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Biomedical subjects

M S Martin

Publications and source records attributed to M S Martin.

At least 19 recordsLinked to original sources
PubMed2004

Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring.

Human adult diseases such as cardiovascular disease, hypertension, and type 2 diabetes have been epidemiologically linked to poor fetal growth and development. Male offspring of rat dams fed a low-protein (LP) diet during pregnancy and lactation develop diabetes with concomitant alterations in their insulin-signaling mechanisms. Such associations have not been studied in female offspring. The aim of this study was to determine whether female LP offspring develop diabetes in later life. Control and LP female offspring groups were obtained from rat dams fed a control (20% protein) or an isocaloric (8% protein) diet, respectively, throughout pregnancy and lactation. Both groups were weaned and maintained on 20% normal laboratory chow until 21 mo of age when they underwent intravenous glucose tolerance testing (IVGTT). Fasting glucose was comparable between the two groups; however, LP fasting insulin was approximately twofold that of controls (P < 0.02). Glucose tolerance during IVGTT was comparable between the two groups; however, LP peak plasma insulin at 4 min was approximately threefold higher than in controls (P < 0.001). LP plasma insulin area under the curve was 1.9-fold higher than controls (P < 0.02). In Western blots, both muscle protein kinase C-zeta expression and p110beta-associated p85alpha in abdominal fat were reduced (P < 0.05) in LPs. Hyperinsulinemia in response to glucose challenge coupled with attenuation of certain insulin-signaling molecules imply the development of insulin resistance in LP muscle and fat. These observations suggest that intrauterine protein restriction leads to insulin resistance in females in old age and, hence, an increased risk of type 2 diabetes.

Aging↗
PubMed2001

Identification of E2F-1/Cyclin A antagonists.

A simple method for the synthesis of a rationally designed (S,S)-[Pro-Leu]-spirolactam scaffold is described. This was expanded to a small biased library of compounds mimicking the 'ZRXL' motif in order to identify E2F-1/Cyclin A antagonists. The synthesized compounds were evaluated in an E2F-1/Cyclin A binding assay and moderately active analogues were identified. In addition, the critical roles of Phe, Leu, Lys, and Arg residues of the identified motif were determined.

Amino Acid Sequence↗
PubMed2001

Four patients with both thrombotic thrombocytopenic purpura and autoimmune thrombocytopenic purpura: the concept of a mixed immune thrombocytopenia syndrome and indications for plasma exchange.

Autoimmune thrombocytopenic purpura (ATP) and thrombotic thrombocytopenic purpura (TTP) are each well recognized clinical syndromes which may appear as single episodes or may have chronic relapsing courses. We present four patients negative for human immunodeficiency virus (HIV) infection who appear to have both diagnoses with either concomitant or intermingled episodes, and we review seven additional patients reported in the literature with similar features. All four of our patients are female, two have underlying connective tissue disorders, and their ATP processes came to our attention because of incomplete response of the platelet count to plasma exchange therapy (PEX) during a TTP phase (Cases 1 and 2) or development of thrombocytopenia in the absence of microangiopathy on the background of prior typical TTP episodes (Cases 3 and 4). Recognition of the ATP diagnosis in each case resulted in discontinuation of PEX (Cases 1 and 2) or not instituting PEX (Cases 3 and 4). In each instance, a satisfactory rise in platelet count followed treatment for ATP. Based upon this experience, we conclude that some individuals may have a mixed immune thrombocytopenia syndrome; careful analysis of the mechanism of thrombocytopenia, especially in recurrent episodes and in patients who respond incompletely to PEX for TTP, is important when deciding whether to initiate or continue PEX, or to consider therapies appropriate for other mechanisms of thrombocytopenia.

Adult↗
PubMed2000

Pell-Gregory classification is unreliable as a predictor of difficulty in extracting impacted lower third molars.

