Search PubMed⌕ Search

Biomedical subjects

M A Mir

Publications and source records attributed to M A Mir.

At least 37 records · Page 2Linked to original sources
PubMed1988

Characterization of Na+ transport in normal human fibroblasts and neoplastic H.Ep.2 cells and the role of inhibitin.

Na+ transport was characterized in normal human fibroblasts and neoplastic H.Ep.2 cells in order to investigate the role of the endogenous peptidic factor 'inhibitin' that is secreted by a variety of neoplastic cells (including H.Ep.2) and inhibits Na+/Na+ exchange in human erythrocytes. Although active (Na+,K+-ATPase mediated) Na+ fluxes were similar in the two cell types, H.Ep.2 cells maintained higher intracellular Na+ concentration (26 mM) compared to fibroblasts (12 mM). An analysis of passive Na+ fluxes showed a difference in the handling of Na+ via ouabain and bumetanide-insensitive transport between the two cell types: H.Ep.2 cells achieved net Na+ influx via an amiloride-sensitive pathway that was only demonstrated in fibroblasts when 10% fetal calf serum (FCS) was present. Kinetic studies were undertaken to investigate the interaction between Na+ flux via Na+/H+ and Na+/Na+ exchanges. For this purpose, an outwardly directed Na+ gradient was created by loading the cells with Na+ (Nai greater than 100 mM) to activate the reverse functioning of Na+/H+ exchange (i.e., Na+out H+in). The rates of ouabain- and bumetanide-insensitive Na+ efflux were measured over a range of extracellular Na+ concentrations (Na+o 14-140 mM). In the presence of 10% FCS, the two cell types showed different responses: in fibroblasts the Na+ efflux rate showed an inverse correlation with extracellular Na+ concentration, while H.Ep.2 cells significantly increased their rate of Na+ efflux as extracellular Na+ concentration increased. So although the thermodynamic force would direct net Na+ efflux when Na+i greater than Na+o, H.Ep.2 cells were under kinetic control to perform Na+/Na+ exchange. When exogenous inhibitin was tested on fibroblasts, the steady-state intracellular Na+ concentration increased from 14 to 19 mM (p less than 0.01). In Na+-loaded fibroblasts, serum-stimulated Na+ efflux was partially inhibitin sensitive and the maximal inhibitory effect was seen when extracellular Na+ concentration was 14 mM and presumably the Na+/H+ exchanger operating in the reverse mode. This study demonstrated that, in contrast to fibroblasts, H.Ep.2 cells have a modified Na+/H+ exchange system whereby it acts in the Na+in H+out mode without exogenous growth factor activation and resists functioning in the reversed mode. It is proposed that inhibitin is the endogenous modifier of this transport system in H.Ep.2 cells with the result that H.Ep.2 cells maintain a higher concentration of intracellular Na+ compared to fibroblasts.

Biological Transport↗
PubMed1988

Calcium retention and increased vascular reactivity caused by a hypothalamic sodium transport inhibitor.

1. Using a previously established method of isolating an active-sodium-transport inhibitor (ASTI) from hypothalamic cell culture medium, the inhibitor was isolated and partially purified from sequential passages through Sephadex G-25 and h.p.l.c., and its effects on de-endothelialized rabbit aortic strips were investigated. 2. ASTI caused a cumulative concentration-dependent increase in tension which reversed slowly after wash, and the wash showed an identical effect on fresh strips. 3. Ouabain, used as a control, also caused a concentration-dependent increase in tension which reached a plateau at a concentration of 10 mmol/l. Both ouabain and ASTI caused a significant potentiation of the vasoconstrictor effect of noradrenaline at concentrations of 1 nmol/l-0.1 mmol/l. 4. Both ASTI and ouabain caused a significantly greater (P less than 0.01) calcium retention than control medium in aortic strips. 5. Incubation of ASTI with prolidase, chymotrypsin and carboxypeptidase A destroyed the vasoconstrictor effects as well as its inhibitory effects on sodium, potassium-dependent adenosine triphosphatase and sodium efflux from erythrocytes, but leucine aminopeptidase was ineffective. 6. These studies suggest that hypothalamic cells in culture release a peptidic inhibitor of active sodium transport which increases vascular reactivity, potentiates vasoconstrictor effects of noradrenaline and causes calcium retention.

Animals↗
PubMed1988

Relationship between red cell sodium transport, blood pressure, and family history of hypertension.

