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Biomedical subjects

D M Smith

Publications and source records attributed to D M Smith.

At least 145 records · Page 8Linked to original sources
PubMed1998

Cocaine use as a risk factor for abdominal pregnancy.

Failure to diagnose abdominal pregnancies can have disastrous morbidity/mortality consequences for mother and fetus. To make the diagnosis of abdominal pregnancy requires that the physician have a high index of suspicion and that he or she have a good understanding of the risk factors of abdominal pregnancy. This article presents data suggesting that maternal cocaine use is a risk factor for abdominal pregnancy, reviews the literature on the maternal/fetal effects of maternal cocaine use and the risk factors of abdominal pregnancy, and analyzes 55 cases of abdominal pregnancy. Maternal cocaine use correlated with a 20% rate of increase in the incidence of abdominal pregnancy compared with the 70% rate of decrease in the "before cocaine" time period. Recommendations are offered for management.

Adult↗
PubMed1997

Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice.

Obesity is associated with diabetes, and leptin is known to be elevated in obesity. To investigate whether leptin has a direct effect on insulin secretion, isolated rat and human islets and cultured insulinoma cells were studied. In all cases, mouse leptin inhibited insulin secretion at concentrations within the plasma range reported in humans. Insulin mRNA expression was also suppressed in the cultured cells and rat islets. The long form of the leptin receptor (OB-Rb) mRNA was present in the islets and insulinoma cell lines. To determine the significance of these findings in vivo, normal fed mice were injected with two doses of leptin. A significant decrease in plasma insulin and associated rise in glucose concentration were observed. Fasted normal and leptin receptor-deficient db/db mice showed no response to leptin. A dose of leptin, which mimicked that found in normal mice, was administered to leptin-deficient, hyperinsulinemic ob/ob mice. This caused a marked lowering of plasma insulin concentration and a doubling of plasma glucose. Thus, leptin has a powerful acute inhibitory effect on insulin secretion. These results suggest that the action of leptin may be one mechanism by which excess adipose tissue could acutely impair carbohydrate metabolism.

Animals↗
PubMed1997

Peptide analogue studies of the hypothalamic neuropeptide Y receptor mediating pituitary adrenocorticotrophic hormone release.

Hypothalamic neuropeptide Y (NPY) is thought to be important in the regulation of feeding and also in the release of Adrenocorticotrophic hormone (ACTH). Intracerebroventricular administration of NPY to male rats significantly increased plasma ACTH 10 min after injection and stimulated 2-h food intake. A series of analogues of NPY that have a greatly reduced affinity for the Y1 [human pancreatic polypeptide (human PP), NPY(3-36)], the Y2 ([Pro34]NPY, human PP), the Y3 (peptide YY), and the Y6 (human PP) receptor, all markedly stimulated ACTH release. Rat PP, which binds with high affinity to the Y4 receptor, was unable to stimulate ACTH release. A novel analogue fragment [Pro34]NPY(13-36) was synthesized as a ligand with low Y1 and Y2 receptor affinity. Interestingly, neither [Pro34]NPY(13-36) nor the selective Y5 receptor agonist [D-Trp32]NPY stimulated food intake, whereas both significantly increased plasma ACTH. Thus the hypothalamic NPY receptor mediating increases in plasma ACTH has a fragment activation profile unlike the Y1-Y4 or Y6 receptors and appears distinct from the NPY receptor controlling food intake.

Adrenocorticotropic Hormone↗
PubMed1997

Class I MHC mediates programmed cell death in human lymphoid cells.

