The influence of organic phosphates on the Bohr effect of human hemoglobin valency hybrids.

The Bohr effect of hemoglobin and that of the aquomet and cyanomet valency hybrids was measured in the presence and the absence of IHP (inositol hexaphosphate) and DPG (2,3-diphosphoglycerate). In the absence of these organic phosphates the four hybrids show similar, but suppressed Bohr effects as compared to hemoglobin. Addition of IHP and DPG results in all cases in an increase of the Bohr effect. The additional phosphate induced Bohr effect of the hybrids with the alpha chain in the oxidized form is almost identical to that of hemoglobin, while this effect of the hybrids with oxidized beta chains is slighly lower than that of hemoglobin. The results suggest (a) that the Bohr effect is correlated to the ligation state of the hemoglobin molecule rather than to its quaternary structure (b) that the additional phosphate induced Bohr effect is related to the change in quaternary structure of the tetramer, and (c) that with respect to the Bohr effect of the hybrids there is no difference between high and low spin species.     

Role of catecholaminergic mechanisms in regulating the autogenic periodic motor activity of rat pups

In 1-, 2- to 3-, 7- to 8-, and 10-day old intact and spinal rat puppies, studies have been made of the effect of l-DOPA (100 mg/kg, intraperitoneally) on autogenic periodic motor activity in the gastrocnemius muscle. In 1- to 3-day old pups, strong stimulating effect was observed up to a prolonged continuous activity for 5-10 or even more minutes. This effect decreases with age. Traces of the inhibitory effect are observed at early stages in the form of total decrease of the activity. The inhibitory effect increases with age. In all spinal animals, at the background of a decreased activity, stimulating effect of l-DOPA was predominantly observed. Age peculiarities of the effect of l-DOPA are discussed in relation to ontogenetic development of catecholaminergic innervation in rats. It is suggested that stimulating effect of l-DOPA is associated with its action on the descending noradrenergic system, whereas the inhibitory one is mediated by the brain structures.     

大鼠肺泡巨噬细胞对人胚肺成纤维细胞增殖的抑制作用

实验采用[^3H]TdR掺入标记法测定微量培养人胚肺成纤维细胞的增殖,观察到健康大鼠的肺泡巨噬细胞（alveolar macrophage,AM)可抑制成纤维细胞增殖。经调理的酵母多糖激活后,AM的抑制作用加强;而经消炎痛处理的AM,抑制作用转为被促进增殖作用所取代;测定AM上清液中前歹腺素E（prostaglandin E,PGE)含量,显示其抑制作用与PGE含量相关。结果提示,AM有抑制作促进肺成纤维细胞增殖的双重作用,正常时以抑制作用占优势;PGE可能是AM产生的主要的肺纤维化抑制因子。     

Effect of negative hydro-aero ions on the structure and functional properties of mitochondria

Studies were carried out of the physical mechanism of biological effect of natural stimulant of the living activity--light negative hydroaeroions. The latter are a hydroxyl separated from water ions and designated here as electrically noncompensated hydroxyl OH-. Unique effect of OH-, i.e. fast restoration and prevention of fine damage of native mitochondria (NM) at storage was revealed on mitochondria preparations by specific procedure, providing preservation of the ability of self-organization--formation of aggregated and denser packing--native mitochondria. This effect of OH- is conditioned by increased formation of native mitochondria aggregates and is concerned with better ADP phosphorylation and Ca2- release. The effect of the air current OH- is produced by water action presaturated with OH-. OH- induces in water cooperative structure formation preserved for many days, which is indicated by an increase of its heat capacity and decrease of surface tension. The principal factor in OH- effect both on mitochondria and water seems to be a decrease of local positive changes. It is of more advantage in NM water suspensions to order (structurate) NM with disordering water, which explains formation of NM stable aggregates. OH- effect supports the main function of the organism struggling with proton excess which destroys biological self-organization. Strengthened structural self-organization under the effect of OH- found in NM seems to be of universal importance for biological macromolecules and membranes and is a primary effect of OH- on the living objects.     

