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Biomedical subjects

R Jacob

Publications and source records attributed to R Jacob.

At least 181 records · Page 10Linked to original sources

Diabetes enhances activity of alanine transport in liver plasma membrane vesicles.

In the present study plasma membrane vesicles were prepared from livers of control and alloxan-induced diabetic rats and the substrate specificity and kinetic characteristics of alanine transport determined in both groups. Sodium-dependent alanine uptake at physiological alanine concentrations (100 microM) was enhanced threefold in diabetic as compared with control animals (0.31 +/- 0.04 vs. 0.11 +/- 0.01 nmol X mg protein-1 X 10 s-1). This accelerated influx corresponded to a three- to fourfold increase in the Vmax of alanine transport in diabetic versus control group (7.1 +/- 2.1 vs. 1.6 +/- 0.2 nmol X mg protein-1 X 10 s-1, P less than 0.05), whereas the Km of alanine uptake was unchanged (2.8 +/- 1.2 vs. 1.4 +/- 0.1 mM). Other neutral amino acids (20 mM) inhibited alanine transport to a similar degree in both groups. The sodium-dependent influx of glutamine (100 microM) was similar in diabetic and control groups (0.17 +/- 0.03 and 0.14 +/- 0.02 nmol X mg protein-1 X 10 s-1, respectively). The initial velocity of 22Na uptake (80 mM) into vesicles and half-maximal stimulation of alanine transport was achieved at essentially identical sodium concentrations (approximately 40 mM) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

Regulation of myocardial amino acid balance in the conscious dog.

The effects in vivo of physiologic increases in insulin and amino acids on myocardial amino acid balance were evaluated in conscious dogs. Arterial and coronary sinus concentrations of amino acids and coronary blood flow were measured during a 30-min basal and a 100-min experimental period employing three protocols: euglycemic insulin clamp (plasma insulin equaled 70 +/- 11 microU/ml, n = 6); euglycemic insulin clamp during amino acid infusion (plasma insulin equaled 89 +/- 12 microU/ml, n = 6); and suppression of insulin with somatostatin during amino acid infusion (plasma insulin equaled 15 +/- 4 microU/ml, n = 6). Basally, only leucine and isoleucine were removed significantly by myocardium (net branched chain amino acid [BCAA] uptake equaled 0.5 +/- 0.2 mumol/min), while glycine, alanine, and glutamine were released. Glutamine demonstrated the highest net myocardial production (1.6 +/- 0.2 mumol/min). No net exchange was seen for valine, phenylalanine, tyrosine, cysteine, methionine, glutamate, asparagine, serine, threonine, taurine, and aspartate. In group I, hyperinsulinemia caused a decline of all plasma amino acids except alanine; alanine balance switched from release to an uptake of 0.6 +/- 0.4 mumol/min (P less than 0.05), while the myocardial balance of other amino acids was unchanged. In group II, amino acid concentrations rose, and were accompanied by a marked rise in myocardial BCAA uptake (0.4 +/- 0.1-2.6 +/- 0.3 mumol/min, P less than 0.001). Uptake of alanine was again stimulated (0.9 +/- 0.3 mumol/min, P less than 0.01), while glutamine production was unchanged (1.3 +/- 0.4 vs. 1.6 +/- 0.3 mumol/min). In group III, there was a 4-5-fold increase in the plasma concentration of the infused amino acids, accompanied by marked stimulation in uptake of only BCAA (6.8 +/- 0.7 mumol/min). Myocardial glutamine production was unchanged (1.9 +/- 0.4-1.3 +/- 0.7 mumol/min). Within the three experimental groups there were highly significant linear correlations between myocardial uptake and arterial concentration of leucine, isoleucine, valine, and total BCAA (r = 0.98, 0.98, 0.92, and 0.97, respectively); P less than 0.001 for each). In vivo, BCAA are the principal amino acids taken up by the myocardium basally and during amino acid infusion. Plasma BCAA concentration and not insulin determines the rate of myocardial BCAA uptake. Insulin stimulates myocardial alanine uptake. Neither insulin nor amino acid infusion alters myocardial glutamine release.