BACKGROUND: Although signaling via class I MHC molecules has been shown to suppress T-cell responses, the mechanisms by which these effects are mediated have not been delineated. Studies were conducted to examine the possibility that 5H7 (a murine anti-human mAb specific for the alpha3 domain of human class I MHC) induces programmed cell death (PCD). MATERIALS: Normal human T cells and lymphocyte tumor lines were used. PCD was assessed by viable cell recovery (VCR) with trypan blue, ethidium bromide/acridine orange staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling techniques. RESULTS: 5H7 induced growth inhibition of lymphocyte tumor cell lines as assessed by [3H]thymidine incorporation. 5H7 also induced marked reductions in VCR of lymphocyte tumors and normal human T and B cells, with the most dramatic reductions occurring in B cells and B cell-derived tumors (JY, BeVD, and 521). Reductions in tumor growth observed with 5H7 monoclonal antibody, however, were not observed with other anti-human class I MHC monoclonal antibodies, TP2599 (alpha3 domain specific) and W6/32 (alpha2/alpha3 domain specific). Cells treated with 5H7 demonstrated typical features of PCD including cytoplasmic vacuolization, DNA condensation, and apoptotic body formation. Reduction in VCR was augmented by anti-CD3 monoclonal antibody and was not reversed by exogenous interleukin 2. Induction of PCD was not observed with soluble 5H7 F(ab)'2 fragments alone, but cross-linking of 5H7 F(ab)'2 fragments by F(ab)'2 fragments of human Ig-absorbed goat anti-mouse Ig partially restored PCD induction, indicating that anti-class I MHC monoclonal antibody can induce PCD in an FcR-independent system and that monoclonal antibody cross-linking is necessary for PCD induction. CONCLUSIONS: These studies provide the first evidence that class I MHC molecules mediate PCD in human T and B cells.

Antibodies, Monoclonal↗
PubMed1997

Possible evidence for endogenous production of a novel galanin-like peptide.

Galanin mRNA and peptide are not detectable in normal islets. We studied the effect of galanin antagonists on insulin secretion in the rat beta cell line, RIN5AH, and in perifused rat islets. In RIN cell membranes galanin and its antagonists showed high affinity for 125I-galanin binding sites [Kd: (galanin) 0.03+/-0.01; Ki for galanin antagonists: (C7) 0.12+/- 0.02, (M35) 0.21+/-0.04, and (M40) 0.22+/-0.03 nM, mean+/- SEM, n = 4]. Galanin (1 microM) inhibited glucose-induced insulin release in islets (control 21.2+/-1.5 vs. galanin 4.5+/-0.2 fmol/islet per min, P < 0.001, n = 6) and RIN5AH cells (control 0.26+/-0.01 vs. galanin 0.15+/-0.02 pmol/10(6) cells per h, P < 0.001, n = 9). In RIN5AH cells, all antagonists blocked the inhibitory effects of galanin and stimulated insulin release in the absence of galanin. C7 and M40 (1 microM) alone significantly stimulated glucose-induced insulin secretion. Purified porcine galanin antibody (GAb) enhanced glucose-induced insulin release from islets (control 100+/- 16.3% vs. GAb 806.1+/-10.4%, P < 0.001, n = 6), and RIN5AH cells (control 100+/-9.6% vs. GAb 149+/-6.8%, P < 0. 01, n = 6). Western blotting of dexamethasone-treated islet extracts using GAb showed a specific band of similar molecular weight to porcine galanin not detected using a rat specific galanin antibody. One possible explanation for these results is the presence of an endogenous galanin-like peptide.

Amino Acid Sequence↗
PubMed1997

Identification of constitutive and gamma-interferon- and interleukin 4-regulated proteins in the human renal carcinoma cell line ACHN.