Molecular events involved in the proaggregating effect of heparin on human platelets

Molecular mechanisms underlying the ability of heparin to enhance the platelet-aggregating effect of various agonists were studied. Heparin potentiates the aggregating effect of adenosine diphosphate (ADP) and epinephrine, but it is uneffective on the aggregation induced by ristocetin and collagen. Heparin inhibits aggregation induced by thrombin in the presence of plasma, but it is uneffective, or sometimes stimulates aggregation, in the absence of plasma. The effects on the platelet-activating factor- (PAF-acether) induced aggregation are very variable. The late phase of the ADP-induced aggregation is sensitive to proteinase inhibitors, but heparin overcomes this inhibitory effect. Drugs which inhibit remodeling of membrane phospholipids abolish the potentiating effect of heparin, while cyclooxygenase inhibitors do not. The proaggregating effect of heparin subfractions correlates with the lipoprotein lipase activity and, slightly, with the molecular weight, but it does not correlate with the anticoagulant activity. Platelets prelabelled with phosphatidyl[U14C]inositol show a very rapid effect of heparin in triggering phosphatidylinositor breakdown and a cooperative effect with ADP, a known agonist of the 'phosphatidylinositol cycle'. Heparin is also effective in stimulating the labelling of polyphosphoinositides in platelets prelabelled with 32Pi. These results, together with the selective sensitivity to drugs, lead to the conclusion that a stimulatory effect on the very early events of remodeling of membrane phospholipids is involved in the platelet proaggregating effect of heparin.     

Isotopic probes of the argininosuccinate lyase reaction

The mechanism of the argininosuccinate lyase reaction has been probed by the measurement of the effects of isotopic substitution at the reaction centers. A primary deuterium isotope effect of 1.0 on both V and V/K is obtained with (2S,3R)-argininosuccinate-3-d, while a primary 15N isotope effect on V/K of 0.9964 +/- 0.0003 is observed. The 15N isotope effect on the equilibrium constant is 1.018 +/- 0.001. The proton that is abstracted from C-3 of argininosuccinate is unable to exchange with the solvent from the enzyme-intermediate complex but is rapidly exchanged with solvent from the enzyme-fumarate-arginine complex. A deuterium solvent isotope effect of 2.0 is observed on the Vmax of the forward reaction. These and other data have been interpreted to suggest that argininosuccinate lyase catalyzes the cleavage of argininosuccinate via a carbanion intermediate. The proton abstraction step is not rate limiting, but the inverse 15N primary isotope effect and the solvent deuterium isotope effect suggest that protonation of the guanidino group and carbon-nitrogen bond cleavage of argininosuccinate are kinetically significant.     

The inhibitory effect of polymeric carboxylic amino-acids and urine on calcium oxalate crystallization

A new method has been established to follow the inhibitory effect of some polymeric-dicarboxylic-amino-acids and other poly-anionic derivatives. The technique is based on using calcium specific electrode to measure continuously free calcium ion activity in solution to assess the formation of calcium oxalate precipitate.The retardation effect of Poly-L-glutamic and aspartic acids has been established in 5–100 ppm range and compared to other monomeric and polymeric compounds with inactivated functional groups. The retardation effect is in agreement with previous reports on inhibition effect on crystal growth rate of seed crystals, with the same retardants.The inhibitory effect was also determined with normal urine and compared to pathological urine.     

Role of arginine in the stabilization of proteins against aggregation

The amino acid arginine is frequently used as a solution additive to stabilize proteins against aggregation, especially in the process of protein refolding. Despite arginine's prevalence, the mechanism by which it stabilizes proteins is not presently understood. We propose that arginine deters aggregation by slowing protein-protein association reactions, with only a small concomitant effect on protein folding. The associated rate effect was observed experimentally in association of globular proteins (insulin and a monoclonal anti-insulin) and in refolding of carbonic anhydrase. We suggest that this effect arises because arginine is preferentially excluded from protein-protein encounter complexes but not from dissociated protein molecules. Such an effect is predicted by our gap effect theory [Baynes and Trout (2004) Biophys. J. 87, 1631] for "neutral crowder" additives such as arginine which are significantly larger than water but have only a small effect on the free energies of isolated protein molecules. The effect of arginine on refolding of carbonic anhydrase was also shown to be consistent with this hypothesis.     

