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Biomedical subjects

S C Johnson

Publications and source records attributed to S C Johnson.

At least 91 records · Page 5Linked to original sources

Synthesis and evaluation of 3-modified 1D-myo-inositols as inhibitors and substrates of phosphatidylinositol synthase and inhibitors of myo-inositol uptake by cells.

A number of 3-substituted 1D-myo-inositols were synthesized and evaluated as substrates for phosphatidylinositol synthase and uptake by intact cells. 1D-3-Amino-, -3-chloro-, and -3-(acetylthio)-3-deoxy-myo-inositols were all synthesized by nucleophilic displacement of the 6-O-(trifluoromethyl)sulfonyl group of 1L-1,2:3,4-di-O-cyclohexylidene-5-O-methyl-6-O-[(trifluoromethyl)-sulfon yl] - chiro-inositol (which was prepared from L-quebrachitol), respectively, by reaction with LiN3, followed by reduction of the azido function, and with LiCl and KSAc to give the O-protected compounds. O-Demethylation using BBr3 and concomitant acetal hydrolysis furnished the free-hydroxy 3-amino- and 3-chloro-3-deoxy-1D-myo-inositols. The 3-mercapto analogue was obtained by removal of the acetal groups of the acetylthio analogue, followed by acetylation and purification of the peracetate, and subsequent O-demethylation and deacetylation. The 3-deoxy derivative was synthesized from the 6-O-(imidazol-1-ylthiocarbonyl) compound via Barton-McCombie deoxygenation. The 3-azido derivative was directly synthesized from 1L-1-O-tosyl-chiro-inositol via displacement with azide. The 3-keto analogue was prepared by Pt-catalyzed air oxidation of 1L-chiro-inositol. The compounds were all evaluated as substrates for phosphatidylinositol (PtdIns) synthase from mouse brain. The 3-NH2, 3-F, 3-deoxy, and 3-keto analogues all showed activity as substrates, as measured by liberation of cytidine monophosphate. These compounds also showed inhibition of the reaction of myo-[3H]inositol with PtdIns synthase. These results taken together indicate that these compounds are likely to be incorporated into phospholipids. As a further indication that these compounds might be useful as probes for the PtdIns pathway, it was demonstrated that the 3-NH2, 3-F, and 3-deoxy compounds are taken up by intact fibroblast cells as evidenced by their competing with myo-[3H]inositol uptake.

Acetates↗

Occurrence of basal cell carcinoma among multiple trichoepitheliomas.

We describe four patients who developed basal cell carcinoma (BCC) among multiple facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size in three of the four patients. None of the lesions ulcerated. Whether the BCCs developed independently or by transformation from a trichoepithelioma is uncertain. Mohs micrographic surgery was helpful in revealing the transition from one tumor type to the other so that as much normal tissue as possible could be saved. The literature on the relationship between multiple hereditary trichoepitheliomas and BCCs is reviewed.

Basal Cell Carcinoma↗

Physiological aspects and injury in elite Alpine skiers.

Alpine skiing requires aerobic and anaerobic power, muscular strength, and a variety of complex motor abilities including quickness, agility, balance and coordination. There is evidence of variability in physical characteristics between skiers of different events. Generally, successful alpine competitors are taller and heavier than in the past. Greater size, specifically lean mass, may be related to technique changes because of the advent of breakaway poles. Aerobic power, although important, does not discriminate competitors of varying ability categories. Aerobic power is more likely to be a result of conditioning for alpine skiing rather than a profound requirement of the sport. Anaerobic power is important for skiing and both laboratory and field power tests correlate well with performance. Tests that measure explosive and sustained anaerobic power such as the Wingate, vertical jump, 60-second repeated jump, and Margaria-Kalamen stair run are valuable in assessing skiers. On-snow lactate and oxygen consumption measurements further substantiate the need for high anaerobic power. Alpine skiers have very high leg strength compared with other athletes. Isokinetic testing has been used to evaluate dynamic leg strength in skiers, but little is known about high speed dynamic or eccentric strength capabilities. A new mechanism of knee injury that is associated with tibial acceleration has been identified in competitive alpine skiers. A release binding that is sensitive to physiological factors in addition to release forces should be developed. Strength profiling of skiers may also be valuable in evaluating injury risk.

Anaerobic Threshold↗

Factors influencing fine-needle aspiration cytology in the management of recurrent gynecologic malignancies.

Over a period of 6.5 years (January 1983 through August 1989) 124 fine-needle aspirations (FNAs) were performed on 95 patients with prior documented primary malignancies of the cervix, ovary, endometrium, and vulva. The significance of clinicopathologic factors which influenced the FNA results was analyzed by statistical methods. The factors studied included the initial patient clinical stage, the time interval between staging and disease recurrence, the treatment modalities, the neoplasm type, the aspiration site, the target lesion size, and the type of radiologic guidance. Primary aspiration sites were pelvic wall and organs (40%), lymph nodes (36%), and liver (21%); 64% were positive, 5% suspicious, 15% negative, and 16% unsatisfactory. The specificity was 100%; sensitivity, 96.3%; predictive value of a positive test, 100%; and predictive value of a negative test, 84.2%. Statistically significant clinicopathologic factors which influenced the FNA results included the target lesion size (P = 0.026) and the aspiration site (P = 0.033). The primary neoplasm type, the time interval between staging and disease recurrence, the initial patient clinical stage, the treatment modalities, and the type of radiologic guidance were not statistically significant. FNA is a reliable procedure in the management of gynecologic malignancy and its results are influenced by clinicopathologic factors.

