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Seroconversion, sexual activity, and condom use among 2915 HIV seronegative men followed for up to 2 years.

A cohort of 2915 HIV-1-seronegative men from the four centers of the Multicenter AIDS Cohort Study (MACS) was followed at 6 month intervals for 24 months to identify men who developed antibodies to HIV-1. Two hundred thirty-two men (8%) seroconverted. The highest attack rate was among men who reported practicing both receptive and insertive anal-genital intercourse. The attack rate among men who reported practicing receptive but not insertive intercourse was 3.6 times higher than among men practicing insertive intercourse although those practicing insertive only reported 38% more different partners. Only two men seroconverted who reported not practicing analgenital intercourse in the 12 month prior to the first antibody-positive visit. Because men were followed every 6 months, one of these men could have been infected within 6 months of the actual development of HIV-1 antibodies. The seroconversion rate was significantly lower among men who reported using condoms with all their partners. The results of this study (a) reaffirm that receptive anal-genital intercourse is the major route of infection among homosexual men of HIV-1, (b) suggest that there is a low risk of HIV-1 infection to the insertive partner in anal-genital intercourse, (c) suggest that infection may rarely occur through sexual activities other than anal-genital intercourse, (d) provide evidence that condoms as currently used by men in the MACS provide significant but not complete protection against HIV-1 infection, and (e) suggest that the number of men in the homosexual community engaging in high-risk behavior is declining.

Bisexuality↗

The effect of RU 486 and related compounds on cultured macrophage differentiation and function.

OBJECTIVE: Our purpose was to examine RU 486 and related compounds on macrophage scavenger receptors and cellular adhesion. STUDY DESIGN: THP-1 cells were activated with phorbol myristate acetate and treated with dexamethasone, levonorgestrel, and RU 486 alone or in combination. Scavenger receptor activity was determined by counting adhered cells. In addition, fluorescently labeled acetyl low density lipoprotein uptake was determined. RESULTS: Both dexamethasone and RU 486 significantly decreased activated macrophages (81% and 26% of control). Levonorgestrel stimulated adherent cells in activated monocytes (130% of control). RU 486 and dexamethasone were antagonistic when combined (p < 0.001). In contrast, dexamethasone could not overcome the stimulatory effect of levonorgestrel (p < 0.001). Fluorescent studies yielded similar results. CONCLUSIONS: RU 486 is a known antiglucocorticoid with novel antioxidant properties. Levonorgestrel has antiglucocorticoid but no antioxidant activity. Glucocorticoids decrease scavenger receptors and antioxidants regulate inflammatory cytokines. RU 486 antagonized the inhibitory effect of dexamethasone on scavenger receptors, whereas levonorgestrel was stimulatory. It is therapeutically important to up-regulate scavenger receptor activity by antiglucocorticoids in the peritoneal cavity of women with endometriosis. However, because these mechanisms also induce inflammatory cytokines, a balance of antioxidants and antiglucocorticoids may prove beneficial.

Antioxidants↗

Spermagglutinating antibodies and beta-spermagglutinins in sera from infertile and fertile women.

Sera from five groups of women were investigated by the tray agglutination technique for the presence of spermagglutinins: (1) 326 women from infertile couples, (2) 51 women in early pregnancy, (3) 65 women in advanced pregnancy, (4) 41 oral contraceptive users, and (5) 109 presumably fertile, nonpregnant women. By absorbing spermagglutinating sera with a cell-free eluate from spermatozoa, agglutination disappeared when due to a high-molecular weight compound with beta-mobility in preparative zone electrophoresis (denoted beta-spermagglutinin), whereas activity due to sperm antibodies was unchanged. Spermagglutinating sera occurred with comparable frequency among women from infertile couples, women in advanced pregnancy, and oral contraceptive users. The absorption study revealed agglutinating antibodies in a significantly higher frequency and in higher titers among women of infertile couples than among fertile women, in whom beta-spermagglutinins were found almost exclusively. These results demonstrate the importance of discriminating between sperm antibodies and beta-spermagglutinins in studies of sperm antibodies as a cause of infertility in women.

Agglutinins↗

Gender issues in the management of inflammatory bowel disease and irritable bowel syndrome.

