. The lability of perselenosulfide bond by cianolysis has been demonstrated.


[Effect of phenethylbiguanide on the respiratory activity of liver mitochondria of rats treated with glucagon]. The effect of PEBG on respiration and oxidative phosphorilation (succinate as substrate) has been studied in liver mitochondria of rat treated with glucagon. The results obtained indicate that, while glucagon, as reported by others, induce a significant increase of respiration rate in state 3 (+ ADP), PEBG, at pharmachological dose, antagonizes this effect. The conclusion is that PEBG exertes its hypoglycemic activity by inhibiting the gluconeogenic reactions promoted by glucagon. This is strongly evident in diabetic or starwed conditions.


[Chronobiological aspects of TSH secretion in control subjects and in subjects with primary hypothyroidism]. The circadian rhythm in plasma TSH concentration was demonstrated in euthyroid subjects and in treated hypothyroid patients. Our results suggest that two hypothalamic areas, involved in TRH secretion, are responsables in basal as well impulsive pituitary TSH dismission.


[Effect of hydration-dehydration treatment (presoaking) on the soluble DNA polymerase activity in wheat embryos]. The subcellular fraction of wheat embryos most rich in DNA-polymerase is the soluble fraction. After presoaking the DNA-polymerase activity localized in this fraction is particularly enhanced. In the present paper a preliminary study on some characteristics of the soluble DNA-polymerase of wheat embryos from seeds treated or not with presoaking is reported.


[Some photometric and fluorimetric characteristics of acridine orange and of its complexes with glycosaminoglycans: proposed method for their spectrophotofluorimetric evaluation. I. Spectrophotometric study]. In spite of the wide use of AO as basic fluorochrome in cytology, histology and histochemistry, however there still persist some queries on the meaning of fluorescence due to the encounter of a such molecule with anionic polymers. From the spectrophotometric data exposed in the present paper, AO is stressed as a metachromatic colouring and therefore, as such, may be used in histochemical investigation. Besides, because of the reliable identificaton of the single types of GAG, screening may be performed at different pH, since metachromasia appears at different pH for the three different types of GAG. A useful counterproof may be performed by means of selective elutions of the AO/GAG complexes, being solutions with increasing ionic power.


[Some photometric and fluorimetric characteristics of acridine orange and its complexes with glycosaminoglycans: proposed method for their spectrophotofluorimetric evaluation. 2. Spectrophotofluorimetric study]. From the present spectrofluorimetric investigation of AO and its complexes with anionic polymers, derives the possibility of a direct quantitative evaluation of GAG as such, and not through the dosage of one of their molecular components. On the other hand, the method proposed is characterized by its simplicity and rapidity. Besides, the noticeable extent of the range in which there exists a correlation between the response intensity at =640 nm and the doses of GAG considered should be stressed.


[Influence in vivo of sorbitol on sorbitol dehydrogenase activity]. Previous researches carried out on the metabolism of sorbitol in the rat showed the influence of this polyalcohol on the activity of some dehydrogenases NAD and NADP-dependent and on lacate/pyruvate, NADH/NAD and NADPH/NADP ratios. Since sorbitol dehydrogenase (SDH, EC 1.1.1.14) is an enzyme with a great affinity for sorbitol, it seemed interesting to investigate the effect of a sorbitol-enriched diet on SDH activity in the rat liver after different periods of dietary treatment (20, 40, 60 days). SDH was assayed by a continuous optical test according to Bücher et al. The data obtained show a repressive action on SDH activity by a sorbitol-enriched diet. In fact, whilst after 20 days of treatment SDH activity decreased of about 18% in respect of the controls, after 60 days a decrease of 80% was observed. This result is so interesting to stimulate other investigations in vitro on the kinetics of such metabolic reaction in the attempt to explain the relation between the enzyme and its substrate.


Involvement of calcium ions in the properties of cardiolipin-associated erythrocyte acetylcholinesterase. Lipoprotein forms of acetylcholinesterase from bovine erythrocytes gave non-linear Arrhenius plots with a break at 20 degrees C and contained cardiolipin. The break in the Arrhenius plot was abolished by incubation of the enzyme in high salt (I = 1.8), but only in Ca2+ -chelating conditions. At I = 1.8 neither NaCl alone, CaCl2 nor sodium phosphate at acidic pH abolished the break. However, at this ionic strength either NaCl in 2 mM sodium phosphate (pH 7.4) or sodium phosphate, pH 8, or 1.0 M Na2CO3/NaHCO3 (pH 8.5--10, were able to remove the break. The Arrhenius plot break was regenerated by the addition of Ca2+ to the high salt-treated enzyme with mild homogenization, but could not be regenerated in the presence of EDTA unless CaCl2 was added in excess of the EDTA. Conditions which abolished the break enabled endogenous cardiolipin to be removed from the enzyme by chloroform/methanol extraction Cardiolipin from acetylcholinesterase incubated in high salt in Ca2+ -chelating conditions was not accessible to digestion by phospholipase A2, and was not separated from the enzyme by flotation in a sucrose density gradient or by Sephadex G-200 chromatography. Thus both Ca2+ and cardiolipin appear to be inaccessible, possibly by being tightly associated in the hydrophobic core of the enzyme by ionic and hydrophobic forces. Ca2+ may modulate the temperature dependence of acetylcholinesterase activity through a functionally linked ionic interaction with the enzyme-cardiolipin complex.


Studies on the turnover of proteins of the rat erythrocyte membrane. The membrane proteins of erythrocytes were labeled by injecting L-[14C]-leucine and later L-[3H]leucine into rats, the two injections being 31 days apart. Control animals received the two isotopic forms of L-leucine simultaneously. Deviations in labeling ratio from control patterns were found on sodium dodecyl sulfate-polyacrylamide gel electrophorograms in restricted regions suggestive of turnover or loss of a few small proteins from the membrane between the 31 days. Most of the ghost proteins show no turnover.


Integral membrane protein interaction with Triton cytoskeletons of erythrocytes. The organization of erythrocyte membrane lipids and proteins has been studied following the release of cytoplasmic components with the non-ionic detergent Triton X-100. After detergent extraction, a detergent-resistant complex called the erythrocyte cytoskeleton is separated from detergent, solubilized lipid and protein by sucrose buoyant density sedimentation. In cytoskeletons prepared under isotonic conditions all of the major erythrocyte membrane proteins are retained except for the integral protein, glycophorin, which is quantitatively solubilized and another integral glycoprotein, band 3, which is only 60% removed. When cytoskeletons are prepared in hypertonic KCl solutions, band 3 is fully solubilized along with bands 2.1 and 4.2 and several minor components. The resulting cytoskeletons have the same morphology as those prepared in isotonic buffer but they are composed of only three major peripheral proteins, spectrin, actin and band 4.1. We have designated this peripheral protein complex the 'shell' of the erythrocyte membrane, and have shown that the attachment of band 3 to the shell satisfies the criteria for a specific interaction. Although Triton did affect erythrocyte shape, cytoskeleton lipid content and the activity of membrane proteases, there was no indication that Triton altered the attachment of band 3 to the shell. We suggest that band 3 attaches to the shell as part of a ternary complex of bands 2.1, 3 and 4.2.


Use of fully deuterated micelles for conformational studies of membrane proteins by high resolution 1H nuclear magnetic resonance. Micellar complexes of melittin with fully deuterated detergents have been studied by high resolution 1H nuclear magnetic resonance (NMR). The synthesis of deuterated micelles is described and it is shown that the 1H NMR spectrum of micelle-bound melittin is well resolved and suitable for detailed analysis by conventional high-resolution NMR methods. A preliminary characterization of micelle-bound melittin shows that interaction with the micelle results in different conformational and dynamic features for the hydrophobic and hydrophilic regions of the melittin amino acid sequence. The present experiments on melittin and preliminary results with other polypeptides and proteins demonstrate that in favourable cases high-resolution 1H NMR studies of the complexes formed between membrane proteins and deuterated micelles provides a viable method for conformational studies of membrane-bound proteins.


Membrane components in the red cells of patients with sickle cell anemia. Relationship to cell aging and to irreversibility of sickling. Cholesterol, phospholipid and sialic acid were measured in red cells from patients with sickle cell anemia to determine whether the cells had abnormal concentrations of these components and whether the amounts of these compounds differed in irreversibly sickled cells as compared to non-irreversibly sickled cells. Sickle cells had significantly higher levels of both lipids than similar populations of normal cells, however, comparisons to populations of young control cells showed that the differences were generally not significant. Sialic acid levels in sickle cells were not significantly different from normal cells. Irreversibly sickled cells had lower lipid and sialic acid concentrations than those not irreversibly sickled, but the differences were either not significant or did not occur when compared to young control cells. The studies show that the increased lipid concentrations in the membrane of sickle cells are not abnormal but are related to cell age and that the decrease in membrane components in irreversibly sickled cells is no greater than would be predicted for similarly aged populations of cells.


Classification of microbial, plant and animal cytolysins based on their membrane-damaging effects of human fibroblasts. 38 cytolytic agents of mainly microbial origin were investigated with respect to membrane-damaging activity on human diploid fibroblasts. Increased plasma membrane permeability was measured as leakage of three defined cytoplasmic markers of various sizes: alpha-aminoisobutyric acid, uridine nucleotides and ribosomal RNA. The relative leakages of these markers, caused by different concentrations of the various cytolysins, yielded a leakage pattern for each substance. Five distinct types of leakage patterns were obtained. These were transformed into numerical expressions by calculating the ratios between the amounts of cytolysin needed to release 50% of the nucleotide and ribosomal RNA markers and the amounts required to release 50% of the alpha-aminoisobutyric acid marker (ED50 ratios). A classification of the cytolysins into five groups was arrived at on the basis of the different types of leakage patterns with the aid of reference cytolysins with well-known mechanisms of membrane interaction. These groups comprised: (1) detergent-like agents, (2) agents interacting with only certain constituents of the cell membrane, (3) agents interacting with specific receptor molecules in the membrane, (4) agents inducing small functional holes of a definable size, and (5) agents inducing only a very limited increase in plasma membrane permeability. The system may be useful for characterization and differentiation of new cytolytic agents of various sources as it divides membrane-damaging agents into separate groups on the basis of their principal function on intact human cells.


