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Biomedical subjects

R E Smith

Publications and source records attributed to R E Smith.

At least 181 records · Page 10Linked to original sources
PubMed1992

The evolution of proteinase substrates with special reference to dipeptidylpeptidase IV.

The design and development of specific substrates for proteolytic enzymes is reviewed. Particular attention is given to substrates containing the leaving groups 4-methoxy-2-naphthylamide (MNA) and 7-amino-4-trifluoromethylcoumarin (AFC). The MNA substrates are used for histochemical and cytochemical purposes, and they yield a coloured final reaction product when azo-coupled with a diazonium salt, an osmiophilic product for electron microscopy when coupled with hexazotized Pararosaniline, or a fluorescent final reaction product when coupled with 5-nitrosalicylaldehyde. AFC substrates are considerably more sensitive, and they yield the fluorescent product AFC after enzymatic cleavage of the substrate. AFC is not sufficiently water-insoluble to allow (intra)cellular localization, but AFC substrates are successfully used for incubations in microwells (Immu-Probe technique) and for the demonstration of banding patterns after gel electrophoresis (enzyme-directed overlay membrane technique). The methods are discussed with the example of the elucidation of the role of dipeptidylpeptidase IV in autoimmune diseases.

Amino Acid Sequence↗
PubMed1992

Esophageal hematoma and tear requiring emergency surgical intervention. A case report and literature review.

Esophageal hematoma is a disorder characterized by the sudden development of pain, hematemesis, or dysphagia, commonly with minimal precipitant. We present the case of 59-year-old man with esophageal hematoma, precipitated by eating, with massive hematemesis requiring surgical intervention. A review of 31 additional cases in the literature since 1980 is discussed. The Mallory-Weiss syndrome and Boerhaave syndrome are distinct entities with some clinical similarities.

Emergencies↗
PubMed1992

Amplification of doxorubicin mutagenicity by cupric ion.

There is a presumption that copper and anthracycline drugs will interact with DNA to produce genotoxicity. This is of concern because serum copper levels are increased in certain neoplastic diseases. To test the interaction, it was determined if the metal ion could alter the mutagenesis of doxorubicin and related drugs in the Salmonella microsome test. In the standard form of the test, doxorubicin was strongly mutagenic against frameshift-sensitive strain TA98. When cupric acetate was added with doxorubicin it amplified the mutagenesis of the antineoplastic with an increase of approximately 19% in peak mutagenic values. This apparent "chemoactivation" was evaluated by additional applications of the Salmonella test. Preincubation of cupric acetate, drug, and bacteria (+/- rat liver S9 fraction) also resulted in a copper-amplifying effect. In the preincubation method copper produced a drug concentration-related increase of more than 700% in the mutagenicity of doxorubicin. This large an increase occurred without S9 in the test. The effects observed in TA98 were not seen with TA102, a strain sensitive to oxidation mechanisms. Copper amplification in the mutagenicity of a positive control, aflatoxin B1, was also observed with TA98 but these effects were not seen with the chelator, EDTA, the antifolate antineoplastic drug, methotrexate, or a test negative amino acid, methionine. Results point to a direct frameshift mechanism to explain the increase in mutagenicity with copper. Amplification of mutagenicity found in this study provides initial experimental support that anthracycline-metal ion-DNA associations might contribute to genotoxicity as has been inferred in the literature.

Copper↗
PubMed1992

Cardiac doses in post-operative breast irradiation.

Data were collected on radiation doses given to the heart and coronary arteries during primary breast irradiation in order to analyze factors which might be important in the aetiology of subsequent cardiac-related disease. Twenty eight patients with breast cancer were studied. Fourteen patients treated from 1957 to 1984 were studied retrospectively (group 1), and 14 treated from 1988 to 1989 were studied prospectively (group 2). All patients had stage I or II disease at presentation, and were under 70 years of age. None had chemotherapy as a primary form of treatment. Patients were given a computed tomography scan of the chest, and three-dimensional reconstruction was made of the heart, lung and body contour. Original dose distributions were super-imposed on these outlines, and doses to the total cardiac volume and three main coronary arteries were estimated using an alpha/beta ratio of 4 Gy. Nine out of 14 patients in group 1 had a mastectomy followed mainly by orthovoltage radiation with similar techniques used up until 1984. Thirteen out of 14 patients in group 2 had conservative surgery followed by a modern two- or four-field megavoltage technique. We found that for patients with left-sided tumours (n = 20), the heart volume irradiated to a minimum extrapolated target dose of 5 Gy is significantly decreased for patients treated with a modern technique (group 2) when compared with those treated with earlier techniques (group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Expression of the gene coding for the major outer capsid protein of SA-11 rotavirus in a baculovirus system.

The gene coding for the major outer capsid protein (VP7) of simian rotavirus SA-11 has been expressed in a baculovirus-insect cell system. The resulting protein is 35 kDa and is primarily associated with the endoplasmic reticulum. Neutralizing SA-11 polyclonal antiserum and VP7 monospecific antiserum reacted specifically with the expressed gene product. Antiserum derived against the recombinant VP7 protein neutralized SA-11 rotavirus infectivity in a fluorescent focus assay.

Animals↗
PubMed1992

Pars plana vitrectomy for intraocular inflammation-related cystoid macular edema unresponsive to corticosteroids. A preliminary study.