Numerous studies have demonstrated that Na+/Li+ countertransport is increased in erythrocytes from hypertensive patients. Since Na+/Li+ countertransport is conducted through the physiologically occurring Na+/Na+ exchange, we studied the latter pathway in 20 subjects with essential hypertension and 20 normotensive subjects matched for age and sex. Ten hypertensives and six normotensives had a positive family history of hypertension. Ouabain (0.1 mM) and furosemide (0.1 mM) were used to assess the active Na+ efflux and Na+-K+-Cl- pathway. There was no significant difference between hypertensive and normotensive subjects in any of the three pathways studied. Among the 16 subjects with a positive family history of hypertension, the mean value for external Na+-dependent Na+/Na+ exchange was significantly higher than in 24 subjects with no family history of hypertension (0.0457 +/- 0.0337 versus 0.0283 +/- 0.0202; P less than 0.05). This study suggests that an inherited membrane transport defect may exist for Na+/Na+ exchange in families of hypertensive subjects.

Biological Transport↗
PubMed1988

An active sodium transport inhibitor released from spontaneously hypertensive and normotensive rat fetal hypothalamic cells in culture.

An inhibitor of active sodium transport (Na+ + K+-ATPase inhibitor), partially purified from the culture medium of fetal rat hypothalamic cells, has been shown to possess vasoactive properties. In order to explore whether fetal hypothalamic neurons from spontaneously hypertensive rats produce higher concentrations of the inhibitor than produced by those from normotensive rats, we cultured hypothalamic cells from both sources. An average of 10(6) cells per hypothalamus was obtained, and heat-treated (80 degrees C for 10 minutes) culture medium (120 ml) after lyophilization yielded 0.8 g of material. After Sephadex G-15 chromatography, 0.5 g of lyophilized medium from fetal hypothalamic neurons of spontaneously hypertensive rats yielded 254 +/- 47 arbitrarily defined units of Na+ + K+-ATPase inhibitory activity compared with 238 +/- 59 units from identical material of normotensive source. These studies show that the production of the hypothalamic Na+ + K+-ATPase inhibitor is not increased at the fetal stage in the spontaneously hypertensive rats.

Animals↗
PubMed1988

The relationship of dietary salt and blood pressure in three farming communities in Kashmir.

The relationship between salt intake and blood pressure was explored in three different areas of Northern Kashmir, where people consume large quantities of salt in tea. Six villages were selected from each area and all the available family members of every second or third house were studied. Food and salt were weighed and the intake of each family member was obtained from the amount consumed out of the total cooked. Complete data were available from 361 subjects (191 males, 170 females). There was no significant difference between the three areas as regards age, height, weight, salt intake and blood pressure. Their age ranged from 15 to 88 yrs (mean 44) and the daily salt intake ranged from 70 to 420 mmol (mean 169 mmol). No correlation was found between age and salt intake or weight but there was a significant correlation between age and systolic blood pressure (r = 0.296; P less than 0.01). Both the systolic and diastolic blood pressure correlated significantly with the salt intake with correlation coefficients of 0.385 and 0.318 respectively (P less than 0.001). Multiple regression analyses showed that the significant relationship between salt and blood pressure was unaltered by adjustment for age. Of the 361 subjects, 46 (12.7%) had a blood pressure of 160/95 mmHg or more. This study suggests a similar relationship between habitual salt intake and blood pressure in each of three different areas of Northern Kashmir.

Adult↗
PubMed1987

Beneficial effects of dietary carbohydrate restriction in chronic cor pulmonale.

To explore the effects of moderate and severe reductions in carbohydrate intake on abnormal pulmonary physiology in chronic hypercapneic respiratory failure, spirometric, metabolic, arterial blood gas tension, and oximetric studies were carried out in eight patients who took, in random order daily for a week, either 50 g or 200 g of carbohydrate in an isocaloric diet. At the end of a week's daily intake of an isocaloric diet containing 200 g of carbohydrate, all patients experienced a subjective improvement; the mean body weight was 55.5 +/- 15.4 kg (1 SD) compared with 56.0 +/- 16.0 kg during the control dietary period, the arterial carbon dioxide tension decreased from a mean of 56.9 +/- 6.7 to 50.9 +/- 6.2 mm Hg (p less than 0.005), and the arterial oxygen tension increased from a mean of 50.6 +/- 7.3 to 62.0 +/- 14.5 mm Hg (p less than 0.02). After a week's intake of 50 g of carbohydrate in an isocaloric diet, the body weight and arterial oxygen tension did not change significantly, but the arterial carbon dioxide tension decreased still further to 48.0 +/- 7.8 mm Hg (p less than 0.05). Mouth pressure at 100 msec after the start of inspiration, as a measure of respiratory center output, was significantly higher during both the low carbohydrate intakes compared with the control dietary period. The spirometric data, ventilation-perfusion distribution measurements, oxygen consumption, and carbon dioxide production did not change significantly during various dietary periods. It is concluded that, under these short-term, hospital-controlled conditions, a reduction in the carbohydrate intake to 200 g a day improves the general well-being of patients with chronic hypercapneic respiratory failure, increases arterial oxygen tension, and decreases arterial carbon dioxide tension. A further reduction in the carbohydrate intake to 50 g a day provides further beneficial effects, and such a diet may be used in patients with intractable respiratory failure.

