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Biomedical subjects

R Lew

Publications and source records attributed to R Lew.

At least 19 recordsLinked to original sources
PubMed1992

Microheterogeneity of dopamine transporters in rat striatum and nucleus accumbens.

Previously we have shown that the [125I]DEEP-labeled dopamine transporter from the rat nucleus accumbens has a higher apparent molecular weight than that from striatum. The present study confirms and extends these observations. Experiments with nucleus accumbens showed [125I]-DEEP to specifically bind to a protein with an apparent molecular weight of 76 kDa and with the pharmacological properties of the dopamine transporter. In exoglycosidase studies, treatment with neuraminidase, but not alpha-mannosidase, reduced the apparent molecular weight of the dopamine transporter from both the striatum and nucleus accumbens; however, a difference in the apparent molecular weight was still observed. N-Glycanase treatment, on the other hand, did reduce the apparent molecular weight of the dopamine transporters from the two regions to a similar value, approximately 56 kDa. In radioligand binding studies examining the effect of partial deglycosylation on striatal dopamine transporters, neuraminidase did not affect specific [3H]WIN 35,428 binding at 4 and 40 nM concentrations. In conclusion, the present study demonstrates that the difference in the apparent molecular weight of the dopamine transporter from these two regions is due to a difference in glycosylation and that the dopamine transporter from both regions contains similar amounts of sialic acid in their carbohydrate structure. Furthermore, the present data also indicate that the polypeptide portion of the dopamine transporter from both regions could be the same gene product.

Animals↗
PubMed1992

Probes for the cocaine receptor. Potentially irreversible ligands for the dopamine transporter.

Several potentially irreversible ligands (i.e., wash-resistant binding inhibitors) for the cocaine receptor site on the dopamine transporter, derived from (-)-cocaine or 3 beta-phenyltropan-2 beta-carboxylic acid methyl ester (WIN 35,065-2), were prepared and shown to produce wash-resistant inhibition of [3H]-3 beta-(p-fluorophenyl)tropan-2 beta-carboxylic acid methyl ester ([3H]WIN 35,428) binding. All the compounds prepared had the same absolute configuration as cocaine; they include analogues possessing chemically reactive groups such as the isothiocyanato and bromoacetamido as well as photoactive azido groups. The potentially irreversible ligands, as well as all the intermediates prepared in this study, were evaluated for their ability to inhibit the binding of [3H]WIN 35,428 in coincubation experiments. Of the potentially irreversible ligands, 3 beta-(p-chlorophenyl)tropan-2 beta-carboxylic acid 2-[p-(bromoacetamido)phenyl]ethyl ester (6c) had the highest apparent potency. The potentially irreversible ligands were also preincubated, and inhibition of [3H]WIN 35,428 binding was determined both before and after washing the ligand-exposed tissues. The most effective ligands in this regard were 3 beta-(3-iodo-4-azidophenyl)tropan-2 beta-carboxylic acid methyl ester (5) and 3 beta-(p-chlorophenyl)tropan-2 beta-carboxylic acid 2-(3-iodo-4-azidophenyl)ethyl ester (6d). The structure-activity relationships of these data are discussed.

Animals↗
PubMed1992

A cocaine analog and a GBR analog label the same protein in rat striatal membranes.

Because some evidence suggests that cocaine and GBR12935 bind to different sites, we utilized photoaffinity probes from both classes of compounds to see if they label the same protein. [125I]RTI-82 a cocaine analog, and [125I]DEEP, a GBR analog, labeled protein(s) showing the same molecular weight, a similar pharmacological profile and a similar sensitivity to neuraminidase.

Animals↗
PubMed1992

Relationship between immune response to melanoma vaccine immunization and clinical outcome in stage II malignant melanoma.

The authors investigated whether there was a relationship between the induction of a delayed-type hypersensitivity (DTH) response to melanoma vaccine immunization and disease recurrence. They studied prospectively 94 evaluable patients with surgically resected Stage II malignant melanoma who were immunized to a partially purified, polyvalent, melanoma antigen vaccine. The DTH response to skin tests to the vaccine was measured before treatment and at the fourth vaccine immunization. Vaccine treatment induced a strong DTH response in 29 (31%) patients, an intermediate response in 24 (25%), and no response in 41 (44%). The median disease-free survival (DFS) of patients with a strong, intermediate, and no DTH response to vaccine immunization was more than 72 months, 24 months, and 15 months, respectively. The relationship between an increase in the DTH response and a prolonged DFS was statistically significant (P = 0.02); clinically meaningful (the median DFS of patients with a strong DTH response was 4.7 years longer than that of nonresponders); and, by multivariate analysis, independent of disease severity or overall immune competence. These findings suggest, but do not prove, that vaccine treatment can slow the progression of melanoma in some patients.