PURPOSE: To determine the role of pars plana vitrectomy in patients with intraocular inflammation-related cystoid macular edema that is unresponsive to corticosteroids. METHODS: Eleven eyes of nine patients underwent a standard three-port pars plana vitrectomy. The primary indication was intraocular inflammation-related cystoid macular edema that was unresponsive to oral, sub-Tenon's, and topical corticosteroids. Preoperative follow-up ranged from 20 months to 144 months (average, 70 months). Postoperative follow-up ranged from 3 months to 108 months (average, 21 months). RESULTS: Seven eyes (64%) improved 4 or more lines of Snellen visual acuity within 4 weeks. Two eyes (18%) remained unchanged and 2 eyes (18%) worsened. Cystoid macular edema improved by clinical examination and fluorescein angiography in 9 eyes (82%) and by clinical examination alone in 2 eyes (18%). No intraoperative complications were noted. Postoperative complications consisted of cataract formation in 1 eye (9%), glaucoma in 2 eyes (18%), and epiretinal membrane formation in 1 eye (9%). CONCLUSION: Pars plana vitrectomy may have a role in the treatment of intraocular inflammation-related cystoid macular edema that fails to respond to corticosteroids. The subgroup of patients who benefit most remains to be identified.

Administration, Topical↗
PubMed1992

Sensation seeking, stress, and adolescent injuries: a test of stress-buffering, risk-taking, and coping skills hypotheses.

The potential stress-buffering effects of sensation seeking were assessed in a prospective study involving high school athletes. A significant positive relation between major negative sport-specific life events and subsequent injury time-loss occurred only for athletes low in sensation seeking. No evidence was obtained for a competing hypothesis that high sensation seeking would constitute an injury vulnerability factor by increasing risk-taking behaviors. Although low sensation seekers reported poorer stress management coping skills, there was no evidence that differences in coping efficacy mediated the injury vulnerability difference. Results indicate that sensation seeking is a stress-resiliency factor and suggest the utility of assessing relations between life stressors and outcomes that occur within the same environmental context.

Adaptation, Psychological↗
PubMed1992

Role of nitric oxide synthesis in the regulation of coronary vascular tone in the isolated perfused rabbit heart.

OBJECTIVE: The aim was to study the effects on coronary vascular tone of three inhibitors of nitric oxide (NO) synthesis. METHODS: Studies were performed on isolated perfused hearts of 74 male New Zealand White rabbits fed normal laboratory diet. Resting coronary perfusion pressure was increased to 40-60 mm Hg with the thromboxane mimetic 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F2 alpha (U46619). The effects of NG-monomethyl-L-arginine (L-NMMA), N-iminoethyl-L-ornithine (L-NIO), and NG-nitro-L-arginine methyl ester (L-NAME) (0.3-300 microM) on resting coronary perfusion pressure were determined. The effects of these compounds, at concentrations that increased the resting perfusion pressure to a similar extent, on the fall in perfusion pressure induced by acetylcholine (0.1 microM) and glyceryl trinitrate (1 microM) were also investigated. In these studies the resting perfusion pressure was maintained at 40-60 mm Hg by reducing the concentration of U46619. RESULTS: L-NMMA, L-NIO, and L-NAME induced concentration dependent increases in resting coronary perfusion pressure (n = 3-9, p < 0.05). L-NAME had the greatest potency and efficacy, increasing the resting pressure by 48.0(SEM 9.6) mm Hg at 30 microM. L-NIO and L-NMMA increased perfusion pressure by 27.3(3.0) and 19.5(5.8) mm Hg respectively at the maximum concentration studied (300 microM). However, at concentrations that were equieffective on resting perfusion pressure (15 mm Hg increase), L-NMMA (100 microM), but not L-NIO (25 microM) or L-NAME (4 microM), significantly inhibited the fall in pressure induced by acetylcholine by 57.2(5.0)%, n = 6, p < 0.05. This effect of L-NMMA++ was attributed to a shorter duration of fall and was reversed by L-arginine (300 microM). L-NMMA (100 microM) and L-NIO (25 microM) potentiated the effect of glyceryl trinitrate by increasing the peak fall in perfusion pressure by 75.6(11.0)% and 68.8(24.1)% respectively (n = 6 for each, p < 0.05). CONCLUSIONS: The differential effects of the three inhibitors on resting coronary perfusion pressure and the acetylcholine induced fall in coronary perfusion pressure suggest that basal and stimulated NO synthesis may be differentially regulated. Reduction in the synthesis of endogenous NO by these compounds potentiates the glyceryl trinitrate induced fall in perfusion pressure, which may have important clinical implications.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

The heterogeneity of 11-beta-hydroxysteroid dehydrogenase activities in the rat hippocampus implies a complex regulation of steroid hormone action.

1. The rat hippocampus 11-beta-hydroxysteroid dehydrogenase (11-HSD) displays a different substrate specificity to that of other tissues. S1 nuclease analysis was used to determine whether the hippocampal messenger RNA is different from that found in other tissues. 2. S1 nuclease analysis using probes spanning the full length cDNA demonstrated that there were no differences in sequence between the hippocampal 11-HSD and the enzyme originally cloned from the liver. 3. These results suggest that there may be multiple 11-HSD isoforms in the hippocampus with different substrate specificities.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1992

Elimination of preventable blindness from diabetes by the year 2000.

"Diabetes 2000" will parallel a major diabetic retinopathy public information campaign recently announced by the National Eye Institute. The NEI's National Eye Health Education Program (NEHEP), which targets both diabetic retinopathy and glaucoma, is fashioned along the lines of earlier federal initiatives against smoking and high blood pressure. By continuously updating our medical knowledge and skills related to this multisystem disorder, and by forging partnerships between physicians in the effective and efficient management of diabetic patients, we have a unique and important opportunity--we can reduce preventable blindness from diabetes by the year 2000.

Blindness↗