Amino Acids↗

Tricyclic antidepressants in obsessive-compulsive disorder: antiobsessional or antidepressant agents? II.

The authors explored the relationship between the antiobsessional and antidepressant effects of tricyclic drugs in primary obsessive-compulsive disorders. Study 1 consisted of a controlled 12-week trial with clomipramine (N = 7) and placebo (N = 5); study 2 analyzed the pooled data from 15 patients uniformly selected and treated with either clomipramine or imipramine. Although the antiobsessional and antidepressant effects of the drugs covaried, their antidepressant action was not a prerequisite for their antiobsessional effect. The findings suggest that clomipramine and probably imipramine possess specific antiobsessive effects that are at least partially independent of their antidepressant effects.

Adult↗

Relationship between the myofibrillar ATPase activity of human biopsy material and hemodynamic parameters.

The myofibrillar ATPase activity and pyrophosphate gel electrophoretic pattern of native myosin of fresh human left ventricular papillary muscles were examined in 52 cases of mitral valve replacement. The myofibrillar ATPase activity of hypertrophied myocardium did not differ from that of non-hypertrophied myocardium (mean +/- SD, 36.2 +/- 8.7 vs 31.8 +/- 8.6 nmolPi/mg/min, ns) and there was no significant difference in myofibrillar ATPase activity as a function of left ventricular enddiastolic pressure. Pyrophosphate gel electrophoresis of myosin revealed the presence of two components. It is questionable whether the component of higher electrophoretic mobility (approximately 25-35% in concentration) is identical with rat ventricular myosin VM-1 because an increase in this component seems to correlate with a decrease of myofibrillar ATPase activity, its concentration was significantly higher in the hearts with left ventricular hypertrophy, high enddiastolic pressure, high aortic pressure or low cardiac index. From these results, it is not necessarily clear whether hemodynamic overload in valvular heart diseases can alter left ventricular myofibrillar ATPase activity, but it can be said that the overload influences the concentration of the two components of native myosin revealed by pyrophosphate gel electrophoresis.

Adenosine Triphosphatases↗

Effects of non-toxic doses of ouabain on sodium, potassium, calcium distribution in guinea pig papillary muscle. Electronprobe microanalysis.

The mechanisms and the cellular structures which are definitely involved in the accumulation and release of calcium in heart muscle treated with cardiac glycosides are not yet known. The distribution of sodium, potassium and calcium in small papillary muscles of the guinea pig right ventricle was examined with the aid of energy dispersive x-ray microanalysis and cryotechniques. The primary aim of the present study was twofold: firstly, to determine whether an increase in intracellular sodium concentration is detectable in muscles showing positive inotropy resulting from treatment with non-toxic doses of ouabain; and secondly, whether at the end of diastole cellular stores are detectable accumulating Ca which could be responsible for the pronounced contraction which normally would follow. Analyses on interstitium, cell membrane, sarcomeres, Z-lines and mitochondria of 7 muscles strips treated with non-toxic doses of ouabain and frozen at the end of diastole showed the following: sodium concentration in the sarcoplasm was significantly higher than over the mitochondria; it was also higher than over the sarcoplasm of non-treated muscles frozen at the end of diastole. High calcium concentrations were also measured over the cell membrane. These calcium concentrations were higher than that detected in sarcomeres, Z-lines and mitochondria. Over the sarcomeres, the calcium concentration was higher than in experiments on non-treated muscles which were also frozen at the end of diastole. Mitochondria did not accumulate any detectable concentration of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metabolic, endocrine, and reproductive changes of a woman channel swimmer.

