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Biomedical subjects

B Jackson

Publications and source records attributed to B Jackson.

At least 145 records · Page 8Linked to original sources
PubMed1991

A novel delta 0 mutation in cis with Hb Knossos: a study of different genetic interactions in three Egyptian families.

We have defined the molecular basis of normal HbA2 beta-thalassaemia associated with Hb Knossos. DNA sequence analysis of the delta globin gene in cis with beta Knossos showed deletion of a single A in codon 59 leading to a premature termination at codon 60. This delta 0/beta Knossos allele has been observed in three unrelated Egyptian families and associated with a single beta haplotype (+----++). One individual who was homozygous for the delta 0/beta Knossos allele as well as heterozygous for a non-deletional alpha thalassaemia, was completely clinically asymptomatic, while others have coinherited the delta 0/beta Knossos allele with different beta and alpha thalassaemia determinants. A study of the different genetic interactions giving rise to a spectrum of clinical phenotypes is reported.

Adult↗
PubMed1991

Angiotensin-converting enzyme in macro- and microvessels of the rat.

1. Angiotensin-converting enzyme (ACE) was measured in the aorta, cerebral and mesenteric microvessels of Wistar-Kyoto rats using a specific radioligand assay. 2. Ligand binding studies revealed a four-fold increase in concentration of ACE in mesenteric microvessels, compared with aorta or brain microvessels. The dissociation constant (Kd) was similar in all tissues. 3. The effects of oral administration of the ACE inhibitor S9650 on vascular ACE in vivo were measured. 4. S9650 produced a dose-dependent inhibition of vascular ACE from brain and mesenteric microvessels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

To establish if the benefit of angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect of the systemic hypotensive effect, we studied the effect of long-term ramipril treatment on blood pressure, glomerular filtration rate, and urinary protein excretion in streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of ramipril was prevented by a high salt diet, which did not alter the degree of renal angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking solution. One week later, groups 2 and 3 received 0.4 mg/kg/day ramipril in their drinking solution, which was continued over a 2-month period. Ramipril produced a blood pressure fall only in water-drinking rats (group 3) despite a similar reduction in plasma and renal angiotensin converting enzyme activity in groups 2 and 3. Salt-loaded rats had a progressive increase in urinary protein excretion over the duration of study. Ramipril treatment prevented an increase in protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular filtration rate was similar in all three groups. Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on proteinuria. Although it is possible that angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Localization of angiotensin converting enzyme in rat heart.

Angiotensin converting enzyme (ACE) was localized in rat heart by quantitative in vitro autoradiography with 125I-351A as the radioligand. The binding association constant (KA) of the radioligand was measured in membrane-rich fractions of atrium, ventricle, and lung by a radioinhibitor binding assay. A single class of high-affinity binding sites was detected in each tissue, and a significant difference was found between KA values for atria and ventricles with a rank order of atria greater than lungs greater than ventricles. For autoradiography, coronal sections (10 micron) of the frozen heart were incubated with 125I-351A and exposed to x-ray film. The autoradiographs were quantitated by computerized image analysis. The highest density of ACE in the heart was found on valve leaflets (aortic, pulmonary, mitral, and tricuspid), which contrasted markedly with very low ACE labeling in the endocardium. The coronary arteries also showed dense labeling of ACE. The right atrium had a moderate density of ACE, which was higher than the left atrium and the ventricles. Both the endothelial and adventitial layers of the aorta and pulmonary artery displayed high densities of ACE, with very low density in the media. ACE was not detected in either the sinoatrial node or atrioventricular node. These results reveal a markedly nonuniform localization of ACE in the rat heart and suggest possible sites for local angiotensin II generation and bradykinin or other peptide metabolism.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Myospherulosis. Complicating wound healing.

Myospherulosis is a complication of wound healing which results from an action between lipids and extravasated erythrocytes. A case of myospherulosis of the mandible is reviewed with its history, histopathology and occurrence.

Adult↗
PubMed1991

Angiotensin-converting enzyme inhibition: prospects for the future.

