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Biomedical subjects

M A Mir

Publications and source records attributed to M A Mir.

At least 19 recordsLinked to original sources
PubMed2026

Integrative Genomic and Transcriptomic Insights into High-Altitude Adaptation in Changthangi Goats.

The Changthangi goat, native to the high-altitude Ladakh Plateau in northern India, thrives in oxygen-deficient environments above 4,000 m. This study investigated the genetic basis of high-altitude adaptation in Changthangi goats by integrating comparative genomics and transcriptomics, using the tropical lowland Jamunapari goat as a comparative model. Whole-genome sequence data from 15 individuals per breed were analyzed using complementary selection sweep metrics, including nucleotide diversity, Tajima's D, iHS, CLR, XP-EHH, and FST. These analyses identified candidate genomic regions under strong selective pressure, encompassing genes involved in hypoxia sensing (HIF-1α, HIF-2α/EPAS1, EGLN1), angiogenesis (VEGFA, AGGF1, ZEB1), cardiovascular regulation (PRKCB, ESR1, RYR2), mitochondrial and energy metabolism (ACADSB, ACSS3, ACSL1), cellular stress tolerance (BCL2, ATM), and thermogenesis (UCP1, FGF21). Unlike previous caprine studies that primarily infer hypoxia adaptation from genomic signals alone, our study integrates cardiac transcriptomics to demonstrate that genomic selection in Changthangi goats is accompanied by coordinated transcriptional remodeling across interconnected physiological systems in a physiologically relevant tissue. Comparative cardiac transcriptomic profiling revealed concordant expression divergence in genes associated with oxygen transport, vascular remodeling, mitochondrial function, substrate utilization, redox balance, and genome maintenance. This integrative multi-omics framework provides a mechanistic view of caprine high-altitude adaptation and highlights the value of combining genomic selection analyses with tissue-specific transcriptional profiling to resolve complex adaptive traits.

Animals↗
PubMed2001

Interaction of antitumor drug, mithramycin, with chromatin.

Mithramycin (MTR) is an anticancer drug that blocks macromolecular biosynthesis via reversible interaction with DNA in the presence of bivalent cation such as Mg2+. Mithramycin forms two types of complexes with Mg2+: complex I (1:1 in terms of MTR:Mg2+) and complex II (2:1 in terms of MTR:Mg2+). In vivo antibiotic would interact with chromatin, a protein-DNA complex. For the first time we have demonstrated and characterized the association of both complexes of MTR with chromatin and nucleosome core. From an evaluation and comparison of the binding and thermodynamic parameters and CD spectra of bound complexes, we have shown the following. Histone(s) stand in the say of the access of the ligand(s) to chromosomal DNA. Chromatin and core particle interact differentially with the same ligand. Mode of interaction of the two complexes, I and II, with the same system is different. Significance of these results to understand the transcription inhibitory property of the drug in eukaryotic chromosome is discussed.

Animals↗
PubMed1997

Iron deficiency in 1- to 3-year-old children. A pediatric failure?

OBJECTIVE: To determine the prevalence of iron deficiency and iron deficiency anemia in children aged 1 to 3 years in an urban population. DESIGN: Venous blood was measured for levels of hemoglobin, ferritin, free erythrocyte protoporphyrin, and lead in children seen for well-child visits. Children with histories of chronic illness, prematurity, blood dyscrasias, and acute illness were excluded. SETTING: The private practice offices of 4 pediatricians in the New York City area. PATIENTS: A consecutive sample of 504 children aged 1 to 3 years was included. RESULTS: More than one third (35%) of the children demonstrated evidence of iron insufficiency; 7% were iron deficient without anemia, and 10% had iron deficiency anemia. CONCLUSION: Because the association of iron deficiency anemia with mental and psychomotor impairment during the first 2 years of life no longer seems to be in doubt, the high prevalence of iron deficiency anemia found in the 1- to 2-year-old children in this study is disturbing. This suggests the need for greater efforts at the prevention of iron deficiency during the second year of life.

Anemia, Iron-Deficiency↗
PubMed1996

A new breakfast cereal containing guar gum reduces postprandial plasma glucose and insulin concentrations in normal-weight human subjects.

A new guar-containing wheatflake product was developed to assess its effect on carbohydrate tolerance in normal-weight, healthy subjects. The extruded wheatflake breakfast cereals containing 0 (control) or approximately 90 g guar gum/kg DM were fed to ten fasting, normal-weight, healthy subjects using a repeated measures design. The meals were similar in energy (approximately 1.8 MJ), available carbohydrate (78 g), protein (15 g) and fat (5.4 g) content. The guar gum content of the test meals was 6.3 g. Venous blood samples were taken fasting and at 15, 30, 45, 60, 90, 120, 150 and 240 min after commencing each breakfast and analysed for plasma glucose, insulin and C-peptide. The guar wheatflake meal produced a significant main effect for glucose and insulin at 0-60 min and 0-240 min time intervals respectively, but not for the C-peptide levels compared with the control meal. Significant reductions in postprandial glucose and insulin responses were seen following the guar wheatflake meal compared with the control meal at 15 and 60 min (glucose) and 15, 60, 90 and 120 min (insulin). The 60 and 120 min areas under the curve for glucose and insulin were significantly reduced by the guar gum meal, as was the 240 min area under the curve for insulin. Thus, it can be concluded that the use of a severe method of heat extrusion to produce guar wheatflakes does not diminish the physiological activity of the guar gum.

