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Biomedical subjects

W Martin

Publications and source records attributed to W Martin.

At least 163 records · Page 9Linked to original sources

Biocompatibility of cardiopulmonary bypass: influence on blood compatibility of device type, mode of blood flow and duration of application.

The biocompatibility of artificial organs is recognised as an area presenting difficulties in terms of the complexity of the situation. The nature of the blood response involving interactions of systems, pattern and extent of change, patient status and the influence of the whole device contribute to the complexity. Recognising these, the profile of the blood response to cardiopulmonary bypass (CPB), with respect to type of device, mode of blood flow, duration of the procedure and patient status, has been evaluated by monitoring contact phase activation [Factor XII-like activity (FXIIA)], fibrinolytic activity [Fibrin degradation products (X-FDP's)], complement activation (C3a, C5a), leucocyte activation [Granulocyte elastase (GE)] and platelet and white cell imaging. FXIIA, X-FDP's, and GE rose gradually during CPB, with levels remaining elevated post-operatively for up to 48 h. In contrast, C3a levels rose sharply with no significant elevation in the post-operative period, while C5a did not show significant changes during bypass. The use of pulsatile perfusion resulted in lesser activation of the parameters, although these were significantly less only for GE. The alterations in FXIIA, X-FDP's, C3a and GE correlated positively with the duration of CPB, with this effect pronounced in the post-operative period for FXIIA, X-FDP's and GE. However, these changes had no apparent influence on clinical outcome and the majority of patients had uncomplicated post-operative recoveries. With respect to the use of bubble/membrane oxygenators, platelet and white cell deposition and the patterns of change for FXIIA and C3a were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

Functional identification and molecular cloning of a rat gene mediating growth inhibition and programmed cell death in normal and transformed rat cell lines.

We wished to identify DNA sequences conferring suppression of proliferation and transformed phenotypes. Thus, we have transfected DNA from normal rat cells, covalently linked to neo DNA coding for neomycin resistance into a tumorigenic, HRAS transformed rat cell line. Phenotypic revertants were selected after the first cycle of transfection by enrichment procedures that served to eliminate transformed cells. The revertant clones continued to express the HRAS oncogene, but exhibited a lower tumorigenicity, loss of anchorage-independent proliferation, flat morphology, and retardation of growth in monolayer culture. The reverted phenotype could be transferred in a second cycle of transfection into the HRAS transformed rat cells. Neo DNA ligated to genomic donor DNA was used as a tagging sequence to molecularly clone the transferred DNA sequence in a recombinant phage. Fragments of the cloned DNA detect a 2.5 kb transcript in parental cells and revertants. Thus, the recombinant phage harbors a putative growth inhibitory gene, designated trg, that is expressed at a higher level in rat embryo fibroblasts and in the REF52 cell line. Introduction of recombinant phage DNA into established 208F and Rat-2 cells and into HRAS-, v-fgr-, v-fms- and v-raf-transformed rat cell lines resulted in inhibition of growth and induction of programmed cell death.

Animals↗

Epidemiologic studies of Escherichia coli diarrheal infections in a low socioeconomic level peri-urban community in Santiago, Chile.

The incidence of diarrhea due to six categories of diarrheogenic Escherichia coli was determined in two pediatric cohorts in a low socioeconomic level community in Santiago, Chile, with access to chlorinated water. An age cross-sectional cohort of 340 children aged birth to 47 months was assembled. A newborn cohort was assembled by enrolling 10-12 newborns monthly for 12 months. Episodes of diarrhea were detected by twice weekly household visits. E. coli from stool cultures of cases and matched controls were hybridized with DNA probes specific for enterotoxigenic, enteroinvasive, enteropathogenic, enterohemorrhagic, enteroaggregative, and diffuse adherence E. coli. Overall, the incidence of diarrhea was low (2.1 episodes/infant/year). Nevertheless, a putative E. coli enteropathogen was found in a large proportion of diarrheal episodes, particularly during the summer. In both cohorts, enterotoxigenic E. coli were important pathogens. Enteropathogenic E. coli were incriminated during the first year of life in the newborn cohort, where they were found significantly more often in cases (p = 0.021) than in controls; beyond this age, isolation rates were similar. In contrast, the relative risk of isolation of diffuse adherence E. coli increased with age in the age cross-sectional cohort, where, overall, the difference in rate of isolation between cases and controls was significant (p = 0.0024). Enteroinvasive and enterohemorrhagic E. coli were isolated infrequently. Enteroaggregative E. coli were encountered equally in cases and controls. Facile transmission of E. coli enteropathogens is occurring in this community despite the availability of potable water.