Effect of association with adenylyl cyclase-associated protein on the interaction of yeast adenylyl cyclase with Ras protein.

Posttranslational modification of Ras protein has been shown to be critical for interaction with its effector molecules, including Saccharomyces cerevisiae adenylyl cyclase. However, the mechanism of its action was unknown. In this study, we used a reconstituted system with purified adenylyl cyclase and Ras proteins carrying various degrees of the modification to show that the posttranslational modification, especially the farnesylation step, is responsible for 5- to 10-fold increase in Ras-dependent activation of adenylyl cyclase activity even though it has no significant effect on their binding affinity. The stimulatory effect of farnesylation is found to depend on the association of adenylyl cyclase with 70-kDa adenylyl cyclase-associated protein (CAP), which was known to be required for proper in vivo response of adenylyl cyclase to Ras protein, by comparing the levels of Ras-dependent activation of purified adenylyl cyclase with and without bound CAP. The region of CAP required for this effect is mapped to its N-terminal segment of 168 amino acid residues, which coincides with the region required for the in vivo effect. Furthermore, the stimulatory effect is successfully reconstituted by in vitro association of CAP with the purified adenylyl cyclase molecule lacking the bound CAP. These results indicate that the association of adenylyl cyclase with CAP is responsible for the stimulatory effect of posttranslational modification of Ras on its activity and that this may be the mechanism underlying its requirement for the proper in vivo cyclic AMP response.     

Analysis of variance delimitation of factors influencing studies of acoustic evoked potentials]

The effect of the variables "stimulus intensity", "residual effect of previous stimulus intensity", "period effect" and "subject effect" on the amplitudes and on the peak latencies of the N1 and P1 components of the acoustical EEG evoked potentials was studied in human subjects with the use of an orthogonal experimental design. The stimulus intensity (30, 50 and 80 dB) accounts for the greatest part of the total variance of the amplitudes and of the peak latencies of N1.-The existence of a totalvariance component due to differences between the subjects is also statistically significant (P equals 5%), As far as the period effect (habituation effect) is concerned, only its effect on the amplitude of N1 - P2 is statistically significant. - The residual effect of the stimulus intensity used in the previous series was not significant.     

超声介入聚桂醇硬化剂治疗肝囊肿疗效的分析

目的:探讨超声介入聚桂醇硬化剂治疗肝囊肿疗效的疗效。方法:将在我院76例被确诊为肝囊肿患者,随机分成治疗组(n=38)和对照组(n=38),治疗组在超声介入下囊肿内注入聚桂醇注射液,对照组采用乙醇治疗,比较两组住院时间、住院总费用、疗效以及不良反应。结果:治疗组患者抽出液(81.57±5.86)ml,对照组患者抽出液(91.71±7.80)ml,两组抽出液的差异有显著性(p0.05);治疗组和对照组患者住院时间分别为(4.86±0.90)天、(7.29±1.38)天,两组住院时间差异有显著性(P0.05);治疗组住院总费用为(4580.14±945.01)元,对照组患者住院总费用分别(4965.86±796.72)元;两组住院总费用差异无显著性(P0.05);治疗组总有效率为94.74%,对照组总有效率为81.58%,两组临床治疗效果差异有显著性(P0.05);两组患者不良反应发生例数无统计学差异(P0.05)。结论:聚桂醇作为新型硬化剂,疗效较好,不良反应少,可以成为囊肿超声介人治疗的首选硬化剂。     

Inhibition of ADP-induced aggregation of human platelets by beta, gamma-methylene-ATP.

