Search PubMed⌕ Search

Biomedical subjects

L Smith

Publications and source records attributed to L Smith.

At least 361 records · Page 20Linked to original sources
PubMed1992

Characterization of rat encephalitogenic T cells bearing non-V beta 8 T cell receptors.

In this study, we demonstrate that T cell lines specific for a synthetic peptide representing sequence 87 to 99 of myelin basic protein (MBP) are encephalitogenic in Lewis rats. However, unlike syngeneic T cells specific for MBP residues 68 to 88 which exclusively use V beta 8 in their antigen receptors, these cells do not. None of the 10 T cell lines and T hybridomas specific for MBP (87-99) used V beta 8 in their T cell receptors. Our results document for the first time that rat encephalitogenic T cells do not exclusively use V beta 8 in T cell receptors that rat encephalitogenic T cells specific for MBP (87-99) are heterogeneous and that MBP (87-99) contains at least two epitopes for rat T cells.

Amino Acid Sequence↗
PubMed1992

Gamma probe location of 111indium-labeled B72.3: an extension of immunoscintigraphy.

Eight colorectal and 5 ovarian cancer patients were evaluated with preoperative immunoscintigraphy and intraoperative gamma probe detection of 111indium-labeled monoclonal antibody B72.3. Immunoscintigraphy detected the presence of tumor in every patient shown to have tumor at surgery. There was one false-positive scan. A total of 21 pathologically verified lesions were identified at surgery in the 11 patients with tumor. Immunoscintigraphy localized 12 (57%) and intraoperative gamma probe detection located 17 (81%) of the lesions. Intraoperative probe detection located 6 of 8 lesions smaller than 1 cm and 3 lesions that were not identified on initial surgical exploration. The gamma probe offers information that is complementary to immunoscintigraphy in that (1) it aids the surgeon in locating intra- and extra-abdominal lesions previously identified by immunoscintigraphy, (2) it locates lesions too small to be seen by immunoscintigraphy alone, (3) it locates lesions that otherwise might be missed at surgery, and (4) it provides objective evidence for adequacy of surgical resection of cancer in the abdominal cavity.

Aged↗
PubMed1992

Absence of the dawn phenomenon and abnormal lipolysis in type 1 (insulin-dependent) diabetic patients with chronic growth hormone deficiency.

To determine the role of growth hormone in overnight insulin requirements and lipolysis, five patients with chronic growth hormone deficiency and Type 1 (insulin-dependent) diabetes mellitus and six control patients with diabetes were each studied on two separate nights. Insulin was infused at a variable rate throughout one night to maintain euglycaemia and fixed at 04.00 hours on another. During the variable infusion, euglycaemia was maintained in control patients by a 36% increase in insulin infusion rate between 03.00 and 08.00 hours while a 46% decrease in the rate was required in growth hormone deficient patients (p less than 0.02). Despite this difference, mean free insulin values were equivalent. This finding is suggestive of increased insulin clearance in growth hormone sufficient patients. Glucose levels rose in control and fell in growth hormone deficient patients when insulin infusion rates were fixed at 04.00 hours. Glycerol production and non-esterified fatty acid concentrations were significantly lower in the growth hormone deficient diabetic patients, p less than 0.001, and when normalized with a heparin infusion, had no effect on insulin requirements. We conclude that: (1) growth hormone contributes to the development of the "dawn phenomenon," possibly by increasing insulin clearance (2) growth hormone helps sustain nocturnal lipolysis in Type 1 diabetes and (3) non-esterified fatty acids are not involved in the dawn phenomenon.

3-Hydroxybutyric Acid↗
PubMed1992

Transanal endoscopic microsurgery.

Transanal endoscopic microsurgery (TEM) has emerged as a minimally invasive means of resecting rectal tumors. Developed in Germany and now being used with increasing frequency in the United States, TEM utilizes a 40-mm operating rectoscope, which is sealed with an airtight facepiece. Carbon dioxide is constantly infused, thereby distending the rectum and maintaining visibility. A variety of instruments, such as tissue graspers, a high-frequency knife, suction, and needle holders, are inserted through the facepiece. Adenomas that are small, large, or even circumferential, as well as selected carcinomas up to 24 cm, can be removed with TEM instrumentation. The optics provide sixfold magnification, and this, combined with the constantly distended operative field, allows for a precise excision of the tumor as well as closure of the wound. For lesions in the mid and upper rectum, TEM is an alternative to a transsacral or transabdominal approach, with subsequently shorter hospital stay and fewer complications.