The effects of IFN-gamma and interleukin 4 (IL-4) on cell proliferation and two-dimensional gel electrophoretic protein patterns of the human renal carcinoma cell line ACHN were studied. Treatment of the cells with IFN-gamma resulted in a 40-50% decrease in their proliferation. IL-4 treatment resulted in a 30-40% decrease. Treating cells with both cytokines had the same effect as with IFN-gamma alone, thus precluding a synergistic antiproliferative interaction of these two cytokines. To identify IL-4- and IFN-gamma-regulated proteins in ACHN, two-dimensional preparative gel electrophoresis was used, combined with either capillary electrophoresis or high-performance liquid chromatography and either Edman or mass spectrometric sequencing. The following cytokine-induced proteins were identified: tropomyosin, heat shock protein 27, manganese superoxide dismutase, glutathione S-transferase pi, and protein kinase C inhibitor I. Tropomyosin increased 2-fold when cells were treated with IFN-gamma. Levels of heat shock protein 27 increased 2-fold with IL-4, 3-fold with IFN-gamma, and 4-fold when the cytokines were used in combination. Manganese superoxide dismutase increased 3-fold with IFN-gamma but was unaffected by IL-4. Glutathione S-transferase pi increased 3-fold with IFN-gamma. Levels of protein kinase C inhibitor I increased greater than 3-fold with IL-4, 4-fold with IFN-gamma, and 7-fold when both cytokines were used. In addition, the following constitutive ACHN proteins were identified: copper zinc superoxide dismutase, 60S acidic ribosomal protein P2, and a second heat shock protein 27 isoform. These findings help define the biochemical modes of action of IFN-gamma and IL-4 and their potential in the biological therapy of renal cell carcinoma.

Amino Acid Sequence↗
PubMed1997

Anti-human class I MHC antibodies induce apoptosis by a pathway that is distinct from the Fas antigen-mediated pathway.

5H7, an anti-human class I MHC mAb that recognizes a monomorphic determinant of the alpha3 domain, profoundly inhibits T lymphocyte activation. The present study was designed to determine the role of programmed cell death in 5H7-mediated immune suppression. Incubation of PBMC with 5H7 mAb induced a marked reduction in viable cell recovery (VCR) of T cells (<10% VCR), NK cells (<1% VCR), and B cells (<1% VCR). In addition, 5H7 inhibited proliferation and VCR of JY, DBS-521, and BevD tumor lines as well as cells transfected with HLA-B27. Morphologic changes characteristic of apoptosis were induced by 5H7, including cell membrane blebbing, cytoplasmic vacuolization, condensation of nuclear chromatin, and nuclear fragmentation. Furthermore, DNA fragmentation was demonstrated in 5H7-treated PBMC using a TdT-mediated end-labeling (TUNEL) technique. 5H7, but not anti-Fas mAb, induced apoptosis of cell lines derived from patients with Niemann-Pick disease that lack acidic sphingomyelinase activity. In addition, induction of cell death by 5H7 was not inhibited by IL-1beta-converting enzyme (ICE) inhibitors under conditions that fully suppressed Fas-mediated apoptosis. These findings suggest that signal transduction through "classical" human class I MHC molecules induces apoptosis by a Fas-independent pathway that does not require acidic sphingomyelinase, is independent of ICE protease, and may represent a unique pathway of cell death in human lymphocytes.

Adult↗
PubMed1997

Target complicity in the confirmation and disconfirmation of erroneous perceiver expectations: immediate and longer-term implications.

The authors explored the role of target self-presentational goals in the expectation confirmation process within the context of simulated employment interviews. As predicted, applicants encouraged to be deferential inadvertently succumbed to their interviewers' expectation; applicants encouraged to be challenging, to advance their own agenda, did not. The challenging-motivated applicants succeeded in disconfirming negative expectations by presenting favorable information about themselves even in the face of negatively constraining interviewer questions; other theoretically relevant behaviors were not supported as mediators. Of added interest, the self-fulfilling prophecies observed for the deference-motivated applicants carried over to a 2nd interview because of changes in applicant self-perceptions following the 1st interview.

Adult↗
PubMed1997

Species, muscle type, and formulation influence the residual concentrations of three endpoint temperature indicators in poultry products.