Case-Control Studies↗

Evidence for a chimeric nature of nuclear genomes: eubacterial origin of eukaryotic glyceraldehyde-3-phosphate dehydrogenase genes.

Higher plants process two distinct, nuclear gene-encoded glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins, a Calvin-cycle enzyme active within chloroplasts and a glycolytic enzyme active within the cytosol. The gene for the chloroplast enzyme was previously suggested to be of endosymbiotic origin. Since the ancestors of plastids were related to cyanobacteria, we have studied GAPDH genes in the cyanobacterium Anabaena variabilis. Our results confirm that the nuclear gene for higher plant chloroplast GAPDH indeed derives from the genome of a cyanobacterium-like endosymbiont. But two additional GAPDH genes were found in the Anabaena genome and, surprisingly, one of these sequences is very similar to nuclear genes encoding the GAPDH enzyme of glycolysis in plants, animals, and fungi. Evidence that the eukaryotic nuclear genes for glycolytic GAPDH, as well as the Calvin-cycle genes, are of eubacterial origin suggests that eukaryotic genomes are more highly chimeric than previously assumed.

Amino Acid Sequence↗

Structures of sialylated oligosaccharides of human erythropoietin expressed in recombinant BHK-21 cells.

The native structures of the Asn-linked oligosaccharides and the O-glycans at Ser126 of human erythropoietin expressed from recombinant BHK cells have been elucidated. Enzymatically released N-glycans were studied by methylation analyses, fast-atom-bombardment mass spectrometry as well as one- and two-dimensional 1H-NMR spectrometry at 600 MHz. Many (82.7%) were found to be tetraantennary N-acetyllactosamine-type (22.8% with one, 3.6% with two and 0.4% with three N-acetyllactosamine repeats) being tetrasialylated (41%), trisialylated (29.6%) and disialylated (12.2%). A few (9.7%; 4.1% 2,4-branched, 5.6%, 2,6-branched) of the chains were triantennary (5.4% trisialyl, 4.3% disialyl) and 4.6% were of the disialyl diantennary type. Almost all of the innermost GlcNAc residues were alpha 1-6 fucosylated and NeuAc was exclusively alpha 2-3 linked to Gal beta 1-4GlcNAc-R; 60% of the protein was found to be O-glycosylated at Ser126; structures were monosialylated (70%) or disialylated (30%) forms of the Gal beta 1-3GalNAc core type. Glycosylation patterns at individual Asn-Xaa-Thr/Ser sites were determined by analytical high-pH anion-exchange chromatography with pulsed amperometric detection. Only tetraantennary chains with 0-3 N-acetyllactosamine repeats were detected at Asn38 and Asn83, while almost all of the di- and triantennary oligosaccharides were attached to Asn24. Batch analysis of different preparations of recombinant erythropoietin revealed the high reproducibility of the production procedure. Structures containing terminal GalNAc-GlcNAc were detected in small amounts in a few batches.

Amino Acid Sequence↗

Characterization of a multigene family encoding an exopolygalacturonase in maize.

Genes coding for exopolygalacturonase in plants are abundantly expressed during the development of the male gametophyte (pollen). We have analysed genomic and cDNA clones for several representatives of the small multigene family encoding exopolygalacturonase from Zea mays. Structures for both actively transcribed genes and non-transcribed pseudogenes are reported. Comparisons of the nucleotide sequences for coding and flanking regions of different members of the gene family reveal surprisingly few base substitutions, suggesting that the exopolygalacturonase gene family of maize arose through very recent multiple duplication events. The pseudogenes are shown to possess an 80 bp insertion within the coding region, which may represent a relictual intron that has been lost in the active genes. We estimate that 12 exopolygalacturonase genes exist in maize. None appear to be expressed at a detectable level in tissue other than those associated with pollen development.

Base Sequence↗

A comparison of dobutamine and maximal exercise as stress for thallium scintigraphy.

