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Biomedical subjects

J A Johnson

Publications and source records attributed to J A Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Tissue distribution of enzymic methylation of glutathione S-transferase and its effects on catalytic activity. Methylation of glutathione S-transferase 11-11 inhibits conjugating activity towards 1-chloro-2,4-dinitrobenzene.

Glutathione S-transferases (GSTs) were isolated from rat liver, lung, heart, kidney, testis and brain by coupled affinity chromatography and subunits were resolved by reverse-phase h.p.l.c. The reverse-phase h.p.l.c. technique was improved from our previously published work [Johnson, Neal, Collins & Siegel (1990) Biochem. J. 270, 483-489] by changing from a C4 to a C18 wide-pore reverse-phase column; this resulted in baseline or near-baseline resolution of all GST subunits. There were significant tissue-dependent differences in the expression of GST subunits and the level of GST subunits present was quantitatively determined for each of the tissues. The extent of methylation of GSTs in vitro and distribution of GST methyltransferase (GST-MT) was determined in cytosolic fractions from each of these tissues. Purified GST isoenzymes were methylated with partially purified liver GST-MT. Methylation of Mu class subunits 3 and 4, the preferred substrates of methylation in liver, was substoichiometric in all tissues. The extent of methylation of subunit 3 ranged from 0.13% to 0.94% and subunit 4 from 0.03% to 0.60%. Methylation of Alpha class subunits was either not detectable or 5-10-fold less than that of Mu class subunits 3 and 4. Pi class subunit 7 was methylated to a greater extent than the Alpha class subunits but less than Mu class isoenzymes. A notable exception to this low level of methylation was GST 11-11, found mainly in testis and brain. Methylation of subunit 11 reached 21.9% (219 pmol of methyl group/nmol of subunit 11) when this isoenzyme was incubated with partially purified liver GST methyltransferase. Methylation of GST 11-11 was found to inhibit the conjugating activity of this isoenzyme towards 1-chloro-2,4-dinitrobenzene; the degree of inhibition of conjugating activity correlated with the extent of methylation of GST 11-11. GST-MT activity toward GST subunits 3, 4 and 11 was present in kidney and liver, detectable in lung and heart, but absent from brain and testis. Anion-exchange chromatography of GST-MTs from liver and kidney suggested the presence of four different forms of GST-MT (I-IV) and indicated that GST-MT isoenzymes III and IV were present at significantly lower concentrations in kidney than liver. The present paper shows that methylation is an enzyme-catalysed reaction that differs in substrate-specificity with respect to different GST isoenzymes, that expression of GST-MT is tissue-dependent and multiple forms of the enzyme are present in liver and kidney, and that methylation inhibits GST activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1992

Clinical spectrum of paraesophageal herniation.

Paraesophageal herniation is a potentially devastating condition of the gastroesophageal hiatus commonly manifesting in patients of advanced age with other significant medical problems. Surgical treatment is generally indicated to avoid catastrophe related to gastric volvulus. The operative approach utilized should be individualized to the patient's pathophysiologic condition rather than attempting to apply a single repair for all patients with this heterogeneous clinical problem.

Aged↗
PubMed1992

Thoracoscopic resection of 85 pulmonary lesions.

Advances in endoscopic surgical equipment and laser technology have expanded the role of thoracoscopy to include thoracoscopic pulmonary resection. Eighty-five thoracoscopic pulmonary resections were performed on 61 consecutive patients with small lesions (less than 3 cm) in the outer third of the lung. Patients with preoperative histologic evidence of bronchogenic carcinoma were excluded unless there was impairment of cardiopulmonary function, advanced age, or concomitant extrathoracic malignancy. These thoracoscopic pulmonary resections were accomplished with the neodymium:yttrium-aluminum garnet laser (31), endoscopic stapler (29), or both (25). The mean diameter of the lesions was 1.3 cm (range, 0.4 to 2.7 cm). There has been one late death (38th postoperative day) unrelated to the operation. Morbidity consisted of postoperative atelectasis (2), pneumonia (2), bleeding requiring transfusion (1), and bronchopleural fistula of greater than 7 days duration (3). There were no wound problems. The mean period of chest tube drainage was 3.3 +/- 3.0 days. Mean postoperative stay was 5.7 +/- 4.9 days. The pathologic diagnosis was benign disease in 28 patients (interstitial fibrosis/pneumonitis, 15; radiation fibrosis, 1; sclerosing hemangioma, 1; rheumatoid nodules, 1; granuloma, 2; nocardia, 1; infarct, 1; hamartoma, 4; scar, 1; cytomegalovirus pneumonia, 1), metastatic malignancy in 20 patients, and bronchogenic carcinoma in 13 patients. Five patients found at thoracoscopic pulmonary resection to have bronchogenic cancer had adequate pulmonary function and therefore underwent formal segmentectomy (3) or lobectomy (2). Thoracoscopic pulmonary resection was the only operation performed on patients with benign disease, patients with metastatic lesions, and selected patients with limited stage bronchogenic carcinoma at increased risk for thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1992

17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells with those from heterologous expression of the cDNA.

