Search PubMed⌕ Search

Biomedical subjects

W Martin

Publications and source records attributed to W Martin.

At least 91 records · Page 5Linked to original sources

The hydrogen hypothesis for the first eukaryote.

A new hypothesis for the origin of eukaryotic cells is proposed, based on the comparative biochemistry of energy metabolism. Eukaryotes are suggested to have arisen through symbiotic association of an anaerobic, strictly hydrogen-dependent, strictly autotrophic archaebacterium (the host) with a eubacterium (the symbiont) that was able to respire, but generated molecular hydrogen as a waste product of anaerobic heterotrophic metabolism. The host's dependence upon molecular hydrogen produced by the symbiont is put forward as the selective principle that forged the common ancestor of eukaryotic cells.

Archaea↗

Sequences of rDNA internal transcribed spacers from the chloroplast DNA of 26 bryophytes: properties and phylogenetic utility.

We determined the sequence of the region of the chloroplast DNA inverted repeat spanning from the 3'-terminus of the 23S rRNA gene to the 5'-terminus of the tRNA[Arg](ACG) gene (about 700 bp) from 25 bryophytes and from the charophycean alga Chara australis. Phylogenetic analysis of these sequences using the neighbor-joining method suggests an early dichotomy of bryophytes and their paraphyly relative to the tracheophyte lineage. A monophyly of liverworts (Marchantiidae plus Jungermanniidae), a deep divergence of Metzgeriales among Jungermanniidae and a close affinity of the two subclasses of mosses, Sphagnidae and Andreaeidae, are evident. The branching pattern observed is consistent with the phylogenetic distribution of several prominent indels observed in the alignment.

Base Sequence↗

Alterations in renal microcirculation during cardiopulmonary bypass.

BACKGROUND: This study was designed to investigate renal microvascular changes during cardiopulmonary bypass. METHODS: Kidneys were harvested from each of four groups of 6 pigs. Group A were anesthetized and heparinized only. The remaining three groups underwent cardiopulmonary bypass at 28 degrees C, group B for 30 minutes and groups C and D for 120 minutes; group D had an additional 30 minutes of normothermic perfusion at the end of the experiment. Renal cortical blood flow was measured using radiolabeled microspheres. Microvascular morphology was defined by corrosion casting and scanning electron microscopy. RESULTS: In group A, renal vascular resistance was 61+/-5.1 mm Hg x mL(-1) x min(-1). This value decreased to 28+/-7.8 in group B and 25+/-4.0 in group C (p < 0.05), and increased in group D to 40+/-4.1 (p < 0.05 versus groups A, B, and C). Cortical thickness, as measured by microvascular casts in groups A, B, and C, was 33, 34, and 31 mm, respectively, with equal distribution of the resin to the superficial and deep cortex but was significantly reduced in group D to 22 mm (p < 0.05 versus groups A, B, and C), with failure of the resin to fill the superficial cortical layer. Diameters of glomeruli as seen on the casts were 111+/-10.38 microm in group A, 100+/-9.24 microm in group B, and 82+/-4.4 microm in group C (p < 0.05 group A versus group C). The glomeruli from group D were still significantly smaller than group A (93+/-10.35 microm, p < 0.05). Mean glomerular capillary diameters were 4.65+/-0.26 microm in group A, 3.9+/-0.16 microm in group B, 3.6+/-0.19 microm in group C, and 3.65+/-0.3 microm in group D (p < 0.05 group A versus groups B, C, and D). CONCLUSIONS: Hypothermic nonpulsatile cardiopulmonary bypass decreased renal vascular resistance, but the superficial and deep layers of the cortex were perfused equally. Glomeruli were reduced in size because of capillary narrowing. This was consistent with diversion of blood through bypass channels. With restoration of normothermia, underperfusion of the superficial cortex occurred, with potential for damage to these nephrons during the increased metabolic demands of rewarming.

Anesthesia, Inhalation↗

Ventricular remodelling and revascularization in severe left ventricular dysfunction.

