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Biomedical subjects

B Jackson

Publications and source records attributed to B Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effect of specimen storage on absolute CD4 counts.

We have evaluated the effect of specimen storage on absolute CD4 counts by a commercially available manual assay. This assay utilizes latex particles coated with CD4 monoclonal antibodies that are mixed with lymphocytes in whole blood. Thirty blood samples were analyzed on days 1, 2, 4, and 7 postcollection. Linear regression analysis and Pearson correlation coefficients were used to determine the relationship between the absolute CD4 count and the storage time after sample collection. There was a significant decrease in absolute CD4 counts from baseline over time, dropping 3.6% at day 2, 10.1% at day 4, and 18.8% at day 7. However, the standard error of the B coefficient was constant [SE (B) = 0.031] up to day 4, indicating that reliable estimates of the baseline CD4 counts could be made from the CD4 counts determined up to day 4 from the time of sample collection. In addition to being sample, rapid, and inexpensive, the manual assay is capable of giving a reliable absolute CD4 count after specimen storage of up to 4 days. The application of this assay in the limited facilities of developing countries' laboratories is attractive.

Blood Specimen Collection↗
PubMed1994

As-needed psychotropic medications: prevalence, indications, and results.

1. Approximately 50% of inpatients are receiving p.r.n. psychotropic medications. 2. The most prevalent reasons reported in the literature for giving p.r.n. medications were to prevent/contain agitation, physical aggression, disruptive behavior in children, and aggressive behavior in children. 3. Nurses are responsible for providing a safe milieu; nurses must have the option of giving p.r.n. medications to protect patients and staff members.

Adult↗
PubMed1993

Bile acid synthesis in hamster hepatocytes in primary culture: sources of cholesterol and comparison with other species.

The synthesis of bile acids by primary hamster hepatocytes in culture has been studied. Measurable rates of bile acid synthesis were obtained from cells prepared from livers of animals fed 2% w/w cholestyramine to induce the synthesis of bile acids through the rate-limiting enzyme cholesterol 7 alpha-hydroxylase. The effects of various sources of substrate for bile acid synthesis in these cultured cells were examined over a period of 24 h and the results compared with published or parallel studies in primary rat hepatocytes or in the human hepatoma cell line, HepG2. In all the cells, bile acid synthesis was stimulated by the addition of 7 alpha-hydroxycholesterol, indicating the rate-limiting role of the cholesterol 7 alpha-hydroxylase. Bile acid synthesis in the hamster hepatocytes was also stimulated by a variety of sources of cholesterol as substrate, mevalonic acid (increasing the production of newly-synthesised cholesterol in the cell), and as an exogenous source, hamster LDL. Similarly, if cholesterol was diverted from intracellular esterification using the ACAT inhibitor Dup128, a further increase in bile acid synthesis could be demonstrated. These results show that hepatocytes obtained from cholestyramine-treated hamsters are deficient in substrate cholesterol for bile acid synthesis. A similar conclusion can be drawn from the published work with rat hepatocytes and is further supported by experiments on the regulation of cholesterol 7 alpha-hydroxylase activity at the mRNA and the protein level, although some in vivo studies in animals and studies in man have led authors to suggest that cholesterol 7 alpha-hydroxylase is saturated with substrate.

Animals↗
PubMed1993

Follow-up of preterm infants treated with dexamethasone for chronic lung disease.