The objectives were to determine 1) the effect of muscle type and temperature on the concentration of lactate dehydrogenase (LDH), IgG, and serum albumin (SA) in turkey and chicken, and 2) the concentrations of these marker proteins in four turkey products processed to the USDA required endpoint temperature (EPT) of 68.3 C. Ground turkey and chicken breast and thigh meat were placed in thermal death time tubes and heated to 65.5, 68.3, 71.1, or 73.8 C. Turkey bologna, pastrami, smoked sausage, and frankfurters were cooked by a local processor to target temperatures between 65.5 and 73.8 C. Proteins were extracted and quantified by an LDH sandwich ELISA or indirect competitive ELISA for SA and IgG. Although all indicators decreased in concentration as EPT were increased, turkey contained higher (P < 0.0001) residual concentrations of the indicators than chicken. In both turkey and chicken, thigh muscle contained higher concentrations of SA (P < 0.0001) and IgG (P < 0.0001) and lower concentrations of LDH (P < 0.0001) than breast muscle at the same EPT. The concentrations of the three indicators decreased as the EPT of the four turkey thigh products were increased. At an EPT of 68.3 C, pastrami contained the lowest concentrations of SA and IgG, whereas bologna contained the lowest concentration of LDH. The LDH ranged from 441.7 ng/g bologna to 1,283.6 ng/g sausage at 68.3 C. Minimum residual concentrations of each indicator need to be established for each product before the ELISA can be used to verify processing to the USDA minimum EPT.

Analysis of Variance↗
PubMed1997

Composition and functional properties of cholesterol reduced egg yolk.

The composition and functional properties of cholesterol reduced egg yolk (CREY) were compared to those of control egg yolk (EY). The CREY was prepared by absorbing cholesterol with beta-cyclodextrin after dilution and dissociation of granules at pH 10.5. The CREY contained less lipid and protein and more carbohydrate and ash than EY. Egg lipids were fractionated into triglycerides, cholesterol esters, free cholesterol, phosphatidyl choline, and phosphatidyl ethanolamine. Free and esterified cholesterol in CREY were reduced by 91.6 and 94.4%, respectively. Triglycerides were the major lipid class in CREY. The CREY contained more oleic acid and less linoleic acid than the control. Protein solubility in 0.1 and 0.6 M NaCl and sponge cake volume did not differ. The composition of proteins soluble in 0.6 M NaCl in both egg preparations were similar as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The electrophoretic profiles of proteins soluble in 0.1 M NaCl were similar, except that lipovitellin form EY was insoluble under these conditions. The CREY was less yellow than EY, as indicated by beta-carotene concentrations and Hunter b values. These results suggest that beta-cyclodextrin can be used to produce a low cholesterol egg product with compositional and functional properties similar to EY.

Animals↗
PubMed1997

The risk of hospitalization for congestive heart failure among older adults.

OBJECTIVES: The purpose of the study was to estimate the 8-year rate of hospitalization for congestive heart failure (CHF), to report the resources consumed, and to evaluate previously reported risk factors in a nationally representative sample of 7,286 older white and black adults. METHODS: Secondary analysis of baseline interview data was linked to Medicare hospitalization and death records for 1984 to 1991. Hospitalization for CHF was defined as having one or more episodes with an International Classification of Diseases (ninth revision, clinical modification) discharge code of 428. Combined and separate analyses of first-listed and second-through fifth-listed CHF discharge diagnoses were conducted. Multivariable proportional hazards models were used to evaluate the risks in pooled analyses of all white and black men and women and in separate stratified analyses of white men and white women. RESULTS: Over the 8-year period, 1,102 or 15.1% of the 7,286 older white and black adults were hospitalized for CHF (7.1% with first-listed and 8.1% with second- through fifth-listed diagnoses). The 1- and 5-year combined postdischarge mortality rates were 34.7% and 69.0%, respectively. In descending order, the major risk factors for being hospitalized for CHF in the combined, pooled analysis were age, being a white man, having lower body functional limitations, and having self-reported medical histories of coronary heart disease, heart attack, diabetes, and angina. The increased risk associated with age was not linear, and it diminished significantly over the course of life. Some significant differences were observed in the risk factors for hospitalization for first-listed versus second- through fifth-listed CHF and in the risk factors for white women versus white men. CONCLUSIONS: Hospitalization for CHF among older adults is a common, costly event with a poor prognosis. The differential risk for white men remains unexplained and warrants further study.

Black or African American↗
PubMed1997

Depression and mortality in medically ill older adults.