We report the coordinated metabolic, hormonal, and reproductive data of a female channel swimmer during the pre-swim training period, immediately post-swim, and in the post-swim untrained state. Urine and blood samples collected at these times were assayed for diurnal urinary catecholamines, urinary C-peptide and 3-methylhistidine, total blood ketone bodies, glycerol, the reproductive hormones, adrenal androgens, and thyroid hormones. Subcutaneous fat was measured by ultrasonography. All of the metabolic and hormonal data post-swim except cortisol reflected the severe physiological stress. Urinary catecholamines returned to near-normal levels by 12 hours post-swim. The metabolic changes were associated with reproductive changes, including a shortened luteal phase, absence of ovulation, and increased LH secretion relative to FSH. The swimmer maintained high levels of body fat; she did not become amenorrheic. Metabolic and reproductive hormone levels returned to normal by 2 months post-swim.

Adipose Tissue↗

Effects of relaxation and mnemonics on memory, attention and anxiety in the elderly.

We measured attentional capacity as 25 normal elderly subjects were trained in techniques to improve face-name recall. Techniques consisted of relaxation training and a mnemonic device. Anxiety was measured simultaneously with attentional measures. We hypothesized that our techniques would increase available memory processing capacity by improving attention and reducing anxious rumination. Results indicated that subjects showing the greatest reduction in anxiety and cognitive interference and the greatest increase in attention also showed the most face-name recall following training. The results suggest that the elderly's anxiety has a cognitive component that interferes with performance on attentional and memory tasks, but which can be reduced through relaxation training.

Aged↗

Theoretical effects of transmembrane electroneutral exchange on membrane potential.

Transmembrane electroneutral transport mechanisms [e.g., Na/H exchange, Cl/HCO3 exchange, (K + Cl) cotransport] have recently been identified in a wide variety of cell types. If these exchanges sum to give a net electroneutral Na/K exchange, they may hyperpolarize the membrane potential beyond the value calculated from the Mullins-Noda equation, provided the cell maintains steady state intracellular ionic concentrations. In extreme circumstances, the membrane potential could hyperpolarize beyond the potassium reversal potential. This effect is mediated by the electrogenic Na/K pump. If either Na or K exchanges electroneutrally against a third ion (e.g., Na/Ca exchange), then the exchange may depolarize the membrane potential.

Bicarbonates↗

Cardiac alterations at the myofibrillar level: is a redistribution of the myosin isoenzyme pattern decisive for cardiac failure in haemodynamic overload?

Cardiac muscle physiology, cardiac dynamics and energetics of normotensive and hypertensive rats [Goldblatt II, spontaneously hypertensive rats (SHR)] are analyzed in the light of the question of whether a shift in the isoenzyme pattern of myosin in favour of the isoenzyme VM-3--i.e., transformation towards a slower muscle--is the essential factor for manifestation of cardiac insufficiency under chronic haemodynamic overload. Earlier investigations on chemically skinned myocardial preparations with homogeneous VM-3 and VM-1 patterns revealed that the decrease in unloaded shortening velocity attributable to extreme redistribution of the isoenzyme pattern can amount to approx. 40% whereas isometric tension development at the myofibrillar level is not significantly reduced. Findings from old normotensive and spontaneously hypertensive rates show that even substantial prevalence of VM-3 permits adequate ventricular pumping function. The decrease in the systolic parameters observed in later stages of chronic pressure overload may be attributed primarily to regressive alterations (fibrosis, structural dilatation). Under chronic haemodynamic overload, experimentally imposed isoenzyme redistribution towards a faster myocardium (small thyroxine doses) as well as transformation towards a slower muscle (thyrostatic treatment) affects the time parameters of contraction and oxygen consumption more than left ventricular work capacity. Signs of congestive heart failure are absent. It is concluded that mere transformation of myocardium towards a more slowly functioning muscle should not be considered the cause of cardiac failure in the rat model although this adaptive process may have detrimental consequences under certain conditions.

Adenosine Triphosphatases↗

Modulation of myosin isoenzyme populations and activities of monoamine oxidase and phenylethanolamine-N-methyltransferase in pressure loaded and normal rat heart by swimming exercise and stress arising from electrostimulation in pairs.