OBJECTIVE: To study the outcome of prolonged treatment with dexamethasone sodium phosphate in preterm infants who depend on assisted ventilation. DESIGN: Longitudinal follow-up using historic controls. SETTING: Regional intensive care nursery. PARTICIPANTS: Sixty-one very-low-birth-weight infants treated with a 42-day course of dexamethasone and 61 historic controls matched for birth weight, gestational age, race, and sex. All 122 subjects required assisted ventilation for at least 15 days. INTERVENTION: Infants were given dexamethasone sodium phosphate at a dose of 0.5 mg/kg per day. The dose was then tapered over 42 days. MEASUREMENTS/MAIN RESULTS: Infants treated with dexamethasone received assisted ventilation for a median of 33 days; controls, a median of 47 days (P < .05). One hundred infants survived; 94 were examined at age 1 year. The two groups were similar with respect to the proportions hospitalized for respiratory infection in the first year of life and the proportions with weight, length, and head circumference below the fifth percentile. Rates of cerebral palsy were also similar between the two groups, as were median Bayley Mental and Psychomotor developmental index scores. CONCLUSIONS: Dexamethasone treatment was associated with fewer days of assisted ventilation, but not with improved outcome at age 1 year. More assessment should be made of dexamethasone's effect on long-term outcome before dexamethasone becomes widely used in preterm infants who depend on assisted ventilation.

Chronic Disease↗
PubMed1993

SK&F 97426-A a more potent bile acid sequestrant and hypocholesterolaemic agent than cholestyramine in the hamster.

SK&F 97426-A is a novel bile acid sequestrant which was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. The effects of the two sequestrants on faecal bile acid excretion, plasma total cholesterol, VLDL + LDL and HDL cholesterol and triglyceride concentrations and on liver enzymes involved in the synthesis and metabolism of cholesterol were investigated in normocholesterolaemic hamsters. Four studies were conducted to determine the relative potencies of the two resins using a range of doses of the sequestrants over treatment periods of up to 2 weeks. Curves fitted to the resulting data allowed common maximum responses and separate ED50s to be calculated for each sequestrant. The maximum response of both sequestrants was to increase bile acid excretion by 352% and lower plasma total cholesterol by 37-58%. LDL + VLDL and HDL cholesterol were reduced by 56-75% and 25-41%, respectively. SK&F 97426-A was 3 times more potent than cholestyramine at increasing the excretion of bile acids in the faeces and 2.1-3.4-fold and 2.3-3.2-fold more potent at lowering total plasma cholesterol and LDL plus VLDL cholesterol, respectively. In some of the experiments SK&F 97426-A was also more potent than cholestyramine at lowering HDL cholesterol. Plasma triglycerides were also lowered by both sequestrants by up to 31% after 1 week but the relative potency could not be determined. These HDL cholesterol and total triglyceride lowering effects of bile acid sequestrants in the hamster are known not to occur in people treated with cholestyramine. There were minimal differences between hamsters treated for 1 or 2 weeks in the relative potencies or ED50s calculated for the total plasma cholesterol, LDL + VLDL and HDL cholesterol. Both sequestrants may have been slightly more efficacious on these parameters after 2 weeks of treatment. Liver weights were reduced by about 15% by both sequestrants at 2% (w/w) in the diet for 1 week. The activities of the liver HMG-CoA reductase and cholesterol 7 alpha-hydroxylase were increased as expected, whilst the activity of the acyl-CoA:cholesterol acyltransferase was reduced by both sequestrants at this dose. SK&F 97426-A was, therefore, 2-3-fold more potent as a bile acid sequestrant and hypocholesterolaemic agent than cholestyramine when tested in the hamster.

Animals↗
PubMed1993

Plasma total glutathione in humans and its association with demographic and health-related factors.

The tripeptide glutathione is proposed to be protective against a number of chronic diseases including cardiovascular disease and cancer. However, there have been few studies of plasma glutathione levels in humans and in those studies the numbers of participants have been very small. In an exploratory analysis the determinants of plasma total glutathione (GSHt) were investigated in a group of 100 volunteers aged 18-61 years in Atlanta, Georgia, USA during June and July 1989. Data on demographic and health-related factors were collected by interview and plasma GSHt was measured using a recently modified laboratory method. The mean concentration of plasma GSHt for all 100 participants was 761 micrograms/l, with a standard deviation of 451 micrograms/l, a range of 86-2889 micrograms/l and a median of 649 micrograms/l. Men had significantly higher levels of plasma GSHt than women (924 v. 692 micrograms/l; P = 0.006). Seventh-day Adventists participating in the present study had higher plasma GSHt levels than other subgroups defined by race and/or religion. Among Seventh-day Adventists consumption of a vegetarian diet was associated with increased plasma GSHt concentration (P = 0.002). Plasma GSHt levels also appeared to vary by race, but relationships with race could not be clearly disassociated from relationships with religion. Among white participants plasma GSHt concentration decreased with age in women but increased with age in men (P = 0.05). Few other factors were associated with plasma GSHt concentration, although use of oral contraceptives (P = 0.10) was somewhat associated with decreased plasma GSHt levels. These findings suggest that plasma GSHt levels may vary with several demographic and health-related attributes and support the need for further research on this potentially important disease-preventive compound.

