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Biomedical subjects

I Wells

Publications and source records attributed to I Wells.

13 recordsLinked to original sources
PubMed1993

Inactivation of prostaglandin endoperoxide synthase by acylating derivatives of indomethacin.

Derivatives of the potent antiinflammatory agent and cyclooxygenase inhibitor indomethacin were synthesized in which the carboxylic acid moiety was converted into reactive acylating agents. Indomethacin imidazole (indomethacin-IM) and indomethacin N-hydroxysuccinimide (indomethacin-NHS) inactivated both the cyclooxygenase and peroxidase activities when incubated with the apo form of purified prostaglandin endoperoxide synthase (PGH synthase) at a stoichiometry of 1:1. Treatment of the inactivated enzyme with hydroxylamine at neutral pH led to recovery of all peroxidase and about 50% of the cyclooxygenase activity. Hydroxylamine did not regenerate the cyclooxygenase activity of indomethacin-inactivated protein. Reconstitution of the apoprotein with heme protected against inactivation by indomethacin-NHS. Visible spectroscopy established that indomethacin-NHS-inactivated apoenzyme had a reduced capacity to bind heme. Indomethacin-NHS also substantially protected the apoenzyme from cleavage at the trypsin-sensitive Arg277 site. Incubation of [2-14C]indomethacin-NHS with PGH synthase led to incorporation of radioactivity into the protein, but no adduct was detected by reversed-phase HPLC, suggesting it was unstable to the chromatographic conditions. Incubation of indomethacin-NHS with apoprotein followed by HPLC analysis led to the formation of greater amounts of the hydrolysis product indomethacin than did similar treatment of holoprotein. The results suggest that indomethacin-IM and indomethacin-NHS covalently and selectively label PGH synthase near the heme binding site, leading to loss of both catalytic activities of the enzyme.

Acylation↗
PubMed1992

Acetylation of prostaglandin endoperoxide synthase by N-acetylimidazole: comparison to acetylation by aspirin.

Treatment of prostaglandin endoperoxide (PGH) synthase apoprotein with a 100- or 1000-fold excess of N-acetylimidazole (NAI) led to time-dependent inactivation of both cyclooxygenase and peroxide activities. Reconstitution of apoprotein with heme prior to incubation with NAI substantially protected the enzyme from inactivation. Pretreatment of the protein with either acetylsalicylic acid (aspirin) or (+/-)-2-fluoro-alpha-methyl-4-biphenylacetic acid (flurbiprofen), which inhibit cyclooxygenase activity, did not alter the time course of peroxidase inactivation by NAI. Treatment of NAI-inactivated apoPGH synthase with hydroxylamine led to substantial regeneration of both cyclooxygenase and peroxidase activities. Quantitation of radioactivity following incubation of PGH synthase with [3H-acetyl]NAI indicated incorporation of 1.7 +/- 0.9 acetyl groups/70-kDa subunit. Cleavage of acetylated protein with trypsin under nondenaturing conditions followed by high-performance liquid chromatography analysis demonstrated that most of the radioactivity was incorporated into the 33-kDa fragment although significant radioactivity was also detectable in the 38-kDa fragment. Chymotryptic peptide mapping of acetylated protein revealed numerous potential sites of acetylation distributed in widely divergent regions of the protein. No apparent differences were observed between the chymotryptic maps of apo- and holoenzyme, suggesting that the adduct responsible for loss of catalytic activity is unstable to the chromatographic conditions. The different biochemical properties of PGH synthase acetylated by NAI or aspirin suggest that a major determinant of the specificity of aspirin for Ser530 is binding of the salicylate moiety to this region of the PGH synthase protein.

Acetylation↗
PubMed1987

Plasma thyroid hormones, thyroid stimulating hormone, and insulin during acute hypometabolic states in man.

Acute behavioral rest states in man are associated with marked hormonal and metabolic changes. In order to complete a hormonal profile of these states and to identify possible metabolic regulators, we measured thyroid hormones (T3 and T4), thyroid stimulating hormone (TSH), and insulin during the stylized mental practice of "transcendental mediation" (TM) and during ordinary unstylized eyes closed rest. Except for TSH, which declined acutely, hormone levels were normal and stable throughout the experiment. The stability of T3 and T4, and insulin make it unlikely that these hormones regulate the acute metabolic changes associated with these behavioral states. Decreased TSH, along with stable thyroid hormone levels, may suggest change of the set point for feedback control of TSH secretion during TM and is consistent with primarily neural modulation of TSH secretion by this behavior.

Adult↗
PubMed1986

Renal carcinoma: duplex Doppler evaluation.

Doppler ultrasound has a clearly defined role in the assessment of carotid and peripheral vascular disease. In these situations vessel pathology produces alterations in velocity and volume flow and in the flow-velocity spectrum. Flow in the renal arteries is affected not only by disease of the renal vessels but also by the peripheral resistance to flow within the kidney. Alterations in this peripheral resistance resulting from renal disease are reflected in the Doppler flow spectrum analysis. In 14 patients with renal carcinoma, three different blood flow patterns were observed, reflecting the differing vascularity of the renal tumours. These were compared with blood flow in normal kidneys and in kidneys containing renal cysts. Doppler ultrasound adds further information to the study of renal carcinomas, allowing the prediction of tumour vascularity, and may be useful as a preliminary investigation prior to angiography and embolisation.