The question of whether the effects of physical exercise on the heart of 15-weeks normotensive and hypertensive rats can be modulated by additional stressors was studied. Intermittent swimming (33-35 degrees C water, maximum 2 X 1.5 h/day, 2-6 weeks) was employed as a model of exercise. Electrostimulation of rats in pairs (maximum 2 X 1.5 h/day, 6 weeks) served as a model leading predominantly to stress. When the above procedures were combined, electrostimulation in pairs was performed in one session and was followed up by swimming. The myosin isoenzyme population was used as a marker of changes in contractile performance of myofibrils. Activities of the catecholamine-degrading enzyme monoamine oxidase (MAO) and the adrenaline-synthesizing enzyme phenylethanolamine-N-methyltransferase (PNMT) served to monitor chronic alterations of catecholamine turnover in myocardium. Redistribution in favour of VM-1 (ventricular myosin isoenzyme 1) occurred as early as 2 weeks after the onset of intermittent swimming and was observed under several experimental conditions. The redirection of genetic expression of the isoenzymes was not linked to the presence of an increased ratio of right to left ventricular weight, most probably arising from intermittent hypoxia during drownproofing. The myosin isoenzyme population of swimming spontaneously hypertensive rats (SHR) resembled that of sedentary Wistar rats. The enzyme activities of MAO and PNMT were both significantly reduced following 6 weeks intermittent swimming in Wistar rats and SHR. This can most probably be attributed to the exercise component of swimming which, on average, led to reduced catecholamine turnover in heart. Electrostimulation of rats in pairs for 6 weeks, which resulted in aggressivity and aggressions, did not alter the myosin isoenzyme population in Wistar rats; in SHR, it further augmented the proportion of VM-3 (ventricular myosin isoenzyme 3), which had already increased in the sedentary state. Furthermore, electrostimulation increased PNMT activity, but did not affect MAO activity. Electrostimulation in pairs, followed by swimming, altered the myosin isoenzyme population in the same way as did swimming alone. However, the activities of PNMT and MAO seemed to be governed by the routine involving stress and not by the exercise routine. This demonstrates that stressors supplementing exercise can decisively modify or even prevent reactions of the organism in response to exercise.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Influence of exercise on urea, creatinine, and 3-methylhistidine excretion in normal human subjects.

To evaluate the effects of exercise on net protein catabolism, the losses of urea in sweat and urine and urinary creatinine and 3-methylhistidine (3MH) excretion were determined in eight healthy subjects during cycle ergometer exercise performed at approximately 45% of VO2max for 90 min. The subjects ingested a meat-free diet for 5 days starting 3 days before and continuing for 1 day after the day of exercise. During exercise, total urea excretion (urine + sweat losses) increased 100% above pre- and postexercise values. Thirty percent of the total urea excretion during exercise was in the form of sweat losses. Total protein breakdown (as reflected by urea excretion), however, could account for less than 5% (21 +/- 4 kcal) of total calorie expenditure during the exercise (567 +/- 83 kcal). Urinary creatinine excretion increased by 50% during exercise. Urinary excretion of 3MH also tended to rise, but the ratio of urinary 3MH to creatinine showed no change in response to exercise. We conclude that 1) light to moderate exercise results in an increase in net protein catabolism and an increase in creatinine excretion; 2) sweat losses are an important route for urea excretion during exercise; 3) there is no evidence of a disproportionate increase in breakdown of myofibrillar contractile proteins; and 4) in spite of the increase in the rate of protein catabolism, protein is only a minor source of energy during light to moderate exercise.

Adolescent↗

Physiologic criteria for electrogenic transport in tissue-cultured heart cells.

