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Biomedical subjects

J Harry

Publications and source records attributed to J Harry.

At least 19 recordsLinked to original sources

Identification of three transforming proteins encoded by cottontail rabbit papillomavirus.

Cottontail rabbit papillomavirus (CRPV) provides an animal model for human papillomaviruses associated with a high risk of cancer development. So far, nothing is known about the transforming functions of CRPV genes because of the lack of an assay system. We have recently developed two systems to assay for CRPV transforming functions. One is based on the finding that transformation of NIH 3T3 cells by CRPV is considerably increased by deleting sequences in open reading frame L2. The second one is based on the use of a cottontail rabbit skin epithelial cell line, sf1Ep (C. Meyers and F. O. Wettstein, Virology 181:637-646, 1991). Mutations were introduced which abolished expression of the full-length E6 protein (LE6), the short E6 protein (SE6) initiated at the second ATG of E6, the E7 protein, or the E5 protein. Mutations affecting LE6 or E7, but not SE6, reduced transformation of NIH 3T3 and sf1Ep cells. Transformed NIH 3T3 cell lines with mutations in LE6 and E7 did not grow in soft agar, while those with mutations in SE6 and E5 grew with a reduced efficiency. The cell lines with mutations in LE6, SE6, or E7 still did induce tumors in nude mice. These mutations, however, abolished the ability to induce papillomas in rabbits. When expressed individually with a retroviral vector, LE6, SE6, or E7, but not E5, conferred anchorage-independent growth. The level of viral protein expression in these cell lines was generally low, and a comparison of the abundance of virus-specific mRNA showed that cell lines contained 20 to 50 times less mRNA than a cottontail rabbit papilloma. These data demonstrate that CRPV encodes at least three transforming proteins.

3T3 Cells

The effects of a 5-HT2 receptor antagonist (ICI 169,369) on changes in waking EEG, pupillary responses and state of arousal in human volunteers.

1. ICI 169,369 (2-(2-dimethylamino ethylthio)-3-phenyl quinoline) is a potent selective competitive antagonist of the 5-HT2 receptor in animal models. Effects of ICI 169,369 as single oral doses (80 and 120 mg) separated by 1 week, on the power spectrum of waking EEG, dark adapted pupil responses and sedation score, were studied in a double-blind, placebo controlled, randomised cross over within subject comparison, in six healthy male volunteers. 2. Pupillary responses were measured using a portable infrared pupillometer following 15 min dark adaptation, assessing resting vertical pupil diameter (RPD), light constricted diameter (MPD) and recovered final diameter (FPD) at the end of a 3 s measurement cycle. 3. Both doses of ICI 169,369 produced a mean 36% (range 10-54%) decrease in log 10 power of the waking EEG alpha activity with eyes closed (P less than 0.02), and mean 38% (range 2-86%) increase in theta activity at 2 h compared with placebo. 4. Both 80 and 120 mg doses of ICI 169,369 reduced RPD by approximately 30% from a predose value of 6.25 mm (+/- 0.87; 95% CI) and from placebo values 6.41 mm (+/- 1.06) and 7.48 mm (+/- 1.49) at 3 and 5 h after dosing. MPD was reduced by 50% with the 120 mg dose at 5 h after dosing (placebo 5.2 mm; ICI 169,369 2.7 mm; P less than 0.05). FPD was significantly reduced (P less than 0.01) by both doses at 3 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Quantitative analysis of myelin protein gene expression during development in the rat sciatic nerve.

We determined the temporal profile of expression of the genes encoding the P0 glycoprotein, the myelin-associated glycoprotein (MAG), the myelin basic protein (MBP), the proteolipid protein (PLP), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in the sciatic nerve of rats. The level of expression of the MAG gene occurred maximally in animals 13 days of age, approximately one week earlier than the peak expression of the MBP and P0 genes. The genes encoding PLP and CNP were not expressed developmentally in a manner that correlated with the myelination of the sciatic nerve. Furthermore, using RNA synthesized in vitro, specific for each of the myelin protein genes, we have determined the absolute amounts of messenger RNA for the various myelin proteins in total RNA from sciatic nerves. P0 and MBP RNA were present at very high levels, whereas the amount of MAG, PLP and CNP RNA were much less.

