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Biomedical subjects

M A Mir

Publications and source records attributed to M A Mir.

At least 55 records · Page 3Linked to original sources
PubMed1985

A reproducible procedure for measuring sodium transport in cultured human fibroblasts from normal and obese donors.

Studies on erythrocyte sodium pump activity in obesity have yielded conflicting results probably because the erythrocyte is an atypical cell, and it may not reflect ATPase activity of other cells in the body. This study was undertaken to establish a reproducible procedure to measure sodium transport in human diploid fibroblasts, and apply this method to explore any differences in the cells from obese and nonobese humans. Cell cultures were established from 12 nonobese (body mass index (BMI) = wt in kg/height in m2 (Khosla and Lowe, Br J Prev Soc Med 1967; 21: 122-128); less than 27 kg/m2) and 10 obese (BMI) greater than 35 kg/m2) subjects. Triplicate measurements of sodium efflux rate constant were made with and without ouabain (1 mmol/l) to determine the total, active (ouabain-sensitive) and passive (ouabain-insensitive) components. Reproducible results were obtained as suggested by a coefficient of variation (CV) of less 10% on successive experiments on the same cell-line, and 11 and 15% of the active sodium efflux rate constant measured in fibroblasts from nonobese and obese subjects, respectively. The active sodium efflux rate constant in fibroblasts from nonobese (0.202 +/- 0.023 (SD)) was not significantly different from that obtained in the cells from obese subjects (0.21 +/- 0.030; p greater than 0.10). These results suggest that there is no intrinsic differences in basal sodium pump activity in fibroblasts related to obesity.

Biological Transport↗
PubMed1985

Characterization and partial purification of the sodium-potassium-ATPase inhibitor released from cultured rat hypothalamic cells.

An inhibitor of sodium-potassium-ATPase has been partially purified from the culture medium obtained from hypothalamic cells maintained in a capillary membrane perfusion system, and some of the properties of this inhibitory factor have been investigated. Gel filtration (Sephadex G-25 Superfine) of heat-treated medium (80 degrees C for 10 min) resulted in elution of inhibitory activity in the post-salt fraction. These fractions inhibited active (i.e. sodium-potassium-ATPase-mediated) sodium transport in intact human erythrocytes, displaced [3H]ouabain from its binding site, and directly inhibited canine kidney sodium-potassium-ATPase as measured by NADH oxidation. High-performance liquid chromatography (on Hypersil ODS) of these fractions after desalting yielded one region which showed inhibitory activity on all three assays. Inhibition of sodium-potassium-ATPase was dose-related and filtered through an Amicon UM10 membrane. Incubation of this material with dispase, carboxypeptidase A, chymotrypsin, and prolidase destroyed inhibitory activity, whereas trypsin and leucine aminopeptidase were ineffective. These studies show that hypothalamic neurones release a low molecular weight heat-stable peptide which inhibits active sodium transport, ouabain binding, and sodium-potassium-ATPase.

Animals↗
PubMed1985

Leukaemic promyelocytes and normal bone marrow cells release a passive sodium transport modifier (inhibitin).

Previous studies have shown that leukaemic immature cells, specifically promyelocytes but not mature leucocytes, contain and release an inhibitor of ouabain-insensitive sodium transport (inhibitin). In the present study, medium from cultured leukaemic promyelocytes significantly reduced the ouabain-insensitive sodium efflux from erythrocytes, whereas medium from the same cell line which had been made to differentiate did not have this effect. Culture medium from normal bone marrow cells (containing promyelocytes) also significantly (P less than 0.001) reduced ouabain-insensitive sodium efflux. These data suggest that inhibitin is secreted by primitive but not by mature leukaemic cells and normal bone marrow cells.

Biological Transport↗
PubMed1984

Erythrocyte sodium pump activity in human obesity.

In an attempt to resolve the prevailing confusion about erythrocyte sodium pump activity in obesity, we measured sodium-potassium-ATPase, ouabain-inhibitable (active) sodium efflux rate constant and intracellular sodium concentration in erythrocytes from 107 non-obese and obese subjects, with a body-mass index ranging from 17 to 54 kg X m-2. All the three independently measured variables were not significantly different between the two groups and no correlations were found between these three indices and body-mass index. The expression of ATPase activity in units of membrane protein allowed our previous data to be compared with this study and other reports. Our studies and most of the published reports suggest that there is no difference in erythrocyte sodium-potassium-ATPase and sodium transport between the vast majority of obese and non-obese subjects, but there is a subgroup of obese subjects (about 5%) with abnormally high erythrocyte sodium pump activity. The variable treatment of data from this subgroup and the small numbers of obese subjects studied by various investigators are largely responsible for the conflicting results about erythrocyte sodium pump activity.