Exposure of MCF-7 breast cancer cells to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes an elevated cytochrome P450 content and a marked increase in the microsomal hydroxylation of 17 beta-estradiol (E2) at the C-2, C-4, C-15 alpha, and C-6 alpha positions. In this study we investigated the involvement of cytochromes P450 of the 1A gene subfamily in this metabolism of E2. Hydroxylation at each of these four positions of E2 was inhibited by P450 1A-subfamily inhibitors, alpha-naphthoflavone, benzo[a]pyrene, and 7-ethoxyresorufin. Northern blots showed that treatment of MCF-7 cells with TCDD resulted in production of the 2.6-kb CYP1A1 mRNA, but not the 3.0-kb CYP1A2 mRNA. Immunoblot analyses with anti-P450 1A antibodies confirmed the production of P450 1A1 protein in TCDD-treated MCF-7 cells. Anti-rat P450 1A IgG inhibited the hydroxylation of E2 at C-2, C-15 alpha, and C-6 alpha, but not hydroxylation at C-4. E2 hydroxylation by human cytochromes P450 1A1 and P450 1A2 was assessed in experiments with microsomes from Saccharomyces cerevisiae after transformation with cDNAs encoding the two cytochromes. The major hydroxylase activities of expressed human P450 1A1 were at the C-2, C-15 alpha, and C-6 alpha positions of E2; expressed human P450 1A2 catalyzed hydroxylation predominately at C-2. While both expressed P450s 1A1 and 1A2 had minor hydroxylase activities at the C-4 position, neither catalyzed a low-Km hydroxylation at C-4 similar to that observed with microsomes from TCDD-treated MCF-7 cells. These results provide strong evidence that P450 1A1 catalyzes the hydroxylations of E2 at the C-2, C-15 alpha, and C-6 alpha in incubations with microsomes from TCDD-treated MCF-7 cells, but suggest TCDD may also induce a cytochrome P450 E2 4-hydroxylase that is distinct from P450 1A1 or P450 1A2.

Breast Neoplasms↗
PubMed1992

Racial differences in propranolol pharmacokinetics.

Racial differences in the antihypertensive response to propranolol are well documented. This study was conducted to determine whether differences between black subjects and white subjects in propranolol enantiomer pharmacokinetics and protein binding exist that may contribute to the response differences. Twenty-six healthy men (13 black and 13 white subjects) took 80 mg propranolol orally three times daily for 16 doses. Serum samples were collected for 12 hours after the last dose for analysis by chiral HPLC. Protein binding was determined by equilibrium dialysis. Area under the serum concentration-time curve (AUC) for both propranolol enantiomers was lower in black subjects than in white subjects (e.g., l-propranolol AUC: 292 +/- 100 versus 394 +/- 121 ng.hr/ml, p less than 0.05) and apparent oral clearance was higher in black subjects than in white subjects (e.g., l-propranolol apparent oral clearance: 27.6 +/- 8.2 versus 20.6 +/- 7.0 ml/min/kg, p less than 0.05). Fraction unbound and unbound AUC were not statistically different between black subjects and white subjects for either enantiomer, although the lack of statistical significance may have been attributable to the small sample size. In summary, racial differences in unbound l-propranolol concentration probably do not explain the clinically observed differences in response to propranolol. However, the racial differences in apparent oral clearance suggest there may be racial differences in hepatic metabolism of propranolol.

Administration, Oral↗
PubMed1992

Non-O1 Vibrio cholerae NRT36S produces a polysaccharide capsule that determines colony morphology, serum resistance, and virulence in mice.

Non-O1 Vibrio cholerae produced two distinct colony types, designated as opaque and translucent. NRT36S, a clinical isolate shown to be virulent in volunteers, produced predominantly opaque colonies, but translucent colonies appeared on subculture. Opaque variants were recovered exclusively following exposure to normal human serum or animal passage. A nonreverting translucent mutant of NRT36S, JVB52, was isolated following mutagenesis with the transposon Tn5 IS50L::phoA (TnphoA). Only translucent colonies were produced by a nonpathogenic environmental isolate, A5. Electron microscopic examination of the opaque form of NRT36S revealed thick, electron-dense, fibrous capsules surrounding polycationic ferritin-stained cells. The ferritin-stained material around translucent NRT36S or A5 was patchy or absent. JVB52 had a thin but contiguous capsular layer. The amount of ferritin-stained capsular material correlated with the amount of surface polysaccharide determined by phenol-sulfuric acid assay: opaque NRT36S had approximately three times as much polysaccharide as translucent NRT36S or A5 and four times as much as JVB52. The encapsulated, opaque variant of NRT36S was protected from serum bactericidal activity, while translucent non-O1 V. cholerae was readily killed. The encapsulated form also had increased virulence in mice. Our data provide the first indication that non-O1 V. cholerae strains can have a polysaccharide capsule. This capsule may be important in protecting the organism from host defenses and may contribute to the ability of some non-O1 V. cholerae strains to cause septicemia in susceptible hosts.

