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Biomedical subjects

R M Mitchell

Publications and source records attributed to R M Mitchell.

At least 19 recordsLinked to original sources

Comparative evaluation of treated bovine pericardium as a xenograft for hernia repair.

Two forms of bovine pericardium (BPC) were assessed as hernia repair materials: non-cross-linked (lyophilized) and cross-linked through treatment with glutaraldehyde (GA). These were compared with polypropylene mesh (Marlex) in a rabbit model. Over 52 wk implantation, the GA BPC grafts developed a strong, stable, fibrous tissue replacement with good incorporation into the abdominal muscle wall. The lyophilized BPC grafts were substantially resorbed within 12 wk of implantation, however the thin, fibrous replacement tissue was inadequate for abdominal wall support. Marlex grafts provided sufficient abdominal support, however these grafts were associated with extensive adhesion formation and, in this model, fat deposition around the perimeter of the graft. Control (ungrafted) rabbit abdominal muscle in the transverse orientation had an ultimate tensile load (UTL) of 11.4 +/- 5.1 N (x +/- s.d.) and a strain at UTL of 35 +/- 12% (n = 169). At 52 weeks the UTL of the repair sites was 7.3 +/- 4.5 N (n = 6), 5.1 +/- 3.5 N (n = 6) and 5.6 +/- 2.7 N (n = 6) for GA BPC, lypophilized BPC and Marlex grafts, respectively.

Animals

Radionuclide uptake by trees at a radwaste pond in Washington State.

This paper presents work conducted in the summer of 1980 by Rockwell Hanford Operations, Hanford, WA, in support of a proposed effort to decommission and decontaminate a Hanford radwaste pond (216-U-10 Pond). The radionuclide values presented here are in addition to the U-Pond work that was recently published (La83) and are below any levels of environmental concern and within state and federal guidelines. U-Pond was constructed in 1944 for the surface disposal of industrial waste waters from nuclear separation processes and is one of the longest used aquatic, low-level, radioactive waste-disposal sites in the world. Tree leaf/twig, root, core and soil samples were collected and analyzed for 137Cs, 90Sr and 239Pu/240Pu. Strontium-90 was more readily taken up by trees than 137Cs or 239Pu/240Pu. Soil concentration values for 137Cs and 239Pu/240Pu were significantly greater (p less than or equal to 0.05) than all tree component parts. Radionuclide concentration ratios were higher for 90Sr (0.01-1355.0) than for 137Cs and 239Pu/240Pu for all tree components examined. Concentration ratios for 239Pu/240Pu ranged from 10(-6) to 10(-2) and are comparable to other studies conducted at the U.S. Department of Energy's Oak Ridge and Savannah River laboratories. These data represent the first quantitative information with respect to radionuclide uptake by trees on the Hanford Site.

Cesium Radioisotopes

On the site of action of the anti-adrenal steroidogenic effect of cyproterone acetate.

Cyproterone acetate (CA) inhibited 1-24 ACTH (50 ng/l)-stimulated cortisol production by dispersed guinea-pig adrenal cells in a dose-related manner. Inhibition occurred over the range 10(-6) to 5 X 10(-5) moles/l. The concentration of drug which induced 50% inhibition was 4.6 X 10(-6) moles/l. The sites of action of this anti-steroidogenic effect have been established. Dispersed adrenal cells were challenged with the cortisol precursor steroids (all at 10(-5) moles/l) pregnenolone (Pe), 17 alpha hydroxypregnenolone (17-OH Pe), 17 alpha-hydroxyprogesterone (17-Po), and 11 deoxycortisol or 1-24 ACTH (100 ng/1) in the absence and presence of increasing concentrations of CA (10(-5) to 10(-4) moles/l). In the absence of drug, the steroid precursors or ACTH provoked cortisol secretion greater than 10-fold that secreted by cells incubated in their absence. ACTH-stimulated cortisol secretion was inhibited greater than 68% at concentrations of CA greater than 10(-5) moles/l. CA (10(-5) moles/l) had no significant effect on steroid-stimulated cortisol production when the delta 4, 3 ketosteroids 17-OH Po and 11-deoxycortisol were used, but depressed secretion by greater than 61% (P less than 0.001) when the delta 5 3 beta hydroxysteroids (Pe, 17-OH Pe) were employed. Increasing CA concentrations to 10(-4) moles/l had little effect on cortisol secretion provoked by 11-deoxycortisol, but significantly (P less than 0.05) depressed cortisol secretion stimulated by 17-OH Po. These results suggest that the major site of action of CA is delta 5, 3 beta hydroxysteroid dehydrogenase (3 beta-HSD) with a secondary effect on 21-hydroxylase activity. To confirm these findings cortisol secretion provoked by 17, 21, dihydroxypregnenolone (17, 21 diOH Pe) and 21 deoxycortisol (21-DOC) was measured in the absence and presence of increasing concentrations of CA. At the lowest concentration of CA (5 X 10(-6) moles/l), cortisol secretion provoked by 17, 21 diOH Pe was inhibited by 28% (P less than 0.01) whereas secretion provoked by 21-DOC was not significantly affected. At the highest concentration of CA (10(-4) moles/l), the relative inhibition was 80% for 17, 21 diOH Pe and 38% for 21-DOC. We conclude that cyproterone acetate inhibits adrenal steroidogenesis at both 3 beta-HSD and 21-hydroxylase, the degree of inhibition being more pronounced at 3 beta-HSD.