Examination of intramolecular heterogeneity of plasma membrane protein degradation in canine renal tubular epithelial cells and in rat liver. We have examined the hypothesis that hydrophilic portions of membrane-bound proteins which lie on either side of the phospholipid bilayer may be degraded at a different rate than are the hydrophobic portions of membrane proteins which are within the bilayer. Plasma membrane fractions from cells of the Maden-Darby canine kidney cell line and rat liver were digested with papain and pronase to cleave a mixture of peptides which is enriched in hydrophilic amino acids. It is proposed that these peptides are derived from regions of membrane-bound proteins which lie outside the bilayer. The residual particulate protein is enriched in hydropholic amino acids and presumably contains the portion of membrane-bound proteins which are in direct contact with the bilayer. A double-isotope method was used to assess the relative degradation rates of these two protein fractions. There was no measurable difference in protein degradation rates between the two fractions and the initial plasma membranes. These results suggest that the intramolecular heterogeneity which results from insertion of membrane-bound proteins into a bilayer is not a factor in their degradation.


The use of octyl beta-D-glucoside as detergent for hog kidney brush border membrane. Octyl beta-D-glucoside was synthetized from alpha-acetobromoglucose with an improved method yielding a very pure product with a sharp melting point (108-109 degrees C) and free of intermediate products as judged by IR and NMR spectra. The yield of the synthesis is 66% when referred to alpha-acetobromoglucose. The potency of this compound as a detergent on hog kidney brush border membranes was compared to the action of Triton X-100. Octyl glucoside preferentially extracts aminopeptidase M and gamma-glutamyltranspeptidase in a concentration-dependent manner. The more deeply imbedded membrane enzyme, alkaline phosphatase, was relatively resistent to the action of octyl glucoside. In contrast, Triton X-100 extracted all membrane proteins to about the same extent. Additionally it was found that octyl glucoside can be removed from membrane extracts by Biobead SM 2. The capacity of the beads is about 170 mg detergent/g of dry Biobead SM 2. Thus octyl glucoside seems to be a useful tool for solubilization and purification of brush border membranes proteins.


Biochemical aspects of the visual process. XL. Spectral and chemical analysis of metarhodopsin III in photoreceptor membrane suspensions. The late photointermediates of rhodopsin photolysis have been analyzed spectrally and chemically in bovine rod outer segment membrane suspension at 25 degrees C and pH 6.5. The decay of metarhodopsin II follows two spectrally distinct routes, resulting 40 min after illumination in a stable mixture of photo-products with absorbance maxima around 380 and 452 nm, free retinal and metarhodopsin III, respectively. Chemical analysis shows that three different products are involved: free retinal (approx. 34%), protein-bound retinal (approx. 51%) and lipid-bound retinal (approx. 15%). The latter fraction consists of retinylidene-phosphatidylethanolamine exclusively. Photolysis of membranes reconstituted with various phospholipids gives a qualitatively normal spectral picture, but the production of metarhodopsin III  may vary with the phospholipid composition, i.e. with the percent of phosphatidylethanolamine present. Chemical analysis shows that with increasing phosphaatidylethanolamine content of the membrane, the retinylidene phosphatidylethanolamine fraction increases proportionally at the expense of free retinal, while the fraction of protein-bound retinal remains unaffected. The results indicate that under these conditions metarhodopsin III (defined as a long wavelength product of metarhodopsin II decay) is composed of two chemically distinct components: opsin-bound retinal and retinylidene phosphatidylethanolamine.


Zero extracellular K+ and prostaglandin E release in the guinea-pig taenia coli. Prostaglandin E release rates from isolated strips of guinea-pig taenia coli increased during exposure to zero K+ bathing fluid, from control values of 0.78 +/- 0.11 ng/g per min to levels as high as 29.2 ng/per min. Release rates increased for 40-50 min and then remained constant or fell despite progressive increases in intracellular sodium [Nai+] or fall in intracellular potassium [Ki+]. Readmittance of K+ to the bathing solution resulted in rapid reversal of elevated prostaglandin E release rates. [Nai+] and [Ki+] were markedly more abnormal in strips exposed to zero K+ for 70-201 min compared to 30-min exposures. Upon the readdition of K+ after long zero K+ exposure, the rate of prostaglandin E release fell long before  [Nai+] and [Ki+] returned to control levels. After K+ was readded to the bathing solution, the ion concentration of tissues exposed to zero K+ for 30 min returned to normal much more quickly than did those of tissues exposed for the longer time periods, yet the exponential rate constants for fall of prostaglandin E release rate after K+ was added were not significantly different after short or long zero K+ exposure. Thus there was a dissociation between the return of [Nai+] and [Ki+] and the fall of prostaglandin E release rate to control levels. Ouabain augmented prostaglandin E release under conditions where [Ki+] could not fall. Addition of known neurotransmitters present in this tissue to the bathing fluid did not augment prostaglandin E release. Guinea-pig taenia coli strips that had been incubated with [3H]arachidonic acid, constantly released [3H]arachidonic acid and [3H]prostaglandin E and a prostaglandin which cochromatographed with prostaglandin E but could not be converted to prostaglandin B by alkali and was shown to be 6-ketoprostaglandin F1 alpha. Release of [3H]arachidonic acid and [3H]prostaglandin E plus 6-[3H]ketoprostaglandin F1 alpha was increased when strips were exposed to zero K+. Data obtained in this study suggest the augmented prostaglandin E release seen during zero K+ or ouabain is related to increased availability of unbound arachidonic acid at the site of cyclooxygenase in the cell. Augmented prostaglandin E release is apparently not related to alterations in intracellular electrolyte concentrations or release of known neurotransmitters.


Properties of bilayer membranes in the phase transition or phase separation region. The increase in passive permeability of bilayer membranes near the phase transition temperature is usually explained as caused by either the increase in the amount of 'boundary lipid' present in the membrane, or by the increase in lateral compressibility of the membrane. Since both the amount of 'boundary lipid' and the lateral compressibility show a similar anomaly near the transition temperature, it is difficult to distinguish experimentally between the two proposed mechanisms. We have examined some details of both of the proposed pictures. The fluid-solid boundary energy, neglected in previous work, has been computed as a function of the domain size. For a single component uncharged lipid bilayer, the results rule out the existence of even loosely defined solid domains in a fluid phase, or vice versa. Thermodynamic fluctuations, which are responsible for anomalous behaviour near the phase transition temperature, are not intense enough to approximate the formation of a domain of the opposite phase. Turning next to lateral compressibility of bilayer membranes we have considered two-component mixtures in the phase separation region. We present the first calculation of lateral compressibility for such systems. The behaviour shows interesting anomalies, which should correlate with existing and future data on transport across membranes.


Inhibition of anion permeability of sarcoplasmic reticulum vesicles by 4-acetoamido-4'-isothiocyanostilbene-2,2'-disulfonate. The permeabilities of sarcoplasmic reticulum vesicle membrane for various ions and neutral molecules were measured by following the change in light scattering intensity due to the osmotic volume change of the vesicles. 4-Acetoamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS), which is a potent inhibitor for the anion permeability of red blood cells membrane, inhibited the permeability of sarcoplasmic reticulum for anions such as Cl-, Pi and methanesulfonate, while it slightly increased that for cations and neutral molecules such as Na+, K+, choline and glycerol. Binding of 5 mumol SITS/g protein was necessary for the inhibition of anion permeability. These results suggest the existence of a similar anion transport system in sarcoplasmic reticulum membrane as revealed in red blood cell membrane.


The interaction of n-octanol with black lipid bilayer membranes. The electrical capacities of black lipid films formed from monoolein + n-hexadecane and monoolein + squalane (or squalene) solutions have been measured in the presence of various concentrations of n-octanol. In addition, partition coefficients for n-octanol between n-hexadecane and 0.1 M NaCl, dielectric constants for octanol-hexadecane mixtures and the interfacial tension of films and film-forming lipid solutions against the aqueous phases have been determined. It is concluded that in "solvent-free" bilayers the octanol is unlikely to have changed the bilayer thickness by more than about 1 A. The bilayer tension, on the other hand, increases appreciably in the presence of octanol.


A comparative study of the phase transitions of phospholipid bilayers and monolayers. Phase transitions in bilayers and monolayers of various synthetic phospholipids with different chain lengths as well as different polar head groups were studied by differential scanning calorimetry or with the film balance technique, respectively. With the film balance, area versus temperature curves (isobars) were recorded at different surface pressures. The monolayer phase transition from the fluid-condensed to the fluid-expanded phase is shifted towards higher temperature when the lateral pressure in the monolayer is increased. The temperature dependence of the equilibrium pressure as well as the magnitude of the area change at the transition depends only on the nature of the phospholipid head group and not on the chain length of the hydrocarbon chains of the lipid. Phospholipids with strong intermolecular attractive interactions between the head groups show low values for dpi/dTm and for the area change, deltaf, whereas phospholipids with negatively charged head groups without intermolecular attractive forces exhibit higher values for dpi/dTm and deltaf. The shift of the monolayer phase transition temperature when increasing the chain length of the lipid is almost identical to the shift in Tm observed for the bilayer system of the same phospholipids. A comparison of monolayer and bilayer systems on the basis of the absolute value of the molecular area of the phospholipid in the bilayer gel phase and the change in area at the bilayer and monolayer transition leads to the following conclusions. The behaviour of the bilayer system is very similar to that of the respective monolayer system at a lateral pressure of approx. 30 dyne/cm, because at this pressure the absolute area and the area change in both systems are the same. Further support for this conclusion comes from the experimental finding that a lateral pressure of 30 dyne/cm the shift in Tm due to the increase in charge when the methyl ester of phosphatidic acid is investigated is the same for the bilayer and the monolayer system.


