Effects of DL-propranolol on exercise heart rate and maximal rates of oxygen consumption inScaphiopus intermontanus

Summary Lymphatic injection of propranolol (0.2–10 g) into toads decreased exercise heart rate in a dose-dependent manner. There was a significant linear corrleation between exercise heart rate and maximal oxygen consumption rates . These data are consistent with the hypothesis that blood oxygen transport is the limiting process for max in anuran amphibians.This work was supported by a grant from the National Science Foundation (PCM-8021808). I am grateful to Dr P.C. Withers for logistical support and Dr S. Yokota for the initial idea.     

Scaling of respiratory areas in relation to oxygen consumption of vertebrates

Summary Resting oxygen consumption is generally related to the 0.75 power of the body mass. More recent studies on the morphometry of the lungs and gills of vertebrates indicate that the respiratory surfaces increase in area more closely to M^1.0. A possible explanation is that the gas exchange surface is more to be related to themaximum oxygen uptake capacity, rather than to the resting condition. However, recent studies, especially in African mammals, suggest that scales to a power similar to that for resting oxygen consumption and hence cannot be directly related to the respiratory surfaces.In fishes the situation seems to be different as appears to increase more rapidly than standard . Consequently, the ratio between these two is greater in larger specimens and hence they have a greater scope for activity. A possible interpretation of this apparent difference may be related to differences in ventilation, as the tidal ventilation of lungs can lead to a reduction in the difference in oxygen pressure across the exchange surface, whereas in fish gills with increasing size and increasing water velocity there would be a reduction in the resistance to gas transfer. However, it is important to appreciate that such generalizations probably do not hold in all cases and the position of intermediate groups of vertebrates needs to be more closely assessed.This paper is based upon part of a lecture given at the Conference of Comparative Respiratory Physiology, Göttingen, BRD, August 1982.     

Reduced deformability of erythrocytes exposed to hypercapnia

Summary The effect of hypercapnia on the deformability of erythrocytes was studied by means of a nuclepore membrane filter method. A decrement of the deformability by 20–40% was observed when was increased from 50 mm Hg to 200 mm Hg, accompanied with an increment of 5% in hematocrit value.     

Interaction of extrinic fluoresence probes with E. coli glutamine synthetase

Summary Binding of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) to adenylylated glutamine synthetase is cooperative and time-dependent, with 3 dye sites per subunit. In fluorescence polarization experiments TNS and pyrene butyrate give normalized Perrin plots that indicate a symmetrical arrangement of dye excited state dipoles, relative to the rotational axis of the oblate ellipsoid of the dodecameric native enzyme.Acknowledgment. Drs G. Weber and L. Brand are thanked for helpful comments on this work. — Supported in part by grants from the National Science Foundation (BMS 72-02165 and GU-3182). Portions of this work were presented in preliminary form at the 9th International Congress of Biochemistry, Stockholm, Sweden, July 1973.     

Ginkgo biloba extract inhibits oxygen species production generated by phorbol myristate acetate stimulated human leukocytes

Summary A Ginkgo biloba extract (Gbe) containing flavonoids, among other compounds, was tested for the release of activated oxygen species ( , H₂O₂, OH^.) during the stimulation of human neutrophils (PMNs) by a soluble agonist. The extract slows down O₂-consumption (respiratory burst) of stimulated cells by its inhibitory action on NADPH-oxidase, the enzyme responsible for the reduction of O₂ to . Consequently, superoxide anion ( ) and hydrogen peroxide (H₂O₂) production is significantly decreased when the PMNs stimulation is done in the presence of the extract at concentrations of 500, 250 and 125 g/ml. Moreover, the hydroxyl radical generation (OH^.) is very much decreased at concentrations as low as 15.6 g Gbe/ml, which indicates that the extract also has free radical scavenging activity. Gbe is able at least to reduce very severel the activity of myeloperoxidase contained in neutrophils. This enzyme, secreted into the intra and extracellular medium, catalyzes the oxidation of chloride (Cl^–) by H₂O₂ to yield strong oxidants (HOCl, chloramines) which are implicated in inflammatory processes     

Improved response to heat after moderate physical training in man

Summary 7 young men marched for 6 days (35 km daily) in a cool climate at about 35% of their . Sweat output was measured at rest in a climatic chamber during a controlled hyperthermia test performed before and after the trial. 4 subjects served as controls. The main finding of the study was that sweat output increased 17.3%±1.5 SEM on the posttrial test, without any change in . It is concluded that moderate physical training can improve heat responses in resting man.This investigation was supported by Direction des Recherches et Etudes Techniques (Délégation Ministérielle pour l'Armement) grant No. 77/1198.The authors wish to thank Dr B. Roussel for the helpful discussions on the results of this study.     

