How human immunodeficiency virus ravages the immune system.

The immune system of individuals infected with human immunodeficiency virus is affected in two distinct ways: by loss of CD4+ cells and by loss of T-helper-cell function. Neither of these processes is yet fully understood. Research during 1991 that investigated the interaction between human immunodeficiency virus and the immune system has raised as many questions as it answered. Nevertheless, many of the issues raised are relevant to mechanisms responsible for the ravaging of the immune system by human immunodeficiency virus.     

Use of histological samples for assessing skeletal calcium.

Bone samples were decalcified using 5% formic acid. Their calcium content was then quantified by analysing the calcium extracted in the decalcification solution. This was correlated with matched samples digested in hydrochloric acid. No significant differences were found. This indicates that bone biopsy specimens taken for histological analysis can be used for the direct assessment of skeletal calcium. The method can therefore simplify investigations into metabolic bone diseases and provide a direct correlation between skeletal calcium and bone histology.     

Fetoscopic photography

Fetoscopic visualization may be used for the prenatal diagnosis of external structural malformations of the fetus. Objective documentation of these fetoscopic findings would be desirable. The photographic equipment and techniques required for fetoscopic photography have been investigated, and the results of these investigations with standard fetoscopic instruments in current clinical usage are described. The factors evaluated include the light source, camera equipment, camera settings and film.     

Depressed type 1 cytokine synthesis by superantigen-activated CD4+ T cells of women with human papillomavirus-related high-grade squamous intraepithelial lesions

Carcinoma of the cervix is causally related to infection with the human papillomavirus (HPV), and T cells play a pivotal role in the immune response of the host to rid itself of HPV infection. Therefore, we assessed the T-cell function of women with HPV-related cervical neoplasia against a superantigen, Staphylococcus enterotoxin B (SEB). Each woman provided a cervical brush specimen for HPV DNA testing and Papanicolaou (Pap) smears for the staging of cervical lesions. They also provided a blood specimen for determination of the ability of CD4(+) T and CD8(+) T cells to synthesize Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and Th2 (IL-10) cytokines in response to activation with SEB. Compared with control subjects with self-attested negative Pap smears, women with high-grade squamous intraepithelial lesions (HSIL) had significantly lower percentages of activated CD4(+) T cells that produced IL-2 (P = 0.045), IFN-gamma (P = 0.040), and TNF-alpha (P = 0.015) and a significantly lower percentage of activated CD8(+) T cells that produced IL-2 (P < 0.01). These data indicate that women with HPV-related cervical HSIL show a decrease in Th1 cytokine production by activated CD4(+) T cells and suggested that compromised T-helper functions may negatively impact the function of cytotoxic CD8(+) T cells.     

Factors influencing help seeking in mentally distressed young adults: a cross-sectional survey.

BACKGROUND: Young adults, especially men, are among those least likely to consult healthcare professionals when mentally distressed or suicidal. AIMS: To investigate the help-seeking behaviours of mentally distressed young adults. Design of study: Cross-sectional survey. SETTING: Bristol and surrounding areas, including inner-city, suburban and urban locations. METHOD: A questionnaire was sent to a sample of 3004 young adults aged 16-24 years. This assessed probable mental disorder (using the 12-item general health questionnaire [GHQ-12]), suicidal thoughts (GHQ-28 suicide subscale), and help-seeking behaviours. RESULTS: Most responders who were assessed as having probable mental disorders (GHQ "cases") had not sought help. Help seeking was more common in female GHQ cases than male cases (34.8% and 21.8%,respectively; P = 0.003) and women with suicidal thoughts more commonly sought help than men with suicidal thoughts (41.6% and 30.9%, respectively; P = 0.15). Small proportions of male and female GHQ cases (7.5% and 8.9%, respectively; P = 0.6), and less than one in five responders with suicidal thoughts, had consulted a general practitioner. In more female than male cases, help was sought from family and friends (30.7% and 18.4%, respectively; P = 0.004). GHQ score was the strongest predictor of help seeking. Men had a higher threshold of severity at which they would seek help than women. Recent experience of suicidal thoughts appeared to be a stronger predictor of formal help seeking in mentally distressed women than mentally distressed men. CONCLUSION: Distressed young adults are reluctant to seek help. Men are particularly unlikely to do so unless severely distressed and tend not to seek lay support. Sex differences in help seeking may be important in understanding the high suicide rate for men.     