Angiotensin-converting enzyme (ACE) is a widely distributed dipeptidyl carboxydipeptidase. Using computer analysis of the binding of radiolabeled ACE inhibitors, we have mapped the distribution of ACE in normal animals and in models of disease, and have studied the tissue effects of ACE inhibitors. In the myocardium, ACE is located in vascular and valvular structures as well as in the atria and ventricles. Its concentration is increased in myocardial hypertrophy in the infarct model of heart failure. Chronic ACE-inhibitor therapy prevents myocardial hypertrophy. In the brain, ACE is localized in multiple specific sites where its role is unknown. Following oral ACE-inhibitor treatment, effects are restricted predominantly to areas devoid of blood-brain barrier. Early studies suggest ACE inhibitors enhance cognition. In the testis, ACE is located in the seminiferous tubules where its function is unknown. It is not inhibited following oral ACE-inhibitor treatment. In the kidney and gastrointestinal tract, ACE is in high concentration in the epithelial brush border where its function is unknown. In clinical use ACE inhibitors primarily affect the cardiovascular system. With pharmacological developments, ACE inhibitors targeted for specific organs may have effects predominantly in the brain, heart, reproductive system, or gastrointestinal tract.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Impaired cyclic AMP generation in outer medullary tubules of gentamicin-treated rats.

We have examined the effects of chronic gentamicin treatment on arginine8-vasopressin (AVP)-dependent cyclic AMP (cAMP) metabolism in rat medullary collecting tubules (oMCT) and medullary thick ascending limbs of Henle's loop (mTALH). Gentamicin attenuated AVP-stimulated cAMP accumulation to a greater extent in the mTALH (delta -51%) than in the oMCT (delta -25%). The mechanism of attenuation differed between segments, and could not be attributed to either direct inhibition of adenylate cyclase activity nor direct potentiation of cAMP-phosphodiesterase activity. These data suggest that the gentamicin-induced decrease in renal concentrating ability may be due at least in part to reduced AVP-dependent cAMP accumulation in the oMCT and mTALH.

1-Methyl-3-isobutylxanthine↗
PubMed1990

The effects of feeding a saturated fat-rich diet on enzymes of cholesterol metabolism in the liver, intestine and aorta of the hamster.

The effects of two dietary treatments on parameters of cholesterol metabolism were studied. Hamsters were maintained on diets containing 2% (w/w) cholesterol or 20% (w/w) hydrogenated coconut oil for 4 weeks. Both diets induced a hypercholesterolaemia. The effects of the two treatments on hepatic and intestinal acyl-CoA:cholesterol acyltransferase activity and 3-hydroxy-3-methylglutaryl-CoA reductase activity were measured. As expected, cholesterol feeding stimulated cholesterol esterification and inhibited cholesterol synthesis. Saturated fat-feeding had no effect on cholesterol synthesis but markedly inhibited cholesterol esterification in both liver and intestine. The diet-induced hypercholesterolaemia was strongly correlated with an increase in acyl-CoA:cholesterol acyltransferase activity in the activity. In contrast, the hypercholesterolaemia induced by feeding either of the two diets tended to increase aortic uptake of cholesterol and hence acyl-CoA:cholesterol acyltransferase activity. We suggest that the changes in cholesterol esterification correlate well with the expected flux of cholesterol into each tissue.

Animals↗
PubMed1990

Regulation of cholesteryl ester metabolism in the hamster liver.

