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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 397 records · Page 22Linked to original sources
PubMed1996

Characteristics, management, and outcome of patients with acute myocardial infarction treated with bypass surgery. Myocardial Infarction Triage and Intervention Investigators.

BACKGROUND: Although multiple studies have addressed the efficacy of bypass surgery in patients with stable angina, there are relatively few studies that have evaluated the optimal timing, risk of hospital mortality, and long-term outcome for patients with bypass surgery performed in the setting of acute infarction. METHODS AND RESULTS: With data collected from all admitted patients with acute myocardial infarction to 19 Seattle-area hospitals between 1988 and 1994, we studied the characteristics, hospital course, and long-term outcome in 1299 patients who underwent bypass surgery. There was no difference in hospital mortality in patients operated on during the first 24 hours after admission compared with those operated on later in the hospital course (8.3% versus 7.2%; P=.60). Factors that predicted hospital mortality in those who underwent bypass surgery included increased age, prior bypass surgery, infarct extension, and stroke. Long-term outcome in those who underwent bypass surgery was excellent, with low rates of subsequent coronary angiography (7.4% at 3 years) and coronary angioplasty (2.6% at 3 years). Three-year survival was better in bypass recipients than in those treated medically (83% versus 66%; P < .0001), and this difference remained after multivariate adjustment for baseline differences (hazard ratio, 0.68; 95% CI, 0.55 to 0.85). CONCLUSIONS: Patients can be safely operated on early in the course of acute infarction, risk factors for hospital mortality are not substantially different from factors identified in the noninfarct setting, and bypass surgery in select patients after acute infarction is associated with low repeat procedure use and excellent long-term survival.

Adult↗
PubMed1996

Gene-directed enzyme prodrug therapy with a mustard prodrug/carboxypeptidase G2 combination.

The gene for the bacterial enzyme carboxypeptidase G2 (CPG2) was expressed internally in mammalian cells. Mammalian-expressed CPG2 had kinetic properties indistinguishable from bacterially expressed CPG2. Human tumor cell lines A2780, SK-OV-3 (ovarian adenocarcinomas), LS174T, and WiDr (colon carcinomas) were engineered to express constitutively either CPG2 or bacterial beta-galactosidase. These cell lines were subjected to a gene-directed enzyme prodrug therapy regime, using the prodrug 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid (CMDA). The lines which expressed CPG2 had enhanced sensitivity to CMDA. Comparing IC50S, WiDr-CPG2 and SK-OV-3-CPG2 were 11-16-fold more sensitive, whereas A2780-CPG2 and LS174T-CPG2 were approximately 95-fold more sensitive than the corresponding control lines. CPG2-expressing cells and control cells were mixed in differing proportions and then treated with prodrug. Total kill occurred when only approximately 12% of cells expressed CPG2 with the WiDr and SK-OV-3 lines and when only 4-5% of cells expressed CPG2 with the LS174T and A2780 lines, indicating a substantial bystander effect. These results establish this CPG2 enzyme/CMDA prodrug system as an effective combination for the gene-directed enzyme prodrug therapy approach.

Animals↗
PubMed1996

Expression of the LMP1 oncoprotein in the EBV negative Hodgkin's disease cell line L-428 is associated with Reed-Sternberg cell morphology.

The latent membrane protein 1 (LMP1) oncogene is one of the major proteins synthesized by the Epstein-Barr virus (EBV) and is expressed in Reed-Sternberg (RS) cells of EBV-associated Hodgkin's disease (HD). We have studied the effect of this oncoprotein on the formation of RS cells in the EBV-negative HD cell lines L-428 and KM-H2 as well as on the formation of multinucleated cells in the mononuclear human embryonic kidney cell line 293. LMP1 prototype (B95-8) and its naturally occurring carboxy terminal 30 base pair deletion variant LMP1-del were transfected into the cell lines and cytocentrifuge preparations were analysed after 24, 48, 72, 144, 216, and 240 h. While no oncoprotein expression was seen in the KM-H2 cell lines, expression of LMP1 and LMP1-del was observed in the L-428 and 293 cell lines. In the HD cell line L-428 oncoprotein expression was infrequent but when observed was very strong and preferentially associated with multinucleated RS cell morphology (71% of LMP1 positive cells). This is in contrast with the untransfected or transfected but not expressing cells where intermediate mononuclear elements predominated over multinucleated RS cells (< 3%). Frequent oncoprotein expression was observed in the 293 cells and again was associated with multinuclearity. These LMP1 expressing 293 giant cells showed strong expression of ICAM-1(CD54), not detectable in the untransfected cells. In the LMP1-del transfectants giant cells with more than four nuclei were frequently observed. However, giant cells were much less frequent in 293 cells transfected with the amino terminal deletion variant of LMP1 or the lytic form of LMP1, known to induce low NF-kappa B activation compared to the LMP1 prototype. Therefore, LMP1 mediated NF-kappa B activation appears to be involved in polycaria formation. The strong association of LMP1 expression with multinuclearity in a genetically unstable condition -the L-428 and 293 cells show multiple chromosomal abnormalities-suggests that this oncoprotein including its naturally occurring carboxy terminal deletion variant promote the formation of multinuclear cells, in particular of RS cells in EBV-associated HD.

