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Biomedical subjects

B Lewis

Publications and source records attributed to B Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1993

Interaction between transcription factors Sp1 and YY1.

A basal level of transcription is usually observed when all but a small region of DNA has been deleted from a eukaryotic gene promoter. These promoter elements, which are necessary and sufficient for specific transcription initiation, are referred to as minimal or core promoter elements. One element that is commonly present in a core promoter is the initiator. It has been demonstrated that the presence of Sp1 binding sites can greatly enhance the level of transcription initiation at initiator elements. A binding site for the YY1 transcription factor, located at the initiation site of the adeno-associated virus P5 promoter, functions as an initiator element; a synergistic enhancement of its activity is observed in vitro when upstream Sp1 binding sites are present. Here we report that this synergistic activation probably occurs through protein-protein interactions.

Animals↗
PubMed1993

Hypo- and hyperresponse of serum cholesterol level and low density lipoprotein production and degradation to dietary cholesterol in man.

Serum cholesterol in man rises when cholesterol intake increases, but the extent of the elevation varies between subjects. Part of the variation between subjects is spurious and not reproducible; it is caused by random diet-independent fluctuations of serum lipid levels. Part is due to consistent metabolic differences between subjects. We have earlier found that responsiveness was associated with higher initial total and HDL cholesterol, lower habitual cholesterol consumption, and lower body mass index, and unrelated to gender, age, or apo E phenotype. We have now investigated the metabolic basis of variability by measuring turnover rates of low density lipoprotein (LDL) apolipoprotein B (apo B) on a low-cholesterol diet (140 mg/day) and a high-cholesterol diet (900 mg/day) in 8 volunteers with well-defined differences in the responsiveness of their serum cholesterol to diet. Autologous 125I-LDL was injected on day 23 of each diet period. Its fractional catabolic rate (FCR) was estimated from the ratio of 125I in urine over that in plasma, seven days after injection. FCR (mean +/- SD) increased from 0.24 +/- 0.02 pools/day on the low- to 0.31 +/- 0.20 on the high-cholesterol diet. LDL-apo B concentration rose from 49 +/- 13 to 63 +/- 12 mg/dl, and LDL-apo B production rate, calculated as FCR x concentration/body weight, from 4.8 +/- 1.2 to 8.0 +/- 1.4 mg/kg/day. The individual rise in production rate was significantly correlated with the rise in the serum concentration of LDL-apo B (r = 0.90) or LDL-cholesterol (r = 0.75), and also with the rise in total serum cholesterol measured in these same subjects in similar experiments 3-4 years earlier (r = 0.74). Degradation of LDL by freshly isolated blood mononuclear cells and by mononuclear cells incubated for 72 h in lipoprotein-deficient medium (derepressed cells) was measured on both diets in these and in additional volunteers. The rate of degradation (mean +/- SD) of standard human LDL by fresh cells was 336 +/- 166 ng LDL protein/mg cell protein per 8 h on the low-cholesterol diet, and decreased by 147 +/- 180 ng/mg per 8 h or 44% on the high-cholesterol diet (n = 23, p < 0.01). The catabolic activity of derepressed cells obtained when subjects were on the low-cholesterol diet was negatively related to the LDL cholesterol response (r = -0.57, n = 18, p < 0.05), and to the total cholesterol response in earlier experiments (r = -0.45, n = 18, p < 0.10).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Identification of a GBR12935 homolog, LR1111, which is over 4,000-fold selective for the dopamine transporter, relative to serotonin and norepinephrine transporters.

The di-substituted piperazines, GBR12909 (1-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-4-[3- phenylpropyl]piperazine) and GBR12935 (1-[2-(diphenyl-methoxy)-ethyl]-4-(3-phenylpropyl)piperazine), are potent and selective (20-to 100-fold) inhibitors of [3H]dopamine reuptake, relative to [3H]5-HT and [3H]norepinephrine uptake. The GBR12935 analog, 1-(2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl)homopiperazine (LR1111), was synthesized as part of a systematic structure-activity study of analogs of GBR12935 and GBR12909. LR1111 differs from GBR12935 by the addition of a methylene group into the piperazine ring to yield a compound with a seven-member homopiperazine ring. The IC50 values for LR1111 at the dopamine, norepinephrine, and serotonin transporters were 7.2 nM, 34,072 nM, and greater than 20,000 nM, respectively, whereas the IC50 values of GBR12935 were 3.7 nM, 289 nM, and 1261 nM for these same transporters. This demonstrates that the addition of a single methylene group in the piperazine ring results in a compound with similar affinity but significantly higher selectivity for the dopamine transporter. LR1111 increased motoric activity in rats after intravenous administration. These indicate that LR1111 is a potent and highly selective inhibitor of the dopamine transporter.