Adult↗
PubMed1992

Estrogen receptor immunohistochemistry in carcinoma in situ of the breast.

Although estrogen receptor (ER) content and its clinical significance have been extensively evaluated in invasive breast cancer, ER expression in carcinoma in situ (CIS) of the breast and its correlates are less well understood. Thus, using an indirect immunoperoxidase technique and paraffin-embedded tissue, the authors studied ER expression in 100 breast tumors containing CIS with or without invasive carcinoma. The percentages of positive and of strongly positive nuclei were compared among histologic categories of CIS and between CIS and invasive carcinoma. The relationships between histologic features of CIS (cell size, nuclear pleomorphism, necrosis, extent of CIS) the patient's age, and the ER status of CIS also were evaluated. ER expression in pure CIS was compared with that of CIS with adjacent invasive carcinoma. Significant differences were observed between comedo CIS, which was frequently ER negative, and non-comedo and lobular CIS, which usually were positive. A predominance of large cells, independently from other features, was the best morphologic predictor of ER negative status in CIS. ER in CIS correlated with ER in invasive carcinoma in 98% of cases (r2 = 0.677). CIS without invasive carcinoma was more frequently ER weak or negative than CIS associated with invasive carcinoma. There was no difference in the overall percentage of nuclear staining in CIS of women of premenopausal versus postmenopausal age; however, a higher proportion of strongly positive cells occurred in the postmenopausal group. The authors conclude that the ER expression in CIS correlates with pathologic features of differentiation and is similar to that of invasive carcinoma.

Adult↗
PubMed1992

Suspected low-grade glioma: is deferring treatment safe?

Deferring therapeutic intervention may worsen outcome in patients with low-grade glioma. To address this issue, we searched our records and located 26 patients who presented with a transient event (most often seizures), who had radiographic evidence strongly suggestive of a low-grade primary supratentorial neoplasm, and for whom all therapy (except anticonvulsants) was withheld until deemed necessary (WAIT Group). For comparison, 20 patients who presented similarly, but for whom immediate intervention was elected, served as a comparison group (NOWAIT Group). Fifteen patients in the WAIT Group required eventual surgery or radiation therapy at intervals ranging from 4 to 123 months (median, 29 months) between radiographic diagnosis and therapeutic intervention; reasons for such intervention included increasing tumor size, uncontrollable seizures, or malignant transformation of tumor. At surgery, there was an increased number of anaplastic tumors noted in the patients in the WAIT Group (p less than 0.02); nevertheless, if the rate of malignant transformation was examined from time of diagnosis, no differences were noted between the patients in the two groups. Similarly, no difference in survival or quality of life could be demonstrated from time of radiographic diagnosis. Therefore, we could not demonstrate that deferring therapy worsens outcome for these patients.

Brain Neoplasms↗
PubMed1992

The relationship between ultrasound and densitometric measurements of bone mass at the calcaneus in women.

Broadband ultrasound attenuation (BUA) of the calcaneus predicts axial density in women and is decreased in women who sustain hip fractures. To determine the relationship between ultrasonic and densitometric assessments of bone mass at the same site, BUA and velocity of sound (VOS) were correlated with bone density as measured by dual energy x-ray absorptiometry (DXA) at the calcaneus in 64 Caucasian women aged 35-83 years. BUA, VOS, and bone density in these women decreased annually as a function of age by 1.0%, 0.3%, and 0.9%, respectively. Holding age, years since menopause, height and weight constant, BUA correlated with VOS (r = 0.74, P < 0.001), and calcaneal density correlated with BUA (r = 0.73, P < 0.001) and with VOS (r = 0.66, P < 0.01). The results indicate that both BUA and VOS measurements reflect density at the calcaneus, but suggest that they measure properties of bone other than density and different from each other. The assessment of these additional properties may be useful in the prediction of fracture risk.

Absorptiometry, Photon↗
PubMed1992

Histopathologic differences in the photoaging process in facial versus arm skin.

We used clinical criteria to study skin biopsy specimens with mild to moderate photoaging taken from the face and dorsal forearms of 74 Caucasian volunteers between the ages of 30 and 50. Facial skin had a greater number of granular cell layers, a higher degree of keratinocytic atypia, and more often showed a compact stratum corneum than arm skin. Furthermore, the dermis of facial skin had a more extensive perivascular and perifollicular lymphocytic infiltrate, more perifollicular fibrosis, a greater number of mast cells and melanophages, and thinner vascular walls than forearm skin. This study demonstrated that the photoaging process is different for face and arm skin. Appreciation of these differences should permit more refined studies of photoaging and the development of more efficient therapies.

Adult↗
PubMed1992

Relationship between serum total cholesterol, infarct size, and early clinical outcome following acute myocardial infarction.