Allosteric proteins after thirty years: The binding and state functions of the neuronalα7 nicotinic acetylcholine receptors

A key statement of the 1965 Monod-Wyman-Changeux (MWC) model for allosteric proteins concerns the distinction between the ligand-binding function ( ) and the relevant state function ( ). Sequential models predict overlapping behavior of the two functions. In contrast, a straightforward experimental consequence of the MWC model is that for an oligomeric protein the parameters which characterize the two functions should differ significantly. Two situations, where \bar Y$$ " align="middle" border="0"> and the system ishyper-responsive or where and the system ishypo-responsive, have been encountered. Indeed, the hyper-responsive pattern was first observed for the enzyme aspartate transcarbamoylase, by comparing with monitored by a change in sedimentation. Extensions of the theory to ligand-gated channels led to the suggestion that, on the one hand, hyper-responsive properties also occur with high-affinity mutants. On the other hand, native channels of the acetylcholine neuronal7 receptor and low-affinity mutants of the glycine receptor can be interpreted in terms of the hypo-responsive pattern. For the ligand-gated channels, whereas is detected directly by ion flux, ligand binding has rarely been measured and the formation of desensitized states may complicate the analysis. However, stochastic models incorporating both binding and channel opening for single molecules predict differences that should be measurable with new experimental approaches, particularly fluorescence correlation spectroscopy.     

Effect of norepinephrine and vasopressin on carotid sinus baroreceptor activity in the anesthetized rabbit

Summary Norepinephrine (NE) 10^–6 M or vasopressin (VP) 12.5 U/ml were injected into the isolated carotid sinus of anesthetized rabbits. The sinus was exposed either to the arterial pressure or to a pressure controlled reservoir. Multifiber and single fiber recordings were made. Both NE and VP increased baroreceptor activity at all sinus pressures but decreased activity in a few fibers. The results are consistent with the drugs having their effects on smooth muscle fibers in the adventitia.Acknowledgments. This work was supported by grants from the Medical Research Council of Canada and the B.C. Heart Foundation. The authors are grateful to J. Sharp and D. Morton for their excellent assistance.     

Dynamic laser light scattering studies of the effects of pyrophosphate on cyclic motions of cross-bridges in isolated thick myofilaments fromLimulus striated muscle

Pyrophosphate (PP_i) is a non-hydrolyzable ATP analogue known to affect the binding between myosin heads and actin. By using a dynamic laser light scattering method, we have shown that 1–2 mM PP_i enhances the increase in values induced by Ca²⁺ in isolated thick myofilaments fromLimulus striated muscle. However, similar treatment has no effect on the values of filaments suspended in either relaxing solution or ATP-free solution. is the average linewidth of the photoelectron count autocorrelation function of the light scattered. PP_i had no effect on the increase of values by Sr²⁺ but it substantially increased the values of the thick myofilaments suspended in Ba²⁺-substituted Ca²⁺ activating solution. The results show that PP_i also affects the energy-requiring cyclic cross-bridge motions.     

Superoxide anion scavenging effect and superoxide dismutase activity ofGinkgo biloba extract

Summary Ginkgo biloba extract is known to be efficient in diseases associated with free radical generation. The purpose of this work was to study, under in vitro conditions, the action ofGinkgo biloba extract (Gbe) against superoxide anion ( ), which is directly or indirectly implicated in cell damage.Gbe appears to have both an scavenging effect and also a superoxide dismutase activity. Its antiradical effect was demonstrated by low temperature electron spin resonance and in a non-enzymatic system (phenazine methosulfate-NADH), and its enzymatic activity was shown by polarographic determination.     

Proton-induced dismutation of superoxide in aprotic media by bile pigments

Summary Cyclic voltammetry of molecular oxygen in aprotic media (dimethylformamide) and in the presence of bilirubin and other bile pigments shows that superoxide anion ( ) undergoes proton-induced dismutation. Lactam hydrogens of bile pigments are sufficiently acid to induce disproportionation to O₂ and H₂O₂. Because of its characteristic lipophilic behavior, a biological role for natural bilirubin similar to that of other non-enzymatic lipophilic scavengers of is suggested.     

Diurnal variations in thermoregulatory responses to intrahypothalamic and intravenous injections of noradrenaline in the pigeon

Summary The differences in responses of T_b, T_f and both to intrahypothalamic and i.v. administration of NA were measured both at noon and at midnight in the pigeon. Although the T_b and were at a higher level in the daytime, no differences in the magnitude of the fall in and T_b were obtained after either intrahypothalamic or i.v. injections of NA, whether it was measured during the day or at night. The only marked difference was the more prominent vasodilatation in the daytime after both routes of injection.     

Effects of isoxazolyl-naphthoquinoneimines on growth and oxygen radical production inTrypanosoma cruzi andCrithidia fasciculata

Several 4-(aminomethylisoxazolyl)-1,2-naphthoquinones inhibited growth and DNA synthesis inTrypanosoma cruzi and stimulated O₂ uptake and generation by the parasite epimastigotes and their mitochondrial and microsomal membranes; these results support the idea that oxygen radicals play a role in quinone toxicity. Maximal effects on respiration and generation were observed with antimycin-inhibited cells. Similar results as well as stimulation of H₂O₂ production were obtained withCrithidia fasciculata despite the presence of catalase in this organism.Acknowledgments. This work was aided by grants from the University of Buenos Aires, the Scientific Office of the American States Organization and CEDIQUIFA (Buenos Aires). S.G.G. and M.P.M.P. are Research Fellows and A.O.M.S. is Career Investigator of CONICET (Argentina). L. T. Viñas and M. G. Gutierrez lent able technical assistance.     