Neutral cholesteryl ester hydrolase activity has been described in the cytosolic and microsomal fraction of rat liver, but the relationship of these activities to other parameters of hepatic cholesterol metabolism is not known. We have studied this in the hamster by manipulating the flux of cholesterol across the liver by dietary modifications. A bile acid sequestrant was used to stimulate LDL receptor activity and hence flux of cholesterol into the liver. A cholesterol-rich diet caused a hypercholesterolaemia and substantial uptake of cholesterol and deposition in the liver. Hypercholesterolaemia was also induced by a saturated fat-rich diet, but in contrast this reduced the flux of cholesterol into the liver. Animals were fed these diets for 1 week and then the livers removed and enzyme activities determined. These were 3-hydroxy-3-methylglutaryl-CoA reductase, cholesterol 7 alpha-hydroxylase, acyl-CoA: cholesterol acyltransferase, microsomal cholesteryl ester hydrolase and cytosolic cholesteryl ester hydrolase. Feeding the bile acid sequestrant increased the hydrolysis of cholesteryl ester in the liver over its synthesis. In contrast, both fat feeding and cholesterol feeding caused a reduction in the relative rate of hydrolysis of cholesteryl ester compared with synthesis. This was particularly marked with the cholesterol-rich diet. These results show that the hydrolysis of cholesteryl ester in hamster liver responds to dietary manipulation in a way that reflects the needs of the cell for cholesterol or the presence of an excess. It is suggested that a metabolically significant cholesteryl ester cycle may operate in the liver to a greater extent that had previously been thought.

Animals↗
PubMed1990

High salt diet ameliorates effects of angiotensin converting enzyme inhibition in spontaneously hypertensive streptozotocin diabetic rats.

1. To dissociate the effects on the development of diabetic renal injury of angiotensin converting enzyme (ACE) inhibition per se, and a reduction in systemic blood pressure, we have studied the effects of chronic ramapril treatment in streptozotocin diabetic spontaneously hypertensive rats, with modulation of the hypotensive effect by a high salt diet. 2. Three weeks following uninephrectomy and induction of diabetes with streptozotocin, spontaneously hypertensive rats were allocated to three treatment groups. Groups 1 and 2 received 1% sodium chloride and Group 3 water as drinking solution. Groups 2 and 3 received 0.4 mg/kg per day ramapril in drinking solution over the subsequent 2 month study period. 3. Sodium chloride drinking solution (1%) completely prevented any hypotensive effect of ramapril. Blood pressure was reduced in Group 3 rats over the entire period of study, when compared with Group 2 rats (P less than 0.001). 4. Urinary protein excretion progressively increased in Group 1 and 2 rats, and was significantly reduced (P less than 0.001) in Group 3. After 2 months treatment, urinary protein (expressed as mean and s.e.m.) was 160 +/- 30 mg/day in Group 1, 240 +/- 50 mg/day in Group 2, and 60 +/- 11 mg/day in Group 3. 5. Angiotensin converting enzyme inhibition per se was not associated with a reduced protein excretion in diabetic nephropathy, requiring concomitant control of systemic blood pressure to become renoprotective.

Animals↗
PubMed1990

Increased cardiac angiotensin-converting enzyme in rats with chronic heart failure.

1. Chronic heart failure was induced in rats by ligation of the left coronary artery to produce a left ventricular myocardial infarct. 2. Cardiac angiotensin-converting enzyme (ACE) was estimated by radioligand binding in myocardial homogenates and by autoradiography studies of radioligand binding to ACE in heart sections. 3. Radioligand binding studies demonstrated an increase in binding sites in animals with myocardial infarction, compared with sham operated animals. Mean increases were 457% in right atrium, 295% in left atrium, 326% in right ventricle, 187% in left ventricle and 530% in the region of the left ventricular infarct, compared with the sham left ventricle. 4. Autoradiography studies confirmed tissue homogenate binding studies, demonstrating (i) a marked increase in ligand binding in the infarct area and (ii) an increase in binding density in the hypertrophied myocardium of right and left atrium, and right and left ventricle. 5. The induction of cardiac ACE in the myocardium of rats with chronic heart failure may participate in the pathophysiology of cardiac hypertrophy.

Animals↗
PubMed1990

Characterization of cardiac angiotensin converting enzyme (ACE) and in vivo inhibition following oral quinapril to rats.