Adult↗
PubMed1983

Association of IgE antibodies to sodium aurothiomalate and adverse reactions to chrysotherapy for rheumatoid arthritis.

The relationship between adverse reactions to chrysotherapy and specific IgE antibodies to sodium aurothiomalate (auIgE) was studied in 67 patients with rheumatoid arthritis (62) or psoriatic arthritis (5). Thirty patients (45 percent) had such antibodies versus none of the 27 control patients. Of the 34 patients in whom reactions to chrysotherapy developed, 23 (68 percent) had auIgE versus 7 (21 percent) without reactions (p less than 0.001). Mucocutaneous lesions were significantly associated with auIgE (p less than 0.001). All five patients with thrombocytopenia, but only one of five with the nephrotic syndrome, had auIgE. The patients with IgE response had higher total serum IgE levels (p less than 0.005), were more likely to be atopic (four to one), and had more recently received chrysotherapy (mean 2.8 +/- 1.95 years versus 7.0 +/- 5.75 years, p less than 0.001) than those without response, but did not differ by either the gold product or the total dose used. Chrysotherapy is associated with the production of specific IgE antibodies to a gold salt, and some mucocutaneous and hematologic reactions may be immunologically mediated.

Adult↗
PubMed1981

Alcoholism.

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Adult↗
PubMed1981

Incidence of fungal precipitins in patients treated with beclomethasone dipropionate aerosol.

The authors followed the development of serum precipitins to aspergillus and Candida albicans in 14 asthmatic patients placed on beclomethasone dipropionate inhalation at a mean duration of five months. Three sera positive for aspergillus precipitins became negative during treatment. One patient had clinical oropharyngeal candidiasis and another patient's serum became positive for candida precipitin. The authors conclude that the incidence of oropharyngeal candidiasis and candida or aspergillus precipitins are rare among patients treated with beclomethasone.

Adult↗
PubMed1980

Increased C1q binding and arthritis in primary biliary cirrhosis.

Using the C1q binding assay, circulating immune complexes were detected in 31 of 50 (62%) patients with primary biliary cirrhosis and 17 of these had arthritis. This took the form of a seropositive inflammatory polyarthritis in 12 of 18 patients with C1q binding greater than or equal to 20%, whereas a milder seronegative arthritis associated with scleroderma and Raynaud's phenomenon was found in five of 13 patients with C1q binding < 20%. Only two of the 19 patients with normal binding had arthritis and this was of a mild and transient nature. There was a positive correlation between C1q binding and the serum concentrations of IgG and IgM. Results also supported the hypothesis that circulating immune complexes may be involved in the development of arthritis in patients with primary biliary cirrhosis.

Aged↗
PubMed1977

Bronchocentric granulomatosis: a complication of allergic bronchopulmonary aspergillosis.

Hypersensitivity to the fungal antigens of Aspergillus fumigatus may result in a spectrum of immune injury collectively known as allergic bronchopulmonary aspergillosis (ABPA). This report describes a 14-yr-old boy who presented clinical findings consistent with ABPA,including a history of asthma, blood eosinophilia, serum precipitins, and IgE antibodies to Aspergillus fumigatus. Sputum Aspergillus, pulmonary infiltrates, and dual types I and III skin reactions to Aspergillus fumigatus were observed also. Pathology of the resected right upper lobe revealed severe bronchial destruction with the findings of bronchocentric granulomatosis. Noninvasive septate fungal hyphae compatible with Aspergillus were identified. Cultures from sputum and surgical specimens grew Aspergillus and Mycobacterium intracellulare avium. The PPD-B (purified protein derivative-Batty) intradermal skin test produced a 6 mm induration (PPD-S was negative). The patient's condition has been well controlled with prednisone and several antituberculous drugs. In addition, inflammatory and immunologic parameters have begun to return to normal. The relationship between ABa and the atypical mycobacterial infection is not clear. The association of ABPA with the severe bronchial destruction seen in bronchocentric granulomatosis is emphasized to alert physicans to this serious sequelae of ABa seen in the asthmatic.

Adolescent↗
PubMed1977

The effect of endotoxin on the mast cell c'AMP system.

To determine whether the endotoxin induced release of histamine is mediated via the mast cell c'AMP system, hamster mast cells were isolated and incubated (prior to endotoxin-serum stimulates (ET-S) with disodium cromoglycate, isoproterenol and aminophylline. All drugs caused significant inhibition of the ET-S histamine release. The authors conclude that ET-S utilizes the c'AMP system to release histamine.

Aminophylline↗
PubMed1976

Aryl-hydrocarbon hydroxylase activity in lymphocytes from lung cancer patients and normal controls.

A radiometric assay for the determination of AHH activity in lymphocytes is described. Subjects included eleven male patients with histologically verified lung cancer (nine squamous cell carcinoma and two adenocarcinoma) and eleven age- and sex-matched controls. Lung cancer patients exhibited considerably greater variation and elevated levels of both AHH activity per se and AHH activity adjusted for total cellular DNA than control individuals. Methodology for AHH determinations and implications for lung cancer epidemiology and control are discussed.

Adenocarcinoma↗