Fusion of phosphatidylserine and mixed phosphatidylserine-phosphatidylcholine vesicles. Dependence on calcium concentration and temperature. Dynamic light scattering has been used to study the temperature dependence of Ca2+-induced fusion of phosphatidylserine vesicles and mixed vesicles containing phosphatidylserine and different phosphatidylcholines. The final vesicle size after Ca2+ and EDTA incubation serves as a measure of the extent of fusion. With phosphatidylserine vesicles, the extent of fusion shows a sharp maximum at an incubation temperature which depends on the Ca2+ concentration between 0.8 and 2 mM. The shift in the fusion peak temperature with Ca2+ concentration is similar to the typical shift in the phase transition temperature with divalent cation concentration in acidic phospholipids. The results suggest a direct correlation between the fusion peak temperature and the phase transition temperature in the presence of Ca2+ prior to fusion. With mixed vesicles containing up to 33% of a phosphatidylcholine in at least 2 mM Ca2+, the extent of fusion as a function of incubation temperature also shows a maximum. The fusion peak temperature is essentially independent of the quantity and type of phosphatidylcholine and the Ca2+ concentration, and identical to that with pure phosphatidylserine in excess Ca2+. The results imply that Ca2+- induced molecular segregation occurs first, and fusion subsequently takes place between pure phosphatidylserine domains.


The interaction of various lanthanide ions and some anions with phosphatidylcholine vesicle membranes. A 31P NMR study of the surface potential effects. The interaction of various lanthanide ions with vesicles of phosphatidylcholine from egg yolk has been followed by 31P NMR at 30 degrees C. From known magnetic properties of these ions, separation of the paramagnetic shift into a pure contact and a pseudo-contact part was carried out. Binding curves for the contact contribution (F curves) were obtained from vesicles in solutions of sodium salts with monovalent anions over a wide concentration range. These curves should be insensitive to any conformational effects due to ion binding. Indication of a conformational change in the lipid head group at low ion binding was obtained by studying the ratio between the contact and the pseudo-contact contributions. Besides the adsorption of lanthanide ions, specific anion binding to the surface was introduced to account for the enhanced chemical shifts (Cl- <  Br- < NO3-). The results were analyzed in terms of the theory for the diffuse double layer (Gouy-Chapman-Grahame) with equilibrium conditions for the adsorbing cations and anions. Simulations of the titration curves furnished parameters for the ion-lipid interactions. The synergism between the cations and anions follows from the potential effects. Comparison of results with lanthanide ions and Ca2+ indicates that the anion adsorption probably depends on the nature of the adsorbed cation. Lanthanide ion binding to L-glycerophosphorylcholine is not influenced by sodium salts. The binding constant for this complex is weaker than with phosphatidylcholine. The chemical shifts for the lanthanide ion complexes with these two phosphorus compounds seem to be about the same.


Enzyme changes associated with mitoichondrial malic enzyme deficiency in mice. A genetically determined absence of mitochondrial malic enzyme (EC 1.1.1.40) in c3H/c6H mice is accompanied by a four-fold increase in liver glucose-6-phosphate dehydrogenase and a two-fold increase for 6-phosphogluconate dehydrogenase activity. Smaller increases in the activity of serine dehydratase and glutamic oxaloacetic transaminase are observed while the level of glutamic pyruvate transaminase activity is reduced in the liver of deficient mice. Unexpectedly, the level of activity of total malic enzyme in the livers of mitochondrial malic enzyme-deficient mice is increased approximately 50% compared to littermate controls. No similar increase in soluble malic enzyme activity is observed in heart of kidney tissue of mutant mice and the levels of total malic enzyme in these tissues are in accord with expected levels of activity in mitochondrial malic enzyme-deficient mice. The divergence in levels of enzyme activity between mutant and wild-type mice begins at 19--21 days of age. Immunoinactivation experiments with monospecific antisera to the soluble malic enzyme and glucose-6-phosphate dehydrogenase demonstrate that the activity increases represent increases in the amount of enzyme protein. The alterations are not consistent with a single hormonal response.


Flavoprotein-linked substrate oxidation in preparations of hamster brown adipocytes. A discrimination between internally and externally oxidized substrates. Noradrenaline-stimulated oxidative metabolism in isolated hamster brown fat cells is very reproducible between different cell preparations, 565 +/- 81 (S.D.) nmol O/min per 10(6) cells (n = 25). In contrast, the oxygen consumption rate induced by the addition of succinate or sn-glycerol 3-phosphate strongly varies between different cell preparation, although these substances have been reported to be potent substrates for isolated hamster brown fat cells. By filtration and by successive washings we demonstrate that the flavoprotein-linked substrate oxidation is mainly dependent on extracellular succinate and sn-glycerol 3-phosphate-oxidizing enzymes. These enzymes originate from damaged and broken cells and are present in different amounts in different cell preparations. In discriminating between intra- and extracellular succinate oxidation 5,5'- dithiobis(2-nitrobenzoate) is used as an inhibitor of the extracellular portion. This application of 5,5'-dithiobis(2-nitrobenzoate) ought to be useful also in other cell or tissue preparations. Added succinate can, however, be oxidized by the intact brown adipocyte but at very low rate, probably as a result of a limited transport rate over the membrane(s). In the presence of noradrenaline, added succinate can potentiate the noradrenaline-inducible oxygen consumption by catalytically increasing the oxidative capacity of the citric acid cycle. Our conclusions is that the only effectors which significantly increase oxidative metabolism in intact isolated hamster brown fat cells are catecholamines and free fatty acids. Provided the cells are uncoupled, also pyruvate can function as substrate for these cells.


The relationship between energy generation and cholesterol side-chain cleavage reaction in the mitochondria from human term placenta. 1. The interrelationship between progesterone (from cholesterol) biosynthesis and oxidative phosphorylation in human placental mitochondria was examined. 2. ADP and ATP stimulated the malate, succinate and alpha-ketoglutarate-supported progesterone biosynthesis probably via the energy-dependent pyridine nucleotide transhydrogenase activation. The effect of ADP was abolished by rotenone and antimycin in the presence of malate or alpha-ketoglutarate. 3. In the non-energized state of mitochondria malate may supported progesterone biosynthesis by the malic enzyme-dependent pathway. 4. The inhibitory effects of antimycin or cyanide, and the stimulatory effect of rotenone on the succinate-supported progesterone biosynthesis indicate that the succinate to malate conversion is a necessary condition for the stimulation of progesterone biosynthesis from cholesterol. 5. alpha-Ketoglutarate plus malonate did support progesterone biosynthesis also in the presence of ADP or ATP and to a lesser degree in the presence of DNP and rotenone. Arsenate in the presence of alpha-ketoglutarate, malonate, dinitrophenol and rotenone did not affect significantly progesterone biosynthesis. These results indicate that NADPH may be generated also by a non-energy-dependent transhydrogenation in placental mitochondria.


Endocytic vesicles in liver carry polymeric IgA from serum to bile. The distributions both of endogenous IgA and of injected 125I-labelled IgA were determined amongst the components of a liver homogenate. Rate zonal sedimentation, under conditions where separation was principally determined by particle size, showed that IgA was tightly bound to material which sedimented in the size range of the larger endoplasmic reticulum fragments. Further fractionation of the components within this size range according to their densities, by isopycnic centrifugation, showed that the IgA was associated with small vesicles with a density range of 1.12--1.17 g/ml, quite distinct from endoplasmic reticulum fragments. We therefore conclude that the IgA is present in liver cells in a distinct class of vesicles, which are, presumably, responsible for the transport of IgA from blood to bile.


Characterization of glycopeptides isolated from membranes of F9 embryonal carcinoma cells. From cells of a nullipotential line of embryonal carcinoma was isolated a membrane fraction enriched in the cell surface F9 antigen. More than 40% of the radioactive fucose and galactose incorporated by cells into nondialyzable material was recovered in this membrane preparation, corresponding to an approximately 10-fold purification of the labeled material. Extreme heterogeneity of membrane glycoproteins labeled with these sugars was revealed by sodium dodecyl sulfate gel electrophoresis. Glycopeptides prepared by extensive pronase digestion of membranes labeled with fucose or galactose showed properties similar to those already described for fucose-labeled glycopeptides from whole cells. Namely, large glycopeptides eluted near the excluded volume of Sephadex G-50 column were the predominant glycopeptide species, while complex glycopeptides of molecular weight around 2500 were minor components. Therefore, these large glycopeptides, characteristic of embryonal carcinoma cells, are derived mainly from a variety of glycoproteins closely associated with the membrane system, most probably cell-surface membrane of the cells. The large glycopeptides were also significantly labeled with glucosamine, but only slightly with mannose; major components of mannose-labeled glycopeptides from the membranes were high-mannose glycopeptides of low molecular weight. Several experiments excluded the possibility that the larg glycopeptides are mucopolysaccharides, glycolipids or mucin-type glycoproteins with short oligosaccharide chains.


Stereochemical structure recognized by the L-fucose-specific hemagglutinin produced by Streptomyces sp. A hemagglutinin has been purified 4000-fold from the culture filtrate of a strain of Streptomyces by affinity chromatography. The purified preparation was judged to be homogeneous by gel electrophoresis and its molecular weight was estimated to be about 70 000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It may exhibit its full hemagglutinating activity in the monomer form. This hemagglutinin strongly agglutinated human blood group O erythrocytes and was inhibited by L-fucose. It was, however, distinct from the known L-fucose-specific hemagglutinins; first, the hemagglutinating activity of the purified preparation was more than 100-times stronger than that of others; second, D-mannose was a potent inhibitor of this hemagglutinin besides L-fucose but not or scarcely inhibitory to others; and third, p-nitrophenyl-beta-L-fucoside was more inhibitory to this hemagglutinin than p-nitrophenyl-alpha-L-fucoside as opposed to the case of others.