Like ATP the analogue beta, gamma-methylene-ATP (AMP-PCP) is shown to be an inhibitor of both ADP-induced shape change and aggregation of human platelets. The effect of AMP-PCP on aggregation is not dependent on its conversion to adenosine, though in the presence of plasma adenosine is produced and the inhibitory effect is enhanced. Since AMP-PCP cannot be enzymatically cleaved at the beta, gamma-position the inhibitory effect cannot be attributed to utilisation of the analogue by a surface-located ATPase as has been suggested for ATP. Alternative explanations for the effect are considered with respect to some current theories of ADP-induced platelet aggregation.     

Hormonal disturbances and effect of pharmaca.

The hormonal milieu of the organism may exert certain influences on the activity and lasting of the effect of some drugs. This was demonstrated in female rats with the example of a steroid hormone (estrone) and a short acting barbiturate derivative (hexobarbital). Estrus produced with estrone is not to be influenced by ovariectomy. Hyperthyrosis lead to the cumulation of estrogens in active form and lengthened their effect. Hypothyrosis accelerated estrogen metabolism inducing a relatively ephemer effect of estrone. Hexobarbital metabolism is faster in ovariectomised rats as well as in thyroidectomised ones than in controls. The catatoxic effect of testosterone is bringing about a short anesthesia. Hyperthyrosis reduced the effect of hexobarbital to one fourth of the control values. A special care is necessary in administering drugs when endocrine disorders are present. Individual dosages of the pharmaca may be taken into consideration to adapt the right dosages to the hormonal disturbances.     

Influence of glucose on the kinetics of maltodextrin hydrolysis using free and immobilized glucoamylase

The study of the effect of glucose addition to the kinetics of maltodextrin hydrolysis catalyzed with free and immobilized Aspergillus niger glucoamylase does not show any significant glucose inhibitory effect. This result is in contradiction with data previously reported in the literature. On the contrary, a slight glucose-activating effect was observed. This effect was greater in the case of the immobilized enzyme. The glucose inhibitory effect may thus not be involved in the case of practical saccharification conditions catalyzed with glucoamylase when maltodextrins are used as substrate.     

The effect of potassium chloride on the Bohr effect of human hemoglobin.

The normal and differential titration curves of liganded and unliganded hemoglobin were measured at various KCl concentrations (0.1 to 2.0 M). In this range of KCl concentrations, the curves for deoxyhemoglobin showed no salt-induced pK changes of titratable groups. In the same salt concentration range oxyhemoglobin showed a marked change in titration behavior which could only be accounted for by a salt-induced increase in pK of some titratable groups. These results show that the suppression of the alkaline Bohr effect by high concentrations of neutral univalent salt is not caused by a weakening of the salt bridges in deoxyhemoglobin but is due to an interaction of chloride ions with oxyhemoglobin. Measurements of the Bohr effect at various KCl concentrations showed that at low chloride ion concentration (5 times 10-3 M) the alkaline Bohr effect is smaller than at a concentration of 0.1 M. This observation indicates that at a chloride ion concentration of 0.1 M, part of the alkaline Bohr effect is due to an interaction of chloride ions with hemoglobin. Furthermore, at low concentrations of chloride ions the acid Bohr effect has almost vanished. This result suggests that part of the acid Bohr effect arises from an interaction of chloride ions with oxyhemoglobin. The dependence of the Bohr effect upon the chloride ion concentration can be explained by assuming specific binding of chloride ions to both oxy- and deoxyhemoglobin, with deoxyhemoglobin having the highest affinity.     

Role of the GABA-ergic link in the development of the tranquilizing effect in cats

The development of the tranquilizing effect of n-dipropylacetate (n-DPA) selectively increasing the GABA level in the nerve terminals was studied in experiments on cats in comparison with diazepam effect. The changes in the spectrum of emotional-behavioral reactivity were estimated. In doses of 50 and 200 mg/kg n-DPA caused a marked antiphobic effect which was not accompanied by the activating component characteristic of diazepam. The n-DPA-induced increase in the GABA level in the nerve terminals is suggested to be important for the development of the anxiolytic effect of tranquilizers. The total increase in the GABA level in the nerve terminals is suggested to be important for the development of the anxiolytic effect of tranquilizers. The total increase in the GABA content in the brain correlates to a greater extent with the sedative effect of drugs.     