OBJECTIVE: To evaluate the role of surgical revascularization in the presence of severe, global impairment of left ventricular function without discrete aneurysm formation or mitral regurgitation. The high mortality and morbidity associated with this group, together with the limited benefits tend to prompt referral for cardiac transplantation. METHODS: Fifty-three patients initially referred for transplantation, in addition to coronary revascularization, underwent mitral annuloplasty (group A = 23), free wall remodelling by endoaneurysmorrhaphy (group B = 17) or mitral annuloplasty and free wall reconstruction (group C = 13). The mean ages were 59, 56 and 57 years for groups A, B and C, respectively. Detailed assessment of pre- and post-operative physical and psychological status were carried out. RESULTS: Follow-up was for a mean period of 22-26 months. All patients reported substantial improvement in quality of life, both physical and psychological parameters and in NYHA functional class status. Objective evidence of improvement in ejection fraction was seen in all three groups but especially in group A. There were five early deaths, four were due to inadequate revascularization due to the poor quality of target vessels. There were three late deaths and one patient that required transplantation. CONCLUSION: We conclude that patients with severe left ventricular dysfunction can be candidates for surgical revascularization and optimization of ventricular geometry with acceptable mortality. The importance of achieving complete revascularization is emphasized in this series.

Aged↗

Inhibition of nitrergic neurotransmission in the bovine retractor penis muscle by an oxidant stress: effects of superoxide dismutase mimetics.

1. A number of superoxide dismutase (SOD) mimetics were examined both biochemically for their ability to inhibit the superoxide-catalyzed reduction of cytochrome c and nitro blue tetrazolium, and functionally for their ability to mimic authentic Cu/Zn SOD in restoring nitrergic neurotransmission in bovine retractor penis (BRP) muscle following its inhibition by oxidant stress. 2. The SOD mimetics investigated were CuSO4, MnCl2, CuDIPS (copper [II] [diisopropylsalicylate]2), MnTBAP (manganese [III] tetrakis 4-benzoic acid porphyrin), MnTMPyP (manganese [III] tetrakis 1-methyl-4-pyridyl porphyrin pentachloride), tiron (4,5-dihydroxy-1,3-benzene disulphonic acid), PTIYO (4-phenyl,2,2,5,5,-tetramethyl-3-imidazolin-1-yloxy-3-oxide) and tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl). 3. The rank order of potency in inhibiting the reduction of cytochrome c was: CuSO4 > or = MnCl2 > or = CuDIPS > or = MnTMPyP > MnTBAP > tempol > or = tiron > PTIYO. 4. The requirement for EDTA (0.1 mM) prevented assessment of the activity of CuSO4, MnCl2 and CuDIPS in the assay involving inhibition of reduction of nitro blue tetrazolium. However, the rank order of potency for those agents which could be examined (MnTMPyP > MnTBAP > tiron > or = tempol > PTIYO) was essentially similar to that seen in the cytochrome c assay. 5. Inhibition of endogenous Cu/Zn SOD with diethyldithiocarbamate (DETCA, 3 mM, 120 min) in BRP muscle strips, followed by addition of the superoxide anion generator, LY 83583 (1 microM), resulted in almost complete abolition of nitrergic relaxation (4 Hz, 10 s). 6. Authentic Cu/Zn SOD (1-300 u ml(-1)), CuSO4 (0.1-300 microM), MnCl2 (0.1-100 microM) and MnTMPyP (10-300 microM) each restored nitrergic transmission by around 50%. However, CuDIPS (0.1-30 microM), MnTBAP (0.1-100 microM), tempol (10 microM - 3 mM), PTIYO (1-300 microM) and tiron (10 microM - 10 mM) all failed to restore nitrergic transmission. 7. The ability of MnTMPyP to restore nitrergic neurotransmission may therefore provide a lead in the development of SOD mimetics as therapeutic agents in the treatment of neuropathies associated with oxidant stress.

Animals↗

Loss of endothelium-derived nitric oxide in rabbit aorta by oxidant stress: restoration by superoxide dismutase mimetics.