In the assessment and evaluation of patients with suspected coronary artery disease there is a need for pharmacological stress combined with thallium scintigraphy. Thallium images were obtained following stress both with dobutamine infusion (5-20 micrograms kg-1 min-1) and with symptom-limited bicycle ergometry in 20 patients (age 39-70 years) with chest pain who had been admitted for coronary angiography. Percentage thallium uptake was calculated using a region of interest technique. Detailed comparison was performed of the presence, size and distribution of left ventricular thallium perfusion defects; the percentage thallium uptake in ventricles, lung and liver; and the haemodynamic response to stress. Each stress produced a similar number of abnormal segments in each of three views (total EX 166/300; DOB 167/295), but exercise produced larger defects in the anterior view (P < 0.025). Thallium uptake in left and right ventricles and relative uptake to lungs were similar, but dobutamine produced higher relative liver uptake [EX 1.55 (0.67); DOB 2.97 (1.23) P < 0.0001]. Fourteen patients were able to tolerate dobutamine 20 micrograms kg-1 min-1. The ratio of peak stress to rest double product was smaller with dobutamine in both patients with (DOB 1.3; EX 2.0; P < 0.0047) and patients without beta-blockade (DOB 1.5; EX 2.4; P < 0.008). Dobutamine produced fewer conventional stress endpoints of chest pain and ST depression. In conclusion, dobutamine produces a well-tolerated incremental pharmacological stress with thallium images similar to maximal exercise, and provides a useful alternative stress in patients unable to perform adequate dynamic exercise.

Coronary Angiography↗

Use of polymerase chain reaction in an epidemiologic investigation of Pontiac fever.

In June 1992, 13 (38%) of 34 resort guests experienced illness that met a symptom-based case definition of Pontiac fever. Each ill guest reported using an indoor hot tub compared with 6 (29%) of 21 nonill guests (P < .001). Water samples from the indoor hot tub were culture-negative for legionellae using standard techniques, coculture with amebae, and intraperitoneal inoculation of guinea pigs. However, polymerase chain reaction (PCR) testing of the water samples indicated the presence of Legionella pneumophila. Direct fluorescent antibody testing identified the organism as serogroup 6. Seroconversion to L. pneumophila serogroup 6 occurred in 7 (64%) of 11 ill guests and none of 5 nonill guests (P = .03). These results suggest that in certain circumstances, culture of environmental samples should be supplemented with additional tests such as PCR. These results are also consistent with the concept that Pontiac fever can be caused by nonviable legionellae.

Animals↗

Molecular phylogenies in angiosperm evolution.

We have cloned and sequenced cDNAs for the glyceraldehyde-3-phosphate dehydrogenase of glycolysis, gapC, from a bryophyte, a gymnosperm, and three angiosperms. Phylogenetic analyses are presented for these data in the context of other gapC sequences and in parallel with published nucleotide sequences for the chloroplast encoded gene for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcL). Relative-rate tests were performed for these genes in order to assess variation in substitution rate for coding regions, along individual plant lineages studied. The results of both gene analyses suggest that the deepest dichotomy within the angiosperms separates not magnoliids from remaining angiosperms, but monocotyledons from dicotyledons, in sharp contrast to prediction from the Euanthial theory for angiosperm evolution. Furthermore, these chloroplast and nuclear sequence data taken together suggest that the separation of monocotyledonous and dicotyledonous lineages took place in late Carboniferous times [approximately 300 Myr before the present (Mybp)]. This date would exceed but be compatible with the late-Triassic (approximately 220 Mybp) occurrence of fossil reproductive structures of the primitive angiosperm Sanmiguelia lewisii.

Base Sequence↗

Actions and interactions of NG-substituted analogues of L-arginine on NANC neurotransmission in the bovine retractor penis and rat anococcygeus muscles.

1. The effects and interactions of a series of NG-substituted analogues of L-arginine known to inhibit nitric oxide synthase were examined on non-adrenergic, non-cholinergic (NANC) neurotransmission in the bovine retractor penis (BRP) and rat anococcygeus muscles. 2. Treatment of BRP muscle strips with either NG-nitro L-arginine (L-NOARG: 0.1-10 microM) or NG-nitro L-arginine methyl ester (L-NAME; 0.1-100 microM) produced a concentration-dependent blockade of NANC relaxation: blockade was complete at the highest concentration of each. 3. Pretreatment with L-arginine (1-10 mM) had no effect on NANC relaxation by itself, but inhibited, in a concentration-dependent manner, the subsequent ability of both L-NOARG (0.1-300 microM) and L-NAME (0.1-1 mM) to produce blockade. L-Arginine (1-10 mM) reversed established submaximal blockade of NANC relaxation induced by L-NOARG (1 microM) or L-NAME (1 microM), but had little effect on maximal blockade induced by these agents. 4. In contrast to L-NOARG and L-NAME, NG-monomethyl L-arginine (L-NMMA; 1 microM-1 mM) had no effect by itself on NANC relaxation of the BRP. L-NMMA (0.1-1 mM) did, however, like L-arginine, inhibit, in a concentration-dependent manner, the subsequent ability of both L-NOARG (0.1-1 mM) and L-NAME (0.1-3 mM) to produce blockade, but was more potent. As with L-arginine, L-NMMA (0.1-1 mM) reversed established submaximal blockade of NANC relaxation induced by L-NOARG (1 microM) or L-NAME (1 microM), but had little effect on maximal blockade induced by these agents. 7. These findings suggest a complex series of interactions between L-arginine and certain of its NG-substituted analogues that are commonly used to inhibit nitric oxide synthase. The most striking new finding is that L-NMMA does not block NANC relaxation in the BRP, but acts with greater potency than the endogenous substrate, L-arginine, to inhibit the blockade induced by L-NOARG or L-NAME.Even on rat anococcygeus where L-NMMA acts as a partial blocker of NANC relaxation, further blockade by L-NOARG is inhibited.

