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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
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↗
PubMed1987

Pressor responses to laboratory stresses and daytime blood pressure variability.

We studied 56 patients with essential hypertension to determine whether responses to standardized laboratory mental and physical challenges accurately reflect blood pressure variability during routine daily activities. Four activities were performed in the laboratory: mental arithmetic, a reaction time test, isometric exercise, and submaximal bicycle exercise. Blood pressure was measured directly from a brachial artery catheter. We then recorded intra-arterial ambulatory blood pressure away from hospital over 24 h. A frequency histogram was constructed from all cardiac cycles when subjects were awake. Variability of ambulatory blood pressure was defined as the standard deviation about the mean waking value. The increase in mean arterial pressure (MAP) during each of these four challenges correlated significantly with the variability of mean arterial pressure (highest correlation: reaction time test, r = 0.53, P less than 0.00001; lowest correlation: mental arithmetic, r = 0.26, P less than 0.03), and five subjects who were highly reactive to all four challenges also demonstrated increased blood pressure variability. We therefore conclude that these commonly used laboratory tests can give some information about the behaviour of blood pressure in daily life in some subjects, but overall the variance in blood pressure variability that can be accounted for by the pressor response to these standardized challenges is low.

Activities of Daily Living↗
PubMed1987

Carbon dioxide laserabrasion: a new approach to management of familial benign chronic pemphigus (Hailey-Hailey disease).

Familial benign chronic pemphigus (FBCP), or Hailey-Hailey disease, can be a debilitating condition. Treatment is palliative and only excision of lesional skin followed by split-thickness grafting may be curative. The success of surgery is attributed to the removal of adnexal structures and a decrease in sweating and maceration. This is the first report of successful carbon dioxide (CO2) laserabrasion of a patient with FBCP. The procedure spared the underlying adnexae which contributed to the reepithelialization of the epidermis. The selective destructive property of the CO2 laser may contribute to understanding the pathophysiology of FBCP.

Carbon Dioxide↗
PubMed1987

Experimental hypersensitivity pneumonitis: transfer with cultured cells.

The importance of antibody and sensitized cells in hypersensitivity pneumonitis (HP) is unknown. In an attempt to create a model suitable for investigation of the mechanisms of HP, we transferred cells and serum from sensitized (Micropolyspora faeni in Freund's adjuvant) strain 2 guinea pigs to naive animals. Cells (peritoneal exudate, lymph node, or spleen) were cultured for 72 hours with either concanavalin A (Con A, 1 microgram/ml) or a soluble extract of M. faeni (10 micrograms/ml). We then injected the cells intravenously (IV) into naive guinea pigs, skin tested with purified protein derivative (PPD), challenged the animals intratracheally (IT) with M. faeni 48 hours after the cell transfer, and killed them 4 days (IT) with M. faeni 48 hours after the cell transfer, and killed them 4 days after IT challenge. We also transferred noncultured cells and antibody-containing serum from sensitized animals. Randomly selected microscopic fields of the lung (150 per animal) were judged to be normal or abnormal. All guinea pigs were maintained in high-efficiency particulate accumulator-filtered air. Compared with control animals that received media IV, there was a substantial increase (P less than 0.01) in the extent of pulmonary abnormalities in the animals receiving lymph node cells or spleen cells cultured with M. faeni, and peritoneal exudate cells cultured with Con A. Findings in recipients of peritoneal exudate cells cultured with M. faeni, or lymph node cells or spleen cells cultured with Con A did not differ from those in the control group. In contrast to cultured cells, noncultured cells and antibody-containing serum did not transfer susceptibility. PPD skin reactivity was present only in recipients of noncultured cells and not in recipients of serum or cultured cells. We conclude that experimental HP can be transferred with cultured cells from sensitized animals and that HP appears to be a cell-mediated process.

Alveolitis, Extrinsic Allergic↗
PubMed1987

Prolonged exposure to M. faeni in strain II guinea-pigs: pulmonary interstitial inflammation.

Models of hypersensitivity pneumonitis (HP) should exhibit progression of pulmonary histological abnormalities during continuing challenges. Strain II guinea-pigs were sensitized with Micropolyspora faeni and received 2, 4, or 8 weekly intratracheal (i.t.) particulate M. faeni challenges. Control animals received normal saline (NS). Four days after the last exposure, randomly selected microscopic fields of lung (200/animal) were judged to be normal or abnormal. If abnormal, the location and nature of the abnormalities were determined. Compared with NS treated guinea-pigs, those exposed to 2, 4 and 8 weekly M. faeni challenges exhibited more extensive (P less than 0.001) pulmonary histological abnormalities which involved both the intraalveolar and interstitial compartments. More extensive abnormalities in the 8 week group compared with the 4 week group were caused by increased extent of interstitial mononuclear cell infiltration. The extent of pulmonary interstitial histological abnormalities transiently (four challenges) decreases, but then increases, so that progressive pulmonary inflammation occurs during continuing challenges.

Actinomycetales↗
PubMed1986

Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans.