2',3'-Cyclic-Nucleotide Phosphodiesterases

A probability sample of gay males.

Data are presented from a national probability sample of males interviewed by telephone and asked their sexual orientation. Of these males 3.7 percent reported that they were homosexual or bisexual. Homosexual/bisexual men were compared with heterosexual ones on the demographic variables. This sample produced larger numbers in those groups which appear to be underrepresented in the usual samples drawn from the gay world. These groups include those with little education, married men, older men, minorities, and those living in small towns. It is suggested that probability samples which do not draw directly or heavily from the gay world for homosexual respondents obtain a broader sampling of those having homosexual feelings or behaviors.

Adolescent

Parental physical abuse and sexual orientation in males.

Because male homosexuals have usually been found to have poorer relationships with their fathers than male heterosexuals, and because children who are disappointments to their parents are more likely to be physically abused than other children, it was hypothesized that gays are more likely than heterosexual men to have been physically abused by parents. This hypothesis was tested comparing 17 gay male college students and 67 heterosexual male college students. Gay males were found to have been more abused during adolescence. Abuse was related to a history of childhood femininity, to having poor relationships with fathers, and to having engaged in gay sex during adolescence. A history of childhood femininity and engaging in gay sex may provoke parental abuse.

Adolescent

Healthy volunteer studies in Great Britain: the results of a survey into 12 months activity in this field.

1. A survey has been conducted amongst 459 members of the Clinical Section of the British Pharmacological Society to ascertain facts about the administration of drugs to healthy volunteers over the period October 1986 to September 1987. 2. A response rate of 87.1% was obtained with 114 individuals being involved in healthy volunteer studies. After exclusion of duplicate returns from the same unit 98 questionnaires were analysed. 3. Drugs were given in the year under review to 8163 healthy volunteers for research purposes. Minor adverse effects were reported in 565 (6.9%), moderately severe adverse effects in 45 (0.55%) and potentially life threatening adverse effects in 3 (0.04%). No lasting sequelae were reported. 4. Drugs were given to 7607 healthy student volunteers as part of class teaching practicals. Minor adverse effects were reported in 6.0% of student exposures but no moderately severe or life threatening adverse effects were reported. 5. The risk involved in healthy volunteer studies is very small indeed but some suggestions are made as a result of the questionnaire to improve further the safety of these studies.

Drug Evaluation

Does atenolol improve physical and psychological function after coronary artery bypass surgery: a controlled study.

A double-blind prospective randomized trial of atenolol (100 mg once daily) was carried out on 88 patients (78 men) awaiting coronary artery bypass graft surgery. Standardized ratings of both psychiatric morbidity and functional capacity were made before, 3 months (n = 82) and 12 months (n = 81) after surgery. One year after surgery men in the atenolol group had a significantly shorter treadmill exercise time than those on placebo (7.21 +/- 0.28 min vs 8.32 +/- 0.40 min; p less than 0.05), but the frequency of reported anginal attacks during the year was similar in both drug groups. Improvement in functional capacity (measured in exercise time) in the 71 men following surgery was related to both physical and psychological variables assessed before the operation. Men with more severe occlusive disease, lower neuroticism and higher extraversion scores pre-operatively showed greater percentage improvement in exercise time after surgery. Women had significantly levels of psychiatric morbidity and shorter treadmill exercise time than men both before and after surgery. Of the psychiatric and psychological variables, only ratings of Type A behaviour fell significantly in the atenolol group (170.9 +/- 5.3 vs 163.0 +/- 5.2; p less than 0.05). This change, which is probably not clinically important, occurred independently of any reduction in either overall psychiatric morbidity score or ratings of somatic symptoms mediated by beta-adrenergic receptors. The atenolol group reported more side-effects of both psychological and physical symptoms than the placebo group. We do not recommend the routine use of atenolol after bypass graft surgery. Our findings failed to support the suggestion that Type A characteristics may reflect an underlying sympathetic nervous system reactivity.

Angina Pectoris

Defeminization and social class.