A description of the physiologic criteria for electrogenic transport in cultured heart cells must consider the direct as well as the indirect contributions of the electrodiffusive and electroneutral transport mechanisms of the kind described in this chapter. It is important to recognize that fundamental transport processes whether active, passive, or coupled-passive, do not operate in isolation but function rather as an interrelated network represented by the example in Fig. 8. The results of our studies point to the importance of providing an accurate, quantitative description of the transmembrane movement of sodium, because this ion is intricately involved in the overall regulation of several transport mechanisms in cardiac muscle. Cultured heart cell preparations enable the rapid exchange of extracellular space essential to the study of complex transport mechanisms. These preparations have thus enhanced our understanding of the magnitude and interplay of exchange fluxes that may eventually be implicated in the repolarization phase of the cardiac action potential and genesis of pacemaker potentials.

Biological Transport↗

[Seroprevalence of Q fever in an endemic area of southern Germany].

In a random study among inhabitants of a village in a region of South Germany in which Q fever is endemic, seroprevalence and the significance of known risk factors for Q fever were investigated. Of the 1150 inhabitants, 948 (older than 14 years, resident in the endemic region for more than six months) were included in the study (target group). Within eight months 715 subjects (total group) were actually tested. The total group did not differ from the target group demographically. There were 136 seropositive persons (19%) with a dominance of males (n = 86). Relatively at risk of seropositivity were: males, aged 14-19 years, women, aged 40-49 years; those resident less than 200 m from the next farmhouse; agricultural workers; those in contact with animal products and farm animals. The known greater risk for males is, as shown in these results, due to the specific agricultural activity of this population group, with increased contact with lamb meat, pigs and chickens.

Adolescent↗

Transmembrane chloride flux in tissue-cultured chick heart cells.

To evaluate the transmembrane movement of chloride in a preparation of cardiac muscle lacking the extracellular diffusion limitations of natural specimens, intracellular chloride concentration ( [Cl] i) and transmembrane 36Cl efflux have been determined in growth-oriented embryonic chick heart cells in tissue culture. Using the method of isotopic equilibrium, [Cl]i was 25.1 +/- 7.3 mmol x (liter cell water)-1, comparable to the value of 24.9 +/- 5.4 mmol x (liter cell water)-1 determined by coulometric titration. Two cellular 36Cl compartments were found; one exchanged with a rate constant of 0.67 +/- 0.12 min-1 and was associated with the cardiac muscle cells; the other, attributed to the fibroblasts, exchanged with a rate constant of 0.18 +/- 0.05 min-1. At 37 degrees C, transmembrane Cl flux of cardiac muscle under steady-state conditions was 30 pmol x cm-2 x s-1. In K-free, normal, or high-Ko solutions, the responses of the membrane potential to changes in external Cl concentration suggested that chloride conductance was low. These results indicate that Cl transport across the myocardial cell membrane is more rapid than K transport and is largely electrically silent.

Animals↗

Characterisation of left ventricular collagen in the rat.

Collagen of the normal and hypertrophied rat left ventricle was successively extracted with neutral salt and dilute acid solutions, and pepsin digestion. The yield of dilute-acid soluble collagen was only 0.3 to 0.6% of total collagen; the solubility with neutral salt was even lower. Limited pepsin digestion permitted extraction of 50 to 65% of total collagen. The distribution of the various types of collagen molecules was analysed in pepsin-solubilised collagen in the presence of 3.6 mol . litre-1 urea with the aid of electrophoresis on polyacrylamide gels. In all samples of nonreduced and reduced left ventricular collagen of the rat, disc patterns of pepsin-soluble collagen revealed the occurrence of dimeric and trimeric components, as well as aggregates of higher molecular weight. Such observations suggest the presence of an extensive interchain and intermolecular cross-linking network. Electrophoretic analysis of nonreduced and reduced pepsin-solubilised collagen also revealed heterogeneity of left ventricular rat collagen due to its occurrence as a mixture of type I and type III collagen. The proportion of type I collagen molecule components was substantially higher than that of type III components in all investigated samples of rat left ventricular connective tissue. Postnatal growth, aging and myocardial hypertrophy may affect the ratio of type I to type III components.

Age Factors↗