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Biomedical subjects

M O Hassan

Publications and source records attributed to M O Hassan.

At least 19 recordsLinked to original sources
PubMed2006

Insertion-deletion polymorphism in the angiotensin-converting enzyme (ACE) gene among Sudanese, Somalis, Emiratis, and Omanis.

The angiotensin-converting enzyme (ACE) gene in humans contains an insertion-deletion polymorphism in its intron 16. Because of its involvement with the renin-angiotensin system, the insertion-deletion polymorphism of the ACE gene has been widely investigated in different populations and in case-control studies. However, similar studies for Arab populations are limited in number. Therefore we have investigated the frequencies of the *I and *D alleles of the ACE gene among Sudanese, Somalis, and Arab nationals of the United Arab Emirates and Oman using previously described methods. Our data indicate a preponderance of the *D allele among the Arab and African populations studied (Sudanese, 0.64; Somalis, 0.73; Emiratis, 0.61; and Omanis, 0.71).

Africa, Eastern↗
PubMed2005

A family study in Oman: large, consanguineous, polygamous Omani Arab pedigrees.

OBJECTIVE: To establish a suitable human model for the study of the genetics of complex diseases. METHODS: We have selected an Omani Arab population to provide the statistical power required to study the genetics of complex diseases with confidence. This model consists of five multigenerational highly inbred pedigrees, descending from a small number of founders just a few generations ago with environmental homogeneity, restricted geographical distribution, detailed records and well-ascertained and -validated pedigrees. Stringent criteria were adopted for defining the phenotypes of hypertension, diabetes mellitus, dyslipidemias and obesity. The SOLAR genetic software package was used to draw the pedigree structure. RESULTS: Outstanding statistical power to detect susceptibility loci was obtained. CONCLUSIONS: This model represents a large homogeneous human family-based population for the study of genetic and environmental factors contributing to complex diseases.

Consanguinity↗
PubMed2001

Ischemic injury to mitochondrial electron transport in the aging heart: damage to the iron-sulfur protein subunit of electron transport complex III.

The aging heart sustains greater injury during ischemia and reperfusion compared to adult hearts. Aging decreases oxidative function in interfibrillar mitochondria (IFM) that reside among the myofibers, while subsarcolemmal mitochondria (SSM), located beneath the plasma membrane, remain unaltered. Aging decreases complex III activity selectively in IFM via alteration of the cytochrome c binding site. With 25 min of global ischemia, complex III activity decreases in SSM and further decreases in IFM in the aging heart. Ischemia leads to a marked decrease in the electron paramagnetic resonance signal of the iron-sulfur protein (ISP) in both SSM and IFM, despite a preserved content of ISP peptide. Thus, ischemia results in a functional decrease in the iron-sulfur center in ISP without subunit peptide loss. In the aging heart, at the onset of reperfusion, IFM contain two tandem defects in the path of electron flow through complex III, providing a likely mechanism for enhanced oxidant production and reperfusion damage.

Age Factors↗
PubMed2001

Blood pressure and its reactivity in the offspring of first cousin hypertensive and first cousin normotensive parents: a preliminary report.

The aim of this preliminary study was to determine whether young offspring of first cousin hypertensive parent(s), have higher blood pressure (BP) reactivity in response to their first BP measurement, as compared to the offspring of first cousin normotensive parents. The BP of 135 boys aged 9-10 years was measured, for the first time ever, after a 10-min supine rest, and subsequently, twice at 10-min intervals. The offspring of first cousin hypertensive parent(s) reacted with significantly higher systolic and diastolic BP than the offspring of normotensive first cousin parents in all three measurements. This study indicates that at an early age, the offspring of first cousin hypertensive parents, react with exaggerated BP response at their first casual BP measurement. We hypothesise that familial aggregation of BP may show more expression amongst the offspring of consanguineous marriage of hypertensive parent(s).

Blood Pressure↗
PubMed1999

Aging selectively decreases oxidative capacity in rat heart interfibrillar mitochondria.