Strategies designed to decrease coronary heart disease (CHD) associated morbidity and mortality have focused primarily on established risk factors, including hypercholesterolemia, systemic hypertension, and cigarette smoking. Indeed, primary and secondary intervention trials have provided evidence for cholesterol lowering as an efficient method of CHD risk reduction. To test the hypothesis that serum total cholesterol influences the clinical outcome following acute myocardial infarction, infarct size, left ventricular ejection fraction, infarct-related vessel patency, and in-hospital cardiac events were determined in 106 consecutive patients given thrombolytic therapy within 5 h of symptom onset. Cumulative 48-hour creatine kinase (CK) release, peak CK, and calculated infarct size did not differ significantly between patients with an admitting serum total cholesterol level less than 200 mg/dl (group 1) and those with a cholesterol level greater than 250 mg/dl (group 2). Total cholesterol did not correlate with either cumulative CK release, peak CK, infarct size, vessel patency, or left ventricular ejection fraction. The vessel patency correlated inversely with cumulative CK release (r = -0.27; p = 0.03) and directly with left ventricular ejection fraction (r = 0.24; p = 0.03). The incidence of in-hospital cardiac events including recurrent infarction, congestive heart failure, and death was 6.9, 13.9, and 2.6%, respectively, and did not differ significantly between patient groups. Thus, although serum total cholesterol has been shown to influence CHD incidence, morbidity, and overall mortality, the findings of our study suggest that it does not impact directly on infarct size, left ventricular function, or in-hospital clinical outcome among patients sustaining acute myocardial infarction.

Cholesterol↗
PubMed1992

Trends in prevalences of behavioral risk factors: recent Hawaiian experience.

Recent time trends were studied for the prevalences of behavioral risk factors in Hawaii during the 5-year period from 1986 through 1990. The presence of linear time trend was analyzed by the multiple logistic regression method on weighted data, adjusting for confounding factors. The risk factors studied were seatbelt nonuse, lack of exercise, obesity, hypertension, smoking, acute drinking, chronic drinking, and driving while intoxicated. Seatbelt nonuse showed a significant decline, from 8.6% to 4.8%, with a mean annual decrease of 0.9 percentage point. Lack of exercise and obesity increased steadily, from 48.0% to 62.4% and from 16.7% to 21.6%, respectively, with respective annual mean increases of 3.3 and 1.4 percentage points.

Chronic Disease↗
PubMed1992

Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.

The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.

Blood Loss, Surgical↗
PubMed1992

Computer applications in quality assurance.

The computer is rapidly becoming an essential tool for the physician. Proper use of computers in practice will help physicians achieve both higher levels of quality and greater consistency in patient care. Only with computers can physicians rapidly access and process all the data now needed to best address the needs of their patients. As computer use in practice becomes the standard, the inability to use these tools will be incompatible with quality care. The computer is rapidly becoming essential to modern medical management strategies that demand efficiency, accuracy, and cost effectiveness in response to patient demands for assurance that quality care is being delivered.

Computer Systems↗
PubMed1991

Dopamine transporter: deglycosylation with exo- and endoglycosidases.

The dopamine transporter from rat caudate-putamen was photolabeled with [125I]DEEP as previously described. Treatment of photolabeled membranes with neuraminidase and N-glycanase reduced the molecular weight of the [125I]DEEP photolabeled dopamine transporter complex, whereas treatment with alpha-mannosidase had no effect. The solubilized [125I]DEEP photolabeled dopamine transporter complex readily bound to wheat-germ agglutinin but not to concanavalin-A sepharose columns. These results suggest that the carbohydrate moiety of the dopamine transporter is N-linked and contains significant quantities of sialic acid but not high mannose residues. A DEEP binding protein was readily detectable in other brain regions including the nucleus accumbens and olfactory tubercle, but not in the prefrontal cortex, olfactory bulb or hypothalamus under similar conditions. The DEEP binding protein in the other brain regions was similar to that in the striatum.

Animals↗
PubMed1991

Broadband ultrasound attenuation of the calcaneus predicts lumbar and femoral neck density in Caucasian women: a preliminary study.

Recent studies have demonstrated the ability of ultrasound techniques to differentiate normal and osteoporotic women. To define the ability of broadband ultrasound attenuation (BUA) of the calcaneus to predict axial bone mass, the ultrasound value was correlated with lumbar vertebral and femoral neck density in 22 Caucasian women. The three measures of bone mass inversely correlated with age: lumbar density (r = 0.54), femoral neck density (r = 0.65), and BUA (r = 0.73). BUA correlated with lumbar (r = 0.83) and femoral neck (r = 0.87) density. Lumbar vertebral density predicted femoral neck density with a standard error of estimate (SEE) of 0.07 g/cm2, and femoral neck density predicted lumbar density with a SEE of 0.09 g/cm2. BUA of the calcaneus was as effective as either axial bone mass measure in predicting the other value: the SEE for lumbar density was 0.09 g/cm2 while that for femoral neck density was only 0.06 g/cm2. The results of this preliminary study indicate that this rapid, radiation-free technique can accurately predict axial bone mass, and may be of value as an initial procedure to discriminate those women warranting more extensive radiologic evaluations.