Adult↗
PubMed1987

Problems and pitfalls in the isolation of an endogenous Na+, K+-ATPase inhibitor.

Plasma from volume-expanded and salt-loaded hypertensive animals and from patients with essential hypertension has been reported to inhibit Na+, K+-adenosine triphosphatase (ATPase). Inhibition of the sodium pump in vascular smooth muscle caused by such a circulating factor could increase vascular tone and sensitivity to vasoactive agents, and thereby result in arterial hypertension. Numerous efforts in the past failed to isolate the putative factor from urine and plasma. Recent studies have suggested that the hypothalamus is an important source of an endogenous Na+, K+-ATPase inhibitor, but its isolation from the tissue extracts has been rendered difficult by the presence of other cellular constituents that cause artifactual interference with the assays and purification procedures. Using an alternative approach of isolating the inhibitor from culture medium, we found that dispersed fetal rat hypothalamic neurons in a capillary culture system release a heat-stable, peptidic, low-molecular-weight, active sodium transport inhibitor that causes a reversible increase in vascular tone, sensitizes vascular smooth muscle to the vasoactive effect of norepinephrine, and possesses several characteristics of the putative endogenous digitalislike factor. This inhibitor may be a chemical mediator linking kidney, brain, and cardiovascular system in the genesis of experimental volume-expanded and salt-loaded hypertension and human essential hypertension.

Animals↗
PubMed1986

Serum stimulation of sodium transport in human fibroblasts containing low and high levels of intracellular sodium.

The relationships between intracellular sodium content, sodium transport and serum effects were investigated in human fibroblasts. In the cells with low intracellular sodium (Na+iL; 0.04 mumol sodium/mg protein), serum stimulated the sodium-potassium pump as measured by ouabain-sensitive sodium efflux and rubidium influx and also exerted a transstimulation of ouabain-insensitive sodium transport resulting in net influx. In cells with high intracellular sodium (Na+iH; 0.42 mumol sodium/mg protein) all aspects of sodium transport were increased compared to Na+iL cells. In these cells serum caused no change in sodium-potassium pump activity but significantly increased the ouabain-insensitive sodium fluxes resulting in net efflux. In Na+iL cells, serum promoted net sodium influx through an amiloride-sensitive pathway that was undetectable in the basal state. In Na+iH cells the serum-stimulated net efflux was amiloride sensitive but this pathway also contributed to a major portion of sodium transport in the basal state. This study demonstrated that sodium-potassium pump activity is directed by the supply of internal sodium and that serum can increase this supply by promoting net influx, and that serum-induced sodium transport can be modified by intracellular sodium content.

Animals↗
PubMed1986

Cardiorespiratory response to exercise before and after acute beta-adrenoreceptor blockade in nonsmokers and chronic smokers.

To evaluate the effects of chronic smoking on exercise performance we studied 5 smokers and 7 nonsmokers of comparable age and physical characteristics. The resting heart rate in smokers (75 +/- 3 beats/min; mean +/- SD) was significantly (P less than 0.01) higher than in nonsmokers (64 +/- 5). During exercise on a bicycle ergometer the heart rate remained significantly (P less than 0.01) higher in smokers than in nonsmokers. After exercise, the heart rate in nonsmokers settled to 78 +/- 9 beats/min at 10 minutes compared with 105 +/- 11 (P less than 0.01) in smokers. Oxygen consumption was similar in both groups throughout. Beta-adrenergic blockade reduced the exercise tachycardia in both groups but the heart rate for the same workload remained significantly (P less than 0.01) higher in smokers. Beta-blockade significantly reduced (P less than 0.05) oxygen consumption in nonsmokers but not in smokers who also incurred a significantly (P less than 0.05) greater oxygen debt and had higher serum lactate levels. These differences were attributed mainly to carboxyhaemoglobinaemia and partly to the effect of prolonged smoking on the heart and on intermediary metabolism.