Mitochondrial-derived oxidative injury contributes to cellular aging as well as to reperfusion-induced tissue damage. While the aging-heart suffers greater tissue damage following ischemia and reperfusion than the adult heart, the occurrence of aging-related alterations in mitochondrial oxidative metabolism in the elderly heart has remained uncertain. We determined if aging altered oxidative metabolism in either of the two populations of cardiac mitochondria, subsarcolemmal mitochondria (SSM) that reside beneath the plasma membrane or interfibrillar mitochondria (IFM) located between the myofibrils. SSM and IFM were isolated from 6-month adult and 24- and 28-month elderly Fischer 344 rat hearts. Aging-related alterations were limited to IFM, while SSM remained unaffected. Aging decreased the rate of oxidative phosphorylation in IFM, including when stimulated by electron donors specific for cytochrome oxidase. Cytochrome oxidase enzyme activity was decreased in IFM from aging hearts, while activity in SSM remained similar to adult controls. These findings allow future studies of aging-related decrements in oxidative function to focus upon IFM, while SSM provide an inherent control group of mitochondria that are free of aging-related alterations in oxidative function. The selective alteration of IFM during aging raises the possibility that the consequences of aging-induced mitochondrial dysfunction will be enhanced in specific subcellular regions of the senescent myocyte.

Adenosine Diphosphate↗
PubMed1999

Baroreflex sensitivity and the blood pressure response to beta-blockade.

The objective of this analysis was to determine whether changes in baroreflex sensitivity (BRS) within 35 hypertensive patients (25 M, 10 F, mean age 47 years) treated with beta-blockade as monotherapy relate to reductions in ambulatory blood pressure (BP) or its variability. BP was recorded intra-arterially directly from the brachial artery before and during submaximal exercise. BRS was determined by the phenylephrine injection technique. MAP and its variability were determined for the awake period of 24-h BP monitoring. Subjects were randomised to one of atenolol, metoprolol, pindolol, or propranolol, and restudied after a mean of 5 months. Beta-blockade increased BRS in 24 patients and decreased BRS in 11. BRS increased from 6.53+/-4.94 to 9.40+/-8.62 ms/mm Hg (mean +/- s.d.) (P<0.01). Waking ambulatory MAP decreased from 125.8+/-15.8 to 106.4+/-16.2 mm Hg (P<0.0001), but its variability did not change. Higher BRS after chronic beta-blockade was associated with a decrease in waking ambulatory MAP (r = -0.55, P<0.001), but not with its variability (r = -0.08). Beta-blockade attenuated the pressor response to exercise, but there was a positive relationship between the effect of beta-blockade on BRS, and on the rise in systolic BP during bicycling (r = 0.63; P<0.001). Any dampening effect of beta-blockade on BP variability at rest in hypertensive patients with the greatest increase in BRS may be offset by increased pressor responses to physical activity such as exercise. Consequently, BP variability is unaffected, even though reductions in ambulatory BP during chronic beta-blockade are inversely related to changes in BRS. BP responses to beta-blockade may be a function of the action of this class of drugs on BRS. However, there is considerable variation, between subjects, in their effect on BRS. This may have implications for other conditions, such as dilated cardiomyopathy, or following myocardial infarction, in which improvement in BRS is one mechanism by which beta-adrenoceptor blockade could improve survival.

Adolescent↗
PubMed1999

Effects of prolonged ACTH-stimulation on adrenocortical accumulation of lipofuscin granules in aged rats.

Subcellular deposition of lipofuscin granules is a marker of aging. Human and rodent adrenal cortices accumulate lipofuscin granules with age, but the mechanism that leads to the accumulation is not known. The ultrastructural appearance of lipofuscin granules resembles that of secondary lysosomes. Since adrenocortical subcellular events are predominantly influenced by ACTH action, we therefore studied the effect of prolonged ACTH-stimulation on adrenocortical accumulation of secondary lysosome-like granules, designated herein as lipofuscin granules. Using aged Fischer 344 male rats as a model, we found that a 7 day ACTH stimulation exerts a reducing effect on adrenocortical lipofuscin accumulation. Thus, adrenocortical accumulation of lipofuscin granules with age in vivo may not be an irreversible process.

Adrenal Cortex↗
PubMed1993

Fibronectin expression on surgical specimens correlated with the response to intravesical bacillus Calmette-Guerin therapy.

Attachment of bacillus Calmette-Guerin (BCG) organisms to the bladder during intravesical therapy is thought to be mediated exclusively by the glycoprotein fibronectin, which is expressed variably on epithelial surfaces and on basement membranes. We examined the relationship between the degree of fibronectin expressed on surgical specimens obtained from 50 candidates for BCG therapy and the subsequent clinical response. Immunoperoxidase staining for fibronectin was performed on tumor, nonadjacent normal mucosa and basement membrane tissues, and the intensity of the staining was scored on a scale of 0 to 3+ (control 2+). In the absence of recurrence at quarterly surveillance cystoscopy, a course of Tice BCG therapy consisted of 6 weekly and 12 monthly instillations. Recurrence of noninvasive tumor prompted a second BCG course. Followup ranged from 24 to 66 months (median 40 months). Of the 50 patients (11 with carcinoma in situ) disease progression occurred in 9 (none with carcinoma in situ). Compared to the results for tumors or for basement membranes, the degree of fibronectin expression on normal mucosa was well correlated with the clinical response (r = 0.59, p < 0.001 by Kendall Tau B). Routine assessment of fibronectin expression on the normal mucosa associated with superficial bladder cancer may be useful for predicting the clinical response to BCG therapy.