Adolescent↗
PubMed1993

A rapid manual method for CD4+ T-cell quantitation for use in developing countries.

OBJECTIVE: To evaluate a manual method (Cytosphere) for quantifying CD4+ T-cell numbers. DESIGN: Cross-sectional study of HIV-1-seronegative and HIV-1-seropositive individuals evaluated for absolute CD4 counts by both standardized flow cytometric measurements and manual Cytosphere technology using a hemacytometer. SETTING: University research hospitals in both the United States and Africa. PATIENTS, PARTICIPANTS: Blood specimens from 382 patients were evaluated. These were broken down into 294 samples obtained from HIV-1-seropositive patients and 88 samples obtained from HIV-1-seronegative patients. INTERVENTIONS: None. OUTCOME MEASURED: Absolute CD4 cell number. RESULTS: Evaluation of samples obtained from HIV-1 patients in both the United States and Africa demonstrated an overall correlation of the Cytosphere assay with flow cytometry of 0.912 (95% confidence interval, 0.895-0.928; P < 0.001). When samples were stratified based on CD4+ T-cell counts determined by flow cytometry, the Cytosphere assay had a 96% predictive value for correctly identifying individuals with CD4 T-cell counts > 200 x 10(6)/l and a 92% predictive value for correctly identifying individuals with CD4 T-cell counts < 200 x 10(6)/l. CONCLUSIONS: This assay appears to have the potential for the quantitation of CD4 cells in the limited laboratory facilities in developing countries and to have a strong correlation with standard flow cytometric technology.

Adult↗
PubMed1993

Distribution and functional significance of cardiac angiotensin converting enzyme in hypertrophied rat hearts.