3-Hydroxysteroid Dehydrogenases

Anatomical localization of atherosclerotic lesions using the pulse volume recorder.

The pulse volume recorder has been used in studying 62 limbs to assess its accuracy in localization of arteriosclerotic lesions of the lower limbs, realizing the limitations of clinical examination and simple pressure measurements. Its advantages over simple pressure measurements are illustrated. It was shown to be most accurate in locating isolated stenoses. The technique helps differentiate aorto-iliac from high superficial femoral artery obstruction. It can be used when severe medial sclerosis is present and is very helpful when distal pulses cannot be detected for technical reasons.

Adult

DNA organization of Methanobacterium thermoautotrophicum.

The organism Methanobacterium thermoautotrophicum, an archaebacterium, is envolutionarily very distant from both traditional prokaryotes and eukaryotes. Its genome (DNA) has physical characteristics typical of most prokaryotes except that it is quite small (about 10(9) daltons, less than half the size of the genome of Escherichia coli) and contains a significant amount (6 percent) DNA which renatures extremely rapidly.

Base Sequence

Calculation of evolutionary trees from sequence data.

Evolutionary trees are usually calculated from comparisons of protein or nucleic acid sequences from present-day organisms by use of algorithms that use only the difference matrix, where the difference matrix is constructed from the sequence differences between pairs of sequences from the organisms. The difference matrix alone cannot define uniquely the correct position of the ancestor of the present-day organisms (root of the tree). Furthermore, methods using the difference matrix alone often fail to give the correct pattern of tree branching (topology) when the different sequences evolve at different rates. Only for equal rates of evolution can the difference matrix (when used with the so-called matrix method) yield exactly the correct topology and root. In this paper we present a method for calculating evolutionary trees from sequence data that uses, along with the difference matrix, the rate of evolution of the various sequences from their common ancestor. It is proven analytically that this method uniquely determines both the correct topology and root in theory for unequal rates of sequence evolution. How one would estimate an ancestral sequence to be used in the method is discussed in particular for the 5S RNA sequences from prokaryotes and eukaryotes and for ferredoxin sequences.

Amino Acid Sequence

The prognosis of breast cancer based on histological assessment.

Histopathology data from 298 patients with breast cancer have been stored in a computer, and features influencing survival have been analysed by the life table method and presented in survival curves. Prognostic features assessed were the size, type, and grade of neoplasm, the amount of stromal elastosis and lymphocytic infiltrate, and the presence and number of axillary metastases. The most reliable indications of short survival are the presence of axillary metastases and a high tumour grade. These two features are correlated, as high-grade tumours are much more likely to have metastases at presentation. No statistical difference is found in the survival of patients with metastases in one or two axillary nodes compared with those with larger numbers involved. There are differences in survival in different types of carcinoma; the well-differentiated infiltrating duct carcinoma with tubular pattern has the best prognosis, followed by the medullary carcinoma. The size of the tumour has some prognostic significance, but this is outweighed by its grade.

Adenocarcinoma

A fifteen-year study of breast cancer in Tasmania.

Seven hundred and seventy-nine patients presenting with breast cancer in Tasmania between 1930 and 1975 have been studied. No comparisons of different treatment have been made, but overall survival has been assessed. Median survival in the group was only 3-3 years, but 30% of patients were still alive at ten years. Other factors assessed in relation to survival were axillary node involvement, site, size, age, parity, breast feeding and place of birth.

Adult

An electrophoretic study of reversible protein denaturation: chymotrypsinogen at high pressures.

When reversible denaturation of chymotrypsinogen is produced at elevated hydrostatic pressures, conformational relaxation can occur quite slowly, allowing electrophoretic separation of the principal states from the equilibrium mixture. In this work we report experimental concentration distribution patterns obtained at pH 2.03 at a temperature of 20.5 degrees and find them to be reasonably consistent with the behavior that is expected from a simple two-state isomerism. However, the results do not at all rule out the existence of low levels of intermediate states.

Chymotrypsinogen