The hypothesis that there might occur selective defeminization by social class between childhood and adulthood among homosexual men was explored. Interview data on 686 homosexual men were employed. It was found that there is a greater tendency for cross-gender propensities to persist into adulthood among respondents from blue-collar backgrounds. Effeminate respondents from such backgrounds were found to be disproportionately involved in same-sex sexual activities during adolescence. They were also sexually responsive to same-sex persons earlier. The interpretation is offered that early homosexual experiences reinforce cross-gender propensities among blue-collar respondents because of the greater gender role dichotomization found in blue-collar culture. Such reinforcement may explain the tendency for there to be greater persistence of cross-gendering among blue-collar men.

Adult

Age and sexual culture among homosexually oriented males.

It is here argued that the thesis has been overgeneralized that the culture of homosexually oriented males is heavily youth oriented. It is suggested that any "youth orientedness" is due to their largely single "marital status" rather than to sexual orientation. Utilizing data from 243 males from the Detroit area, several qualifications to the thesis of youth orientedness are indicated. It was found that a majority of males aged 18-24 prefer a male partner who is older, a majority of those aged 25-34 years prefer a same-age person, and 50% of theose over 35 prefer a younger partner. These relationships were found to be especially strong among those segments of the sample who attend gay bars infrequently or who are of lower occupational levels. Also, higher occupational status was found to be associated with preference for the younger, independent of age. It is suggested that, because of the heterogeneity of the male homosexual community, the degree of emphasis of youth will be found to vary with social setting.

Adolescent

Lymphocytic tumours of indeterminate nature: a 5-year follow-up of 98 conjunctival and orbital lesions.

Ninety-eight adnexal lymphocytic tumours of indeterminate nature have been followed up for at least 5 years. Both non-disseminating and disseminating tumours have either very similar or identical histopathological features. It is not possible to make a definitive diagnosis when the lesions are first seen, and a conclusion can be reached only after a prolonged follow-up. The nature of the non-disseminating tumours is unknown.

Adolescent

[Electron microscopic study of kidney biopsy specimens from children].

Investigation of kidney-biopsy taken from 17 children was carried out. The techniques used were: light-microscopic investigation of paraffin sections and ultrathin sections, electron microscopic investigation of the latter and basal-membrane measurements. According to the author's opinion electron microscopic investigation of kidney-biopsy is reasonable only in selected cases, representing special clinical and therapeutic problems. In cases of nephrosis syndrome electron microscopy helps in differentiation of the "mimimal lesion" and the early phase of the focal sclerotizing glomerular lesion. Further it gives good results in observation of mono- and olygosystemic diseases of the kidney. In the author's material electron microscopy contributed to more differentiated morphological diagnosis in 2/3 rds of the cases investigated. The authors join to the opinion of other investigators stressing that light-microscopical investigation should be completed by the light-microscopy of uktrathin scretions even then, when there are no possibilities of electonmicroscopical study.

Basement Membrane

[Permeability of post-ischemic aortic wall in rats].

Examinations were carried out in order to reveal details of process of the permeability damage, its degrea and fate of the plasma-substances getting into the vessel all. Abdominal aorta has been cross-clapped for one hour by the aid of a double ligature. In a recirculatory period from 1 hour to 10 days material serving for labeling of the plasma has been determined in the vessel using histochemical and microchemical methods. Colloidal iron was administered to animals one hour before removing the aorta. The highest quantity of colloidal iron in the aortic wall could be revealed after 24--48 hours of recirculation. By the 10th day the vessel wall contained physiological iron quantity. Colloidal iron administered on the second day of recirculation--when damage to permeability is most marked--in the early phase could be seen in the whole aortic wall. By the 7th day it could be detected only in the outer part of media and in the adventitia. Endothelium inhibits the flow of plasma-substances into the vessel wall, when they got through it, only elastic lamina form a temporary mechanical obstacle for transfusion.

Animals

[Effect of transient hypoxia on the permeability of rat aorta. Electron microscopic study].

Infrarenal part of the abdominal aorta in rats was closed out from the circulation by the aid of a doubled ligature. Changes of the permeability at different intervals after recirculation were investigated using colloidal iron as a labelling substance. The latter in an hour after recirculation could already be detected in the interendothelial junction and in the subendothelial space. The lesion of the permeability was most striking on the second day, and on the tenth day no more lesion could be observed. Increase of the permeability of the endothelium was paralelly followed by an inhibition of the media, which leads to significant ultrastructural changes.

Animals