Animals↗

Arterial endothelial barrier dysfunction: actions of homocysteine and the hypoxanthine-xanthine oxidase free radical generating system.

1. Endothelial barrier function was assessed by use of an in vitro model in which transfer of trypan blue-labelled albumin was measured across monolayers of bovine aortic endothelial cells grown on polycarbonate membranes. 2. Addition of either hypoxanthine (0.2 mM) or xanthine oxidase (20 mu ml-1) alone during a 90 min incubation did not affect albumin transfer across endothelial cell monolayers, but a combination of both increased transfer. 3. The increase in albumin transfer induced by hypoxanthine and xanthine oxidase was abolished by catalase (3 u ml-1), reduced by allopurinol (4 mM), but unaffected by superoxide dismutase (6000 u ml-1), the hydroxyl radical scavengers, mannitol (15 mM), dimethylthiourea (10 mM) and N-(2-mercaptopropionyl)-glycine (1 mM), the iron chelator, deferoxamine (0.5 mM), ferric chloride (50 microM), an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (30 microM), or the antioxidant, dithiothreitol (3 mM). 4. Hydrogen peroxide (0.1-30 mM) itself increased albumin transfer across endothelial cell monolayers, exhibiting a biphasic concentration-response curve. The increase induced by 0.1 mM hydrogen peroxide was abolished in the presence of 0.3 u ml-1 catalase whilst that induced by 10 mM hydrogen peroxide was abolished by 3000 u ml-1 catalase. 5. Homocysteine (0.5-1.5 mM) did not affect albumin transfer across endothelial monolayers when added alone, but when added in combination with copper sulphate (50 microM), which catalyses its oxidation, a significant increase in albumin transfer was observed. 6. The increase in albumin transfer induced by the combination of homocysteine (1.5 mM) and copper sulphate was abolished by catalase (1 u ml-1), but was unaffected by superoxide dismutase (6000 u ml-1), mannitol (15 mM), dimethylthiourea (1 mM) or deferoxamine (0.5 mM).7. The data suggest that the endothelial barrier dysfunction induced by the combination of hypoxanthine and xanthine oxidase is mediated solely by the action of hydrogen peroxide and not by superoxide anion, hydroxyl radical, peroxynitrite anion or hypochlorous acid. The copper-catalysed oxidation of homocysteine also induces endothelial barrier dysfunction through the generation of hydrogen peroxide.These findings may have relevance to the endothelial barrier dysfunction associated with ischaemia reperfusion injury and the atherogenic actions of homocysteine.

Albumins↗

Selective inhibition of basal but not agonist-stimulated activity of nitric oxide in rat aorta by NG-monomethyl-L-arginine.

1. Two inhibitors of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMMA, 1-100 microM) and NG-nitro-L-arginine (L-NOARG, 3-300 microM), each produced a concentration-dependent augmentation of phenylephrine-induced tone in endothelium-containing but not endothelium-denuded rings of rat aorta. Pretreatment with L-arginine (10 mM) prevented the augmentation of tone induced by L-NOARG and L-NMMA. 2. Following induction of sub-maximal tone with phenylephrine in endothelium-containing rings, acetylcholine (1 nM-3 microM) induced relaxations which were inhibited in a concentration-dependent manner by L-NOARG (10-100 microM). 3. In contrast to the action of L-NOARG, L-NMMA (100-1000 microM) had no effect on acetylcholine-induced relaxations. L-NMMA (100-300 microM) also had no effect on the endothelium-dependent relaxant actions of ATP (0.1-100 microM), whereas L-NOARG (100 microM) produced powerful blockade. 4. Unexpectedly, pretreatment with L-NMMA (30-300 microM), as with the endogenous substrate L-arginine (10 microM-10 mM), inhibited in a concentration-dependent manner the ability of L-NOARG (30 microM) to block acetylcholine-induced relaxation. 5. The ability of L-NOARG to augment phenylephrine-induced tone and inhibit relaxation by acetylcholine and ATP in endothelium-containing rings is consistent with blockade of basal and agonist-stimulated production of nitric oxide, respectively. 6. The ability of L-NMMA to augment phenylephrine-induced tone without affecting relaxation to acetylcholine or ATP in endothelium-containing rings suggests a selective ability to block basal but not agonist-stimulated production of nitric oxide in rat aorta.