Identification of calcium antagonist receptor binding sites using (3H)nitrendipine in bovine tracheal smooth muscle membranes

Summary (³H)Nitrendipine binding to the bovine tracheal muscle membrane at 25°C was rapid, saturable (B_max=14.8±3.9fmol/mg protein) and of high affinity (K_d=0.15±0.04 nM). The rank order of Ca²⁺ antagonists competing for airway (³H)nitrendipine binding was nitrendipine nisoldipine nifedipine » verapamil. Cromolyn, however, neither inhibited nor increased the binding.J.B.C. is a visiting associate professor at the NYMMC. We thank Ms. Pang-jang Chang for technical assistance. This work is supported by a grant (NSC 72-0412-BO10-R20) from the National Science Council, ROC. To whom reprint requests should be addressed: Allergic Disease Center, Creighton University School of Medicine, Omaha, Nebraska 68178.     

β-alanine and α-L-alanine inhibit the exploratory activity of spontaneously hypertensive rats

Summary 1% -alanine and -L-alanine, when given for 7 days as the only drinking fluid, inhibited the exploratory activity of adult male spontaneously-hypertensive rats (SHR)_but not that of the normotensive Wistar-Kyoto rats (WKR). -Alanine decreased the taurine level in the liver of both strains and in the platelets of SHR. -Alanine decreased the taurine level in the liver of WKR and in the platelets of SHR.This study was supported by the Sigrid Jusélius Foundation.     

Bildung von Reaktionsholz durch Zentrifugalbeschleunigung

Summary In leaning stems, reaction wood can be formed as a response to gravitation stimulus. In seedlings ofAesculus hippocastanum, reaction wood formation could likewise be stimulated by centrifugation. This proved the differentiation of wood cells to be affected by mass acceleration. The reaction wood formation is related quantitatively to mass accelerationb and timet, the formation of reaction wood being described by quantitative stimuli law as . The threshold of stimulation lies in the dimension . The arrangement of the experiments permits a direct approach to cambium physiology and the following differentiation of wood cells.     

The mensuration of quadrilaterals and the generation of Pythagorean triads: A mathematical,heuristical and historical study with special reference to Brahmagupta's rules

Summary The ancient rule for the area of a quadrilateral, , is examined to show its inaccuracy and its arbitrariness, and in order to see how those using it might have become aware of its shortcomings. Consideration ofBrahmagupta's vastly more sophisticated rule, , and of the Hindu schedule of recognized quadrilateral types, leads to the question of the proper assessment to be made of this strand of Indian mathematics. The work on quadrilaterals was intimately connected with the generation of Pythagorean triangles out ofbja (=seed) numbers by the same method as had probably been used by the mathematicians of Old Babylonia. Ways in which this procedure could have arisen by induction from particular numerical calculation are shown and the rest of the study consists primarily of an investigation as to whether the same kind of approach might not also have been used to obtain the remarkable rules on quadrilaterals given byBrahmagupta. It is found that there is no compelling need to adopt the common assumption thatBrahmagupta must have had access to Alexandrian mathematics. But even if he did chance to learn of some helpful items from the works ofHero orPtolemy, it still seems necessary for a proper appreciation of his understanding of the mensuration of quadrilaterals to suppose that he would have worked such items into the contemporary Indian mathematical context in some such way as is indicated here. In particular, it is argued thatBrahmagupta, far from indulging in reckless generalization, could well have proceeded with great caution, from one amenable type of quadrilateral to another, verifying his inductions by comparing them with results given by alternative calculation methods.     

An improved method for calculating colony forming ability in soft agar with special reference to malignancy

Summary We examined the correlation between the tumorigenicity and the growth capacity in soft agar of various malignant cell lines. The colony forming rates were calculated in (a) 0%, (b) 0.15%, (c) 0.30%, and (d) 0.40% soft agar medium. An approximate value for the colony forming capacity, y, was then established for the formula (x=concentration of soft agar, f(x)=rate of appearance of colony forming cells with x% soft agar medium).We would like to thank Miss Kimiko Tabuchi for her expert technical assistance during the course of these investigations.     

Effects of 2-β-D-glucosyl-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one onSchizaphis graminum (rondani) (insecta,aphididae) feeding on artificial diets

Summary 2--Glucosyl-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc), the main hydroxamic acid from maize and wheat, and its aglucone, decreased survival ofSchizaphis graminum reared on artificial diets. Both compounds were toxic for aphids and acted as feeding deterrents, at concentrations as low as 1 mM. The natural concentrations of glucosides of hydroxamic acids in wheat leaves reach up to 6 mmoles/kg fresh weight, thus falling within the range in which DIMBOA-Glc causes delecterious effects to diet-fed aphids.To whom correspondence should be addressed. THis work was supported by grants from International Foundation for Science (484), Universidad de Chile (N-1654) and the Agency for International Development.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

Summary N-acyl dehydroalanines react with and scavenge mainly superoxide radical and hydroxyl radical (HO^.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD₅₀ at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.