BACKGROUND: The intracardiac conversion rate of angiotensin (Ang) I to Ang II and the expression of angiotensin converting enzyme (ACE) mRNA are amplified in rat hearts with left ventricular hypertrophy (LVH). To examine whether the accelerated intracardiac Ang II generation in LVH is related to an induction of cardiac ACE, we studied localization and function of cardiac ACE in hypertrophied rat hearts using specific ACE inhibitors. METHODS AND RESULTS: Cardiac ACE was localized and quantified in hearts from male Wistar rats with LVH due to chronic experimental aortic stenosis and from control rats. With the ACE inhibitor 125I-351A, a derivative of lisinopril, as a radioligand on coronal sections of LVH and control hearts, in vitro autoradiography demonstrated ACE binding in aorta, coronary arteries, atria, and ventricles of both groups. Quantitative analyses revealed that ACE density (counts per minute per cross-sectional area of tissue) was twofold higher within the myocardium of hypertrophied left ventricles compared with controls (p < 0.005). Quantitative morphometry demonstrated a modest increase in the fractional volume of myocytes as well as capillary volume without an increase in the fractional volume of endothelial cells in left ventricular tissue from aortic stenosis rats. These data suggest that an increase in endothelial cell volume per se cannot alone account for the observed doubling of ACE density and support an upregulation of ACE production in hypertrophied tissue. The role of cardiac ACE in intracardiac conversion of Ang I to Ang II and its specific inhibition was studied in isolated, isovolumic beating, buffer-perfused LVH and control hearts. Biochemical conversion rates as well as functional changes in response to 3 x 10(-7) M Ang I were examined in the absence or presence of the ACE inhibitor enalaprilat (4 x 10(-6) M). After a brief stabilization period, groups of LVH and control hearts were subjected to the following infusion protocols: 15 minutes of vehicle followed by 30 minutes of Ang I plus vehicle, 15 minutes of enalaprilat followed by 30 minutes of Ang I plus enalaprilat (enal/Ang I), or 45 minutes of vehicle only to allow comparison with a time control. Intracardiac Ang I-to-Ang II conversion rate was fourfold higher in LVH than in control hearts (p < 0.05). Infusion of enalaprilat reduced the intracardiac Ang I-to-Ang II conversion rate in LVH hearts by 70% (p < 0.05 versus Ang I). At similar levels of constant coronary flow per gram, Ang I increased coronary perfusion pressure by 23 +/- 5 mm Hg (p < 0.01 versus vehicle) in LVH hearts and by 36 +/- 10 mm Hg (p < 0.005 versus vehicle) in control hearts. When enalaprilat was infused with Ang I, the increase in perfusion pressure was limited to 5 +/- 5 mm Hg (NS versus vehicle) in LVH hearts and 12 +/- 3 mm Hg (p < 0.05 versus vehicle) in control hearts and was significantly lower than in hearts infused with Ang I only (p < 0.05 in LVH and p < 0.05 in control hearts, respectively). Systolic function was not affected by either infusion protocol. In contrast, Ang I infusion was associated with diastolic dysfunction. In LVH hearts, left ventricular end-diastolic pressure (LVEDP) increased from 10 +/- 1 mm Hg at baseline to 25 +/- 2 mm Hg at the end of the Ang I infusion (p < 0.001 versus vehicle), which was inhibited by infusion of enalaprilat. In control hearts, there was a lesser increase in LVEDP from 10 +/- 1 mm Hg to 15 +/- 1 mm Hg in response to Ang I (p < 0.05 versus LVH). Control hearts treated with enalaprilat with Ang I displayed no increase in LVEDP: CONCLUSIONS: These observations indicate that ACE protein is increased within the myocardium of LVH hearts, extending recent findings of increased cardiac ACE activity and mRNA levels in this model of pressure-overload LVH in the rat. Blockade of the enzyme by an ACE inhibitor decreases intracardiac Ang I-to-Ang II conversion rate and prevents the functional changes of Ang I-to-Ang II activation

Angiotensin I↗
PubMed1992

Glutathione in foods listed in the National Cancer Institute's Health Habits and History Food Frequency Questionnaire.

Glutathione (GSH) is an antioxidant and anticarcinogen that is present in plant and animal tissues that form the bulk of the human diet. Recent studies show that GSH is absorbed intact in rat small intestine and that oral GSH increases plasma GSH concentration in humans. To provide a database for epidemiological studies of dietary intake of GSH and risk of diseases in humans, we have measured the content of GSH in the foods listed in the National Cancer Institute's Health Habits and History Questionnaire. Foods were purchased in the Atlanta area and prepared as most commonly consumed in the United States. GSH analyses were performed using a high-performance liquid chromatography technique with a method of additions to correct for losses during sample preparation. A separate set of samples was run after treatment with dithiothreitol to measure the total of GSH and its disulfide forms (GSH). The results show that dairy products, cereals, and breads are generally low in GSH; fruits and vegetables have moderate to high amounts of GSH; and freshly prepared meats are relatively high in GSH. Frozen foods generally had GSH contents similar to fresh foods, whereas other forms of processing and preservation generally resulted in extensive loss of GSH. Thus this database will allow researchers to examine the relationship between dietary GSH and risk of cancers and other diseases.

Beverages↗
PubMed1992

Characterization of angiotensin converting enzyme in isolated cerebral microvessels from spontaneously hypertensive and normotensive rats.