Acetylcholine↗

Endotoxin-induced arterial endothelial barrier dysfunction assessed by an in vitro model.

Using an in vitro model in which albumin transfer across monolayers of bovine aortic endothelial cells (BAEC) was measured, we have shown that lipopolysaccharide (LPS) induces a concentration-dependent increase in endothelial permeability. This increase was biphasic, having an early peak at 2 h and rising again by 24 h. Both peaks were abolished by polymixin B (PMB) but were unaffected by N omega-monomethyl-L-arginine, N omega-nitro-L-arginine methyl ester or dexamethasone. Furthermore, LPS did not stimulate nitric oxide production by BAEC following 24 h exposure. Thus, the LPS-induced increase in permeability may account for the vascular leakage of septic shock, but the L-arginine-nitric oxide system does not appear to be involved.

Albumins↗

Oral health problems and involuntary weight loss in a population of frail elderly.

OBJECTIVE: To evaluate whether poor oral health is a potentially reversible contributor to the development of significant involuntary weight loss in elderly rehabilitation patients. DESIGN: Survey (cross-sectional study). SETTING: Geriatric Rehabilitation Unit (GRU) of a Veterans Administration hospital. PATIENTS: One hundred ten consecutive admissions to the GRU, of whom 99% were male and 80% were white. The average age of the study patients was 77 years. MEASUREMENTS: At admission each patient completed a comprehensive medical, neuro-psychological, social, nutritional, and dental assessment. Previous weights were documented by review of old medical records. Involuntary weight loss was considered significant if it was greater than 5% of pre-weight-loss weight within 6 months or 10% of pre-weight-loss weight within 1 year. Of the 97 variables evaluated, the strongest predictors of significant involuntary weight loss prior to GRU admission were identified using univariate and multivariate (stepwise logistic regression) analyses. RESULTS: The number of general oral problems was the best predictor of significant involuntary weight loss within 1 year prior to GRU admission, followed by household income, age, smoking status, adequacy of nutrient intake prior to admission, and education. When all six of the variables were included in the stepwise logistical regression analysis, the model had a sensitivity of 63.2%, a specificity of 91.1%, and overall predictive accuracy of 86.2%. The number of general oral problems was also a strong predictor of significant weight loss within 6 months prior to GRU admission. CONCLUSIONS: Poor oral health may be an important contributing factor to the development of significant involuntary weight loss among the frail elderly. If this is true, it places even greater emphasis on the need for maintaining an optimal state of oral health in our elderly patients.

Aged↗

Multifocal renal cell carcinoma of collecting duct origin.

In kidney tumors arising from the collecting duct epithelium (Bellini duct carcinoma), histologic examination shows both tubular and papillary architecture, which can lead to misinterpretation as renal cell or transitional cell carcinoma. A case of multifocal bellini duct carcinoma is described, to the authors' knowledge the first to be reported.

Aged↗

[TULIP--transurethral ultrasound-controlled laser-induced prostatectomy: an alternative to TURP?].

Transurethral resection of the prostate (TURP) is the most effective treatment for prostatic obstruction secondary to benign prostatic hyperplasia (BPH). This procedure has a high success rate with a very low mortality rate. Over the last 30 years, however, an unchanged morbidity rate of about 20% following TURP has been reported in the literature. In addition, haemorrhage requiring blood transfusion may occur in 6.5-22% of cases, and 68-92% of sexually active men have retrograde ejaculation following TURP. The side-effects and complications associated with TURP have led to the search for alternative therapies. The TULIP system represents a new treatment modality. TULIP is an acronym for transurethral ultrasound-guided laser-induced prostatectomy. The basic TULIP system consists of an ultrasound imager and a 20-F transurethral probe with an ultrasound transducer and a laser window at the distal end. Under ultrasound guidance laser treatment results in a coagulation necrosis effect in the hyperplastic prostate tissue. Coagulation necrosis is basically a bloodless tissue removal procedure as the tissue subsequently sloughs away in the fine particles during spontaneous micturation within 4-6 weeks after the procedure. Early results obtained in the first 18 patients with symptomatic, obstructive BPH treated by TULIP and with a follow-up of 6 weeks to 6 months demonstrate a significant improvement in both subjective and objective symptoms. The peak flow rate increased by up to 142% on average; the residual volume decreased by up to 75%; and there was a 77% decrease in average symptom scores compared with preoperative scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