Adult↗
PubMed1986

The relationship of salt intake and arterial blood pressure in salted-tea drinking Kashmiris.

In this study we attempted to explore the relationship between salt and blood pressure in a salted-tea drinking population of Northern Kashmir which has not been exposed to a Western way of life. All the available family members of randomly selected houses in 14 villages were studied. Dietary intake was documented for the whole month of the study period to estimate the daily salt consumption in 281 subjects (193 males, 88 females), whose ages were reliably known. Their age ranged from 15 to 85 years (median 35) and their mean daily salt intake was 150 +/- 52 mmol (range 80-440). Both the systolic and diastolic blood pressures showed a significant increase with the salt intake and age; multiple regression analysis suggested an independent effect of salt intake on blood pressure after adjusting for age. Twenty-six subjects (9.3%) had hypertension (blood pressure greater than or equal to 160/95 mm Hg); their daily salt intake was significantly higher than that of normotensive subjects (mean 167 +/- SD 53 vs 142 +/- 46 mmol; P less than 0.001). These studies suggest a relationship between habitual high salt intake and blood pressure.

Adolescent↗
PubMed1986

Effects of a low carbohydrate isoenergetic diet on sleep behavior and pulmonary functions in healthy female adult humans.

To study the effects of a low carbohydrate, isoenergetic diet on pulmonary physiology and sleep behavior, we measured pulmonary functions and respiratory gas exchange and carried out ambulatory electroencephalographic studies after a week's intake of isoenergetic diet containing only 50 g carbohydrate per day in 6 healthy female adult humans in a free-living condition. Compared with their normal intake, during the week of low carbohydrate intake there was a rise in the level of fasting plasma 3-hydroxybutyrate from 0.12 +/- 0.07 (mean +/- SD) to 1.01 +/- 0.40 mmol/L(P less than 0.01, paired t-test); a fall in serum bicarbonate from 26.2 +/- 0.75 to 25.0 +/- 1.41 mmol/L (P less than 0.05) and in serum chloride from 107 +/- 1.3 to 105 +/- 1.8 mmol/L (P less than 0.05). Serum urea rose from 4.3 +/- 0.71 to 5.7 +/- 0.70 mmol/L (P less than 0.01), and serum uric acid from 0.34 +/- 0.08 to 0.39 +/- 0.10 mmol/L (P less than 0.05). Functional residual capacity was increased from 2.07 +/- 0.35 to 2.26 +/- 0.34 L (P less than 0.01). Respiratory gas exchange ratio fell from 0.81 +/- 0.05 to 0.75 +/- 0.04 (P less than 0.05) and partial pressure of expired carbon dioxide reduced from 22 +/- 3.3 to 21 +/- 3.1 mmHg (P less than 0.05). There was a reduction in endogenous carbon dioxide production and arterial carbon dioxide tension. An analysis of ambulatory electroencephalogram showed that REM latency increased from 66 +/- 8 to 111 +/- 38 min (P less than 0.05), with no significant changes in sleep time and stages. These studies show that a low carbohydrate isoenergetic diet is tolerable, influences sleep behavior, reduces carbon dioxide production and respiratory gas exchange ratio, and may be therapeutically useful in patients with hypercapnic respiratory failure.

Adult↗
PubMed1986

Teaching medical history-taking: a comparison between the use of audio- and videotapes.

The efficacy of audiotape was compared with that of videotape as a way of teaching students the essentials of the medical interview. Two consultants--a general physician and a neurologist--were videotaped as they took histories from two patients. The neurologist described his methods and summarized his findings, but his interview was conducted conventionally without interruptions (continuous interview). In a contrasting style, the general physician frequently explained his methods and findings in steps, interrupting his interview to do this (discontinuous interview). Fifty students starting their main medical term were divided into two groups (A and B). Group A was shown the videotape of the discontinuous interview while group B was played an audiotape of that interview. Groups A and B were then crossed over, but this time group A was allowed only to hear the audiotape of the continuous interview, while the videotape of it was played to group B. After each tape the students were tested on its content. There was no significant difference between the mean scores of Group A and Group B when tested on the discontinuous interview and both groups scored well. For the continuous interview the group who saw the videotape scored significantly better than the group who only heard this tape. Both groups scored significantly better in the test based on the discontinuous interview than they did in the test based on the continuous interview. The results indicate that videotapes are a good medium for teaching history-taking, but also suggest that audiotape recordings of medical history-taking can be effective teaching aids if the interview is explained in stages.