Administration, Intravesical↗
PubMed1993

Loss of the nocturnal dip and increased variability of blood pressure in normotensive patients with noninsulin-dependent diabetes mellitus.

Eleven normotensive diabetics with noninsulin-dependent diabetes mellitus (NIDDM) (mean age 52.5 +/- SD 8.2 years) and 11 controls (mean age 47.4 +/- SD 8.9 years) had their ambulatory blood pressure and heart rate recorded non-invasively by the Oxford Medilog System in standard hospital conditions. The results were averaged as hourly means of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), and heart rate (HR) for the 24-h period and similarly for the 'awake' period (14-16 h) and the 'asleep' period (8-10 h). Hourly means for diabetics and controls showed no differences in blood pressure and heart rate over the 24 h. During sleep, control subjects showed a significant drop in SBP (P < 0.001), DBP (P < 0.001), MAP (P < 0.001) and HR (P < 0.001). However, this nocturnal dip in blood pressure could not be demonstrated in the diabetic group. Blood pressure variability was significantly increased in diabetics compared to controls during waking hours (P < 0.01). These results indicate that in noninsulin-dependent diabetics during sleep there is loss of the nocturnal dip of BP seen in normal subjects, and they have increased BP variability. These may be contributing factors to the development of hypertension and the accelerated target organ damage (TOD) seen in diabetes.

Adult↗
PubMed1992

Increased muscle protein catabolism caused by carbon tetrachloride hepatic injury in rats.

This study was undertaken to determine the pathogenesis of muscle atrophy that frequently accompanies liver disease. Hepatic injury was induced in rats by giving weekly intragastric doses of carbon tetrachloride (CCl4) in combination with phenobarbital in the drinking water. Muscle protein catabolism was assessed during three stages of liver injury and compared with pair-fed controls: group A had hepatic necrosis and inflammation without significant fibrosis; group B had cirrhosis as well as necrosis and inflammation; and group C had cirrhosis with minimal necrosis and inflammation. In group A, vastus lateralis white muscle, which contained predominantly fast glycolytic fibers, showed a significant increase in protein catabolic rates compared with pair fed controls (0.95 +/- 0.05 nmol tyrosine released.mg-1.2 h-1 vs. 0.86 +/- 0.04; P less than 0.05). In group B, protein catabolic rates were significantly increased in vastus lateralis white muscles, as well as two muscles that have a mixed fiber composition, diaphragm, and triceps. Protein catabolic rates were not increased in soleus muscle that predominantly contained slow oxidative fibers in either group A or B. In group C rats there was no increase in catabolic rates in diaphragm or vastus lateralis white muscle. None of the muscles from group B had any impairment in protein synthesis. In diaphragms from group B animals, there was a selective reduction in the cross-sectional areas of fast glycolytic fibers (3725 +/- 224 mm2 control vs. 2926 +/- 208 mm2 experimental; P less than 0.01). This study indicated that liver injury characterized by inflammation and hepatocyte necrosis, with or without cirrhosis, was associated with muscle atrophy that selectively affected fast glycolytic fibers. This muscle atrophy was caused by an increase in protein catabolism and was not the result of an inhibition of protein synthesis.

Animals↗
PubMed1991

Platelet-derived growth factor expression in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells and expansion of mesangial matrix are common histologic features of proliferative glomerular disease, a frequent cause of renal failure. Proliferation of glomerular mesangial cells occurs in response to platelet-derived growth factor (PDGF), and these cells release PDGF and express PDGF A and B chain mRNAs. However, all studies relating PDGF to potential changes in glomerular structure and function to date have been performed in vitro. To explore the role of PDGF in proliferative glomerulonephritides, we studied the expression of PDGF in vivo in two animal models of IgA nephropathy with different histologic patterns of glomerular injury: either predominant mesangial proliferation or expansion of mesangial matrix. Increased expression of PDGF and PDGF B-chain mRNA in whole kidneys from diseased mice was demonstrated by immunohistochemical techniques and by solution hybridization assay, respectively. Immunohistochemically, PDGF was localized primarily within the mesangial area of glomeruli and to a much lower extent in interstitium. The increased PDGF expression correlated with the degree of hypercellularity and clinical features of the disease. In addition, PDGF expression was increased in some forms of human glomerulonephritis, characterized by mesangial proliferation. These findings suggest that PDGF may be a major contributor to mesangial cell proliferation seen in proliferative glomerulonephritides.