OBJECTIVE: Abnormalities in the vascular renin-angiotensin system have been hypothesized to contribute to the pathogenesis and complications of hypertension. In animal models of hypertension, there is wide variation in reported vascular angiotensin converting activity, particularly in cerebral microvessels. In this study, we sought to characterize, quantitate and compare cerebral microvessel angiotensin converting enzyme (ACE) in genetically hypertensive rats and normotensive rats. DESIGN: Brain microvascular ACE from 14-week-old spontaneously hypertensive rats (SHR) was measured and compared with ACE from brain microvessels of normotensive Wistar-Kyoto (WKY) controls. METHODS: Isolated cerebral microvascular ACE was measured using two methods, enzyme kinetic assay or radioligand binding assay. RESULTS: In SHR, cerebral microvessel ACE was of similar activity and concentration and had similar ligand binding affinities to WKY rats. Plasma ACE activity was significantly elevated in WKY rats compared with SHR. CONCLUSION: Cerebral microvascular ACE is similar in SHR and WKY rats. Microvascular ACE is unlikely to participate in the pathogenesis or complications of hypertension in this model.

Animals↗
PubMed1992

Steady-state pharmacokinetics and pharmacodynamics of cilazapril in the presence and absence of cyclopenthiazide.

Twenty-two patients with essential hypertension received a single dose of 2.5 mg cilazapril and were then randomised into a double-blind parallel group study to receive either placebo, 1.25 mg cilazapril + 0.5 mg cyclopenthiazide (CPTZ), 2.5 mg cilazapril + 0.5 mg CPTZ, or 2.5 mg cilazapril alone for 1 month. After oral administration of a single dose of 2.5 mg cilazapril, the active diacid cilazaprilat appeared rapidly in the plasma (Tmax 2.0 +/- 0.2 h). With the radioinhibitor assay used in this study, a single elimination phase of cilazaprilat was evident, with a half-life (t1/2) of 2-3 h. At steady state, the pharmacokinetics of cilazaprilat were similar to single-dose administration and were not altered by CPTZ. The Cmax and area under the curve (AUC) of cilazaprilat were directly proportional to dose. Cilazapril administration in the dose range of 1.25-2.5 mg produced a dose-proportional inhibition of angiotensin-converting enzyme (ACE) activity that was maximum 2 h after drug administration. The degree of ACE inhibition correlated with the plasma concentration-time profile of cilazaprilat and the maximum decrease in blood pressure (BP). The EC50 for ACE inhibition by cilazaprilat was 7.7 ng/ml after acute treatment and was not significantly altered during chronic administration or by concomitant administration of CPTZ. There was no evidence of a dose-related antihypertensive effect of cilazapril at steady state and, with the small numbers of subjects used in this study, there was no evidence of 24-h BP control with monotherapy.

Aged↗
PubMed1992

Mesenteric vascular angiotensin-converting enzyme is increased in experimental diabetes mellitus.

1. Diabetes mellitus was induced by streptozotocin in male Wistar rats, and angiotensin-converting enzyme measured in plasma and mesenteric vessels 3 weeks later. 2. Diabetes was associated with increased mesenteric wet weight/bodyweight ratio (control 0.2 s.e.m. 0.02 mg/g, n = 21, vs diabetes 1.0 s.e.m. 0.3 mg/g, n = 27, P less than 0.01, ANOVA). 3. Plasma angiotensin-converting enzyme activity was increased in diabetic rats (98 s.e.m. 3 nmol HL/mL per min) compared with controls (64 s.e.m. 6 nmol HL/mL per min, P less than 0.01, ANOVA). 4. Mesenteric vessel angiotensin-converting enzyme was increased in diabetes mellitus estimated by radioligand binding site density (fmol/mg protein; 1407 s.e.m. 166 fmol/mg protein) compared with controls (890 s.e.m. 56 fmol/mg protein, P less than 0.05, ANOVA) and by enzyme kinetic assay (diabetes, 15.5 s.e.m. 1.5 nmol HL/mg protein per min, controls, 8.3 s.e.m. 0.7 nmol HL/mg protein per min, P less than 0.01, ANOVA). The equilibrium dissociation constant of ligand-angiotensin-converting enzyme interaction was unchanged. 5. Increased vascular angiotensin-converting enzyme concentration may contribute to vascular hypertrophy and diabetic vasculopathy by increased local synthesis of angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