Attitude of Health Personnel↗
PubMed1986

Effect of a long acting beta-adrenoceptor blocker on diurnal variation of cardiac dysrhythmias.

To investigate circadian variation of cardiac arrhythmias ambulatory electrocardiogram monitoring was carried out before and after one week's treatment with a long acting beta-adrenoceptor blocker, nadolol, in 26 patients who presented with symptoms attributable to arrhythmias. Analysis of the 24 hour profile of premature ventricular contractions showed a significantly (P less than 0.05) higher frequency during midday to midnight than between midnight and midday. The frequency of supraventricular tachycardia was significantly (P less than 0.05) higher during the periods from 12.00 hours to 16.00 hours (11.0 +/- 12) and 16.00 hours to 20.00 hours (11.3 +/- 11) than during the periods of 00.00 hours to 04.00 hours (3.6 +/- 3) and 04.00 hours to 08.00 hours (6.0 +/- 8). The period of the highest incidence of all arrhythmias was between 16.00 hours to 24.00 hours, and that of lowest during the period between 04.00 hours to 12.00 hours (P less than 0.01). After one week's treatment with nadolol the frequency of all arrhythmias was strikingly reduced but their pattern of occurrence remained unchanged. These studies suggest that patients who present with symptoms attributable to arrhythmias tend to have these more frequently during the physical and mental activities of the day and evening presumably due to the accompanying sympathetic overactivity.

Adrenergic beta-Antagonists↗
PubMed1986

Inhibitin: a specific inhibitor of sodium/sodium exchange in erythrocytes.

An inhibitor of ouabain-insensitive sodium/sodium exchange in erythrocytes has been isolated from leukemic promyelocytes. To explore the specific effects of this inhibitor, named inhibitin, sodium transport experiments were carried out in human erythrocytes. Inhibitin reduced ouabain-insensitive bidirectional sodium transport. It did not change net sodium fluxes, had no significant effect on rubidium influx, and did not inhibit sodium-potassium-ATPase activity. The inhibitory effect of inhibitin was studied on sodium/sodium exchange and on sodium/lithium countertransport in 140 mM sodium and in sodium-free media. In the presence of sodium, inhibitin reduced sodium and lithium efflux to that observed in sodium-free medium. Inhibitin showed no reduction in sodium or lithium efflux when sodium was replaced by choline chloride or Mg2+. When inhibitin was combined with one or more of the other transport inhibitors (i.e., ouabain, furosemide, or bumetanide and amiloride), its inhibitable component remained distinct and it did not overlap with that of the other inhibitors. These studies show that inhibitin is a specific inhibitor of carrier-mediated sodium/sodium exchange and sodium/lithium countertransport processes in human erythrocytes.

Cell Line↗
PubMed1986

Release of a sodium transport inhibitor (inhibitin) from cultured human cancer cells.

In this study we investigated whether the sodium transport inhibitor, inhibitin, originally isolated from leukemic promyelocytes, was also elaborated by some other neoplastic cells in culture. Like culture medium from the leukemic promyelocytes (HL60), the media from two other leukemic cell lines (erythroblasts K562 and monoblasts U937) also showed significant inhibitory activity on ouabain-insensitive sodium efflux rate constant in normal erythrocytes. Similarly, culture media from three neoplastic cell lines (H.Ep2, MRC5, and HX99) also showed significant inhibitin-like inhibitory activity. Using high-performance liquid chromatography to isolate inhibitin, culture media from HL60 and H.Ep2 cells were identically treated, and inhibitin isolated from H.Ep2 cells had the same retention time as that shown by promyelocyte inhibitin. H.Ep2 inhibitin reduced ouabain- and bumetanide-insensitive sodium efflux rate constant from 0.1510 +/- 0.0275 (SD) to 0.0988 +/- 0.0110 (P less than 0.005). Like promyelocyte inhibitin, H.Ep2 inhibitin reduced sodium efflux and influx by equivalent amounts suggesting thereby that it is a sodium/sodium exchange inhibitor. These studies show that a factor exhibiting inhibitory activity on sodium/sodium exchange is secreted by a variety of leukemic and neoplastic cells in culture.

Biological Transport, Active↗