Blotting, Western↗
PubMed1996

The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family type I receptors.

The immunophilin FKBP12 is an evolutionarily conserved abundant protein; however, its physiological roles remain poorly defined. Here we report that FKBP12 is a common cytoplasmic interactor of TGF beta family type I receptors. FKBP12 binds to ligand-free TGF beta type I receptor, from which it is released upon a ligand-induced, type II receptor mediated phosphorylation of the type I receptor. Blocking FKBP12/type I receptor interaction with FK506 nonfunctional derivatives enhances the ligand activity, indicating that FKBP12 binding is inhibitory to the signaling pathways of the TGF beta family ligands. Overexpression of a myristylated FKBP12 in Mv1Lu cell specifically inhibits two separate pathways activated by TGF beta, and two point mutations on FKBP12 (G89P, I90K) abolish the inhibitory activity of FKBP12, suggesting that FKBP12 may dock a cytoplasmic protein to the type I receptors to inhibit TGF beta family mediated signaling.

Activin Receptors, Type I↗
PubMed1996

Contraception and the under-16s: the legal issues.

This article discusses the legal issues and the implications of consent related to providing contraceptive services within general practice for girls under the age of 16. Possible scenarios and interactions are also discussed to allow the reader to apply principles to practice.

Adolescent↗
PubMed1996

Protein folding in the central cavity of the GroEL-GroES chaperonin complex.

The chaperonin GroEL is able to mediate protein folding in its central cavity. GroEL-bound dihydrofolate reductase assumes its native conformation when the GroES cofactor caps one end of the GroEL cylinder, thereby discharging the unfolded polypeptide into an enclosed cage. Folded dihydrofolate reductase emerges upon ATP-dependent GroES release. Other proteins, such as rhodanese, may leave GroEL after having attained a conformation that is committed to fold. Incompletely folded polypeptide rebinds to GroEL, resulting in structural rearrangement for another folding trial in the chaperonin cavity.

Amino Acid Sequence↗
PubMed1996

Recombinant human granulocyte colony-stimulating factor reduces hepatitis C virus replication in mononuclear cells from chronic hepatitis C patients.

Hepatitis C virus infects mononuclear leukocytes of patients with chronic hepatitis C. Treatment with rhG-CSF led to a dose-related reduction in the genomic and antigenomic hepatitis C viral strands in cultures of mitogen-stimulated, naturally-infected peripheral blood mononuclear cells from patients with chronic hepatitis C. Hepatitis C virus genomic strand of subtype 1b was suppressed in 5 of 11 cases, and concurrently with suppression of the viral antigenomic strand in two of them. The treatment also resulted in a significantly increased release of interleukin 6, but not of other cytokines. However, the biological response of hepatitis C virus-infected mononuclear cells to treatment with recombinant human granulocyte colony-stimulating factor was unrelated to any particular pattern of cytokine production.

Antiviral Agents↗
PubMed1996

Identification of divergent homologs of Chironomus tentans sp185 and its Balbiani ring 3 gene in Australasian species of Chironomus and Kiefferulus.

A 185-kDa silk protein (sp185) from Chironomus tentans, present in both larval and prepupal silks, contains a striking amino acid sequence motif, Cys-X-Cys-X-Cys, which occurs about every 22-26 residues. Homologous proteins have been found in Chironomus pallidivittatus (sp185) and Chironomus thummi (sp220), which apparently differ in size but are very similar in overall composition and sequence. While surveying Australasian species of Chironomus and Kefferulus we obtained evidence for immunologically related silk protein having similar size and amino acid composition, but noticeably less Cys. Interspecies in situ hybridization to polytene chromosomes with C. tentans and C. pallidivittatus cDNA probes indicated that each species had a related gene. One pair of C. tentans cDNA-derived primers enabled polymerase chain reaction amplification of a discrete fragment of this gene from Kiefferulus 'cornishi'. Preliminary sequence information for this fragment confirmed the presence of an encoded Cys-X-Cys-X-Cys motif in what appeared to be a similar protein region containing less Cys. We conclude that homologs of C. tentans sp185 and its gene have been identified which may contain significant deviations in structure. Once suitable libraries are available, probes described here will be useful for selecting cDNA and genomic clones for detailed study.

Amino Acid Sequence↗
PubMed1996

Bone mass and metabolism in women aged 45-55.