The kinetics of myofibrillar protein breakdown in perfused rat skeletal muscle. Nt-Methylhistidine, a non-reutilised amino acid present in some myofibrillar proteins, was radioactively labelled in vivo with [Me-3H]methionine. The specific radioactivities of protein-bound methylhistidine and free methylhistidine in perfusate after perfusion of rat hind limbs taken from prelabelled rats was determined. The decrease in urinary methylhistidine activity with time was determined for rats similarly labelled. Comparison of the specific activities of free and bound methylhistidine and the non-linear semilogarithmic plot of urinary methylhistidine activity suggest that the myofibrillar protein catabolism, as indicated by methylhistidine release, may not be a simple exponential process. The possibility of non-random decay is discussed and an alternative model proposed.


Vasopressin-sensitive adenylate cyclase. Reversibility of hormonal activation. The reversibility of adenylate cyclase activation induced by vasopressin was studied by reducing the concentration of active peptide in contact with kidney medullo-papillary membranes. Reversibility of hormonal activation was only partial. The use of antagonists failed to demonstrate the reversibility of an adenylate cyclase activation induced by high affinity agonists. When antagonist was added after the agonist to membranes, a non-competitive inhibition was apparent. Active peptide was also eliminated from the incubation medium by treatment with agents capable of reducing the disulfide bridge of the hormonal molecule. Direct effects of reducers on adenylate cyclase activity were measured on enzyme activation induced by peptides lacking a disulfide bridge. There was no apparent correlation between the abilities of different reducers to inactivate free peptide in solution and their abilities to promote the reversibility of hormone-induced enzyme activation. Upon the addition of dithiothreitol, enzyme activity could be lowered to basal value and adenylate cyclase was again fully stimulatable. However, when dithiothreitol addition to stiumlated enzyme was combined with a 60-fold dilution of the incubation medium, no reversibility of hormonal activation occurred. These results illustrate that the processes involved in adenylate cyclase activation are only partially reversible.


Mechanism of polycation stimulation of pinocytosis. Synthetic polycations cause a stimulation in the rate of tissue accumulation of colloidal 198Au by the rat visceral yolk sac (at 17.5 days of gestation) and rat peritoneal macrophages cultured in vitro. The mechanism of stimulation has been elucidated in these two cell types by using a dual-substrate technique, and by examining the differential effects of poly(D-lysine) and poly(L-lysine) and of metabolic and cytoskeletal inhibitors. Polycations cause aggregation of colloidal 198Au in the culture medium and increase its affinity for the plasma membrane. In the rat peritoneal macrophage this polycation-colloidal gold complex is pinocytosed, thus enhancing the intracellular accumulation of the radio-labelled substrate. In contrast, the rat visceral yolk sac cannot internalize this complex, and so the substrate accumulates extracellularly. This mechanism of polycation modification affords the opportunity for differential uptake of a substrate into distinct cell types.


Dynamics of habituation in different cortical regions of the cat brain. The dynamics of habituation in the rostral part of the parietal association region and also in the first and second somatosensory areas was studied by the evoked potentials (EP) method in cats anesthetized with chloralose (80-90 mg/kg) and immobilized with flaxedil. During repeated stimulation of the splanchnic nerve brief habituation of EP developed in the cortex. It corresponded in its basic features to habituation observed in other sensory systems. On comparison of the rates of development of habituation in the primary and secondary projection zones of the splanchnic nerve in the cortex differences were found: habituation developed more rapidly in the secondary projection zones. The functional importance of this phenomenon is discussed.


Investigation of the type of induction of microsomal monooxygenases by polycyclic hydrocarbons. The severity of the induced effect of the polycyclic hydrocarbon 3-methylcholanthrene on monooxygenase of the microsomal fraction of the liver as a function of the number of binding sites for this inducer in the active site of cytochrome P-450 was investigated. In vivo models, in which the primary bounding and metabolism of a polycyclic hydrocarbon in the microsomes is increased or sharply inhibited, are presented. It is concluded that in the mechanism of induction by 3-methylcholanthrene, the activation of synthesis of specific protein (cytochrome P-448) is accomplished not by the initial molecule of the inducer, but by products of its primary metabolism in the microsomes.


Competition between species of the aestivo-autumnal group of birch pests for food in Transuralia. The aestivo-autumnal group of birch pests includes 25 species belong to the Notodontidae, Geometridae, Noctuidae, and other families. The larvae of all its species hatch out in mid-July and feed until the end of August. On emerging from the eggs they spread from leaf to leaf, but as the food supply diminishes they crowd together and competition is intensified. The species structure of the group shows some variation over the territory, and only a few species dominate, different species in different places. It is suggested that improvement in the food supply leads to mass reproduction. Biochemical investigations confirmed this hypothesis: different species feeding on the same leaf assimilate different amino acids more completely, and their relative numbers on the leaves vary in different parts and at different times. The composition of secondary metabolites important for resistance of the plants also varies.


Lipid composition of cells and its variation during degradation of a culture of Streptococcus diacetilactis. The process of dying of a culture of Str. diacetilactis under conditions of prolonged culturing is accompanied by substantial changes in the composition of the cell lipids. In the lipids of young cells the basic components are mono- and diglucosyldiglycerides, as well as phospholipids--two glucophospholipids, cardiolipin, and phosphatidylglycerin; triglycerides and sterols are present in negligible amounts. As the Str. diacetilactis culture develops and undergoes degradation, an increase is observed in the total amount of extractable lipids. In this case the fraction of phospholipids increases (chiefly on account of cardiolipin), while the fraction of neutral glucolipids decreases. It was shown that in cell homogenates there is a negligible peroxidation of lipids, which is intensified as the culture dies off. There is a parallel acceleration of the uptake of O2 by cell suspensions from cultures of different ages. The detected changes in the lipids are correlated with the morphological and physiological indices of the state of the culture.


Some general principles of tissue crushing and regeneration during sutureless anastomosis of hollow organs of the alimentary tract. Tissues of the hollow organs of the gastrointestinal tract are crushed in order to create an anastomosis. The processes taking place in the tissues have been inadequately studied. A model of the tissue crushing process is suggested and the results of theory and experiments are compared. Dependence of the rejection time of the crushing influence on the crushing force was demonstrated experimentally. The relationship obtained can be explained on the grounds that migration of cell destruction products from the zone of crushing to the zones of healing stimulates adequate cellular immunologic processes. The views developed in this paper may prove useful for the elaboration of new surgical techniques.


Investigation of the interaction of trypsin with heparin. The reversible inhibition of the enzymatic activity of trypsin by heparin was investigated. On the basis of an analysis of the Lineweaver-Burk and Dixon graphs, a noncompetitive nature of the inhibition of the BAPA amidase activity of trypsin by heparin was detected, and the values of Km and Ki were determined, equal to 3.1 . 10(-4) and 3.7-3.9 . 10(-7) M, respectively. A comparison of these values indicates a great affinity of heparin for the enzyme. It was shown that heparin inhibits the BAEE esterase activity of trypsin and at the same time has no inhibiting effect on acetyltrypsin. Considering that the acetylation of trypsin leads to selective blocking of the epsilon-amino groups, it was concluded that the epsilon-amino groups of the lysine residues of the trypsin molecule participate in the interaction with heparin.


Critical remarks on the theoretical bases of the biological effects of a magnetic field. The article gives a critical analysis of the theoretical approach of the authors to the explanation of the biological effects of a magnetic field (MF), enlisting two hypotheses: the diffusely orienting influence of the MF on the association of diamagnetically anisotropic molecules of biopolymers in solutions and the kinetic influence of the MF on the biochemical reactions in which free radicals participate; typographical errors made in two articles, inaccuracies in formulas, and errors in calculations of the potential energy of deformation of the aromatic residue are corrected. The value of the energy of deformation of the anisotropic aromatic residue, equal to  6.4 . 10(-3) cal/mole, is small in comparison with the energy of deformation of the tetrahedral C-C bond angle and cannot be used as the basis for interpretation of the experimental data obtained. New approaches are outlined for the explanation of the possible diamagnetically anisotropic effect of the MF in specifically nonequilibrium, kinetic, and nonthermodynamic processes in which biopolymers participate. The hypotheses advanced to explain the biological effects of the MF cannot yet be considered entirely supported theoretically, and, consequently, they are in need of further theoretical investigation and experimental proof.


Influence of infralow-frequency magnetic fields of high and ultrahigh intensity on the division of mammalian cells in vivo. The influence of an infralow-frequency magnetic field (IMF) with intensity 3-127 k0e for 1 h on the mitotic activity, frequency of chromosome aberrations, and number of corneal epithelial cells of mice was studied. It was shown that the changes in mitotic activity that arise can be explained by a reversible inhibition of cell division at late stages of the mitotic cycle and synchronous entry into mitosis after the removal of this inhibition. The nature of the dependence of the effect on the intensity of the IMF is evidence of a difference in its molecular mechanisms in the region of high and ultrahigh intensities. As a result of the influence of an IMF of the intensity and duration used, no increase in the frequency of aberrant mitoses in corneal epithelial cells was detected. The number of cells in a standard visual field of the microscope also was practically unchanged.