1. Structurally distinct superoxide dismutase (SOD) mimetics were examined for their ability to protect nitric oxide (NO) from destruction by oxidant stress in rabbit aorta. 2. These were the spin traps, PTIYO (4-phenyl-2,2,5,5-tetramethyl imidazolin-1-yloxy-5-oxide), tempol (4-hydroxy 2,2,6,6,-tetramethylpiperidine-1-oxyl) and tiron (4,5-dihydroxy-1,3-benzene-disulphonic acid), the metal salts, CuSO4 and MnCl2, and the metal-based agents CuDIPS (Cu (II)-[diisopropylsalicylate]2) and MnTMPyP (Mn (III) tetrakis [1-methyl-4-pyridyl]porphyrin). 3. Oxidant stress was generated in isolated aortic rings by inactivating endogenous Cu/Zn SOD with diethyldithiocarbamate (DETCA; 60 min) either alone at 3 mM or at 0.3 mM in combination with superoxide generation using xanthine oxidase (XO; 4.8 mu ml(-1)) and hypoxanthine (HX; 0.1 mM). 4. Acetylcholine (ACh)-induced relaxation was inhibited by DETCA (3 mM, 60 min) and was not restored by exogenous SOD (250 u ml(-1)), suggesting the oxidant stress was intracellular. MnTMPyP (600 microM and 1 mM) and MnCl2 (100 microM) were the only agents to reverse the blockade of ACh-induced relaxation. 5. Addition of XO/HX to DETCA (0.3 mM)-treated tissues powerfully impaired ACh-induced relaxation and exogenous SOD (250 u ml(-1)) fully reversed the blockade, suggesting the oxidant stress was extracellular. CuDIPS (0.1-3 microM), CuSO4 (0.3-3 microM), MnCl2 (1-100 microM) and MnTMPyP (100-600 microM) also reversed blockade powerfully, tempol (30 microM-1 mM) and tiron (0.3-10 mM) reversed blockade weakly and PTIYO (10-300 microM) enhanced the blockade. 6. Thus, MnTMPyP was the only SOD mimetic to restore NO-dependent relaxation in conditions of both extracellular and intracellular oxidant stress. This agent may, therefore, provide a lead in the development of SOD mimetics for the treatment of pathologies associated with oxidant stress.

Acetylcholine↗

Recovery by ascorbate of impaired nitric oxide-dependent relaxation resulting from oxidant stress in rat aorta.

1. In this study we investigated the ability of ascorbate to protect nitric oxide from destruction by superoxide anion. 2. Ascorbate produced concentration-dependent relaxation of rings of rat aorta, comprising two components: the first, seen at 1-300 microM, reached a maximum of 45.3+/-2.8%, and was abolished by endothelial removal or treatment with L-NAME (100 microM), demonstrating involvement of nitric oxide. The second occurred at concentrations of 1 mM and above and was associated with falls in the pH of the bathing fluid. 3. Pretreatment with ascorbate at concentrations up to 3 mM had no effect on the relaxation to acetylcholine (10 nM-10 microM) on endothelium-containing rings or adenosine (0.1 microM-3 mM) on endothelium-denuded rings. 4. An oxidant stress was applied to aortic rings, comprising inhibition of endogenous Cu/Zn superoxide dismutase by diethyldithiocarbamate (0.1 mM) followed by generation of superoxide anion by hypoxanthine (0.1 mM/xanthine oxidase (16 u ml(-1)). This reduced maximal acetylcholine-induced relaxation from 96.7+/-1.3% to 42.4+/-3.5% (P<0.001). Treatment with ascorbate (30 microM-3 mM) reversed this blockade in a concentration-dependent manner. 5. Our findings show that ascorbate has the ability to protect nitric oxide from destruction by superoxide anion. This action is seen with ascorbate at levels normally present in plasma, suggesting that this antioxidant may exert a tonic protective effect on nitric oxide within the vasculature.

Acetylcholine↗

Lung uptake of thallium-201: a marker of defect reversibility?