Adenoma↗
PubMed1992

Reversible desensitization of fibroblasts to cadmium receptor stimuli: evidence that growth in high zinc represses a xenobiotic receptor.

The xenobiotic Cd2+ triggers the production of inositol trisphosphate and releases stored Ca2+ in certain cell types, apparently by binding to a zinc site in the external domain of an "orphan" receptor (no known endogenous stimulus). Cd2+ and bradykinin evoke similar spikes in cytosolic free Ca2+. Growth in high Zn2+ (100-200 microM) abolished the free Ca2+ spike evoked by Cd2+ without affecting the spike produced by bradykinin. Growth in high Zn2+ almost abolished Cd(2+)-evoked production of [3H]inositol mono-, bis-, and trisphosphate. Bradykinin-evoked [3H]inositol phosphate production was not affected by growth in high Zn2+. Growth in high Zn2+ nearly prevented the stimulation of 45Ca2+ efflux by Cd2+ without affecting the stimulation of 45Ca2+ efflux by bradykinin or histamine. Removing Zn2+ from the culture medium and incubating the cells for several hours fully restored responsiveness to Cd2+. Cycloheximide, actinomycin D, or tunicamycin prevented the restoration of Cd2+ responsiveness, indicating that resensitization requires macromolecular synthesis. Growth in high Zn2+ reversibly abolished Ca2+ mobilization evoked by two additional stimuli: a decrease in extracellular pH or Na+ concentration. These findings support the hypothesis that the three stimuli (Cd2+ or a decrease in external pH or Na+ concentration) activate the same orphan receptor. Growth in high Zn2+ apparently desensitizes the cells to the Cd2+ receptor stimuli by repressing receptor synthesis.

Bradykinin↗
PubMed1992

The integration of computed tomography and magnetic resonance imaging in treatment planning for gynecologic cancer.

Both CT and MRI may play an important role in the initial assessment and subsequent management of patients with gynecologic cancer. The different capabilities of these examinations make the choice of test dependent on what portion of the body is visualized (e.g., chest, upper abdomen, or pelvis) and what information is sought. Body imaging can be scheduled appropriately when the findings from the study will have a significant impact on patient management (e.g., operative versus nonoperative management, selection of treating physician, and initial modality of treatment). However, the limitations of each modality must be appreciated. In general, a negative CT or MRI will not exclude the possibility of small volume disease involvement, and a critical positive study should, when practical, be histologically confirmed. Neither test stands alone, but each plays a role when integrated with careful clinical history, physical examination, and other laboratory and radiologic examinations.

Endometrial Neoplasms↗
PubMed1992

Ethical issues in interviewing.

A study of the help-seeking behaviours of alcohol dependent and problem drinking women raised a number of ethical issues. It had been anticipated that the design of the study and the construction and approval of appropriate consent forms would eliminate the majority of problems. While this was true, a number of unforeseen points emerged during the course of the study related to interviewing women, discussing emotive issues and the responsibilities of the researcher vis-à-vis their samples. This paper discusses the issues raised using specific examples drawn from the research study.

Alcoholism↗
PubMed1992

Ca2+ influx via Na(+)-Ca2+ exchange in immortalized aortic myocytes. I. Dependence on [Na+]i and inhibition by external Na+.

We have found that immortalized aortic myocytes have high Na(+)-Ca2+ exchange activity that is similar in amount to that of low-passage myocyte cultures. Replacing all external Na+ with K+ slightly increased 45Ca2+ uptake in cells with basal Na+ and greatly increased 45Ca2+ uptake in cells with increased intracellular Na+. External Na+ competitively inhibited 45Ca2+ uptake (inhibition constant approximately 10 mM). The dependence of exchange activity on intracellular Na+ was sigmoidal. The 50% maximum concentration (K0.5) for Na+ was 33 +/- 1 mmol/l cell water space. The Hill coefficient was 2.9 +/- 0.2, which is consistent with a stoichiometry of 3 Na+/1 Ca2+. Cytosolic free Na+ was estimated from the ratio of sodium-binding benzofuran isophthalate (SBFI) fluorescence and an in vivo calibration curve. Sulfinpyrazone, an inhibitor of anion transport, markedly increased the SBFI content of the cells without affecting cell Na+. Cytosolic free Na+ was 9 mM under basal conditions. Because free Na+ did not differ significantly from total Na+, little or no Na+ is bound or compartmentalized in these cells. The complete replacement of extracellular Na+ with K+ fails to evoke appreciable Ca2+ influx, at least in part, because of the low cell Na+ concentration relative to the K0.5 of the exchanger and its sigmoid dependence on Na+.