Animals↗
PubMed1991

The role of the autonomic nervous system in exercise bradycardia in rats.

The origin of the relative bradycardia found in athletes and in chronically exercised animals is still controversial. To further investigate the role of the autonomic nervous system in exercise bradycardia three groups of Sprague-Dawley rats performed swimming exercises daily for 1.5 hr for a total of 45 hrs. The contribution of the sympathetic and parasympathetic systems to the resultant bradycardia was elucidated by differential autonomic blockade using propranolol hydrochloride and atropine sulphate respectively. This procedure permits the determination of the intrinsic heart rates so that it is possible to observe the contributions of the two divisions of the autonomic nervous system in exercise bradycardia. The results showed that both sympathetic and parasympathetic tones of the trained rats were reduced, being respectively 13% and 5% lower than the control groups. It was concluded that the reduction in heart rate in trained rats was mainly due to a reduction in the sympathetic tone.

Animals↗
PubMed1990

Platelet activating factor receptor blockade ameliorates murine systemic lupus erythematosus.

Untreated 16-week-old MRL/MpJ-lpr/lpr (lpr) mice, when compared to congenic MRL/MpJ-+/+ (+/+) mice, are characterized by a systemic lupus erythematosus syndrome, including severe glomerulonephritis, proteinuria and reduction of renal function. We hypothesized that platelet activating factor (PAF), a potent chemotactic and proinflammatory phospholipid mediator synthesized and released by circulating cells, glomerular mesangial and renal medullary interstitial cells, may play a role in the development of renal injury in lupus mice. We assessed renal PAF synthesis in lpr as well as +/+ mice and the effect of treatment with a PAF receptor blocking agent. Treatment with the PAF receptor antagonist L659,989 for four weeks, starting at 12 weeks of age, significantly reduced acute glomerular infiltration and proliferation, and prevented chronic glomerular histological changes; proteinuria and serum creatinine levels were also significantly reduced in treated mice. Renal PAF production was increased in lpr when compared to +/+ mice, and treatment with L659,989 restored renal PAF synthesis to the control levels. Our results support the hypothesis that PAF can be one of the mediators of glomerular injury characteristic of murine lupus nephritis, and indicate the possible therapeutic utility of PAF receptor antagonists in immunologic renal diseases.

Animals↗
PubMed1990

Enzymolysis of glomerular immune deposits in vivo with dextranase/protease ameliorates proteinuria, hematuria, and mesangial proliferation in murine experimental IgA nephropathy.

The therapeutic effects of saccharolytic and proteolytic enzymes were investigated in models of IgA nephropathy. Mesangial glomerulonephritis was induced in mice by intravenous injection of preformed soluble immune complexes of dextran sulfate and either IgA (J 558) or IgM (MOPC 104 E) anti-dextran MAb (passive model) or by immunization with DEAE dextran (active model). In the passive model, only 30-40% of dextranase-treated mice given IgA or IgM immune complexes had mesangial Ig or dextran deposits, compared with 100% of saline-treated controls (P less than 0.01). There was no significant difference in mice given only protease. In the active model, dextranase and protease separately each reduced glomerular dextran and C3 deposits, and hematuria (P less than 0.01). Dextranase also reduced the glomerular IgA deposits (20 vs. 100% of saline-treated mice) and the frequency and severity of mesangial matrix expansion (both P less than 0.02), but did not reduce the modest IgG or IgM codeposits. Protease reduced IgG and IgM deposits, proteinuria and mesangial hypercellularity compared with saline (P less than 0.02), but did not diminish IgA, and had no effect on mesangial matrix expansion. The combination of dextranase plus protease attenuated all components of glomerular injury as judged by clinical and pathological parameters, but inactivated dextranase plus inactivated protease had no effect on any parameter. We conclude that enzymatic digestion of antigen and antibody can reduce immune deposits, mesangial proliferation, proteinuria, and hematuria in experimental glomerulonephritis.

Animals↗
PubMed1988

Effects of acute and chronic beta-adrenoceptor blockade on baroreflex sensitivity in humans.