High lung uptake of thallium-201 at stress is reported to be associated with a large number of perfusion defects and poor prognosis. This study was performed to assess whether the reversibility of stress perfusion defects was related to lung uptake. Gated planar thallium scans at stress and at redistribution from 102 consecutive patients with essentially normal left ventricular ejection fraction (using 99mTc gated blood pool ventriculography) were graded in terms of defect size. Lung and myocardial uptake of thallium were quantitated by region of interest methods relative to the given activity in a previously validated method. There was no significant correlation (non-parametric) between lung uptake and degree of redistribution (p = ns, rs = 0.140). There was a weak but positive correlation between lung uptake and defect size (p < 0.05, rs = 0.188). Both exercise time and double product showed a negative correlation with lung uptake (e.g. for double product, p < 0.0005, rs = -0.541). In conclusion, contrary to our expectation, lung uptake is not related to the degree of redistribution. High lung uptake seems to reflect poor cardiovascular reserve.

Biophysical Phenomena↗

Single crystal biplane equilibrium radionuclide ventriculography: an improved planar imaging technique.

Radionuclide ventriculography in the best septal view is an established method to assess both global and regional ventricular function. Additional projections may be used to delineate the wall motion of inferior myocardial segments. Radionuclide ventriculography was performed in 65 patients using both a single plane (in the best septal view) and a biplane technique. The biplane collimator allowed simultaneous assessment in two planes 40 degrees apart, allowing simultaneous visualization of all four myocardial walls. Seventeen patients with regional wall motion abnormalities were detected with the single plane best septal view and a further 18 patients with impaired wall motion were identified with the biplane collimator (51% of the abnormal ventricles). The additional abnormal segments were seen in only the steep lateral projection. Left ventricular ejection fraction estimation with the biplane technique remains highly reproducible and correlates well with that derived from the best septal view. Biplane radionuclide ventriculography improves the detection of inferior wall motion abnormalities at no expense of time, and offers the possibility of performing two-view stress ventriculography with inotropic agents.

Coronary Artery Bypass↗

Tolcapone improves motor function in parkinsonian patients with the "wearing-off" phenomenon: a double-blind, placebo-controlled, multicenter trial.

We studied the new catechol-O-methyltransferase inhibitor tolcapone, 100 and 200 mg, three times daily (tid) in a randomized, double-blind, parallel-group trial involving 202 parkinsonian patients who were experiencing the "wearing-off" phenomenon on levodopa therapy. After 3 months, patients receiving tolcapone had a significant decrease in mean daily levodopa dose requirement compared with placebo-treated patients (p < 0.01). In patients treated with tolcapone 200 mg tid, daily "off" time, measured using patient diaries, was reduced from baseline by 3.25 hours; this reduction was significantly different from that seen in the placebo group (p < 0.01). Moreover, the number of daily levodopa intakes was reduced significantly in each tolcapone group compared with placebo (p < 0.01). We found significant improvements in motor function and overall efficacy in the tolcapone groups (p < 0.01). The most frequent adverse events were associated with levodopa treatment. Dyskinesia developed or worsened in 18% of patients receiving placebo, in 51% receiving tolcapone 100 mg tid, and in 64% receiving 200 mg tid, with most cases occurring within the first 30 days of the study. Diarrhea was the most frequent nondopaminergic event, occurring in 14% on placebo, 13% on tolcapone 100 mg tid, and 19% on 200 mg tid. Overall 18% of patients withdrew because of adverse events: 15% on placebo, 17% on tolcapone 100 mg tid, and 22% on 200 mg tid. We conclude that tolcapone as an adjunct offers promise for the relief of the "wearing-off " phenomenon in levodopa-treated parkinsonian patients.

Aged↗

Lesser metatarsal V-osteotomy for chronic intractable plantar keratosis. Retrospective analysis of 40 procedures.

The authors studied 40 V-osteotomies of the lesser metatarsal performed for chronic intractable plantar keratosis. They discuss the effectiveness of the V-osteotomy for this deformity as well as other findings such as whether or not fixation of the osteotomy yields a better result (i.e., a lower incidence of complications). The results show that the V-osteotomy had limited effectiveness for this condition and resulted in a high complication rate.