Adult↗
PubMed1984

Elevated skeletal muscle sodium-potassium-ATPase in human obesity.

To determine whether muscle sodium-potassium-ATPase activity, an expression of energy turnover, is increased in obesity, we studied a group of nine non-obese and seven obese subjects undergoing elective cholecystectomy. The muscle ATPase activity was 87 per cent higher (p less than 0.001) in obese subjects compared with non-obese subjects. The increase in the ATPase activity positively correlated with both the body mass index (r = 0.81) and excess body weight (r = 0.75). No relationship was found between erythrocyte and muscle sodium-potassium-ATPase activities (r = 0.25). These findings demonstrate an increased ATPase activity in skeletal muscle obtained from obese subjects and that the erythrocyte is an inaccurate marker of this enzyme with respect to other body tissue.

Adult↗
PubMed1984

Comparison between videotape and personal teaching as methods of communicating clinical skills to medical students.

The efficacy of video recording in transmitting clinical knowledge and skills to medical students was tested by recording on videotape demonstrations of physical examinations given by five clinicians to a randomly selected group of 12 students (personal group) from the first clinical year and then showing these recordings, under identical conditions, to 13 students from the same year (video group). The efficacy of both the personal and video mediums in terms of whether content was retained was tested by a questionnaire completed by all students at the end of the sessions and by a structured clinical assessment in which students were asked to demonstrate some of the same clinical tasks three weeks after the demonstration. In answering the questionnaire the video group obtained a mean (SD) score of 20.8 (7.0) (maximum possible score 40), which was not significantly different from the score achieved by the personal group (17.4 (7.7)). The video group was able to reproduce 44 (10)% of the total clinical steps demonstrated and the personal group 45 (14)%. Videotaped demonstrations can be as effective as personal teaching of clinical methods, and video should be developed as a medium for first line clinical teaching.

Clinical Competence↗
PubMed1984

Cardiorespiratory effects of isosorbide dinitrate and nifedipine in combination with nadolol: a double-blind comparative study of beneficial and adverse antianginal drug interactions.

Combinations of 2 or 3 drugs are often used to treat angina pectoris, but their combined cardiorespiratory effects have not been investigated. Using a randomized, double-blind, placebo-controlled protocol, the effects of nadolol alone and nadolol in combination with isosorbide dinitrate and nifedipine were compared, in low and high doses, on antianginal efficacy, respiratory functions and arterial blood oxygen saturation (SaO2) in 19 patients with stable angina pectoris. A complete assessment including a bicycle exercise test with the measurement of the sum of ST-segment depression in all leads (sigma ST) was carried out every 2 weeks. The frequency of anginal attacks and nitroglycerin consumption was reduced significantly (p less than 0.001) by nadolol alone and in combination with the other drugs. Nadolol caused a slight reduction in the forced expiratory volume in 1 second, which was improved by isosorbide dinitrate and nifedipine. The sigma ST profile (basal, at peak exercise and 2 and 5 minutes after exercise) was decreased by nadolol alone and in combination with the other drugs, although the greatest reduction was achieved with large doses of nifedipine and nadolol. The rest and postexercise SaO2 decreased after nadolol alone and in combination with isosorbide dinitrate, but recovered to pretrial values after nifedipine and nadolol. With all drug combination, sigma ST depression was greater when the postexercise SaO2 was less than 92%, and decreased (p less than 0.05) in the same patients when their postexercise SaO2 was greater than 92%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1984

Effect of low calorie intake on abnormal pulmonary physiology in patients with chronic hypercapneic respiratory failure.