Aged↗
PubMed1991

A rapid binding assay for solubilized dopamine transporters using [3H]WIN 35,428.

The cocaine analog [3H]WIN 35,428 was used to label digitonin-solubilized dopamine transporters from dog caudate nucleus. The assay consists of incubation of extracts with the ligand followed by separation of free from bound ligand by centrifugation after adding activated charcoal. Specific binding was observed in dog caudate but was absent in dog cerebellar extracts. Binding was linear with tissue, saturable, and of high affinity (Kd = 16 nM). In competition studies, soluble [3H]WIN 35,428 binding was inhibited strongly by mazindol, GBR 12909, and (-)-cocaine but only weakly by citalopram, desipramine, and (+)-cocaine; this is typical of binding to the dopamine transporter. Compared to assays using [3H]GBR 12935, (-)-cocaine was relatively more potent, suggesting that the cocaine and GBR 12935 binding sites are somewhat different. When soluble extract was chromatographed on a wheat germ agglutinin-Sepharose column, [3H]WIN 35,428 binding activity was eluted with N-acetylglucosamine in a manner similar to photoaffinity-labeled dopamine transporters.

Adsorption↗
PubMed1991

Heparin pharmacokinetics and in vitro anticoagulant activity in patients receiving nonionic radiographic contrast media.

Nonionic radiographic contrast media are used frequently in diagnostic and interventional angiography. However, there is concern that they may possess thrombogenic properties, and some studies have suggested that patients receiving nonionic contrast media are difficult to systemically anticoagulate with intravenous heparin. To investigate the potential effects of nonionic contrast media on systemic anticoagulation during diagnostic cardiac catheterization, pharmacokinetics and in vitro anticoagulant activity following a 3,000 U intravenous heparin bolus were assessed in 12 patients assigned randomly to either an ionic or a nonionic contrast agent. Independent of contrast agent, all patients exhibited biphasic (nonlinear) heparin pharmacokinetics characterized by an initial rapid disappearance phase, followed by a second slower phase. Each patient achieved a therapeutic plasma heparin concentration (greater than or equal to 0.2 U/ml) within 10 min of receiving the bolus, and maintained this level throughout the procedure. Heparin anticoagulant activity, as estimated by a standard activated partial thromboplastin time (APTT) was not affected differently by nonionic as compared with ionic contrast media (p greater than 0.05). Each patient rapidly achieved a level of systemic anticoagulation commonly considered therapeutic (APTT greater than or equal to 1.5 times the control), and maintained this level throughout the procedure. In both groups, APTT correlated directly with plasma heparin concentration (r = 0.95; p less than 0.0001), and inversely with the total amount of contrast media used during the procedure (r = -0.25; p = 0.01). Plasma heparin concentration did not correlate with total contrast media (r = -0.16; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1991

Effect of serum total cholesterol on hemorrhagic complications following thrombolytic therapy for acute myocardial infarction.

Despite the well-known and widely publicized adverse effects of hypercholesterolemia on the cardiovascular system, cholesterol is a vital component of cellular membranes, maintaining vascular integrity and normal platelet activatability. To test the hypothesis that a low serum total cholesterol concentration increases bleeding risk following thrombolytic therapy, a comparison of in-hospital hemorrhagic events was made between 132 patients with myocardial infarction divided into three distinct groups. Group 1 patients (n = 44) had an admitting serum total cholesterol of less than 200 mg/dl, while group 2 (n = 57) and group 3 (n = 31) patients had cholesterol levels of 200-249 and greater than or equal to 250 mg/dl, respectively. There were no significant differences between groups in either minor hemorrhagic events (p = 0.85), major hemorrhagic events (p = 0.73) or transfusion requirements (p = 0.45). In addition, the primary sites of bleeding did not differ. Over the 2-year study period, a total of four intracerebral events were identified. As with minor and other major hemorrhagic events, an association with serum total cholesterol and intracerebral hemorrhage was not observed (p = 0.29). However, advanced age (greater than 65 years; p = 0.04) and a total dose of recombinant tissue-type plasminogen activator in excess of 1.5 mg/kg body weight (p less than 0.001) were identified by multivariate analysis as risk factors for intracerebral hemorrhage. Thus, although cholesterol is vital for maintaining vascular integrity and normal hemostasis, relatively low serum levels are not a risk factor for hemorrhagic complications following thrombolytic therapy.

Aged↗