Animals↗
PubMed1993

Independent associations between plasma lipoprotein subfraction levels and the course of coronary artery disease in the St. Thomas' Atherosclerosis Regression Study (STARS).

Associations between plasma lipoprotein subfractions and changes in coronary artery diseases (CAD) were examined in 74 men who completed the St. Thomas' Atherosclerosis Regression Study (STARS). Plasma lipoproteins were isolated by stepwise, preparative ultracentrifugation at repeated intervals during the 38-month trial. Paired coronary angiograms were quantitatively analyzed by a computerized method. In univariate linear regression analysis, changes in mean absolute width (delta MAWS) and minimum absolute with (delta MinAWS) of coronary segments were significantly correlated with in-trial concentrations of cholesterol in intermediate-density lipoprotein ([IDL] d = 1.006 to 1.019 kg/L), low-density lipoprotein ([LDL2] d = 1.019 to 1.040 kg/L; LDL3, d = 1.040 to 1.063 kg/L), and high-density lipoprotein ([HDL3] d = 1.125 to 1.210 kg/L) subfractions; no significant associations were found with other lipoproteins. IDL, LDL3, and HDL3 cholesterol were then selected for multiple linear regression analysis because these variables were not co-correlated and because they attained a significance of P less than or equal to .1 in univariate regression. In this analysis, only LDL3 cholesterol level was a significant negative predictor (P < .05) of both delta MAWS and delta MinAWS; a positive association between delta MinAWS and HDL3 cholesterol level just failed to reach conventional statistical significance (P = .066). Correlations between changes in coronary luminal dimensions and LDL3 cholesterol level were independent of age, smoking, weight, and blood pressure. Most patients showing regression of coronary atherosclerosis had an LDL3 cholesterol level of less than 1.8 mmol/L. The findings suggest that LDL3 is the plasma lipoprotein subfraction that exerts the single most powerful effect on the course of CAD in middle-aged men with hypercholesterolemia.

Analysis of Variance↗
PubMed1993

Prediction of early symptomatic recurrence after intestinal resection in Crohn's disease.

OBJECTIVE: This study was performed to identify clinical criteria that may help recognize patients with Crohn's disease who are at high risk for early symptomatic postoperative recurrence. SUMMARY BACKGROUND DATA: Currently, no reliable criteria are available to help recognize patients who are prone to experience early symptomatic recurrence. METHODS: One hundred sixty-four patients undergoing intestinal resection for Crohn's disease at the Mount Sinai Hospital between 1976 and 1989 were studied prospectively. Patients with symptomatic recurrent disease within 36 months were defined as having an early recurrence. RESULTS: Multivariate analysis revealed that the number of anastomoses was the most important prognostic indicator (p = 0.001), followed by inflammation at the resection margins (p < 0.05). Patients requiring an ileostomy had a significantly lower early recurrence rate than those having single or multiple anastomoses. There was no significant correlation between inflammation at the margins and early recurrence in patients requiring an ileostomy (n = 38), or a single anastomosis (n = 98). When the margins were examined in the 28 patients with 2 or more anastomoses, 10 of 11 patients (91%) with inflammation at either margin experienced early recurrence. Patients having multiple anastomoses with normal margins had the same recurrence rate as patients with single anastomosis (42%). CONCLUSIONS: Patients with extensive Crohn's disease requiring multiple resections with anastomosis, especially when microscopic inflammation is present at the margins, are at very high risk for symptomatic early recurrence. Ileostomy seems to be associated with a significantly lower early recurrence potential than anastomosis. Further study is needed to determine whether avoidance of multiple anastomosis and adjuvant medical treatment can alter the course of the disease after intestinal resection in patients at high risk for early symptomatic recurrence.

Adolescent↗
PubMed1993

Low bone mineral density at axial and appendicular sites in amenorrheic athletes.

Amenorrheic athletes have low axial bone-mineral density (BMD, g.cm-2). We compared 12 amenorrheic and 9 eumenorrheic women athletes to determine whether athletes with amenorrhea have lower BMD in other skeletal regions, including weight-bearing lower limbs. BMD was measured by dual energy x-ray and single photon absorptiometry. Both groups had similar age, body mass, and exercise quantity. Women with amenorrhea missed 86.3 +/- 58.3 menstrual periods since menarche. BMD was lower in the amenorrheic vs eumenorrheic subjects for the lumbar spine (0.928 +/- 0.056 vs 1.050 +/- 0.110, P < 0.005), whole body (1.032 +/- 0.05 vs 1.09 +/- 0.06, P < 0.05), most regions of the whole body (P < 0.05-0.001), all areas of the proximal femur (P < 0.005), and at the femoral mid-shaft (1.333 +/- 0.109 vs 1.491 +/- 0.088, P < 0.005). No significant differences were detected at the mid-radius and tibial shaft. The best predictors of BMD were years of regular menstruation for lumbar spine; and years of amenorrhea for hip, femoral mid-shaft, and whole body. We conclude that low BMD in athletes with amenorrhea is not limited to the axial skeleton but is also present in other regions including appendicular weight-bearing bones.