To explore the effects of low calorie, low carbohydrate intake on abnormal pulmonary physiology in chronic hypercapneic respiratory failure, spirometric, arterial blood gas tension, oximetric, and electrocardiographic studies were carried out before and after weight reduction in eight patients. During a single night of monitoring, the mean basal oxygen saturation was 68.4 +/- 20.7 percent with 38 hypoxemic "dips" (a fall in oxygen saturation of more than 10 percent for one minute or longer); six patients had resting tachycardia, four had a prolonged QTc interval, three showed multiple episodes of ST-T depression, and six patients had multiple atrial and ventricular premature contractions. After a low calorie (600 kcal per day) intake for 4.4 +/- 2.3 weeks, there was a mean weight loss of 8.5 +/- 3.6 kg, the mean arterial oxygen tension increased significantly (p less than 0.005) from 55.6 +/- 9.2 to 69.1 +/- 7.9 torr, the mean arterial carbon dioxide tension fell from 59.9 +/- 9.6 to 52.4 +/- 5.4 torr (p less than 0.01), the mean oxygen saturation increased significantly (p less than 0.05) to 85.0 +/- 9.0 percent with only two hypoxemic "dips," the resting heart rate decreased from a mean of 100 +/- 19 to 90 +/- 18 beats/per minute (p less than 0.05), there was a marked reduction in ectopic activity, the ST-T depression disappeared, and the QTc interval fell in two subjects. Follow-up data in four patients suggest that the improvements achieved in arterial blood gas values can be maintained with a low calorie intake. These studies show that a low calorie, low carbohydrate intake improves all the unfavorable physiologic abnormalities in chronic hypercapneic respiratory failure.

Aged↗
PubMed1984

A passive sodium transport inhibitory factor (inhibitin) released from leukaemic promyelocytes in culture.

Previous studies have shown that myeloid leukaemic blast cells contain a heat stable factor which inhibits bidirectional sodium transport in normal erythrocytes. This study was undertaken to establish whether leukaemic promyelocytes in culture secrete this factor. Two cell-lines of leukaemic promyelocytes (HL-60 and JR) were grown and culture media from both reduced significantly the ouabain-insensitive sodium efflux rate constant, whereas conditioned culture medium (incubated like the cells in culture) had no inhibitory effect. Promyelocyte extract reduced significantly (P less than 0.01) the total sodium efflux rate constant from 0.393 +/- 0.030 (SD) to 0.311 +/- 0.060, and ouabain-insensitive efflux rate constant from 0.131 +/- 0.008 to 0.079 +/- 0.009 (P less than 0.001). The inhibitory factor was heat stable (80 degrees C for 30 min) and it inhibited sodium efflux through a pathway which was not inhibited by ouabain or frusemide. These studies suggest that leukaemic promyelocytes secrete the previously identified passive sodium transport inhibitory factor.

Biological Transport, Active↗
PubMed1984

Isolation of a sodium transport inhibitory factor, inhibitin, from cultured leukemic promyelocytes.

Previous studies have shown that leukemic blood contains a factor that has an inhibitory effect on bidirectional sodium transport in erythrocytes. This study was designed to isolate this factor from cultured leukemic promyelocytes. An extract from the promyelocytes reduced significantly (P less than 0.001) the ouabain-insensitive sodium efflux rate, from 0.096 +/- 0.009 to 0.056 +/- 0.003 SD. Using the inhibition of ouabain-insensitive sodium transport in erythrocytes as an assay to identify the factor, we ran the crude promyelocyte extract through Sephadex G-25 and G-10, with an intermediate ion-exchange step on DE-32, and finally subjected the active fraction to reverse-phase high-performance liquid chromatography. The specific inhibitory activity of the final fraction was 180-fold higher than that of the crude promyelocyte extract. The inhibitory activity could be destroyed by acid hydrolysis and by enzymatic digestion with several proteases but not by heating at 80 degrees C for 30 min; these characteristics suggest that the active factor, called inhibitin, is a peptide. Inhibitin is released by immature myeloid cells but not by differentiated white cells or by leukemic lymphocytes. It has no effect on potassium influx but inhibits sodium/sodium exchange in erythrocytes.

Amino Acids↗
PubMed1984

Release of an active sodium transport inhibitor (ASTI) from rat hypothalamic cells in culture.