Dependence of effects of weak combined low-frequency variable and constant magnetic fields on the intensity of asexual reproduction of planarians Dugesia tigrina on the magnitude of the variable field

It was shown that the stimulating effect of weak combined magnetic fields (constant component 42 microT, frequency of the variable component 3.7 Hz) on the division of planarians depends on the amplitude of the variable component of the field. The effect is particularly pronounced at 40 (the main maximum), 120, 160, and 640 nT. Narrow ranges of effective amplitudes alternate in some cases with equally narrow ranges in which the system does not respond to he treatment. In the range of super weak amplitudes of the variable field (0.1 and 1 nT), the stimulating effect is poorly pronounced. The data obtained indicate the presence of narrow amplitude windows in the response of the biological systems to weak and super weak magnetic fields. In a special series of experiments, it was shown that the effect of fields on planarians is partially mediated via aqueous medium preliminarily treated with weak magnetic fields. It is noteworthy that in experiments with water treated with weak magnetic fields, there were no pronounced maxima and minima in the magnitude of the effect in the range of amplitude of the variable magnetic field from 40 to 320 nT.     

Hyperthermic potentiation of chromosome aberrations by anticancer antibiotics

In view of the success of hyperthermia as a modality in cancer treatment, we have studied its effect on chromosomes in combination with anticancer antibiotics. Three classes of chemicals, one with a non-delayed type of effect (adriamycin), one with a delayed type of effect (mitomycin C), and one with a truely radio-mimetic effect (bleomycin) were selected for study on human lymphocytes and Chinese hamster K-1 cells. Propane sultone was also included because its effect on plants is suppressed by hyperthermia. The data show increased because its effect on plants is suppressed by hyperthermia. The data show increased potential of these chemicals to induce chromosome aberrations when applied at temperatures higher than 37 degrees C, irrespective of the phase of cell cycle. The potentiation may be due to true synergism (bleomycin) of facilitation of entry of larger quantities of the drug (adriamycin). No potentiating effect was observed on the induction of sister chromatid exchanges (SCEs).     

Presence and possible function of root effect hemoglobins in fishes lacking functional swim bladders

The adult hemoglobins of 15 species of teleost and the midgestation fetal hemoglobin of the seaperch Embiotoca lateralis show a pronounced decrease in oxygen-carrying capacity at low pH, a Root effect. All of these fishes lack a functional swim bladder, which is generally thought to be the likely site of Root effect hemoglobin function. All of the teleosts examined, including the fetal sea perch, however, have a choroid rete, a structure that is proposed to be involved in oxygen secretion to the eye. The data are inconsistent with the generalization that only fishes with swim bladders possess Root effect hemoglobins, and that the only function of Root effect hemoglobins is in the secretion of oxygen to a swim bladder. The data for the fishes examined in this study suggests that a better correlation may exist between Root effect hemoglobins and the presence of a choroid rete. This is consistent with the hypothesis that Root effect hemoglobins may be involved in the physiology of the eye in many fishes.     

抗生素对BALB/C小鼠免疫机制的影响

本文给普通BALB/C小鼠口服不同剂量的链霉素、新霉素干扰动物肠道菌群平衡状态,初步研究了肠道菌群平衡紊乱对动物迟发型超敏反应、脾脏抗体形成细胞数、外周血白细胞化功能、腹腔巨噬细胞吞噬活性的影响,以初步探讨普通动物中正常菌群与免疫机制间的微生态关系。结果表明,口服两种抗生素破坏动物正常菌群平衡均可导致机体免疫机能水平降低;免疫机能降低程度与抗生素抗菌谱、药物剂量及用药时间有密切关系。提示,口服抗生素引起机体肠道正常菌群平衡紊乱是导致机体免疫机能下降的重要原因;正常菌群与机体保持稳定的平衡状态对机体免疫机能的正常发挥是必不可少的。