Absorptiometry, Photon↗
PubMed1993

Obscure gastrointestinal bleeding.

I want to convey the notion that enteroscopy has opened many doors, and continues to open up more doors, in understanding and diagnosing diseases of the small intestine. The true nature of small-bowel angiodysplasia is still unanswered. It seems unlikely that the lesions in the small bowel are similar to the lesions that Scott Boley talks about in the right colon. I doubt that the intermittent obstruction to venous outflow, theorized in the colon, is the pathophysiologic change in the small intestine. Those studies, trying to look for the changes that Boley described, need to be done. We are trying to better characterize angiodysplasia of the small intestine, understanding where they occur, with how many lesions, and whether they are associated with any other illnesses. We are looking at the association of small-bowel vascular lesions with lesions in the stomach and colon. Enteroscopy will in the future, we hope, answer these questions. Enteroscopy, especially push enteroscopy, can help us with the treatment of angiodysplasias. We are now evaluating new instruments that reach not just two feet beyond the ligament of Treitz, but the entire jejunum, reaching 6 feet beyond the ligament of Treitz (16). Enteroscopy facilitates clinical research, can be used in patient care, and guides treatment.

Aged↗
PubMed1992

Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS)

To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infarction. Another intervention group received diet and cholestyramine, to determine the effect of a greater reduction in circulating cholesterol concentrations. 90 men with coronary heart disease (CHD), who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to receive usual care (U, controls), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC) mmol/l. The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%), whereas the proportion who showed an increase in luminal diameter rose significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm in group D, and increased by 0.103 mm in group DC (p less than 0.05), with improvement also seen in the minimum width of segments, percentage diameter stenosis, and edge-irregularity index in intervention groups. The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period. Both interventions significantly reduced the frequency of total cardiovascular events. Dietary change alone retarded overall progression and increased overall regression of coronary artery disease, and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter. These findings support the use of a lipid-lowering diet, and if necessary of appropriate drug treatment, in men with CHD who have even mildly raised serum cholesterol concentrations.

Angina Pectoris↗
PubMed1992

A genetic model for control of hypertriglyceridemia and apolipoprotein B levels in the Johns Hopkins colony of St. Thomas Hospital rabbits.

The St. Thomas Hospital (STH) rabbit has been previously shown to have a Mendelian form of hypertriglyceridemia, accompanied by accelerated atherosclerosis, and these animals may serve as a useful model for human dyslipoproteinemia syndromes. Here we describe the establishment of a new colony of these STH animals, and present genetic analysis of triglyceride (TG) and apolipoprotein B (apoB) levels. Segregation analysis of TG in 39 STH animals and 24 controls gave evidence of Mendelian segregation for an allele leading to both elevated TG levels and increased variability in these levels. Predicted means from the most parsimonious model for the Johns Hopkins STH colony were quite similar to that seen in the original London colony, and this model accounted for 80% of the variation in TG seen in the sample. This hypertriglyceridemia locus indirectly influenced the mean apoB levels in these rabbits, and segregation analysis of mean apoB levels suggested a second locus controlling apoB levels. Analysis of residual apoB levels (adjusted for predicted effects of the hypertriglyceridemia locus) revealed clearer evidence for a second locus controlling mean apoB levels in this colony. Arguments for two distinct genetic mechanisms operating in these STH animals are presented.

Animals↗
PubMed1992

Inter-organizational responses to AIDS: a case study of the Worcester AIDS Consortium.

This case study focuses on development and community coordination of AIDS-related services and on coalition building. Its subject is the Worcester (Massachusetts) AIDS Consortium. The objectives are to: (1) describe the environmental conditions and pre-existing networks which facilitated the formation of the Worcester AIDS Consortium; (2) articulate processes which occurred during the formative, organizational and operational phases of the Worcester AIDS Consortium's development; (3) explore social and community goals and Consortium activities; and (4) document Consortium accomplishments. Data were collected through key informant interviews and review of archival materials. Information about the Worcester AIDS Consortium experience is compared with concepts and principles suggested by organizational theories and frameworks.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Plasma triglyceride and high density lipoprotein cholesterol as predictors of ischaemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies.

