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Biomedical subjects

R Jacob

Publications and source records attributed to R Jacob.

At least 163 records · Page 9Linked to original sources
PubMed1986

Characterization of glutamine transport by liver plasma membrane vesicles.

Plasma membrane vesicles were prepared from livers of fed normal and diabetic rats and used to characterize the membrane transport process responsible for glutamine uptake by the liver cell. In vesicles from normal rats the initial velocity of glutamine uptake was fourfold more rapid (0.20 +/- 0.02 vs. 0.05 +/- 0.02 nmol X mg protein-1 X 10 s-1) when Na+ replaced K+ in the extravesicular buffer. In the presence of a Na+-gradient glutamine uptake by vesicles was saturable, with a Km of 1.3 +/- 0.5 mM and a Vmax of 10 +/- 2.3 nmol X mg-1 X min-1. Lithium could fully substitute for Na+ in stimulating glutamine entry. In the presence of an imposed K+-gradient glutamine uptake was a linear function of its extravesicular concentration. In accord with the sodium-stimulated uptake of glutamine occurring via a sodium symport process, we observed that glutamine stimulated the initial rate of 22Na+ entry into vesicles by four- to fivefold. We further observed that glutamine entry was more rapid when lipophilic anions accompanied sodium in the incubation buffer, suggesting that Na+-glutamine flux is electrogenic. Preloading of vesicles with glutamine did not effect subsequent entry of labeled glutamine (no transstimulation), whereas intravesicular alanine did enhance alanine but not glutamine entry. Alloxan diabetes, which is known to stimulate the Na+-alanine cotransporter in these vesicles did not increase glutamine entry at any concentration tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1986

Continuous subcutaneous insulin infusion (CSII) reduces counter-regulatory hormone concentrations in a patient receiving enteral hyperalimentation.

A 61-year-old male, while recovering from a Whipple's procedure for pancreatic carcinoma, was treated for 13 days with an insulin infusion pump for diabetes exacerbated by enteral hyperalimentation. Treatment with continuous subcutaneous insulin infusion resulted in improved blood glucose control. Associated with this improvement was a reduction in plasma cholesterol, triglyceride and free fatty acid levels. Plasma epinephrine, norepinephrine, glucagon and cortisol concentrations were also lowered although growth hormone levels remained unchanged. It is concluded that enhanced metabolic control during hyperalimentation results in a decrease in counter-regulatory hormone levels and an improvement in the catabolic state in this patient. These preliminary observations provide evidence for maintaining euglycemia in diabetic patients while receiving nutritional support.

Blood Glucose↗
PubMed1986

Myocardial and ventricular mechanics as influenced by disopyramide.

The effects of disopyramide (D) on the mechanics of isolated myocardium as well as on the whole ventricle were examined in the rat model. Moreover bipolar leads of the apex and an area at the base of the left ventricle were set up to get indications for changes in the spread of excitation. D in concentrations of 10(-8) to 10(-4) mol/l did not affect the diastolic elastic properties of isolated myocardium. Isometric contraction amplitude was nearly unaltered, while rate of isometric contraction and relaxation were slightly increased. In the whole ventricle in situ D (2 to 10 mg/kg b.w. administered i.v.) induced a dose-dependent decrease in left ventricular isovolumetric peak pressure (16%), max.pos. dP/dt (40%) and max.neg. dP/dt (30%; for highest doses respectively), while time to peak pressure and relaxation time 90% were prolonged. Therapeutic dose of D (2 mg/kg b.w.i.v.) induced no decrease in essential systolic parameters of the whole ventricle under auxotonic conditions. Left ventricular pressure, dP/dt max.pos. and neg., left ventricular end-diastolic pressure and cardiac output were nearly unaltered. Heart rate showed a tendency to decrease, while total time of contraction and left ventricular ejection time increased. Higher doses of D led to marked cardiac depressant effects. The time interval between the excitation of the apex and an area at the base of the heart was increased. It was concluded that the negative dromotropic effect of D and thereby an altered pattern of left ventricular contraction are essential components in the elimination of the pressure gradient between left ventricle and aorta, observed in patients with muscular subaortic stenosis, and are presumably involved in the cardiac depressant effect of the drug in over-therapeutic doses.

Animals↗
PubMed1985

Cytosolic free calcium in chick heart cells. Its role in cell injury.