Adult↗
PubMed1994

Comparison of lipid-lowering effects of low-dose fluvastatin and conventional-dose gemfibrozil in patients with primary hypercholesterolemia.

A total of 123 patients with primary hypercholesterolemia were randomized on a 2:1 ratio to receive either fluvastatin at 20 mg once daily at night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a double-blind, double-dummy comparison of the effects on plasma lipid parameters and tolerability over 8 weeks. All patients had either low-density lipoprotein cholesterol (LDL-C) concentrations > or = 160 mg/dL (4.1 mmol/L) in association with definite coronary artery disease (CAD) or > or = 2 risk factors, or LDL-C > or = 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels < or = 350 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produced significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. High-density lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21.2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL-C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) compared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly reduced apolipoprotein (apo) B and lipoparticles (Lp) E:B, and increased apo A-I but had divergent effects on LpA-I (increased with fluvastatin and reduced with gemfibrozil; p < 0.05). At the end of the study, 43.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels was achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Both drugs were well tolerated; adverse events occurred in 36.6% of fluvastatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransferases, alkaline phosphatase, or creatine phosphokinase occurred. No patient developed new or worsening lens opacities associated with a reduction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were no serious drug-related adverse events.

Adult↗
PubMed1990

Effect of British-made videotapes on clinical performance of medical students in Pakistan.

The efficacy of videotapes, recorded in Cardiff, in improving the clinical performance of final-year medical students in Abbottabad (Pakistan) was tested, by carrying out a structured, stepwise, clinical assessment before and after video teaching in 32 students. All students examined eight systems/subsystems at eight stations and spent 5 min with each patient, during which their performance was checked against structured check-lists by eight examiners. These students had not received any clinical instruction from a specialist rheumatologist, neurologist or endocrinologist during their clinical apprenticeship. Before the video teaching they performed poorly when examining the knee joint, motor system, hands and thyroid status, but when tested again 2 days after video teaching, there was a transformation in their clinical behaviour and their mean (s.d.) score improved from 40 (6.6 per cent) to 57.6 (9.4 per cent; P = 0.001). In contrast to their pre-video performance, they interacted well with the patients and examiners providing a running commentary of their findings, as demonstrated in the videotapes. Among the residual problems were a poor technique of testing tendon reflexes and percussion. All the examiners and 21 of 32 students thought that the structured examination was fairer than the conventional examination. Of the 32 students, 20 thought that video teaching was less effective than personal bedside teaching, while 12 students thought that video was structured better than bedside instruction. All students would welcome video teaching to supplement their existing teaching and would like the structured examination introduced to their curriculum. This study suggests that videotaped demonstrations can be used effectively in transmitting clinical skills to students not exposed to clinical teaching by specialists in various subjects.

Clinical Competence↗
PubMed1989

Interaction of inhibitin with the human erythrocyte Na+(Li+)i/Nao+ exchanger.

The kinetic interactions of inhibitin, a peptide isolated from cultured leukaemic promyelocytes, with erythrocyte Na+/Na+ and Na+/Li+ exchanges have been investigated. Inhibitin (1 microM) reduced the ouabain- and bumetanide-resistant sodium efflux and influx by equivalent amounts indicating an inhibitin-sensitive exchange component of 0.52 mmol/l per h. This value was not significantly different from that measured as the difference in sodium-rich (140 mM) and sodium-free media (0.49 mmol/l per h). Similarly, the inhibitin-sensitive lithium efflux was equivalent to the sodium/lithium countertransport component (0.36 vs. 0.34 mmol/l per h), indicating that both exchanges were mediated by the same transport process, which is inhibitin-sensitive. The dose-response curve revealed the presence of a single inhibitin binding site per exchanger with a Ki of 2.10(-7) M. In kinetic inhibition studies, inhibitin (0.1 microM) decreased the Vmax of ouabain- and bumetanide-resistant sodium efflux with no effect on the Km for external sodium, i.e., inhibitin displayed a non-competitive mechanism of action. These findings indicate that inhibitin interacts with the Na+(Li+)i/Nao+ exchanger at a site distinct from the sodium binding site.

Biological Transport↗
PubMed1989

The use of videorecordings of medical postgraduates in improving clinical skills.

The examination for membership of the Royal Colleges of Physicians has a high failure rate despite intensive clinical coaching provided by many postgraduate courses. One of the main difficulties appears to be the failure of candidates to identify specific shortcomings in their clinical behaviour. In this study videorecording was used as a method of self-appraisal enabling the candidate to identify strengths and weaknesses. The evidence from the study suggests that self-appraisal by videorecording should be used as an adjunct to clinical instruction.

Attitude of Health Personnel↗
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↗