To investigate the hypothesis whether the hypothalamus releases an active (ouabain-sensitive) sodium transport inhibitor, we cultured hypothalamic and cortical cells from day 17 fetal rats. Culture media from hypothalamic cells reduced the total erythrocyte sodium efflux rate constant from 0.487 +/- (SE) 0.014 to 0.408 +/- 0.013 (P less than 0.001), and the ouabain-sensitive rate constant from 0.305 +/- 0.015 to 0.240 +/- 0.016 (P less than 0.01). Hypothalamic media also showed a dose-dependent displacement of [3H]-ouabain-binding to erythrocyte membranes. Neither cortical nor conditioned media (incubated without cells) had any effect. Various well-characterized hormones of hypothalamic origin failed to inhibit sodium efflux rate constant. These studies demonstrate that fetal rat hypothalamic cells contain and release a factor which inhibits sodium transport in human erythrocytes.

Animals↗
PubMed1983

Effects of myeloid leukaemic blast cell extract on sodium transport in human erythrocytes.

1. Previous studies have shown that leukaemic plasma inhibits sodium efflux from erythrocytes. In this study the effect of an extract of myeloid leukaemic blast cells on sodium efflux was investigated. 2. Blast cell extract decreased the sodium efflux rate constant in erythrocytes from 0.395 +/- sem 0.028 to 0.310 +/- 0.018 (P less than 0.02), whereas a leucocyte extract had no significant effect. 3. The extract had an inhibitory effect after heating at 80 degrees C for 30 min, and in the presence of ouabain and frusemide alone or in combination. 4. These studies suggest that myeloid leukaemic blast cells contain a heat stable factor which inhibits the efflux of sodium at least in part through a pathway which is not inhibited by ouabain or frusemide.

Biological Transport, Active↗
PubMed1983

Packed cell volume, haemoglobin, and oxygen saturation changes in healthy smokers and non-smokers.

We have investigated the relationship between cigarette smoking, packed cell volume, haemoglobin concentration, and arterial oxygen saturation (SaO2) in 114 non-smokers, 66 light smokers (1-20 cigarettes a day), and 50 heavy smokers (over 20 cigarettes a day) aged 20-75 years. Packed cell volume was greater in female heavy smokers (p less than 0.001) over 40 years of age and in all female smokers over 60 years (p less than 0.001) than in non-smoking contemporaries. Haemoglobin concentrations were higher in 40-59 year old female heavy smokers (p less than 0.05) and in male and female light (p less than 0.05) and heavy smokers (p less than 0.001) over 60 years of age than in non-smoking contemporaries. SaO2 was lower in 20-39 year old male heavy smokers (p less than 0.02) and female (p less than 0.05) light smokers and also in 40-59 year old male light and heavy smokers (p less than 0.001) and female light smokers (p less than 0.02) than in non-smoking contemporaries. It was also lower in female light (p less than 0.05) and heavy (p less than 0.02) smokers over 60 years, whereas it was higher in male light smokers over 60 (p less than 0.001). Changes in SaO2 were seen at a younger age than changes in haemoglobin concentration and packed cell volume.

Adult↗
PubMed1983

A comparison of nifedipine and isosorbide dinitrate in angina pectoris with particular reference to arterial oxygen saturation.

To explore beneficial and harmful effects of various combinations of antianginal drugs, we compared antianginal and cardiorespiratory effects of nifedipine and isosorbide dinitrate in low and high doses in combination with nadolol, a long acting beta-adrenoceptor blocker in a double-blind study in 19 patients with stable angina pectoris. Nadolol alone and in combination with the other two drugs reduced anginal attack rate and glyceryl trinitrate consumption; the high dose isosorbide dinitrate showed a further significant (P less than 0.05) reduction in both but the high dose nifedipine did not show such a trend. sigma ST depression (all leads) was significantly (P less than 0.05) more reduced by the high dose nifedipine than by the same dose of isosorbide dinitrate in combination with nadolol. Nadolol reduced forced expiratory volume in one sec (FEV1) slightly and this effect was reversed both by isosorbide and nifedipine. Isosorbide dinitrate in combination with nadolol reduced the basal and post-exercise arterial oxygen saturation (SaO2) whereas nifedipine did not reduce the mean SaO2 below the pre-trial level. A significantly greater sigma ST depression was associated with a lower post-exercise SaO2 (less than or equal to 92%) during all treatment periods but the fall of SaO2 occurred more often during isosorbide than during nifedipine treatment periods. These studies show that both isosorbide dinitrate and nifedipine enhance antianginal efficacy of nadolol. Isosorbide dinitrate, unlike nifedipine, reduces SaO2 which is associated with a greater sigma ST depression.

Adrenergic beta-Antagonists↗