The role of cytosolic free Ca2+ (Caf) in cell injury was investigated using two methods for measuring Caf in freshly disaggregated embryonic chick heart cells. The null-point method, using arsenazo III, is based on determining the extracellular Ca2+ concentration at which no net Ca2+ movement occurs when plasma membrane permeability is increased. With this technique, the null point Caf averaged 0.23 +/- 0.07 microM (n = 6) in the basal state. Using quin2, an intracellular fluorescent dye, to measure Caf a value of 0.05 +/- 0.01 microM (n = 5) was obtained. Elevation of Caf by various agents was associated with an increase in cell injury as measured by the release of the cytosolic enzyme, LDH. However, the relationship between Caf and LDH release was not a direct one under all experimental conditions, indicating that the level of Caf is not the sole determinant of cell injury.

Adenosine Triphosphate↗
PubMed1985

Na/H exchange in cultured chick heart cells. pHi regulation.

The purpose of this study was to establish the existence of Na/H exchange in cardiac muscle and to evaluate the contribution of Na/H exchange to pHi regulation. The kinetics of pHi changes in cultured chick heart cells were monitored microfluorometrically with 6-carboxyfluorescein and correlated with Nai content changes analyzed by atomic absorption spectrophotometry; transmembrane H+ movements were evaluated under pH stat conditions. After induction of an intracellular acid load by pretreatment with NH4Cl, a regulatory cytoplasmic alkalinization occurred with a t1/2 of 2.9 min. pHi regulation required external Na+ and was concomitant with transmembrane H+ extrusion as well as a rapid rise in Nai content in an Na/H ratio of 1:1. Microelectrode recordings of membrane potential demonstrated directly the electroneutral character of pHi regulation. Acid-induced net Na+ uptake could be either stimulated by further decreasing pHi or inhibited by decreasing pHo; Na+ uptake was unaffected by tetrodotoxin (10 micrograms/ml), quinidine (10(-3) M), DIDS (10(-4) M), Clo-free solution, or HCO3-free solution. Amiloride (10(-3) M) maximally inhibited both pHi regulation and Na+ uptake; the ID50 for amiloride inhibition of Na+ uptake was 3 microM. Nao-dependent H+ extrusion showed half-maximal activation at 15 mM Nao; Li+, but not K+ or choline+, could substitute for Na+ to support H+ extrusion. Cao-free solution also stimulated acid-induced Na+ uptake. We conclude that pHi regulation following an acid load in cardiac muscle cells is by an amiloride-sensitive, electroneutral Na/H exchange. Stimulation of Na/H exchange up to 54 pmol/cm2 X s indicates the rapidity of this exchange across cardiac cell membranes. Na/H exchange may also participate in steady state maintenance of pHi.

Amiloride↗
PubMed1985

Potassium-chloride cotransport in cultured chick heart cells.

The polystrand preparation of cultured chick heart cells has a unidirectional transmembrane Cl- efflux that is twice K+ efflux. However, Cl- conductance of this heart cell membrane is low [regardless of extracellular K+ (K+o)], suggesting the existence of electroneutral Cl--dependent transport mechanisms. Furosemide (10(-3) M) decreases the 36Cl tracer efflux rate constant from a control value of 0.67 to 0.33 min-1. Extracellular Na+--free solution, which depletes intracellular Na+ within 1 min, has no significant effect on 36Cl efflux. K+o-free solution plus 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 10(-4) M) promotes the loss of Cl- against the Cl- electrochemical gradient; Cl- loss is furosemide sensitive in a dose-dependent manner. Incubating polystrands in 133 mM K+o, normal extracellular Cl- (Cl-o) solution causes net K+ and Cl- uptake in a 1:1 stoichiometry as well as a furosemide-sensitive volume increase; 130 mM extracellular choline or Li+ cannot mimic this high-K+o-induced volume increase. Removal of Cl-o from 133 mM K+o solution prevents K+ uptake and causes a Cl- loss as well as a furosemide-sensitive volume decrease. Adjusting Cl-o concentrations in high-K+o solution plus DIDS, so that the Cl- chemical gradient equally opposes the K+ chemical gradient, prevents high-K+o-induced volume changes. These data suggest that the cardiac cell membrane contains a furosemide-sensitive K+-Cl- cotransport mechanism.

Animals↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