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Biomedical subjects

A Woods

Publications and source records attributed to A Woods.

At least 163 records · Page 9Linked to original sources
PubMed1980

Cytoskeleton changes in fibroblast adhesion and detachment.

The organization of the cytoskeleton in several anchorage-dependent fibroblast types has been compared with the pattern of adhesions to a glass substratum which will support either their growth or just their spreading. Components were stained separately for immunofluorescence microscopy using specific antisera against actin, tubulin, and gizzard 10-nm filament protein, and the adhesions were visualized by interference-reflexion microscopy. Of the cytoskeleton features, only stress fibres could be related to the pattern of focal adhesions; as shown before, each focal adhesion lies directly beneath a stress fibre, often near the terminus. Cells spread on fibronectin-treated glass in serum-free medium to arrest the development of focal adhesions, show correspondingly underdeveloped stress fibres. Actin geodesic domes, microtubules, and 10-nm filaments showed no relations with the adhesion pattern. During cell rounding leading to detachment with either EGTA or trypsin, stress fibres begin to disperse in advance of shape change whereas microtubules and 10-nm filaments seem to alter their distribution as a consequence of shape change. We therefore confirm that stress fibres are the cytoskeleton features most directly related to focal adhesions and are cytoskeleton targets for 2 agents which cause rounding and hence detachment. The sequences of events in dispersal of stress fibres by EGTA and by trypsin showed significant differences in detail. With trypsin, fibres higher in the cell and terminating at the cell edge were more sensitive than most basal fibres and, during disintegration, all types of fibre went through an intermediate 'beaded' structure. With EGTA, all stress fibres seemed to be similarly susceptible and the beaded stage was not seen. The implications of these differences for our understanding of the mechanisms of dispersal of stress fibres are discussed.

Actins↗
PubMedDate not supplied

The disposition of 6-deoxyacyclovir, a xanthine oxidase-activated prodrug of acyclovir, in the isolated perfused rat liver.

The antiviral drug, acyclovir, has been used in the treatment of chronic type B hepatitis. High serum concentrations of acyclovir are required to achieve inhibition of hepatitis B viral replication. Because only 15 to 20% of an oral dose is absorbed, it is necessary to administer acyclovir by intravenous infusion. 6-Deoxyacyclovir, an analog of acyclovir, is well absorbed when given orally, and is converted to acyclovir by xanthine oxidase which is present in the gut and liver. This study has examined the hepatic disposition of 6-deoxyacyclovir in a 100 ml recirculating (12 ml per min) perfused rat liver system. Following administration of a bolus dose of 5 mumoles 6-deoxyacyclovir to the reservoir, perfusate concentrations of 6-deoxyacyclovir declined monoexponentially, as the metabolite acyclovir appeared in the perfusate. Addition of the xanthine oxidase inhibitor allopurinol (5 mg) to the perfusate reservoir prior to the administration of 6-deoxyacyclovir resulted in impaired hepatic metabolism of 6-deoxyacyclovir, as demonstrated by a 47% reduction in systemic clearance rate (4.5 +/- 0.4 to 2.4 +/- 0.9 ml per min; p less than 0.05) (mean +/- S.E., n = 6) and a 1.8-fold increase in terminal elimination half-life of 6-deoxyacyclovir (23.5 +/- 2.7 to 42.7 +/- 4.1 min; p less than 0.05), accompanied by a 30% reduction in appearance of acyclovir. The efficient hepatic conversion of 6-deoxyacyclovir to the active antiviral drug, acyclovir, provides a rationale for trials of oral 6-deoxyacyclovir in the treatment of chronic type B hepatitis.

Acyclovir↗
PubMedDate not supplied

Eradication of diminutive polyps: a prospective evaluation of bipolar coagulation versus conventional biopsy removal.