We present a study of 166 extractions of impacted lower third molars, all vertical and all extracted by the same surgeon. Each tooth was classified according to the Pell-Gregory scales of position for the occlusal plane (scale A-C) and the ascending ram us of the mandible (scale 1-3). The extraction was subsequently rated as 'easy' or 'difficult'.Taking Pell-Gregory class C as a predictor of a 'difficult' extraction, specificity was 88% but sensitivity was low at 15%. Taking Pell-Gregory class 3 as an indicator of 'difficult', sensitivity was somewhat better (50%), but at the expense of specificity (62%). Likelihood ratios for the individual classes also indicated that the scales are of little value for predicting a difficult extraction.

Forecasting↗
PubMed1999

Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists.

Recent studies identified a short peptide motif that serves as a docking site for cyclin/cyclin-dependent kinase (cdk) 2 complexes. Peptides containing this motif block the phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Here we report that cell membrane-permeable forms of such peptides preferentially induced transformed cells to undergo apoptosis relative to nontransformed cells. Deregulation of E2F family transcription factors is a common event during transformation and was sufficient to sensitize cells to the cyclin/cdk2 inhibitory peptides. These results suggest that deregulation of E2F and inhibition of cdk2 are synthetically lethal and provide a rationale for the development of cdk2 antagonists as antineoplastic agents.

Amino Acid Sequence↗
PubMed1999

Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1).

Following earlier work on cystine-bridged peptides, cyclic phosphopeptides containing nonreducible mimics of cystine were synthesized that show high affinity and specificity toward the Src homology (SH2) domain of the growth factor receptor-binding protein (Grb2). Replacement of the cystine in the cyclic heptapeptide cyclo(CYVNVPC) by D-alpha-acetylthialysine or D-alpha-lysine gave cyclo(YVNVP(D-alpha-acetyl-thiaK)) (22) and cyclo(YVNVP(D-alpha-acetyl-K)) (30), which showed improved binding 10-fold relative to that of the control peptide KPFYVNVEF (1). NMR spectroscopy and molecular modeling experiments indicate that a beta-turn conformation centered around YVNV is essential for high-affinity binding. X-ray structure analyses show that the linear peptide 1 and the cyclic compound 21 adopt a similar binding mode with a beta-turn conformation. Our data confirm the unique structural requirements of the ligand binding site of the SH2 domain of Grb2. Moreover, the potency of our cyclic lactams can be explained by the stabilization of the beta-turn conformation by three intramolecular hydrogen bonds (one mediated by an H2O molecule). These stable and easily accessible cyclic peptides can serve as templates for the evaluation of phosphotyrosine surrogates and further chemical elaboration.

Adaptor Proteins, Signal Transducing↗
PubMed1996

T-Cell co-stimulation by the CD28 ligand B7 is involved in the immune response leading to rejection of a spontaneously regressive tumor.

Cell variants from experimental tumors may lose their tumorigenicity or give rise to tumors that regress after a short period of progression in immunocompetent syngeneic animals. Rejection of these tumor cells is often T-cell-dependent. It has recently been reported that, besides the specific signal delivered through the clonogenic receptor, T-cell activation requires a co-stimulatory signal, delivered through its CD28 receptor by B7-1 and/or B7-2 molecules expressed at the surface of the antigen-presenting cells. CTLA4Ig, a fusion molecule that specifically inhibits B7-1 and B7-2 binding to their receptors of T cells, was used to investigate the role of B7 in the spontaneous regression of the tumors induced in syngeneic rats by REGb cells, a regressor cell line established from a chemically induced colon carcinoma. When rats received either 1 or 3 CTLA4Ig injections, REGb tumors grew 3 or 7 times larger than in control animals, respectively. However, in most animals, single or repeated CTLA4Ig injections delayed rather than suppressed REGb tumor rejection. Antibodies to CTLA4Ig appeared in treated rats and could explain this transient effect. Neither REGb cells nor freshly isolated MHC class-II+ antigen-presenting cells infiltrating REGb tumors expressed B7, establishing that the target of CTLA4Ig was not located inside the tumor. In contrast, MHC class-II+ B7+ accessory cells were found in the tissue, rather than the tumor itself, was the site of tumor-antigen presentation to tumor-specific T cells. These results establish the role of B7/CD28 co-stimulation pathway in the control of a spontaneously regressive tumor.

Abatacept↗
PubMed1996

Day-night differences in the effects of gonadal hormones on melatonin release from perifused rat pineals. Evidence of a circadian control.