To determine whether beta-adrenoceptor blockade lowers blood pressure by potentiating arterial baroreflex sensitivity (BRS), we compared the effect of acute i.v. and chronic oral beta-blockade on the BRS (phenylephrine technique) of 51 subjects with essential hypertension. Subjects were randomly assigned in a double-blind protocol to one of atenolol, metoprolol, pindolol or propranolol. There was an increase in BRS, unrelated to changes in heart rate, after both acute and chronic beta-blockade. This effect was most evident in younger and less hypertensive subjects. Decreases in blood pressure after 5-months' treatment were unrelated to increases in BRS, indicating that the hypotensive action of these drugs is not dependent upon augmented baroreflex control of heart rate. Only propranolol, of the 4 beta-blockers, increased BRS significantly after acute and chronic treatment. The acute effect of propranolol was significantly different from that of i.v. metoprolol (P less than 0.008) but the effect of long-term treatment with propanolol was not significantly different from that of the other 3 beta-blockers. We conclude that the impaired reflex regulation of heart rate can be improved in younger and mild-to-moderate hypertensive patients by beta-adrenoceptor blockade. Further studies, involving larger numbers and perhaps fewer drugs are needed to determine the relative importance of lipophilicity and beta 1- or beta 2-receptor selectivity in mediating the increase in baroreflex sensitivity seen with treatment.

Adolescent↗
PubMed1988

Consequences of impaired arterial baroreflexes in essential hypertension: effects on pressor responses, plasma noradrenaline and blood pressure variability.

In 62 untreated patients with essential hypertension, arterial baroreflex sensitivity (BRS) for heart rate, i.e. the change in pulse interval in response to a phenylephrine-induced increase in blood pressure, was compared with (1) haemodynamic changes during mental arithmetic, a reaction time test, isometric and bicycle exercise; (2) plasma noradrenaline (PNA) concentrations at rest, and during bicycle exercise and; (3) the variability of ambulatory intra-arterial blood pressure. Subjects with diminished BRS showed the following responses: (1) higher mean arterial blood pressure (MAP) during all four stimuli; (2) a greater pressor response to cycling; (3) tended to have higher PNA concentrations during bicycle exercise and; (4) greater variation in ambulatory blood pressure. Furthermore, an increased pressor response to the reaction time test and increased ambulatory blood pressure variability was seen in younger subjects with reduced BRS. When subjects were subgrouped according to their WHO stage of hypertension, there were significant inverse relationships between BRS and the pressor responses to mental arithmetic, the reaction time test and cycling, and with ambulatory blood pressure variability only in those subjects without ECG or radiographic evidence of left ventricular enlargement (WHO stage I hypertension; n = 42). None of these correlations were present in subjects with one or both of these clinical findings (WHO stage II; n = 20). Pressor responses to the four laboratory stimuli and ambulatory blood pressure variability were similar in both groups, despite significantly higher arterial pressure and significantly lower BRS in WHO stage II subjects. These results suggest that differing mechanisms may be responsible for the regulation of blood pressure variation in these two groups. The arterial baroreflex can buffer acute changes in blood pressure in subjects with WHO stage I hypertension, but this ability is attenuated with progressive reduction of BRS. With the development of clinically evident cardiac adaptation to hypertension (WHO stage II), the contribution of the arterial baroreflex to the regulation of blood pressure is no longer detectable and the influence of cardiac and somatic afferents to reflex circulatory adjustments to activity may predominate.

Adult↗
PubMed1988

Factors influencing blood pressure and heart rate variability in hypertensive humans.

We examined the influence of baroreceptor reflex sensitivity (the increase in pulse interval in response to a phenylephrine-induced increase in blood pressure), age, blood pressure, and beta-adrenergic receptor blockade on the variability of blood pressure and heart rate in essential hypertension. Fifty-six subjects were studied before treatment; intra-arterial blood pressure was recorded outside the hospital for 24 hours. Variability was defined (from all beats occurring while subjects were awake) as the standard deviation about the average waking value for mean arterial pressure (MAP) or pulse interval. The correlation (r) between baroreceptor reflex sensitivity and blood pressure variability was -0.47 (p less than 0.0002). Baroreceptor reflex sensitivity was the only independent determinant of blood pressure variability on multiple regression analysis. Thirty subjects were restudied after 5 months of beta-adrenergic receptor blockade. Ambulatory blood pressure was lower during treatment, whereas pulse interval, its variability, and baroreceptor reflex sensitivity were higher. Blood pressure variability was unchanged. The variability of MAP was inversely correlated with baroreceptor reflex sensitivity before (r = -0.42, p less than 0.02) and during (r = -0.45, p less than 0.02) treatment, but it was unrelated to the average ambulatory MAP or to the variability of pulse interval either before or during beta-blockade. Sixteen subjects whose average waking ambulatory blood pressure was 140/90 mm Hg or less were not treated. This group of borderline hypertensive subjects had less variable MAP than did the remaining 40 subjects (12.4 +/- 2.3 [SD] vs 14.5 +/- 2.5 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