Animals↗
PubMed1992

Development and testing of a nonradioactive DNA oligonucleotide probe that is specific for Vibrio cholerae cholera toxin.

An alkaline phosphatase-labeled oligonucleotide DNA probe (CTAP) that was specific for the cholera toxin gene (ctxA) was identified. All cholera toxin-producing strains of Vibrio cholerae, regardless of serotype, hybridized with the CTAP probe, while nontoxigenic strains from either environmental sources or from deletion or substitution mutations did not hybridize. Unlike the whole-gene probes for either ctxA or for the heat-labile toxin or Escherichia coli (eltA), this 23-base sequence did not hybridize with E. coli or with vibrios other than V. cholerae that produce related toxins. By using CTAP to identify colonies grown on nonselective medium, V. cholerae was enumerated at concentrations of 10(3) to 10(7)/g from stool samples of volunteers who had ingested V. cholerae O1 strain 569B. CTAP provides a specific and sensitive tool for diagnosis and environmental monitoring of cholera toxin-producing V. cholerae.

Base Sequence↗
PubMed1992

Broad-spectrum photoprotection: the roles of tinted auto windows, sunscreens and browning agents in the diagnosis and treatment of photosensitivity.

Since window glass absorbs sunlight below 320 nm, it provides a means of assessing sensitivity to longer wavelengths, i.e. UVA and visible radiation. Positive responses to the query of whether symptoms develop in the auto with the windows up must now be interpreted with regard to the possible presence of tinted plastic film on side and rear windows. These films block nearly all UVA radiation, as does the plastic interleaf of windshields. Thus, occupants of an auto equipped with plastic film receive photoprotection from UVB radiation and well into the UVA region. We define three classes of topical sunscreens: (1) conventional UVB screens, (2) broad-spectrum preparations containing a UVB screen and a UVA absorber and (3) browning agents such as dihydroxyacetone (DHA) that produce a skin coloration that absorbs in the low end of the visible region, with overlap into long-wavelength UVA. By considering responses of photosensitive persons in autos with tinted or untinted windows, coupled with efficacy of appropriate sunscreens, we produced an algorithm defining three photosensitivity subsets. Persons sensitive to long-wavelength UVA and/or visible radiation will benefit from tinted auto windows. In particular, patients with lupus erythematosus (LE) have actively promoted legislation allowing tinted windows. Support for their position is documented by recent reports of induction of lesions in LE patients by exposure to UVA and visible radiation. The brown color produced by DHA is a useful adjunct to the screening action of broad-spectrum sunscreens. Development of a durable color overnight allows application of the DHA preparation in the evening, thus eliminating possible interference with sunscreen use during the day.

4-Aminobenzoic Acid↗
PubMed1992

Integration of a personal computer workstation and radiology information system for obstetric sonography.

A personal computer workstation has been developed for storage and analysis of obstetric sonographic examinations. The workstation also serves as an interactive data terminal for our radiology information system. A data-base management program locally stores quantitative and descriptive sonographic results. Algorithms are used to analyze growth parameters over serial examinations, plot growth curves, generate a radiologic report, and provide instantaneous diagnostic assistance and suggestions. A bibliographic data-base system containing more than 3000 references (with abstracts) in the obstetric sonographic literature is integrated with the software's analytical functions. A telecommunications software module performs dialogues, such as immediate automatic transcription of the sonographic report, with the radiology information system. An examination summary form, growth curves, and the radiologist's report can be printed or digitally faxed by the workstation after authorization by the radiologist. The workstation has improved the organization of sonographic data, facilitated serial quantitative analysis, supplemented educational resources for our staff radiologists and residents, reduced transcription errors and transcription delays, and shortened to minutes the time necessary to deliver precise examination results to clinicians. This model is suitable for use in many areas in a radiology department.

Female↗
PubMed1992

We need to know more: nurse educators' interest and expertise in gerontology.

An assessment was made of 129 faculty who teach nursing students about the care of aged clients to determine their level of interest and expertise in 21 content areas related to gerontology. Faculty rated their expertise consistently lower than the relevance of, and their interest in, each of the content areas. Areas identified as most important for their professional growth tended to be areas where faculty ranked their expertise as already being high. The mean self-rated expertise of faculty who taught a course in gerontological nursing was significantly higher than those who did not. Most respondents lacked formal education in gerontology: 9% of respondents had gerontology in their undergraduate program; 27% in their graduate program. Only 4% were certified as gerontological nurses or gerontological nurse practitioners.

Adult↗