Adult↗

A dose of reality.

Explore the source record for details and available documents.

Consumer Behavior↗

The effects of peroxynitrite on rat aorta: interaction with glucose and related substances.

Peroxynitrite (1-100 microM) induced a concentration-dependent relaxation of rat aortic rings; the logEC50 and maximum relaxation on endothelium-denuded rings were -5.31 +/- 0.03 and 105 +/- 5%, n = 6, respectively. The presence of the endothelium significantly impaired this relaxation (logEC50, -4.41 +/- 0.04; maximum relaxation, 71 +/- 4%; n = 6); an effect which was reversed by the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (L-NAME; 100 microM). Incubation with a high concentration of peroxynitrite (1 mM, 10 min followed by washout) had no effect on subsequent relaxation to acetylcholine (0.01-1 microM). It did, however, significantly depress subsequent contraction to phenylephrine (1-300 nM). This depression was dependent upon the presence of D-glucose in the Krebs solution, could be reversed by the inhibitor of soluble guanylate cyclase, methylene blue (10 microM) and reversed spontaneously after 2 h. When peroxynitrite (1 mM) was mixed with D-glucose (11 mM) and subsequently neutralised to remove unreacted peroxynitrite, a new more potent relaxant was formed. Despite this, the ability of peroxynitrite (1-100 microM) to produce relaxation of endothelium-denuded rings was similar in normal and glucose-free Krebs. Glycerol (22 mM), which like D-glucose is membrane permeant, also reacted with peroxynitrite (1 mM) to form a new more potent relaxant. L-cysteine (1 mM) had no effect by itself on the tone of aortic rings and when present in the tissue bath had no effect on the ability of peroxynitrite or neutralised peroxynitrite (1-100 microM) to produce relaxation. It did, however, potentiate the relaxant actions of the products formed from the reaction of peroxynitrite with D-glucose or glycerol. The membrane impermeant sugars, mannitol and sorbitol (each 11 mM) also reacted with peroxynitrite (1 mM), but expression of the vasorelaxant properties of their respective derivatives was seen only in the presence of L-cysteine (1 mM). Membrane permeance cannot, however, explain why peroxynitrite reacts with D-glucose and glycerol, but not mannitol or sorbitol to form products with intrinsic relaxant activity, as the product formed from the impermeant sugar, L-glucose (11 mM), also has intrinsic activity. The relaxant potency of this product was equipotent to that formed from D-glucose and was also potentiated by L-cysteine (1 mM). These result confirm that peroxynitrite can react with glucose and other compounds with alcohol functional groups to form vasorelaxant species. The relaxation induced when peroxynitrite is added to rat aortic rings is not, however, dependent upon this reaction since it occurs in glucose-free Krebs.

Animals↗

Floral homeotic genes were recruited from homologous MADS-box genes preexisting in the common ancestor of ferns and seed plants.

Flowers sensu lato are short, specialized axes bearing closely aggregated sporophylls. They are typical for seed plants (spermatophytes) and are prominent in flowering plants sensu stricto (angiosperms), where they often comprise an attractive perianth. There is evidence that spermatophytes evolved from gymnosperm-like plants with a fern-like mode of reproduction called progymnosperms. It seems plausible, therefore, that the stamens/carpels and pollen sacs/nucelli of spermatophytes are homologous to fern sporophylls and sporangia, respectively. However, the exact mode and molecular basis of early seed and flower evolution is not yet known. Comparing flower developmental control genes to their homologs from lower plants that do not flower may help to clarify the issue. We have isolated and characterized MADS-box genes expressed in gametophytes and sporophytes of the fern Ceratopteris. The data indicate that at least two different MADS-box genes homologous to floral homeotic genes existed in the last common ancestor of contemporary vascular plants, some descendants of which underwent multiple duplications and diversifications and were recruited into novel developmental networks during the evolution of floral organs.

Amino Acid Sequence↗