OBJECTIVE: To determine if major depressive disorder influences the survival of older, medically ill veterans. DESIGN: Thirty month follow-up of an inception cohort. SETTING: An academically-affiliated Veterans Affairs Medical Center. PARTICIPANTS: One hundred veterans, half of whom have a depressive disorder, recruited from inpatient medical and surgical units in 1990-1991. At initial evaluation all participants were older than age 65, cognitively intact, and medically but not terminally ill. MEASUREMENTS: Severity of medical illness, functional status, social support and presence of depression were measured at initial evaluation, presence of depression was measured 4 to 6 months after initial evaluation, and survival status was determined at 30 months. Retrospective medical record review was used to determine if patients received depression treatment and to explore whether depressed persons received life-sustaining medical treatment less often than nondepressed persons. RESULTS: At 30 months, 36 of the 100 subjects had died. Only two factors predicted mortality: severity of medical illness and depression. The survival of subjects who had recovered from depression at 4 to 6 months was intermediate to never depressed and continuously depressed subjects. Somatic treatment of depression did not alter outcome. There was no significant difference between depressed and nondepressed in how often life-sustaining medical treatments were withheld or withdrawn. CONCLUSION: Presence of major depression in medically-ill older hospitalized veterans continues to be a risk factor for death 30 months after diagnosis.

Activities of Daily Living↗
PubMed1997

The sequelae of hospitalization for congestive heart failure among older adults.

OBJECTIVES: To estimate the independent effect of hospitalization for congestive heart failure (CHF) on subsequent mortality, readmission for CHF, rehospitalization for any reason, and change in functional status. DESIGN: Secondary analysis of the nationally representative Longitudinal Study on Aging, Baseline (1984) interview data are linked to Medicare hospitalization and death records for 1984-1991 and to functional status reports at three biennial follow-ups. SETTING: In-home and telephone interviews. PARTICIPANTS: a total of 7527 noninstitutionalized older adults aged 70 years or older at baseline. MEASUREMENTS: Hospitalization for CHF was defined as having one or more episodes with primary or secondary discharge ICD9-CM codes of 428. Multivariable proportional hazards, logistic and linear regression, as well as multiple classification analysis, were used to estimate the independent effects of having been hospitalized for CHF. RESULTS: The adjusted risk ratios for having a primary or secondary hospital discharge diagnosis of CHF on mortality (compared with not having any CHF hospital discharge diagnoses) were 1.58 (CI95% = 1.40 to 1.78) and 1.29 (CI95% = 1.15 to 1.45), respectively (P < .001). CHF readmission and rehospitalization rates were substantial, ranging from 16.0 to 47.5% at 1 year, depending on the criteria employed. The adjusted odds ratios for having any subsequent hospitalizations associated with having a primary or secondary hospital discharge diagnosis of CHF (compared with not having any CHF hospital discharge diagnoses) were 7.70 (CI95% = 6.20 to 9.57) and 2.99 (CI95% = 2.51 to 3.56), respectively (P < .001). The percent increases in the number of hospital episodes, total charges, and total length of stay attributable to having been hospitalized for CHF were significant (P < .001) and ranged from 15.5 to 66.7%. Having been hospitalized for CHF was also related significantly to greater increases in the mean number of functional limitations at follow-up. CONCLUSION: Hospitalization for CHF among older adults increases substantially the risk of subsequent mortality, readmission for CHF, rehospitalization for any reason, and greater functional decline. Therefore, greater attention to the prevention and management of CHF is needed.

Activities of Daily Living↗
PubMed1997

Neuropeptide Y induced feeding in the rat is mediated by a novel receptor.