Role of red and far-red light in frost resistance of yarovized winter wheat after thaw. The short day in the thawing of hardened winter wheat, yarovized to a different degree, increased its frost resistance in comparison with uninterrupted illumination. Interruption of darkness of the short-day cycle by red light reduced frost resistance, far-red light had the opposite effect, but to a different degree, on the length of yarovization. Maximal resistance developed toward the end of the yarovization period. There were observed changes connected with the stabilization of the photoacceptor of the phytochrome system in the process of yarovization. The phytochrome complex participated in regulation of the movement and utilization of metabolites. There was revealed the variety specificity of winter wheat in relation to the investigated characters.


Methods of chromatography and quantitative analysis of galacto- and phospholipids of plant leaves. Data in the literature on chromatography of glycerolipids of plant leaves on columns of DEAE-cellulose, Sephadex LH-20, silica gel, florisil, in a thin layer of silica gel, paper are generalized. Methods of obtaining chromatographically pure glycerolipids, their subfractionation, and the quantitative analysis of glycerolipids are described. Experimental data are presented on fractionation of lipids of potato leaves on columns of DEAE-cellulose, silica gel, on paper, and the quantitative determination of phospholipids. A method of rapid division of lipids into classes by means of their elution with silica gel KSC by different solvents is described.


Phage-like infectious virus of the green alga Chlorococcum. A pure culture of the green eukaryotic alga Chlorococcum sp. and a virus infectious for it were isolated. Infection of the culture leads to the destruction of most of the cells, although complete destruction of the culture is not usually observed. The virus particles are similar in morphology to bacteriophage and consist of a hexagonal head 220 nm long and 180 nm wide and a tail which is inside the head in a majority of the particles, but which is on the outside in some. The virus is not adsorbed on the cell membranes, but evidently penetrates into the zoospores through the flagellar channels, where particles of it are regularly found. Destruction of the nucleus and membrane structures of the cytoplasm occurs during growth of the virus, but the chloroplasts and mitochondria are retained. The membranes of infected cells are partially destroyed and the virus particles are released into the medium. The virus is designated as PLVCH (L)--page-like virus of Chlorococcum.


Life forms of Pteridophyta, their origin and evolution. The following separation of the main growth forms of Pteridophyta is proposed: thin-rhizomatous, creeping-rosetted, ascending-rosetted, vertical-rosetted, and arborescent. Each of these can be divided into life forms according to a series of morphological and other characters. The most primitive growth form of Pteridophyta is acknowledged as the thin-rhizomatous. In the course of evolution toward polymerization and integration of fronds, the group of arborescent Pteridophyta were transformed into shoot plants, initially of the Cycas type. Water ferns (Salviniaceae) and seed ferns (Pteridospermae) are known as the arbitrary type of Lycopsida which did not reach the state of shot structure of the body. In this respect, Equisetales occupy an intermediate position. It may be assumed that in the evolution of plants, the change in their life forms was of paramount significance.


Probability model of dibunol pharmakinetics. A mathematical description of the inflow of dibunol from the site of administration and its distribution by organs and tissues in experimental animals and man are examined. Parameters quantitatively characterizing the behavior of the preparation in the organism were obtained. The mechanism of the accumulation of dibunol in the tissues and its subsequent transfer to the blood are described within the framework of the proposed model. The model of the pharmakinetics of dibunol makes possible a calculation of the concentration of the preparation in the tissues depending on the method of administration and special features of the medicinal form. In clinical practice when administered per os microcapsules, which provided maximum absorbability, proved to be the best medicinal form. Satisfactory agreement of the concentrations of the preparation actually observed in a human tumor with those calculated theoretically on the basis of the proposed model was observed.


Changes in dry weight of pyramidal cell nuclei in the motor cortex during local motor-food conditioning. The formation of a local motor-food conditioned reflex in rats, consisting of pressing on a level with the unpreferred paw, in one session led to a decrease in dry weight of the large pyramidal cell nuclei in the area of representation of that paw in the motor cortex. Frequent repetition of the local motor-food conditioned reflex consisting of pressing on the level with the preferred paw was not accompanied by any such changes. It is suggested that changes in dry weight of the large pyramidal cell nuclei in the area of representation of the unpreferred paw are due to involvement of these neurons in the formation of the new motor coordination (the local conditioned reflex).


Temporal organization of the thyroid gland in A/He mice (morphometric investigation). Biological rhythms of structural elements of the thyroid gland of A/He mice were studied by morphometric methods followed by spectral amplitude and phase analysis on the Minsk-32 computer. The morphological data show that the activity of the organ is maximal at night. The biorhythms have a complex frequency spectrum, including intradian, circadian, and ultradian components.


Biological and immunological properties of crystalline proteins from B. thuringiensis var. galleriae and var. insectus. The antigenic and toxic properties of the crystalline proteins from two varieties of B. thuringiensis (var. galleriae and var. insectus) were studied. Methods of double diffusion in agar and two-dimensional disc immunoelectrophoresis revealed four antigens in the crystalline protein from var. galleriae and three in that from var. insectus. A definite correlation was found between the toxicity of the crystalline protein and its capacity to interact with antiserum in a precipitation reaction in agar. It was established that the total protein content cannot be used as the criterion for an evaluation of the activity of preparations from B. thuringiensis. Immunodiffusion methods are recommended for an evaluation of the quality of these preparations.


Dynamics of production of extracellular polysaccharides by nodule bacteria. The dynamics of the accumulation of the extracellular polysaccharides synthesized by nodule bacteria and the possibility of their assimilation by these bacteria as a source of carbon was studied. When nodule bacteria were cultured for 20 days in a medium containing glucose, an increase in the titer of the bacteria and the accumulation of extracellular polysaccharides was observed in the first three days. After this the titer of the nodule bacteria decreased with a decrease in the glucose in the medium, but the amount of extracellular polysaccharide synthesized did not increase. These data suggest that extracellular polysaccharides are not assimilated by nodule bacteria as a source of carbon and evidently are protective substances for the cells.


Antioxidative activity of lipids in mice during aging and administration of an antioxidant with gerontological protective action. Changes in the antioxidative activity (AOA) of the liver were studied during natural aging in noninbred and C3HA mice and during administration of the synthetic anti-oxidant 2-ethyl-6-methyl-3-hydroxypyridine hydroxypyridine hydrochloride to the animals, and the effect of the doses of this compound on the level of AOA in the liver of animals aged 2 months also was investigated. Liver AOA in mice was found to decrease during aging; the decreae in animals with tumors was found to be two or three times slower than in animals without tumors. Administration of the compound after the age of 8 months led to a considerable increase in liver AOA, and this may evidently account for the considerable lengthening of the life of the experimental animals.


Peculiarities of human sleep in the case of double alternation of "sleep-waking" cycles. The dynamics of sleep was studied in seven healthy subjects in two schedules, differing in the magnitude of the sleep intervals and their distribution over the 24 hour period. The first series provided for the use of two four-hour sleep intervals, the second six- and two-hour intervals. The investigations showed that the transition to a new schedule was accompanied by substantial qualitative and quantitative sleep disturbances, followed by a restoration of sleep as the subjects adapted. Less pronounced sleep disorders and more rapid restoration were observed in the schedule with nonuniform distribution of the intervals; more pronounced sleep disorders and a slowed restoration of sleep were observed on the schedule with two four-hour intervals.


Fine structure of vegetative mycelium and spores of Nocardia spp. The fine structure of a fragmenting and sporulating mycelium of cultures of actinomycetes possessing biochemical properties characteristic of the genus Nocardia--a cell wall of type IV and lipid LCN a--was studied. It was found that fragmenting  hyphae are similar in structure to the vegetative hyphae of known actinomycetes. Sporulation takes place through the simultaneous division of a sporulating hypha by numerous septa. Spores differ from vegetative cells in the presence of a thickened electron-dense cell wall, dense internal contents, and the presence of vacuoles.


Probability screening model.

Probability screening model. A comparative analysis is given of various types of systems of selecting biologically active substances. A theoretical probability model of tests on chemical compounds for biological activity (screening) has been constructed which permits an evaluation of the efficacy of screening on the basis of fairly reasonable assumptions. It has been shown that this efficacy decreases in time with a fixed number of types of activity taken into consideration and rises sharply with an increase in the number of types of activity of chemical compounds taken into account in the tests.


Chemical structure and antifungal activity of a number of triterpenoids. Antifungal activity was tested in 49 pentacyclic triterpenoids and their glycosides, of plant and semisynthetic origin. Several of these compounds inhibited the multiplication of the yeast Saccharomyces carlsbergensis. The highest antifungal activity was found in the triterpene glycosides oleanolic acid and hederagenin, which have a free carboxyl group at C 28(27). Triterpenes of the meristotropic acid, macedonic acid, and lupan types had no fungistatic activity at concentrations up to 100 microgram/ml.


Biological effects of radionuclides on plants. On the basis of analysis of the literature and personal data, principles of dosimetry were determined and an analysis was given of biological effects of radionuclides on plants when administered aerially and by root. A comparison was made of radiosensitivity of barley and dependence of sensitivity on the growth phase of the plant at the time of irradiation with a standard LD50 and UD50. The possibility of using correlated paramaters of bioinformation, such as the sensitivity indicator of evaluation of biological effects caused by small radiation doses, is considered. On the basis of correlations of the data obtained a prognosis is made of the probability of losses in harvest of grains subjected to radionuclides at various periods of development.


Principles of classification of life forms of plants. For classifying life forms of plants a proposal was made to use the principle of parallel divergence based on the hypothesis that life forms diverging to any degree preserve further the potential of evolving in a similar way, that is, in parallel series. Life forms of plants are divided into thirteen types corresponding to the nature of their basic metameres. Further, every type is divided into subtypes and sections according to the character of these metameres and then into smaller grades (classification units of the system of living forms corresponding to one trait and its evolutionary level) according to categories of traits: ramification, vegetative flexibility, rate of changes of metameres, types of habitat and environment. On the basis of the principle of parallel divergence scales of traits were constructed for each category. Corresponding to 26 paires of alternative traits 26 degrees of hierarchic classification were devised and within the limits of every type of life form there were 2(26) grades at the lowest rank. Separate systems were developed for single-celled and colonial forms.