Animals↗
PubMed1992

Ca2+ influx via Na(+)-Ca2+ exchange in immortalized aortic myocytes. II. Feedback inhibition by [Ca2+]i.

Depolarization with 50 mM K+ evoked a spike in cytosolic free Ca2+ ([Ca2+]i) and increased 45Ca2+ uptake in immortalized aortic myocytes. The following evidence indicates that the electrogenic Na(+)-Ca2+ exchanger caused the Ca2+ influx that was evoked by K+ depolarization. First, K+ depolarization had no effect on [Ca2+]i and 45Ca2+ uptake in cells with basal Na+ but strikingly increased both in Na(+)-loaded cells. Second, the [Ca2+]i increases produced by K+ depolarization depended hyperbolically on external Ca2+ (50% maximum concentration = 1.5 mM). Third, the increases in [Ca2+]i and 45Ca2+ uptake were greater when external Na+ was replaced with K+ rather than with N-methyl-D-glucamine or choline. A series of K+ depolarizations elicited a sequence of [Ca2+]i spikes, provided there was a short incubation at 5 mM K+ between the depolarizations. A prior K+ depolarization almost abolished the 45Ca2+ uptake response to K+ depolarization. The inhibition of exchange activity by a prior K+ depolarization required external Ca2+ and was completely reversible. A prior incubation with angiotensin II, platelet-derived growth factor, or ionomycin also inhibited exchange activity. Moderate [Ca2+]i increases probably feedback inhibit Ca2+ influx via the exchanger by a kinetic mechanism. Inactivation of the exchanger, together with Ca2+ extrusion or sequestration, causes the rapid decrease in [Ca2+]i from the peak evoked by depolarization.

Animals↗
PubMed1992

Role of GH in regulating nocturnal rates of lipolysis and plasma mevalonate levels in normal and diabetic humans.

To define the role that nocturnal increments in growth hormone (GH) play in maintaining lipolysis, glycerol turnover was measured in six patients with GH deficiency and six normal subjects during sleep. Glycerol production initially decreased in both groups but then increased to 1.44 +/- 0.20 mumol.kg-1.min-1 by 0800 h in normal subjects, whereas GH deficiency was associated with a continuous fall to 0.77 +/- 0.10 mumol.kg-1.min-1, P less than 0.02. Nonesterified fatty acid levels paralleled these changes. Six GH-deficient patients received basal GH replacement including a pulse during sleep, which resulted in normal fasting fatty acid levels (P less than 0.05, replaced vs. chronic deficiency). To assess a possible link between the normal nocturnal increase in plasma mevalonate (the product of the rate-limiting step in cholesterol synthesis) and sleep-associated GH release, 11 GH-deficient patients and 11 normal subjects were studied. Peak nocturnal and fasting mevalonate concentrations were not correlated with GH level. We conclude that nocturnal growth hormone secretion is essential for maintaining lipolysis but that it is not related to normal increments in mevalonate and, by inference, to cholesterol synthesis during sleep.

Adult↗
PubMed1992

The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents.