Augmented sympathetic vasoconstriction in exercising forearms of postmenopausal women is reversed by oestrogen therapy

Sympathetic vasoconstriction is normally attenuated in exercising muscles of young men and women. Recent evidence indicates that such modulation, termed functional sympatholysis, may be impaired in older men. Whether a similar impairment occurs in older women, and what role oestrogen deficiency might play in this impairment, are not known. Based on the strong positive correlation between circulating oestrogen levels and functional sympatholysis previously reported in female rats, we hypothesized that sympatholysis would be impaired in oestrogen-deficient postmenopausal women, and that this impairment would be reversed by oestrogen replacement. To test these hypotheses, we measured vasoconstrictor responses in the forearms of pre- and postmenopausal women using near infrared spectroscopy to detect decreases in muscle oxygenation in response to reflex activation of sympathetic nerves evoked by lower body negative pressure (LBNP). In eight premenopausal women, LBNP decreased muscle oxygenation by 20 ± 1% in resting forearm, but only by 3 ± 2% in exercising forearm  ( P < 0.05)  . In contrast, in eight postmenopausal women, LBNP decreased muscle oxygenation by 15 ± 3% in resting forearm, and by 12 ± 4% in exercising forearm  ( P > 0.05)  . After 1 month of transdermal oestradiol replacement in these women, the normal effect of exercise to blunt sympathetic vasoconstriction was restored (rest, −19 ± 3%; exercise, −2 ± 3%;   P < 0.05  ). These data indicate that functional sympatholysis is impaired in oestrogen-deficient postmenopausal women. The effect of short-term unopposed oestrogen replacement to correct this impairment implicates a role for oestrogen in the sympathetic neural control of muscle haemodynamics during exercise.     

Recombinant human gamma interferon in human immunodeficiency virus-infected children: safety, CD4(+)-lymphocyte count, viral load, and neutrophil function (AIDS Clinical Trials Group Protocol 211)

Nineteen children with human immunodeficiency virus (HIV) infection were treated with recombinant human gamma interferon (rIFN-gamma) (50 microg/m2 subcutaneously three times each week during weeks 1 through 12 and 100 microg/m2 subcutaneously three times each week during weeks 13 through 24) in a phase I/II clinical trial. All children continued to receive previously prescribed therapy with oral zidovudine or didanosine. Children were assessed clinically and with laboratory studies during 24 weeks of study treatment and for 12 weeks after completion of rIFN-gamma therapy. In general, rIFN-gamma therapy was well tolerated. There were two clinical or laboratory adverse events thought to be possibly or probably study drug associated. One child developed acute pancreatitis; another child developed granulocytopenia. Median CD4(+)-lymphocyte counts and plasma HIV RNA concentrations did not change significantly during therapy. In vitro neutrophil bactericidal activity against Staphylococcus aureus and superoxide production were not significantly affected by rIFN-gamma therapy. We conclude that rIFN-gamma therapy in HIV-infected children receiving single-agent antiretroviral therapy is safe and does not produce consistent changes in CD4(+)-lymphocyte count, plasma HIV RNA concentration, or in vitro neutrophil function.     

Cooperation of antigenic determinants in intact mice and interference by antigenic competition

Cooperation between two immunopotent regions (Phe, G) and Pro-L, of a synthetic polypeptide, multichain (Phe, G)-Pro-L, in a secondary response in intact mice 1s described. (Phe, C) behaves as a haptenic group for which the multichain polypeptides, Pro-L and A-L, act as carriers. When C3H/HeJ mice were primed with (Phe, G)-A-L and challenged with (Phe, G)-Pro-L, a strong carrier effect could be demonstrated, 2.e. the response to (Phe, G) was very poor compared with that obtained upon secondary challenge with (Phe, G)-A-L. Since (Phe, G) is larger than the known size of an antibody combining site, this result argues against a local environment contribution to the carrier effect. Mice received, primary inoculation with mixtures of (Phe, G)-A-L and (T, G)-Pro-L in various molar ratios and then were boosted with (Phe, G)-Pro-L. Cooperation in the secondary response was obtained in some cases, as judged by the enhanced anti-(Phe, G) titers, compared with mice primed with (Phe, G)-A-L alone, after challenge with (Phe, G)-Pro-L. However, the molar ratio of (T, G)-Pro-L/(Phe, C)-A-L in the primary immunization was found to be a critical factor, a priming ratio of 1/5 being optimal. With other priming ratios, no cooperation could be demonstrated in the secondary response. This was shown to be due to antigenic competition between (Phe, G) and Pro–L in the primary response, which reduced the degree of priming or memory for the secondary response to either the haptenic or carrier determinants, Thus, antigenic competition may be an important factor to be considered in the design of experiments to investigate cooperation of antigenic determinants.