Content of mitochondrial protein in the planarian Polycelis nigra during starvation and feeding. To discover the possible mechanisms determining the level of energy metabolism during changes in the body size of animals, the content of mitochondrial protein was studied in planarians during starvation and feeding. In the course of starvation, the relative content of mitochondrial protein decreases, whereas during feeding it increases. Comparison of the experimental results with previous observations on respiration of planarians under similar conditions shows that changes in the level of respiration during starvation and feeding correlate with the content of mitochondrial protein. However, the degree of the functional load on the mitochondria must be taken into account under these circumstances.


Causes of the resistance of Chlorella strains to physical and chemical environmental factors. Factors have been studied which are responsible for the resistance of cells of several strains of Chlorella to physical and chemical stresses; measurements have been made of the effects of UV and x irradiation, heat treatment, detergents, cadmium salts, and insecticides. Cells which were resistant to the effects of physical factors were also resistant to chemical intoxication. A positive correlation was found between the resistance of cells to the described factors and the level of endogenous thiols in the cells, as well as the free radical content. This in turn is due to an increased number of reaction centers in the electron-transport chain.


Ecology of Zygnema stellinum Vauch. during desiccation of a shallow body of water. the effect of desiccation on the green alga Zygnema, a typical aquatic form of the order Conjugatae, family Zygnemaceae, is investigated. The vegetative reproduction of Zygnema occurs with the separation of the filaments in two different ways. It is shown that changes take place in cell morphology during desiccation. After division most of the cells acquire the shape of a square. These are usually half as large as the vegetative cells prior to division. Also, the form and color of the chromatophores change; they become green-brown, i.e., Zygnema falls into a state of rest, since no cell division is observed. During this state of rest the filaments suffer the unfavorable conditions of summer drought. In the fall, at the end of August, with the shortening of the day and reduction of temperature, the alga develops parthenospores for overwintering.


Lipid peroxidation induced by cercosporin as a possible determinant of its toxicity. The photodynamic action of cercosporin was assayed in various kinds of natural and artificial membranes. Cerosporin induces lipoperoxidation of liposomes, rat liver and pea internode mitochondria and microsomes, estimated both as malondialdehyde (MDA) formation and O2 consumption. Cercosporin-induced lipoperoxidation is inhibited by either singlet oxygen quenchers, free radical trapping agents or EDTA. Superoxide anion (O2-), hydrogen peroxide and hydroxyl radicals (.OH) are not involved in the activity of cercosporin. In addition cercosporin, by chelating iron, lowers the lipoperoxidation induced by such a metal. Therefore cercosporin stimulates, through singlet oxygen production, the hydroperoxide formation but, at the same time, it inhibits the continuation of the iron-mediated free radical chain. The present results suggest that cellular lipid peroxidation has a certain relevance to toxic activity of cercosporin.


Benzo[a]pyrene metabolism in rat fetal hepatocytes culture. Improved methodology and effect of substrate concentration. The different characteristics of benzo[a[pyrene (BP) metabolism in primary fetal rat liver cell culture have been investigated. We have determined the extent of the in vivo [3H]BP metabolism by measuring all of the metabolites retained in the cell and excreted into the culture medium. The extent of the conjugation as well as the nature of the conjugates was established and the pattern of these metabolites analyzed by high performance liquid chromatography (HPLC). The fetal hepatocytes very actively metabolize BP and readily excrete in the culture medium all the produced metabolites in the form of sulfate and glucuronide conjugates. The relative proportion of those compounds varies as a function of the substrate concentration added to the cell culture, the higher the BP concentration, the more glucuronide conjugates. The HPLC analysis of the metabolites shows that BP-1,6-quinone and -3,6-quinone are the major excreted products, indicating the probable existence of an active 6 hydroxylation reaction in the fetal hepatocytes. On the other hand, the pattern of the different metabolites is influenced by the BP concentration. At low BP doses (0.8 microM), the relative amount of polar metabolites is twice as high and that of primary phenols twice as low, when compared to those produced by cells treated with 80 microM BP. The AHH activity drastically modifies the overall rate of the BP metabolism but does not affect the qualitative pattern of the excreted metabolites. The overall metabolism of [3H]BP by the cell culture can easily be estimated by measuring the release of the tritiated water from the substrate into the culture medium.


Unwinding of supercoiled Col E1-DNA after covalent binding of the ultimate carcinogen N-acetoxy-N-2-acetylaminofluorene and its 7-iodo derivative. The unwinding of superhelical Col E1-DNA was studied by means of gel electrophoresis and electron microscopy after covalent binding of N-acetoxy-N-2-[14C]acetylaminofluorene (N-Aco-[14C]AAF) and its 7-iodo derivative (N-Aco-[14C]AAIF). Studies with both compounds indicated that complete unwinding of the supercoiled DNA required the binding of hydrocarbon residue to about 3% of the bases. Thus the unwinding angle per residue of N-2-acetylaminofluorene (AAF) and its 7-iodo derivative was of 22 degrees +/- 3 and 18 degrees +/- 3 respectively. Our results are in good agreement with those obtained by Drinkwater et al. [9]. Precedent studies from this laboratory have shown that N-Aco-AAF and its 7-iodo derivative induce different local conformation change in native DNA (insertion-denaturation model and outside binding model respectively). The unexpected ability of the 7-iodo derivative to unwind supercoiled DNA is discussed.


The metabolism of deuterated analogues of chlorambucil by the rat. The antitumour agent chlorambucil (4[4-bis(2-chloroethyl)aminophenyl]-butyric acid) is converted by beta-oxidation in vivo into phenylacetic mustard (2[4-bis(2-chloroethyl)aminophenyl]acetic acid). This process may be disadvantageous from a therapeutic viewpoint since the metabolite has half the therapeutic index of the parent drug against the Walker 256 carcinoma in rats. In seeking to retard beta-oxidation, selectively deuterated analogues have been synthesised and administered to rats. Plasma levels of phenylacetic mustard after giving chlorambucil-beta-d2 were lower than those given by unlabelled drug, but the therapeutic activity was not significantly altered by deuteration. A dehydro derivative of chlorambucil was detected as an intermediate in the beta-oxidation pathway. The isotopic compositions of this metabolite, and of recovered chlorambucil, were measured in plasma samples taken after giving labelled chlorambucil (alpha-d2 and beta-d2 variants) to rats. Deuterium was almost totally lost from the alpha-d2 form and from its metabolite after 30 min and partially lost in 10 min. The beta-d2 variant and its dehydro-derivative retained the label. Possible mechanisms for deuteration loss are discussed. The design of novel analogues, based on these metabolic studies, is proposed.


Neurochemical and behavioural effects of extended exposure to isopropanol vapour with simultaneous ethanol intake. Exposure of male Wistar rats to 12.3 mumol/l (300 ppm) isopropanol vapour for 5-21 weeks, 5 days a week for 6 h daily with a simultaneous ethanol administration in drinking water (5% v/v) caused a significant increase in isopropanol removal as assessed by blood isopropanol and acetone determinations. Ethanol treatment caused a marked synergistic effect during early exposure. Neurochemical studies revealed decreased superoxide dismutase and azoreductase activities at the end of the exposure whereas increased protein degradation was found in glial cells isolated from ethanol-fed rats throughout the experiment. Analyses of spinal cord axon lipid composition showed increases in cholesterol content in relation to lipid phosphorus in animals exposed to isopropanol or to the isopropanol and ethanol combination. Behavioural tests indicated minor effects on emotional reactivity from the 10th week onwards with isopropanol exposure whereas caffeine-stimulated activity was augmented only in rats ingesting ethanol. Co-exposure to isopropanol vapour abolished the increased excitability. The data indicate that marked metabolic and functional adaptation towards the small-molecular-weight alcohols takes place at moderate dose levels.


Fluorescence study of DNA alkylation by epoxides. A simple fluorescence assay was devised to measure alkylation of guanine. The assay was tested with simple epoxides: propylene oxide, glycidol, epichlorohydrin, trichloropropylene oxide and styrene oxide, which are known to vary considerably in their mutagenic potency. The order of reactivity parallelled the mutagenic potency, trichloropropylene oxide being the most reactive alkylating agent. Each epoxide alkylated deoxyguanosine faster than single-stranded DNA, at equal concentrations of guanine. Single-stranded DNA was alkylated substantially faster than was double-stranded DNA. The reaction products with each substrate were analysed by thin-layer chromatography and exhibited similar Rf-values. It was concluded that polymers, particularly double-stranded DNA, reacted slower than deoxyguanosine due to the properties of polymers in solution rather than the unavailability of reactive sites for alkylation.


Magnesium ions affect the quantitative but not the qualitative microsome mediated binding of benzo[alpha]-pyrene to DNA. Five distinct hydrocarbon-deoxyribonucleoside adducts are separated by high pressure liquid chromatography after reaction of benzo[alpha]pyrene with calf thymus DNA in the presence of liver microsomes from 3-methylcholanthrene treated rats. The two major adducts co-chromatography with deoxyribonucleoside adducts obtained after hydrolysis of calf thymus DNA previously reacted with liver microsomal metabolically activated 9-hydroxy-benzo[alpha]pyrene or trans-7,8-dihydro-7,8-dihydroxybenzo[alpha]pyrene. High magnesium ion concentrations in the microsomal incubations cause a significant decrease in the covalent binding of the hydrocarbon to DNA but do not affect the qualitative distribution of the individual benzo[alpha]pyrene-deoxyribonucleoside adducts.