There are now six recognized neuropeptide Y (NPY) receptor subtypes (Y1-Y4 and two recently cloned distinct receptors labeled Y5), of which Y1 and one of the Y5's have been suggested could mediate the effect of NPY on feeding. The fragments NPY(2-36) and NPY(3-36), which bind Y1 only poorly, were injected intracerebroventricularly (icv) and found to have similar dose-response relationships to NPY in the stimulation of feeding. However NPY (13-36), which stimulates both Y2 and Y5, caused no increase in food intake, even at high doses. Maximal stimulation with the classical Y1 agonist [Pro34]-NPY produced only 50% of the maximum effect of NPY itself despite fully inhibiting adenylyl cyclase activity in vitro in a Y1 system. The novel fragment [Pro34]-NPY(3-36) is as effective at stimulating food intake as the classical Y1 analogue [Pro34]-NPY but bound to the Y1 receptor with only 1/20th of the affinity of NPY and failed to inhibit adenylyl cyclase through this receptor. [Pro34]-NPY(3-36) is therefore a relatively appetite-selective ligand. Coadministration of high dose NPY(13-36) and [Pro34]NPY did not enhance feeding compared with [Pro34]-NPY alone. In addition, the NPY Y1 receptor antagonist BIBP-3226, which does not bind Y2, Y4, or Y5 receptors, significantly reduced NPY induced feeding. These results indicate that the feeding effect of icv NPY involves a novel receptor and that it is functionally distinct from the recognized receptor subtypes.

Adenylyl Cyclases↗
PubMed1997

Expression of adrenomedullin (ADM) and its binding sites in the rat uterus: increased number of binding sites and ADM messenger ribonucleic acid in 20-day pregnant rats compared with nonpregnant rats.

RIA of nonpregnant rat uterus extracts showed 0.68 +/- 0.08 pmol/g adrenomedullin (ADM) and 3.23 +/- 0.08 pmol/g calcitonin gene-related peptide (CGRP). In the pregnant (20 days gestation) uterus, the ADM content was 0.90 +/- 0.17 pmol/g, and CGRP could not be detected. ADM messenger RNA was detected at high levels in the uterus, with a 1.8-fold increase in expression in pregnancy. Pharmacologically distinct binding sites for ADM (Bmax = 21 +/- 2 fmol/mg protein, dissociation constant = 80 +/- 6 pM), and CGRP (Bmax = 101 +/- 18 fmol/mg protein, dissociation constant = 140 +/- 20 pM) were identified in nonpregnant uterus. Competition for 125I[Tyr0]alphaCGRP binding was shown by both ADM and CGRP (8-37), whereas CGRP and CGRP (8-37) did not compete for 125I-ADM-binding sites. The density of the ADM-binding sites was 10 times greater in pregnant uterus (Bmax = 211 +/- 39 fmol/mg protein, P < 0.01) than nonpregnant uterus. CGRP receptor messenger RNA was identified in both nonpregnant and pregnant uteri. In isolated nonpregnant rat uteri, CGRP and ADM attenuated the contractile response to galanin by 77 +/- 10% and 57 +/- 10%, respectively. The responses to both CGRP and ADM were abolished by CGRP (8-37). These results demonstrate, for the first time, the presence of ADM and specific binding sites for both ADM and CGRP in the rat uterus.

Adrenomedullin↗
PubMed1997

The interaction of CGRP and adrenomedullin with a receptor expressed in the rat pulmonary vascular endothelium.

An abundant, seven trans-membrane domain receptor related to the calcitonin receptor has been studied by a number of groups without identification of its ligand. A recent report claimed that the receptor was a type 1 CGRP receptor (Aiyar et al J. Biol. Chem. 271 11325-11329 (1996)). We have studied the equivalent rat sequence in transfected cells. When expressed in 293 cells the receptor interacts with CGRP and adrenomedullin with KD values of 1.2 nM for CGRP and 11 nM for adrenomedullin. Both ligands cause an elevation of intracellular cAMP with EC50 values of 4 nM and 20 nM respectively and these effects are inhibited by the antagonist CGRP8-37. The receptor is expressed at high levels in the pulmonary vascular endothelium. Both the pharmacological data and the localisation are consistent with the conclusion that the orphan receptor is a type J CGRP receptor. However, when expressed in COS-7 cells, no receptor activity could be demonstrated suggesting that 293 cells contain a factor necessary for functional receptor expression.

Adrenomedullin↗