1. Angiotensin converting enzyme (ACE) from the rat heart and lung was studied by use of the radioligand [125I]-351A. 2. Displacement of the bound radioinhibitor [125I]-351A was used to assess the relative potency of six ACE inhibitors in rat heart and lung homogenates and estimate the binding association constant (KA). 3. The KA for atrial preparations was significantly higher than that of the lung (P less than 0.025) and also the ventricles (P less than 0.005). Ventricular preparations and preparations from the lung also differed significantly (P less than 0.05). These differences in KA were noted for all six ACE inhibitors used to displace the radioligand. 4. The rank order of potency of the ACE inhibitors was quinaprilat = benazeprilat greater than perindoprilat greater than 351A greater than lisinopril greater than fosinoprilat. 5. Cardiac ACE inhibition was studied ex vivo following oral administration of quinapril to rats. Following 0.3 mg kg-1 quinapril, the time course and degree of inhibition of ventricular and atrial ACE were similar. 6. These results suggest that the detected differences in KA noted have only a limited potential biological significance. The difference in KA may reflect variations in the structure or conformation of ACE in different tissues.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Glomerular filtration rate in streptozocin-induced diabetic rats. Role of exchangeable sodium, vasoactive hormones, and insulin therapy.

The interrelationships of sodium and volume status, atrial natriuretic peptide (ANP), plasma renin activity (PRA), insulinlike growth factor I (IGF-I), and kidney weight and their influence on glomerular filtration rate (GFR) were investigated in rats during the first 4 wk of streptozocin-induced diabetes (STZ-D). In each of three experiments, untreated diabetic rats were compared with nondiabetic control rats and rats with varying degrees of glycemic control during insulin therapy. The first experiment evaluated exchangeable sodium, plasma volume, and GFR. In untreated diabetic rats, exchangeable sodium and plasma volume, but not GFR, were increased by approximately 25% compared with control rats. Insulin-treated diabetic rats with plasma glucose levels ranging from 12 to 30 mM had increased GFR, whereas exchangeable sodium and plasma volume were reduced toward control values. Daily insulin therapy, titrated to maintain euglycemia, further reduced exchangeable sodium and plasma volume and decreased but did not normalize GFR. The second experiment evaluated the relationship between vasoactive hormones and GFR. In untreated diabetic rats, plasma ANP levels increased 89% and urinary cyclic GMP (cGMP) excretion increased 94%, with an 85% decrease in PRA, whereas GFR was unchanged. Moderate hyperglycemia (plasma glucose 12-30 mM) was associated with normalized plasma ANP levels and urinary cGMP excretion, a 52% decrease in PRA, and a 13% increase in GFR. The third experiment studied serial changes in food and water intake and vasoactive hormones and end-point measurement of kidney weight, GFR, and plasma IGF-I. In the untreated diabetic group, urinary cGMP excretion was significantly elevated after 3 wk, whereas the reduction in PRA levels was apparent after 1 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Factors affecting alcohol consumption in black women. Part I.

The purpose of this investigation is to evaluate the extent to which a general model for understanding and predicting Black mental health problems accounts for the particular problem of alcohol consumption in an urban sample of 289 African American women. The general model consists of eight variables: life events, social support, religious orientation, internalized racialism, physical health problems, marital status, socioeconomic status, and developmental status. In Part I expected interrelationships among variables are presented, from which a structural equation model for understanding and predicting alcohol consumption is formulated. Methods for evaluating the model are described in Part II (International Journal of the Addictions, Vol. 25, No. 12).

Adult↗
PubMed1990

Factors affecting alcohol consumption in black women. Part II.

An eight-variable model for understanding and predicting alcohol consumption in a sample of 289 African American women is evaluated using a structural equation methodology. We found that life events, physical health problems, and internalized racialism played important roles in accounting for variance in alcohol consumption. Marital status did not have the predicted inverse effect on alcohol consumption. While religious orientation did not have the expected inverse effect on alcohol consumption, it had an unexpected direct effect on internalized racialism, which had a direct effect on alcohol consumption. We found that the effects of socioeconomic status and developmental status on alcohol consumption were mediated through other variables specified in the model. Overall the model, which provided partial to complete support for five of eight hypotheses, provided a statistically adequate fit.

Black or African American↗