Binding mode of chemically activated semiquinone free radicals from quinone anticancer agents to DNA. Chemical reduction of the highly active quinone-containing antitumor drugs, adriamycin and daunorubicin formed the same partially reduced free radical previously reported [9] by microsomal activation. In vitro incubation of the chemically activated free radical intermediates with DNA resulted in covalent binding of these drugs to DNA. The adriamycin semiquinone radical has a greater affinity for DNA and covalent complexes up to one adriamycin per 12 nucleotides were obtained. The daunorubicin semiquinone radical, on the other hand, showed a lesser binding affinity and gave rise to complexes in which one drug molecule was covalently bound per 135 nucleotides. The stronger covalent binding of adriamycin to DNA may account for more severe DNA damage induced by this drug.


Metabolism and covalent binding of benzo[alpha]pyrene in human peripheral lung. Short-term organ cultures of peripheral lung from lung cancer patients metabolise benzo[alpha]pyrene to ethylacetate-soluble metabolites, which covalently bind to tissue macromolecules. The nature and quantities of metabolites formed and the extent of covalent binding are dependent upon the time of incubation, the substrate concentration and interindividual variability in the metabolic activity of the lung. Individuals whose lungs rapidly metabolise the carcinogen exhibit more extensive further metabolism of primary metabolites and higher levels of covalent binding. Certain striking differences in the relative retention in the tissue or release into the extra-cellular medium of different metabolites have been found as illustrated by the observation that the ratio of 7,8-dihydro-7,8-dihydroxybenzo[alpha]-pyrene to 9,10-dihydro-9,10-dihydroxybenzo[alpha]pyrene was always significantly higher in the tissue than in the extracellular medium.


Complex formation between selenium and methylmercury. Methylmercury, after incubation at 3k7 degrees C and pH 7.0 with selenite in the presence of rat erythrocytes, can be extracted into benzene as an unstable 2 : 1 complex with selenium. The same complex, possibly bis-methylmercury selenide, is formed when methylmercury is treated with hydrogen selenide at pH 7.0 in the absence of erythrocytes.


[Echotomography in the diagnosis of abdominal masses]. The contribution of echotomography in the surgical approach to intra-abdominal masses is illustrated through description of several clinical observations. In order to effect frontal reconstruction of ultrasonic seriography, the authors used a manual-scanning B echotomograph probe working in the range of grays. This technic afforded detection of the intraperitoneal and extraperitoneal abdominal masses under investigation as well as precise definition of their location, size, and nature. Because of its rapidity and painlessness, echotomography should be adopted as firstchoice procedure for the diagnostic exploration of intraabdominal masses. Frontal reconstruction enables the surgeon to verify the topography of said masses with remarkable precision, and hence to plan surgery more intelligently.


[Sequential scintiscanning with 99mTc-HIDA in the study of some aspects of post-operative dynamics of the proximal digestive tract]. The authors exploited the elective biliary excretion of 99mTc-HIDA at adequate concentrations to afford visibility of intestinal segments more directly wetted by bile in a study of sequential hepatobiliary scintigraphy designed to explore the parts of the duodenum and jejunum that are excluded to the transit of gastrointestinal contents in many surgical procedures involving the proximal digestive tract. They illustrate their case material with several representative examples; these are described in detail to show the validity, usefulness and versatility of the scintigraphic technic under discussion.


[Pulmonary blastoma. (Personal case)].

[Pulmonary blastoma. (Personal case)]. The authors give a detailed description of one case of pulmonary blastoma recently come to their observation. Then, after a review of pertinent literature, they discuss the more interesting aspects of this pulmonary pathology, namely its rarity, uncertain histogenesis, difficult diagnosis, and above all baffling prognosis. They conclude with an appeal for further contributions on this interesting subject, in the hope of understanding it better through the study of an adequate number of cases.


[Heterotopic pancreas in a gastric site]. The authors describe two cases of heterotopic pancreas tissue involving the stomach. After some general comments on the frequency and anatomopathological aspects of this disease, they discuss the clinical features and modern technics for the diagnosis of heterotopic pancreas tissue, with special emphasis on gastroscopic detection and execution of aimed biopsy specimen collection. Last, they discuss the indications for surgical treatment of the disease.


[Advantages of the use of medium-length colonoscope in the diagnosis of colonic diseases]. On the basis of their own experience, totaling 540 examinations, the authors explain the advantages offered by the medium-length (100 cm) optical fibroscope in the diagnosis of colonic diseases. They claim that the instrument under discussion is the most complete, being at once sturdy and easy to use and affording, despite its limite length, exploration of the ascending colon in 53.3% of the cases--a procedure for which the indications are on the other hand fairly limited.


[A case of giant hamartochondroma of the lung]. The authors present a case of pulmonary hamartochondroma of exceptional size, of which they give a clinical descrition and explain the surgical treatment. Next, aloso in the light of recent literature on the subject, they review the possible causes of this disorder in terms of several histopathogenetic hypotheses, and they discuss problems of differential diagnosis as well as the histopathological aspects of this rare, benign tumor of the lung. They conclude that even though malignant transformation of hamartochondroma is exceptional, these tumors should always be removed surgically as soon as they are diagnosed or reasonably suspected.


[Local anesthesia: contraindications and complications]. The widespread use of local anesthetic agents in connection with minor office and emergency surgery prompted the authors to look into various aspects of this practice. Doubtless, these drugs are extremely handy and constitute a valuable aid in many situations; still, possible complications and contraindications must be clearly assessed. The authors conclude their discussion with an outline of essential things to do in the event of unexpected clinical mishaps.


[Unusual compression of the ulnar nerve caused by a hematic cyst]. Among the various possible causes underlying compressive syndromes of the ulnar nerve at the wrist, classified as "occupational neuritides", we must number the presence of a hematic cyst in Guyon's canal. The authors describe the occurrence of a hematic cyst in the region of the pyramido-unciform joint, with prompt and complete restoration of ulnar nerve function after surgical removal of the cyst.


Suppression of phosphorylcholine-specific IgE antibody formation in BALB/c mice by isologous anti-T 15 antiserum. In order to study the regulation of IgE antibody formation, isologous anti-idiotypic antisera against the phosphoryl choline (PC)-specific BALB/c myeloma proteins T 15 and M 167 were passively administered to BALB/c in the course of an anti-PC IgE response. Isologous anti-T 15 antiserum had a long-lasting suppressive effect on the formation of IgE antibodies with PC specificity, whereas administration of anti-M 167 antiserum had no or only little effect, similar to that of normal BALB/c serum. This indicates that anti-PC IgE antibodies consist mainly of the T 15 idiotype or of cross-reacting idiotypes, and that IgE response is accessible to regulation with anti-idiotypic antibodies. This murine model may permit the study of regulation of an IgE response largely restricted to few defined idiotypes characterized as tumor proteins.


Antibody response to embryonal carcinoma cells in syngeneic mice. The immunoglobulin (Ig) classes and subclasses of the specific antibodies contained in antisera raised in male 129/Sv mice against cells of a syngeneic clonal line of embryonal carcinoma (F9) have been determined. Cytotoxic activity was found associated almost exclusively with anti-F9 IgM (micro kappa) antibodies. A large part of anti-F9 activity was found associated with IgG1 (gamma 1 kappa and presumably also gamma 1 lambda) antibodies, and was detectable only by direct immunofluorescence. Traces of specific IgG2a and IgG2b antibodies were also found. No IgG3 and IgA antibodies reacting with embryonal carcinoma cells were detectable under these conditions. The serum of F9 tumor-bearing animals had a very similar Ig composition. Furthermore, IgM and IgG1, but not IgG2 antibodies, were detected at the surface of in vivo growing F9 tumor cells.


Transferrin can replace serum for in vitro growth of mitogen-stimulated T lymphocytes. Activation of human T cells by mitogens was compared in cultures containing serum, human serum albumin or purified human transferrin as growth support. The mitogenic effect of the lectins leucoagglutinin, concanavalin A and Wistaria floribunda agglutinin was measured as incorporation of [3H]thymidine into the cellular DNA of the lymphocytes. Three different preparations of transferrin were all able to fully substitute serum or serum albumin as growth promotors, when present at concentrations of 10 microgram/ml or more. A small contamination of transferrin in the human serum albumin preparations used was shown to be responsible for their growth-supporting effect, while no need for the presence of albumin itself could be demonstrated.


IgG-binding sites on macrophage cell membrane. I. Identification of two distinct Fc receptors on mouse peritoneal macrophages. Evidence is presented concerning the existence on mouse peritoneal macrophages of two separate and distinct Fc receptors, one for cytophilic monomeric IgG (mIgG) and the other for polymeric IgG. The latter Fc receptor recognizes both heat-aggregated IgG and antigen-complexed IgG. The major findings of our studies are: (a) the different susceptibility of the two Fc receptor types by pronase, trypsin or phospholipase C; (b) the independent modulation of these two binding sites on the cell membrane; (c) the inability of mIgG to inhibit the binding of particulate antigen-complexed IgG ligand; (d) the ability of mIgG molecules which are devoid of the cytophilic property to attach to the macrophage surface upon their polymerization induced by heating or antigen. The results are discussed in terms of "cytophilic" and "opsonic" Fc receptor types which may provide different functional abilities for normal macrophages.


IgG-binding sites on macrophage cell membrane. II. Mobility of Fc receptors induced by the interaction with their corresponding IgG ligands. Mouse peritoneal macrophages were charged with IgG molecules in monomeric (mIgG), heat-aggregated (agIgG) or antigen-complexed (acIgG) form. Upon exposure to 37 degrees C, all bound IgG ligand types are redistributed on the cell surface due to the mobilization of their corresponding Fc receptor (FcR). The major findings regarding the fate of FcR on macrophages bearing IgG ligands are as follows: (a) the FcR involved in the binding of cytophilic molecules has a slow movement on the cell membrane and forms patches but never caps, while the opsonic type of FcR is rapidly capped; (b) the mobility of IgG-binding sites was temperature-dependent and was affected differently by sodium azide; this metabolic inhibitor enhances the disappearance of mIgG from the cell surface but decreases the capping and the disappearance of polymeric ligands; (c) both FcR types are probably ingested when complexed with specific ligand, and consequently, the rebinding of homologous IgG molecules is reduced, the clearing induced by agIgG or acIgG binding being much more extensive; and (d) cells cleared of their opsonic types of FcR are able to regenerate the receptor molecules with 8 h of incubation at 37 degrees C.