Bipolar probe coagulation (BICAP) was evaluated and compared with conventional cold biopsy (CBx) as a potential therapeutic modality for eradication of diminutive colonic polyps (DPs). Seventy-seven and 79 DPs were treated with BICAP and CBx, respectively. Twenty-one percent of the BICAP and 29% of the CBx (p greater than 0.05) group had residual polypoid tissue detected at flexible sigmoidoscopy 3 weeks after treatment. Because of incomplete polyp removal, CBx and BICAP coagulation cannot be recommended as definitive therapies for DPs. Neoplasia was present in 22% of DPs located less than 60 cm from the anus, 73% of proximally located small polyps, and 32% of all DPs. Despite apparent eradication at the time of treatment, the incidence of residual polypoid tissue would suggest the need for critical evaluation of other modalities used to eradicate or remove DPs.

Adult↗
PubMedDate not supplied

Patient attitudes and psychological considerations in dialysis discontinuation.

The authors surveyed 36 adult patients who were maintained with chronic renal dialysis concerning their attitudes about dialysis discontinuation. Few subjects reported having ever considered stopping the life-support treatment. When asked to consider 12 hypothetical scenarios in which they might consider stopping treatment (e.g., onset of dementia or blindness), most subjects would still not consider discontinuation. Consideration of dialysis discontinuation was directly correlated with the patient's educational level. Follow-up after 1 year underscored the substantial differences between the responses the subjects gave to the 12 hypothetical scenarios and their real-life responses when they were later faced with decisions to actually terminate treatment. Psychiatrists have an opportunity to participate in the complex clinical and ethical decisions associated with advance directives and patients' right to refuse life-support treatment.

Adult↗
PubMedDate not supplied

Denying the dying. Advance directives and dialysis discontinuation.

A structured interview was administered to a sample of patients on maintenance dialysis and their attending physicians to obtain information on the documentation of their end-of-life treatment preferences. The majority of the patients reported never having considered stopping dialysis, or having discussed with their nephrologist or family the circumstances in which treatment should be discontinued. Only 7 patients (6%) had completed an advance directive; these patients were all men (P = 0.01) and tended to be better educated (P = 0.02). Only one of the nine physicians had completed an advance directive. In most cases, the dialysis patients and their treatment team staff were preoccupied with the struggles of daily life and had avoided or denied considerations of terminal illness and death. The literature on denial, medical illness, and dying is also reviewed as it relates to dialysis patients, end-of-life treatment, and terminal care.

Adult↗
PubMedDate not supplied

Inactivation of horseradish peroxidase by 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine.

In the presence of H2O2, horseradish peroxidase (HRP) catalyzes the one-electron oxidation of a porphyrinogenic agent, 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP), leading to formation of an ethyl radical, inactivation of the enzyme, and formation of an altered heme product. The loss of heme during the inactivation of HRP was dependent on the duration of exposure to DDEP as well as the concentration of H2O2 and DDEP. The pseudo first order rate constant for the oxidation of DDEP by compound I of HRP at pH 7.4 was 0.07 min-1, and the maximal extent of heme loss was 35%. The altered heme product, which was isolated by reverse phase HPLC, was characterized by the use of mass and 1H NMR spectrometry as a substitution product of a C2H4OH moiety for a meso proton of the prosthetic heme [meso-(hydroxyethyl)heme]. The source of the oxygen in the C2H4OH moiety appeared not to be H2O2 or H2O as 18O was not incorporated in the heme adduct when H2(18)O2 or H2(18)O was used. The DDEP-mediated reaction did not form the expected delta-meso-ethylheme adduct analogous to the ethyl radical-mediated inactivation of HRP by ethylhydrazine (EH) [Ator et al. (1987) J. Biol. Chem. 262, 14954-14960]. However, we have found that meso-(hydroxyethyl)heme was formed in the EH-mediated reaction, albeit in apparently lower amounts than delta-meso-ethylheme. Perhaps the proximity of the heme to the ethyl radical may play a role in determining the nature of the heme products formed.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

The priceless gift.

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Critical Care↗