OBJECTIVE: To assess the roles of plasma triglyceride and high density lipoprotein (HDL) cholesterol concentrations in predicting ischaemic heart disease. DESIGN: Two prospective cohort studies with common core protocols. SETTING AND PARTICIPANTS: Both cohorts are 100% samples of middle aged men. In Caerphilly the 2512 men were living within a defined area. In Speedwell the 2348 men were registered with local general practitioners. MAIN OUTCOME MEASURES: Fasting blood samples were taken at initial examination and plasma lipid concentrations were measured. Major ischaemic heart disease events were assessed from hospital notes, death certificates, and electrocardiograms. RESULTS: At first follow up, after an average of 5.1 years in Caerphilly and 3.2 years in Speedwell, 251 major ischaemic heart disease events had occurred. Men with triglyceride concentrations in the top 20% of the distribution had a relative odds value for ischaemic heart disease of 2.3 (95% confidence interval (95% CI) 1.3 to 4.1) compared with men in the bottom 20%, after adjusting for both plasma total and HDL cholesterol, and non-lipid risk factors. Men in the lowest 20% of the distribution of HDL cholesterol concentration had a relative odds value of 1.7 (95% CI 1.0 to 2.8) compared with the top 20%, after adjustment was made for total cholesterol and triglyceride concentrations, and non-lipid risk factors. These relations were not caused by beta blockers, which were being taken by 5% of the men. CONCLUSIONS: Plasma triglyceride concentration predicts major ischaemic events after allowance is made for total and HDL cholesterol concentrations and other risk factors. In these populations, triglyceride is a more important predictor than total cholesterol concentration.

Adrenergic beta-Antagonists↗
PubMed1992

One year experience in the treatment of familial hypercholesterolaemia with simvastatin.

Patients with heterozygous familial hypercholesterolaemia (FH) have a substantially increased risk of atherosclerosis due to very high plasma levels of cholesterol. Recent evidence has shown that coronary heart disease in these patients may regress with lipid-lowering therapy. In this study the efficacy and safety of simvastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A, was investigated in 30 patients with FH over a period of one year. Substantial reductions in the plasma concentrations of total cholesterol (-28%), low-density lipoprotein (LDL) cholesterol (-32%), intermediate-density lipoprotein (IDL) cholesterol and apolipoprotein (apo) B (-33%) were achieved with 20 mg/day of simvastatin; there were no significant changes in triglycerides high-density lipoprotein cholesterol or apo A. In contrast to previous studies, 40 mg/day of simvastatin did not result in a further statistically significant fall in LDL cholesterol, IDL cholesterol or apo B in the group as a whole. The drug was well tolerated and no adverse clinical or laboratory events were recorded. In particular, no ophthalmological, hepatic or renal disorders were observed and there were no sleep disturbances. We conclude that simvastatin is an efficacious and safe drug to treat patients with heterozygous FH and that rarely will the dose need to be increased above 20 mg/day.

Adult↗
PubMed1992

Influx in vivo of low density, intermediate density, and very low density lipoproteins into aortic intimas of genetically hyperlipidemic rabbits. Roles of plasma concentrations, extent of aortic lesion, and lipoprotein particle size as determinants.

To compare the atherogenic potential of low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) under conditions where plasma levels of these lipoproteins are elevated, the influx of cholesterol in these lipoproteins into the aortic intima was measured in vivo in genetically hyperlipidemic rabbits from the St. Thomas's Hospital strain, an animal model that shares many of the features of the human disorder familial combined hyperlipidemia. Univariate linear regression showed that the arterial influx of LDL cholesterol (n = 25), IDL cholesterol (n = 14), and VLDL cholesterol (n = 10) was positively and linearly associated with plasma concentrations of LDL cholesterol in the range 0.2-6.4 mmol/l, of IDL cholesterol in the range 0.1-7.0 mmol/l, and of VLDL cholesterol in the range 0.7-8.5 mmol/l, respectively, and also with the extent of lesions in the arterial intima in the range 0-100% of the surface area. Multiple linear regression suggested that the arterial influx of LDL, IDL, and VLDL cholesterol was linearly dependent on plasma concentration, independent of lesion size. Furthermore, it appeared that the arterial influx of the three lipoproteins was linearly dependent on the extent of the lesions, independent of lipoprotein concentration. When influx was normalized for plasma concentration (intimal clearance) and for lesion size (compared within the same aorta), the intimal clearance of the larger IDL and VLDL particles was 15-35% less than that of the smaller LDL particles. These findings suggest that the quantitatively most important mechanism for transfer of plasma lipoproteins into the arterial intima involves nonspecific molecular sieving and that at elevated plasma levels, IDL and VLDL share with LDL the potential for causing atherosclerosis.

Animals↗
PubMed1992

AANA journal course: update for nurse anesthetists--blood-brain barrier function alteration during anesthesia.

With some exceptions, the entire central nervous system (CNS) is encircled by the blood-brain barrier (BBB). The function of the BBB is to sustain the CNS in a homeostatic environment. A variety of occurrences during an anesthetic have been shown to disrupt the BBB. Alterations of electrolytes or drugs in the systemic circulation at the time of a disruption in the BBB could result in an abnormal concentration of these molecules in the CNS leading to abnormal CNS neuronal transmissions which may manifest as both intraoperative or postoperative problems.

Anesthesia↗