To determine whether venous plasma norepinephrine concentrations consistently reflect changes in sympathetic nervous activity, the influence of mental arithmetic, static handgrip, and submaximal bicycle exercise on intra-arterial blood pressure, heart rate, and plasma norepinephrine was studied in 51 subjects with untreated essential hypertension (mean age, 46 years; range, 16-69 years). At rest, plasma norepinephrine was unrelated to age or blood pressure. Mental arithmetic increased mean arterial pressure from 108 +/- 18 to 127 +/- 18 mm Hg (mean +/- S.D.; p less than 0.001) and heart rate from 69 +/- 7 to 93 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (547 +/- 297 to 518 +/- 250 pg/ml). Isometric exercise raised mean arterial pressure from 115 +/- 18 to 148 +/- 21 mm Hg (p less than 0.001) and heart rate from 76 +/- 9 to 95 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (683 +/- 253 to 741 +/- 253 pg/ml). Bicycle exercise increased mean arterial pressure from 114 +/- 20 to 146 +/- 26 mm Hg (p less than 0.001), heart rate from 77 +/- 9 to 128 +/- 19 beats/min (p less than 0.001), and plasma norepinephrine from 645 +/- 228 to 1151 +/- 462 pg/ml (p less than 0.001). Both the maximum mean arterial pressure and the peak heart rate attained during bicycle exercise were related to the exercise plasma norepinephrine level (r = 0.33, p less than 0.02 and r = 0.28, p less than 0.03, respectively). Increases in plasma norepinephrine with exercise were not greater in older or more hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Cardioselective and nonselective beta-adrenoceptor blocking drugs in hypertension: a comparison of their effect on blood pressure during mental and physical activity.

The ability of cardioselective and nonselective beta-adrenoceptor blocking drugs, with and without partial agonist activity, to control increases in blood pressure associated with mental and physical activity was compared in 35 subjects with hypertension. Direct measurements of blood pressure and radioenzymatic determinations of plasma norepinephrine were obtained before, during and after four activities, and were repeated after random allocation to treatment with atenolol, metoprolol, pindolol or propranolol. Cardioselective and nonselective drugs modestly reduced the pressor response to reaction time testing, but not to mental arithmetic or isometric exercise. The increase in systolic blood pressure during bicycling was attenuated significantly by the cardioselective drugs atenolol (by 23 mm Hg, or 38%) and metoprolol (21 mm Hg, or 41%), but not by the nonselective agents pindolol (with partial agonist activity) (13 mm Hg, or 20%) and propranolol (10 mm Hg, or 17%) (p less than 0.02 cardioselective versus nonselective; p = NS pindolol versus propranolol). Only bicycle exercise increased plasma norepinephrine concentrations (by 80%). These results suggest that beta-adrenoceptor blocking drugs will not attenuate increases in blood pressure during mental or physical activities unless intense sympathoadrenal activation also occurs. Marked elevations in circulating epinephrine, with or without norepinephrine, and peripheral beta 2-blockade appear necessary for alpha-mediated vasoconstriction to predominate and for the contrasting effects of cardioselective and nonselective drugs to be appreciated.

Adolescent↗
PubMed1981

Cuff and ambulatory blood pressure in subjects with essential hypertension.

Clinic cuff blood-pressure measurements, obtained on at least three occasions, were compared with mean arterial pressures in 59 patients with borderline or essential hypertension who underwent direct ambulatory monitoring of blood pressure. In 22 patients (group I) mean cuff and ambulatory pressures were similar (+/- 10 mm Hg) while in 32 subjects (group II) cuff pressures were more than 10 mm Hg higher. Groups I and II could not be distinguished on the basis of clinical examination, indices of sympathetic nerve activity, or blood-pressure variability, or by the magnitude of pressure rise during physical or mental exercise. Group II had less cardiovascular target organ damage and better baroreflex sensitivity but there was considerable overlap. There was no reliable way of telling which subjects would have lower ambulatory than cuff pressures. 20 out of 59 subjects classified as hypertensive by cuff measurements had awake ambulatory pressures or less than 140/90 mm Hg.

Adolescent↗
PubMed1980

The prostatic perineural space and its relation to tumor spread: an ultrastructural study.

Prostatic perineural structures were studied by electron microscopy in 31 speciments from benign and malignant lesions. Vascular structures seen in these areas have the ultrastructural characteristics of blood capillaries. No lymphatic channels were observed. Spread of tumor cells occurred by direct extension around the prostatic nerves and not within vascular channels. It is possible that these perineural spaces represent areas of least resistance to tumor invasion. These findings were not reported in previous studies on the ultrastruct of the human prostate.

Humans↗
PubMed1980

Adaptation of hypertensives to treatment with cardioselective and non-selective beta-blockers. Absence of correlation between bradycardia and blood pressure control, and reduction in slope of the QT/RR relation.

Thirty mild hypertensives were treated for more than two months with either cardioselective (atenolol or metoprolol) or non-selective (propranolol or pindolol) beta-blockers; the patients were assigned to the drugs in a double-blind manner. A procedure was designed to distinguish between the effects of the drugs themselves while treatment continued, and the development of adaptive changes which would persist when the drugs had been eliminated from the body. Though individual responses to treatment varied in both groups, the mean effect of the cardioselective and non-selective drugs in the control of hypertension was similar. There was no evidence of the development of supersensitivity or "rebound". On the contrary, an adaptive bradycardia (that is a fall of not less than 10% in heart rate persisting 52 hours after stopping treatment) was observed at rest in 17/30 patients, and peak heart rates and blood pressures during exercise were lower in both groups than before treatment. Cardioselective drugs induced a significantly greater bradycardia at rest than non-selective, but on exercise increases in heart rate were reduced more by the non-selective drugs, so that the same peak heart rates were reached on exercise in both groups. Adaptation also affected QT. The results suggest that two factors govern the shortening of QT by increases in heart rate, a "metabolic" effect, determined by sympathetic drive, and a "biophysical" effect determined by heart rate. The adrenergic effect is attenuated by acute beta-blockade, or by adaptation to prolonged blockade, leaving a shallow, rate-determined, slope to the QT/RR regression.

Adaptation, Physiological↗