OBJECTIVE: Changes in calcium homeostasis and bone mass around the climacteric are poorly understood. We examined relations between endocrine factors and indices of bone mass and metabolism in healthy women approaching the menopause. DESIGN: Cross-section study. PATIENTS: Sixty-eight spontaneously menstruating women aged 45-55. MEASUREMENTS: Bone density measured at lumbar spine (LS) and femoral neck (FN) using dual energy X-ray absorptiometry and distal non-dominant forearm using peripheral quantitative computed tomography. We recorded menstrual history, physical activity and dietary calcium, and measured serum calcium, phosphate, alkaline phosphatase, osteocalcin, vitamin D, fT3, T4, TSH, PTH, FSH and oestradiol (E2), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion. RESULTS: Using serum FSH level as a marker of ovarian function, 63 subjects could be classified into one of three groups: group A (serum FSH < 10 U/l, n = 29), group B (10-35 U/l, n = 27) and group C (> 35 U/l, n = 7). Bone density fell with declining ovarian function at the LS, FN and forearm trabecular (but not cortical) sites. Serum PTH was lower in group A vs B (mean (SD) 2.68 (0.97) vs 3.52 (1.17) pmol/l, P < 0.05), but similar to group C (2.90 (1.09) pmol/l, P = NS). Serum phosphate was elevated in group C compared to groups A and B (1.17 (0.15) vs 1.04 (0.11) and 1.05 (0.13) mmol/l, P < 0.05), and urinary PYD (61.1 (8.0) vs 50.4 (11.6) and 43.9 (8.1) mumol/mol creatinine) and DPD (15.9 (3.9) vs 12.0 (3.6) and 11.4 (3.6) mumol/mol creatinine) excretion were also increased. There were no significant differences in vitamin D metabolites or osteocalcin. Multivariate analysis suggested serum osteocalcin was positively related to physical activity and serum 1,25-dihydroxycholecalciferol levels. Serum free T3 was positively correlated with urinary DPD excretion, and inversely related to serum PTH. In all subjects, serum PTH was related to body weight (r = 0.38, P = 0.002). CONCLUSIONS: Declining ovarian function before menopause is accompanied by reductions in bone mass and altered calcium metabolism. Free T3 may regulate bone resorption and indirectly modulate PTH release.

Amino Acids↗
PubMed1996

[Quality management in autologous blood donation].

In many anaesthesia departments, the autologous transfusions concept is an integral part of the perioperative measures catalogue. All patients benefit from this procedure, especially those who face an operation during which much blood will be lost. If a patient donates his/her own blood for their operation, there should not be any increase in risk to this patient. By employing contemporary quality management practices, including computer technology, the quality of the execution and management of the components as well as the quality of the patient care can be evaluated according to the quality of the structure, process and results. By this assessment the efficiency of the procedure can be confirmed and the advantages of using this technique, when utilised by an anaesthesiologist experienced in transfusion, can be underlined. An overview of the pre-existing and expected perioperative risk is of special advantage to the anaesthesiologist to make a realistic and effective decision regarding the possibility of safely processing the autologous blood donation concept.

Adult↗
PubMed1996

[Mobile blood gas and laboratory monitoring. A new technology in clinical routine].

INTRODUCTION: Decision-making on therapy in acute cases involves clinical examination and monitoring of vital parameters and fluid balance; especially, however, laboratory parameters. The present study compared the results of a new bedside laboratory analysis system (PortLab, i-STAT Corp., Princeton NJ) with the analytical results obtained in our central laboratory. In a second phase personnel costs and turnover times of the two methods were evaluated comparatively. MATERIALS AND METHODS: The PortLab system consists of a basic unit (539 g) with an integrated display and disposable silicon cartridges with thin-film electrodes. Up to 8 parameters can be determined simultaneously in 60 microliters of whole blood. Fifty results obtained with the PortLab system of the parameters sodium, potassium, chlorid, glucose, BUN, hematocrit, the calculated haemoglobin and blood gas analysis were correlated with the results obtained by central laboratory analysis. In a second phase, all procedural steps, the time needed and the turnover times for laboratory analysis were compared with the expenditure for the same analyses performed with the PortLab system. RESULTS AND DISCUSSION: The results obtained using PortLab analysis correlated very well with those of the central laboratory (between 0.966 for the hematocrit and 0.994 for pO2). Three steps were required to perform bedside analysis with the PortLap system. The staff was occupied for 1 min. and 15 sec. and the results were ready within 4 min. and 45 sec. (pure analysis time < 2 min.). Analysis in the central laboratory required 8 steps, the intensive care staff was occupied for 6 min. and 15 sec., 5 min. and 15 sec. of which they were away from the patients' side. Analysis of blood gases required 4 steps, the result was ready in 4 min. 15 sec. The personnel was occupied for an equally long time. The use of PortLab saved personnel resources of 5 minutes per laboratory analysis and 3 minutes per blood gas analysis. CONCLUSION: The PortLab system proved easy to handle and reliable. Valuable personnel resources can be saved. This method cannot replace conventional laboratory analyses, but enables more extensive monitoring of patients and their laboratory parameters. The industry should develop analogous monitoring systems for modular solutions.

Blood Chemical Analysis↗