[Tienilic acid in the treatment of arterial hypertension and congestive cardiac insufficiency]. Tienilic acid (TA) is a common new diuretic agent with a potent uricosuric action. In a double-blind cross-over study its antihypertensive effect was compared to that of hydrochlorothiazide (HCT). 20 patients with essential hypertension were studied: after I weeks of placebo wash-out 10 patients received TA (dose range 250-750 mg/die) and 10 HCT (dose range 50-150 mg/die), for 5 weeks. Systolic and diastolic blood pressures were significantly and equally reduced (p < 0.001) after the first week of treatment in both groups. While serum uric acid concentration increased after HCT, it was significantly reduced (p < 0.001) after TA treatment. Serum potassium was slightly reduced with both treatments.  Serum tryglicerides, unchanged after HCT, showed a slight tendency to reduction on TA treatment. Ten patients with congestive heart failure, on full digitalis treatment, were given TA (dose range 250-1000 mg/die): in each patient a prompt diuretic effect was observed, associated to a significant reduction of body weight and to a marked improvement of the clinical signs of heart failure. Therefore, TA is an effective diuretic agent which may be conveniently used in the treatment of arterial hypertension and congestive heart failure, as it induces a diuretic effect comparable to that obtained with HCT, reducing at the same time, serum uric acid levels.


[Short-term and median-term effects of tienilic acid in hypertension]. Fifty nine patients suffering from slight or moderate essential arterial hypertension underwent hypotensive treatment. After one week of wash-out, therapeutic administration of tienilic acid in doses of 500 mg per day was begun; in the third week we combined a non diuretic hypotensive drug (prazosin, propranolol, alfametil-dopa). At the beginning of the study all patients underwent an ECG, a clinical cardiological examiniation, funduscopy examination, funduscopy examination, a heart X - ray in 3 standard positions and a routine blood test which was repeated during and at the end of the treatment. The patients' blood pressure taken in an upright and supine position, showed statistically significant reductions for both systolic and diastolic values in all 3 groups, whereas the routine blood tests gave evidence of a marked reduction in the uriacid, triglycerides and potassium levels. In order to correct the latter we had to administer high oral doses of potassium, and in one case admittance to hospital was necessary since the potassium level was lower then 2.5 mEq/l.


[Efficacy of prazosin in severe cardiac insufficiency]. A new oral vasodilator, prazosin, was evaluated in twenty patients with refractory congestive heart in a double blind non cross-over trial. Patients were divided into two groups. The first (group A) was treated by prazosin (40-50 microgram/Kg/pro die) for 20 days, the second was given placebo for the same period. Ventricular performance was assessed by measurement of the systolic time intervals, the peak time of the first derivative of the apexcardiogram (delta ACG), pressure-rate product and clinical evaluation. After ten days of prazosin left ventricular ejection time (LVET) increased (P < 0.01), pre-ejection period (PEP) and relation PEP/LVET were reduced (respectively: P < 0.05 and P < 0.01). Similarly the peak of delta ACG and pressure-rate product decreased significantly (respectively: P < 0.05 and P < 0.01). Symptomatology improved in NYHA functional class (3.7 to 2.4, P < 0.001). After twenty days of prazosin there was no further significant improvement in myocardial performance. No significant changes of clinical course and of the same parameters were observed in patients of group B. It is concluded that prazosin is effective in improving cardiac performance in refractory heart failure for its balanced dilator action on the arteriolar and venous vessels.


[Hypoxic pulmonary vasoconstriction and angiotensin II blockade in calves (author's transl)]. The pulmonary vascular response to breathing low oxygen containing gas mixture was examined before and during Angiotensin II blockade in five open-chested newborn calves. Angiotensin II blockade was achieved by continuous infusion of Sar1-Ile5-Leu8-Angiotensin II (Saralasin), a competitive inhibitor of Angiotensin II. The hypoxic rise in pulmonary vascular resistance after blockade did not differ from that of control. It is concluded that Angiotensin II does not play a significant role in acute hypoxic pulmonary vasoconstriction in the calf.


[Ventricular septal defect associated with aortic regurgitation. Results and surgical considerations in pediatric age group (author's transl)]. The Authors report their experience on the surgical treatment of ventricular septal defect and aortic regurgitation. Out of 13 patients operated upon, four required aortic valve replacement; five patients were treated with plasty of the aortic leaflets and four with the only patch closure of the V.S.D. There have not been reported hospital or late deaths. In one case, after the aortic plasty, the aortic regurgitation became severe; this patient had shown clinical signs of aortic regurgitation for more than five years before the operation. The Authors emphasize the surgical aggressiveness in this lesion when the aortic regurgitation has recently showed, whereas it is preferable to delay the operation when the aortic regurgitation has been present for more than five years.


[Aortic insufficiency associated with interventricular communication. Natural history, angiographic diagnosis and surgical approach]. Clinical, electrocardiographic, radiological, hemodynamic and angiocardiographic data of 12 patients with ventricular septal defect (VSD) associated to aortic regurgitation (AR) have been analyzed. The trend of evolution of the AR has been evaluated and angiographic criteria to make a correct diagnosis have been pointed out. Nine patients have been followed up for a mean of 3.8 years. The severity of AR seemed to increase only in three cases: this demonstrates that AR associated to VSD is not always a progressive disease. The usefulness of various radiological views in evidencing the anatomy of both VSD and aortic valve has been discussed and findings of left ventriculogram and aortogram are detailedly described. The site of VSD and the type of lesion of the aortic valve may be crucial for indicating surgical intervention and its type. Indication for surgery is briefly discussed. Surgical technics are shortly summarized.


[Effects of acute infusion of verampil on the ST segment elevation measured with the Frank orthogonal leads in patients with acute myocardial infarct]. The effect of verapamil on ST changes was evaluated in 10 selected patients with acute myocardial infarction admitted to the Coronary Care Unit within 8 hours after the onset of symptoms. To evaluate the extent of ischemia it has been used the magnitude and direction of the ST vector derived from X, Y and Z leads of the Frank vector system. After a control period of 2 hours, during which the changes of the ST vector magnitude were assessed, each patient received 0.1 mg/Kg verapamil intravenously, ST vector magnitude (STVM), ST azimuth (STAZ), ST elevation (STEL), heart rate, systemic blood pressure and pressure-rate product were assessed 5, 15, 30, 45, 60, 75, 90, 105 and 120 minutes after the administration of the drug. Verapamil produced a significant progressive decrease in STVM (from a mean of 254 +/- 44 muV at the end of the control period, to 139 +/- 25 muV after 2 hours; P < 0.01). Systolic blood pressure decreased significantly throughout the trial; the most significant decrease was registered immediately after the infusion of verapamil (from a mean of 134 +/- 3 mmHg to 121 +/- 3 mmHg; P < 0.001). Pressure-rate product declined slightly. No significant change in STVM was observed in 10 control patients with acute myocardial infarction examined over a 4 hours period. The apparent protective effect of verapamil in myocardial ischemia is discussed in relation to its calcium-antagonistic properties in excitable tissues.


[Measurement of the stress deformation ratio in the left ventricle in systole]. Thirty-three subjects, fourteen of which with normal heart, ten with aortic insufficiency and nine with myocardiopathy, were studied by echocardiography and sfigmomanometric arterial pressure measurements. The ejection fraction EF, the left ventricular equatorial wall stress sigma, the corresponding left ventricular strain epsilon and the ratio E = sigma/epsilon have been determined for all subjects. The mean values of these quantities, at the onset of ventricular systole, for normal hearts are: EF = 0.67 +/- 0.05; sigma = (2.67 +/- 0.41) . 10(5) dine/cm2; E = (0.99 +/- 0.15) . 10(6) dine/cm2; for patients with aortic insufficiency: EF = 0.51 +/- 0.09; sigma = (2.74 +/- 1.10) . 10(5) dine/cm2; E = (1.51 +/- 0.69) . 10(6) dine/cm2; for patients with miocardiopathy: EF = 0.41 +/- 0.06; sigma = (4.36 +/- 2.08) . 10(5) dine/cm2; E = (3.20 +/- 1.19) . 10(6) dine/cm2. After a discussion on the significance of sigma and E parameters, it is inferred that E may be a useful measure of ventricular function. This parameter is different for distinct cardiac diseases and, within the limits of the same disease, probably will change according to seriousness.


[Hemodynamic observations in a group of hypertensive patients treated with tienilic acid (author's transl)]. In ten patients suffering from slight or moderate essential arterial hypertension, undergoing treatment with tienilic acid at 500 mg per day, various hemodynamic parameters were assessed by means of ecocardiographic and policardiographic studies carried out before, during and at the end of treatment. In all cases a return to normal blood pressure values was achieved. No statistically significant changes in these parameters were observed, whereas the blood tests showed a reduction in the uric acid level and a moderate reduction in the potassium level.


[Cardiovascular complications of severe tetanus (author's transl)]. Cardiovascular complications of severe tetanus are essentially represented by cardiac arrhythmias and hypertension. An excess of catecholamines is responsible for these complications. Tetanus toxin causes indeed a sympathetic overactivity which is due partly to a central stimulation and partly to a peripheral one. All that means the best treatment of cardiovascular complications of tetanus is represented by adrenergic blocking agent.