The effects of testosterone (10(-3) M, 10(-6) M, and 10(-9) M) and 17 beta-estradiol (10(-3) M and 10(-9) M) were looked for upon isoproterenol-stimulated melatonin release by perifused pineal glands removed from male rats and female rats in diestrus. Two different times of a 12/12 hour light/dark cycle, i.e., 7 and 19 hours after light onset, were documented in order to look for the existence of a circadian stage-dependence of the hormone effects. Both testosterone (45-60%) and estradiol (60-80%) markedly increased melatonin release by glands removed during the dark span and not during the light span. These results show a direct effect of gonadal hormones on pineal melatonin release and strongly suggest a time-related effect of these hormones on pineal function.

Adrenergic beta-Agonists↗
PubMed1996

Metered-dose inhaler technique of patients in an urban ED: prevalence of incorrect technique and attempt at education.

The metered-dose inhaler (MDI) techniques of 125 asthma patients who presented to a county hospital emergency department (ED) were evaluated. Correct technique was divided into 7 steps. Twenty-one percent of the patients performed all 7 steps correctly. Mean number of steps +/- SD performed correctly was 4.8 +/- 1.7. Verbal individualized instruction was used to improve the technique of patients whose technique was less than perfect. The instruction required a mean +/- SD of 8.3 +/- 5.8 minutes (range, 0 to 30) for all 7 steps to be done correctly at least once. All patients were able to perform all steps correctly after instruction. The amount of time required for teaching was proportional to the number of steps performed incorrectly. The Vitalograph Aerosol Inhalation Monitor was used to verify correct patient technique and as a teaching aid with variable success. Education in proper use of the MDI is important in the overall care of the asthma patient; however, instruction requires a definite time commitment and may not be feasible for all patients in a busy ED. For some patients, alternatives that require less lengthy instruction, such as the use of breath-actuated devices, spacers, and reservoirs, may be required.

Anti-Asthmatic Agents↗
PubMed1996

The quality information management program database in South Carolina.

BACKGROUND: The Quality Information Management (QIM) Program was initiated in 1987 on the basis of the decision of the South Carolina Hospital Association's Subcommittee on Quality Assurance to develop a statewide database that could provide member hospitals with comparative quality indicator data. There are ten indicators for acute care and seven for psychiatry and substance abuse. Thirty-seven acute care hospitals participate in the QIM program, as do 7 specialty hospitals. For each three-month period, participant hospitals complete a computerized software report from their data sources specifying summary-level and patient-level data elements. REPORTING OF DATA: Participating hospitals are provided detailed, quantitative statistical reports to help them identify variations for further investigation. Risk adjustment is accomplished by peer grouping. Each hospital receives summary data for the peer groups to which it is assigned. During the quarterly users group meetings, participants discuss their successes and failures in collecting, reporting, and presenting indicator data. DISCUSSION: Involvement in the QIM program has educated participants in the use of comparative databases for quality improvement activities. It is a challenge to help providers and practitioners, in the face of increasing demands for dissemination, become more comfortable with the release of data to the public, while still preserving some degree of confidentiality.

Computer Communication Networks↗
PubMed1995

Detection of transjugular intrahepatic portosystemic shunt dysfunction: value of duplex Doppler sonography.