Adult↗

Physiological comparison of international, national and regional alpine skiers.

The purpose of this study was to evaluate the predictive power of physiological tests in categorizing competitive alpine skiers. Sixty-one subjects (30 female and 31 male) were classified into three levels: international, national, and regional on the basis of past competition results. Hydrostatic weighing, maximal cycling, Wingate, 60-s repeated jump, and vertical jump tests were used to assess body composition, aerobic and anaerobic power, respectively. MANOVA revealed a significant group by gender interaction (Hotellings T, p less than .001), and main effects of gender and group (p less than .001). Discriminant analyses performed separately for male and female groups determined which variables were responsible for differences and resulted in selection of the following variables for classification of the men: average work from the repeated jump, absolute power for the vertical jump, and Wingate endurance. For the women, average work from the repeated jump, absolute and relative vertical jump power, absolute maximum Wingate power, and relative repeated jump power were most important. Fat-free mass was a powerful predictor for both sexes because of its strong relationship (r greater than 0.85) with power results. Aerobic power was not useful in group classification. In conclusion, physiological tests of anaerobic power and fat-free mass were the best predictors of group membership.

Adolescent↗

Human immunization with Pgh 3-2 gonococcal pilus results in cross-reactive antibody to the cyanogen bromide fragment-2 of pilin.

In 1983, a gonococcal pilus vaccine failed to show protection in a large, placebo-controlled, double-blind field trial. The epitopic response to this vaccine was investigated in a random subgroup of 20 vaccine recipients. Using Western blot analysis of the immunizing pilus and its cyanogen bromide (CNBr) fragments, IgG antibody to pilin was detected before immunization in all individuals. Preexistent antibody to the CNBr-2 and CNBr-3 fragments of pilin was detected in 65% and 5% of individuals, respectively. Pilus immunization resulted in a vigorous response to the CNBr-2 fragment in 100% of the individuals tested; only 33% developed antibody to the CNBr-3 fragment. Absorptions of postimmunization sera with different gonococcal strains resulted in either complete or partial removal of antibody to the CNBr-2 fragment. In the context of an unsuccessful vaccine trial, these results suggest that antibody to the CNBr-2 fragment of pilin may not be protective.

Adult↗

An observational study of isotretinoin recipients treated for acne in a health maintenance organization.

From September 1982 to June 1987, all members (N = 513) of the Group Health Cooperative of Puget Sound, Seattle, Wash, who were prescribed isotretinoin for acne were observed throughout the first 4- to 5-month course of therapy for effectiveness and adverse effects. The highest rates of use were among male subjects aged 15 to 24 years. Excluding 47 subjects whose prescriptions were stopped because of noncompliance or who left the care of Group Health Cooperative physicians, 39 (8.4%) of the remaining 466 discontinued taking the drug because of the following adverse effects: mucous/skin/musculoskeletal effects (17); elevated triglyceride levels (eight); headaches (five); increased liver enzyme levels (three); amenorrhea (two); and other (four). One subject, excluded from the 466 because of noncompliance, became pregnant while using medication from a previous prescription and had a therapeutic abortion; she was not under the care of a physician at the time of pregnancy. Most subjects (97%) developed a mucocutaneous symptom, and 42% developed musculoskeletal symptoms. Moderate elevations in liver enzyme levels developed in six (1.8%) of 341 subjects with normal baseline values. Of 389 subjects with normal baseline triglyceride values (less than 2.25 mmol/L), nine (2.3%) developed moderate elevations (4.5 to 9.0 mmol/L), and one (0.3%) developed a severe elevation (greater than or equal to 9.0 mmol/L). Of 24 subjects with elevated baseline triglyceride levels, three (12.5%) developed moderate elevations. Of an additional 53 subjects whose baseline serum triglyceride levels were not determined, two developed elevations during therapy, one up to 13.4 mmol/L. Subjects who were overweight or had elevated baseline serum triglyceride values had an increased risk of developing elevations in triglyceride levels during therapy (odds ratio, 6.0; 95% confidence interval, 1.6 to 22.0; and odds ratio, 4.35; 95% confidence interval, 0.9 to 20.2, respectively). Acne was improved for at least 94.0% of subjects.

Acne Vulgaris↗

Purine metabolism in feline lymphomas.

Deficiency of the purine metabolic enzyme adenosine deaminase causes severe immunodeficiency. Retroviruses have been reported to decrease the activity of adenosine deaminase, and many retroviruses, including feline leukemia virus, cause immunodeficiency. Levels of purine metabolic enzymes including adenosine deaminase and consequences of adenosine deaminase inhibition were investigated in feline leukemia virus-infected fresh tumor cells and infected and uninfected cell lines. No evidence of virus effect on levels of adenosine deaminase or other purine metabolic enzymes was detected. Neoplastic cells demonstrated considerable heterogeneity of activity levels of purine metabolic enzymes.

5'-Nucleotidase↗