Recent interest has focused on findings that drugs used to lower blood pressure may adversely modify plasma lipids and lipoprotein metabolism. This observation may explain why pharmacologic control of hypertension has failed to reduce the incidence of morbidity and mortality from coronary artery disease. The present study aims to evaluate the effect of TA-3090, a new calcium channel blocker, on fasting plasma lipids and lipoproteins, as well as on processes of intestinal fat absorption. Rats were treated by gavage with TA-3090 (10 mg/kg twice daily) for 4 days and compared with controls (n = 6 per group). Plasma cholesterol was increased in the treated group to (mean +/- SE) 74 +/- 2 vs 60 +/- 4 mg/dl (P less than 0.01), due mainly to an increased high density lipoprotein-cholesterol level (50 +/- 2 vs 37 +/- 3 mg/dl, P less than 0.005). Notably plasma triglycerides (TG) and low density lipoprotein-cholesterol were not significantly affected. Another group of TA-3090-treated animals was given an intraduodenal fat meal, and the rise in plasma TG and chylomicrons followed over 4 hr. Postprandial hypertriglyceridemia and chylomicronemia were significantly lower at 2 hr (P less than 0.05) and 3 hr (P less than 0.01) compared with controls. In a separate group of animals, the addition of TA-3090 to a 2% intralipid infusion intraduodenally was associated with significantly reduced TG and chylomicron-TG transport into lymph (P less than 0.05). Furthermore, experiments in rats pretreated with TA-3090 intraperitoneally and then given 2% intralipid intraduodenally were shown to have a significant decrease in mean flow rate (27%), TG transport (31%) and chylomicron-TG output (37%), when compared with controls. In vitro studies using jejunal organ culture to examine the effect of TA-3090 on intracellular lipid synthesis and secretion revealed that the addition of the drug to the medium resulted in significantly decreased TG synthesis and secretion. These data suggest that TA-3090 could be effective in increasing HDL-cholesterol and reducing postprandial chylomicronemia. Our findings support a role for TA-3090 directly on enterocyte absorption and/or intracellular lipid transport, and thus indicate the importance of intracellular calcium on these processes.

Animals↗
PubMed1992

Multiple HPV infection: microanatomy by in situ hybridization and immunohistochemistry.

Specific human papillomavirus (HPV) types have been shown to be associated with proliferative epithelial lesions with variable biological consequences in infected patients. Simultaneous infection by more than one HPV type has been infrequently reported, and its clinical significance is unknown. We have examined four biopsies of cervical and vulvar tissue, each with evidence of infection by two different HPVs. Using both in situ hybridization and immunohistochemical techniques, we determined the cellular distribution of the viral infections. Using biotinylated type-specific probes and stringent conditions we were able to demonstrate that in each case the two HPVs occupied distinct, non-overlapping foci within the lesions. The condylomatous tissues contained DNA from HPV types that are associated with high-grade neoplasia and invasive cancer (16 and 18), as well as types commonly associated with benign proliferative lesions. Immunohistochemical analysis of the lesions with antibody to bovine papillomavirus capsid antigen failed to detect HPV in regions shown by in situ hybridization to contain HPV 16 and 18 DNA, whereas type 6 and 11 infected areas were readily identified. These results provide indirect evidence of viral interference between HPV types and indicate that interference may limit the number of HPV types that produce active infections within a single cell.

Cervix Uteri↗
PubMed1992

Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects.

Bronchial lavage and biopsy studies suggest the involvement of eosinophils and T-lymphocytes in allergic inflammation in asthma. There is evidence suggesting that the expression of adhesion molecules on endothelial cells and of their receptors on leucocytes is involved in this process. To investigate these mechanisms we have obtained bronchial mucosal biopsies from 10 normal subjects and from 10 symptomatic atopic asthmatics. Six of the asthmatics were re-biopsied after 6 weeks of inhaled beclomethasone dipropionate (BDP) during which time their clinical response was monitored. Frozen sections were stained by the immunoperoxidase method using monoclonal antibody (MoAb) 6.5B5 to identify expression of intercellular adhesion molecule (ICAM-1) and MoAb 1.2B6 for endothelial leucocyte adhesion molecule (ELAM-1). Araldite-embedded sections were also stained for eosinophils using MoAb EG2 to identify eosinophilic cationic protein (ECP). A significant mucosal eosinophilia was apparent in the asthmatic but not in the normal biopsies. Immunostaining for ICAM-1 was observed in both the epithelium and endothelium and ELAM-1 in endothelium, with no significant differences being apparent between the asthmatic and normal subjects. Topical BDP markedly reduced the mucosal eosinophilia without affecting the expression of either adhesion molecule. Using this method, we conclude that there is basal expression of ICAM-1 and ELAM-1 in normal human bronchial mucosa, which is not significantly different from that in asthmatics, and that it is insensitive to suppression with corticosteroids at an inhaled dose that causes clinical improvement.

Adult↗