OBJECTIVE: Recent reports have shown that a high percentage of patients with transjugular intrahepatic portosystemic shunts (TIPS) have postprocedural shunt complications, including thrombosis of the stent, stenosis of the stent, or stenosis of the hepatic vein draining the stent. We did a prospective study to determine the utility of Doppler sonography as a screening technique for the detection of these complications. SUBJECTS AND METHODS: From September 1991 to September 1992 we placed TIPS in 45 patients. After the procedure, patients were routinely evaluated with both Doppler sonography and angiography. The sonographic protocol consisted of insonation of the stent, portal vein, and hepatic vein to determine the presence of flow, peak velocity, and direction of flow. The angiograms were evaluated for stenoses of the stent or hepatic vein that caused an increase in the portosystemic pressure gradient greater than 15 mm Hg, increased intrahepatic portal venous filling, retrograde filling of the draining hepatic vein, or opacification of varices. The sonographic findings were statistically evaluated to determine if sonography could demonstrate the complications shown by angiography. RESULTS: Adequate follow-up was obtained in 29 of the 45 patients. Sixteen of the 29 patients had shunt complications that consisted of one stent thrombosis, three stent stenoses, nine hepatic vein stenoses, and three concomitant stenoses of the stent and hepatic vein. Flow was not detected by sonography in the stent of the patient with thrombosis. There was a significant difference (p = .003) between the temporal change in peak stent velocity in patients with stenoses versus those without. Use of a change (increase or decrease) in peak stent velocity greater than 50 cm/sec from the post-TIPS baseline sonogram as the diagnostic criterion for the detection of shunt stenoses resulted in a 93% sensitivity and 77% specificity. Five patients with stenosis had reversed flow in the draining hepatic vein. Only one patient with a stenosis had a peak stent velocity less than 50 cm/sec. CONCLUSION: Our results suggest that Doppler sonography is an excellent noninvasive screening technique for the detection of complications of TIPS. We have found a temporal change in peak stent velocity greater than 50 cm/sec to be a more sensitive sonographic sign of TIPS stenosis than the previously reported low-velocity parameters. Our experience suggests that nearly all complications of TIPS can be detected by using three criteria: (1) no flow for thrombosis, (2) a temporal change in peak stent velocity greater than 50 cm/sec for stent and/or hepatic vein stenosis, and (3) reversed flow in the hepatic vein draining the stent for hepatic vein and, rarely, stent stenosis.

Adolescent↗
PubMed1994

In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts.

In various cell systems, an inverse relationship was found between expression of E-cadherin, a molecule involved in the Ca(2+)-dependent homophylic cell-to-cell attachment of epithelial cells, and the capacity to invade extracellular matrix gels or normal tissues in vitro. DHD/K12/TRb (PROb) cells, maintained as a cell line derived from a rat colon carcinoma, homogeneously expressed in vitro immunoreactive E-cadherin, which was functional as shown in cell dissociation-reassociation assays. PROb cells were found to be non-invasive in 3 different assays in vitro. However, tumors resulting from a s.c. injection of PROb cells into syngeneic BD-IX rats were invasive, although PROb cells maintained E-cadherin expression in the tumors. Cells from a freshly dissociated PROb tumor showed, not only PROb cells but also tumor-associated myofibroblasts and were able to cross a Matrigel-coated filter. PROb tumors were indeed infiltrated by numerous myofibroblasts, mainly located at the invasive edge of the tumor. Cells from an established culture of tumor-infiltrating myofibroblasts were able to confer upon PROb cells invasiveness through Matrigel-coated filter or into chick-heart fragments. PROb cells maintained their capacity to express E-cadherin after myofibroblast-enhanced Matrigel invasion. Tumor-associated myofibroblasts, but not PROb cells, secreted a 72-kDa collagenase that could play a role in tumor-cell invasion. These results strongly suggest that cells from the tumor stroma, and more specifically myofibroblasts, may be involved in the invasiveness of epithelial tumor cells in vivo, even when E-cadherin expression prevents tumor-cell invasiveness in different in vitro assays.

Animals↗
PubMed1991

Growth characteristics and metastatic potential of seven intestinal carcinoma lines serially passaged in syngeneic rats.

Transplantable tumour lines were obtained from one duodenal carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine in the Lewis rat and from six colonic carcinomas induced by 1,2 dimethylhydrazine in BDIX or Fisher rats. The tumours were serially transplanted by the subcutaneous route into homologous syngeneic rats. The seven tumours differ from one another in their histological structure, five of them being well or moderately differentiated adenocarcinomas, and in their capacity to produce neutral or acidic mucins. The seven tumours also differ in their growth rate. The seven lines produced metastases; the metastatic potential and the location of the metastases differed from one line to another. The seven lines kept their original differentiation characteristics through multiple passages, representing several years of transplantation into syngeneic hosts. These tumours represent a useful and diversified model of metastatic intestinal carcinoma, available for basic research and therapeutic trials.

Animals↗