Crohn's disease and ulcerative colitis are two chronic inflammatory diseases involving the gastrointestinal tract. While many aspects of the management of these diseases are identical for all patients, there are some issues that are specific to women that are not necessarily part of routine care. Such gender-specific issues as menses, fertility, pregnancy and menopause are often overlooked and mismanaged. Women have different psychological concerns as compared with men with regard to their self-image and impact of disease. Health care providers, regardless of their primary focus, should be aware of these differences and be familiar with general information. Irritable bowel syndrome is a prevalent condition that affects more women than men. Theories as to its underlying pathophysiology are still evolving, but what does appear clear is that women pose specific challenges to the management of this condition.

Adjuvants, Immunologic↗

[Recent progress in epidemiologic research of uterine cancer].

Although the mortality and incidence of cervical cancer have been decreasing, those of uterine-body, or endometrial, cancer have been increasing. The proportion of endometrial cancer was reported to have become 33.6% of primary uterine cancers in 1995. Infection with certain types of human papilloma virus (HPV) is considered to be etiologically important for the occurrence of cervical cancer. Because HPV is sexually transmitted, some risk factors for cervical cancer are associated with certain kinds of sexual behavior such as a young age at first intercourse, multiple partners, and infrequent use of barrier-type contraceptives such as condoms. Frequent conceptions and deliveries and histories of sexually transmitted diseases like infection with herpes simplex virus type 2 or chlamydia also have been suggested to be associated with the risk of cervical cancer. Smoking habits and infrequent intake of vegetables and fruits may be related to the increased risk of cervical cancer by supporting persistent infection of HPV through impaired immunological function. Although host factors such as a variant of a tumor suppressor gene like p53 have been assessed in terms of the risk of cervical cancer, these are not yet clearly elucidated. Estrogen stimulation of the endometrium unopposed by progesterone stimulation, namely, unopposed estrogen stimulation, is thought to be involved in the etiology of endometrial cancer. Frequent intake of animal fat, obesity or being overweight, infertility, and histories of diabetes mellitus, hypertension, and polycystic ovary syndrome have been reported to be risk factors for endometrial cancer, and they are thought to increase unopposed estrogen stimulation. Estrogen replacement therapy for postmenopausal symptoms, tamoxifen therapy for breast cancer, and taking sequential-type oral contraceptives have been shown to be exogenous risk factors for endometrial cancer in that they increase unopposed estrogen stimulation to endometrium.

Adult↗

[Protein-S deficiency in young patients with thrombotic brain infarction].

The observation of protein S deficiency in a family six members of which had recurrent cerebral strokes prompted a prospective study so far including 33 patients (23 women, 10 men) with cerebral arterial thrombosis at the age of 19 to 57 years (mean 31 years) admitted to the neurological departments of several hospitals. Diseases associated with cerebral arterial occlusions, such as arterial embolism or hematological, infectious and immunological disorders were not found. The following parameters were tested: antithrombin III, protein C, plasminogen, fibrinolytic capacity after infusion of DDAVP, and free and total protein S. Prothrombin times of all patients were within normal ranges; no woman had taken oral contraceptives for at least 3 months before examination. In 9 patients (8 women, 1 man) a decrease of free and total protein S was found; in 4 additional patients (2 women, 2 men) only the free protein S was reduced. Protein S deficiency was confirmed as an inherited defect in 5 cases by family studies, but excluded in one (both parents normal). Protein S deficiency was combined with protein C deficiency in 3 cases, plasminogen deficiency in 2 cases and reduced fibrinolytic capacity in two. Venous thromboembolism occurred only in one of the 13 patients with protein S deficiency and cerebral arterial thrombosis. Protein S deficiency may be found-mainly as a familial trait-in a substantial percentage of younger patients with "idiopathic" cerebral arterial thrombosis.

Adult↗

Pelvic inflammatory disease: a clinical syndrome with social causes.

Prevalence of pelvic inflammatory disease (PID) reflects community and individual risk factors. Cultural and behavioural factors influence community prevalence of sexually transmitted disease (STD), illegal abortion, puerperal sepsis and contraceptive usage--all of which influence risk of PID. The relative importance of these factors will vary by region. Individual risk factors for the ascent of a lower genital tract infection are still poorly understood but are thought to be behavioural and immunological. Prevention of PID must be undertaken at several levels. At primary level, it requires a reduction in community risk. At secondary level, individual risk can be modified by ensuring diagnosis and treatment of STD before damage of the upper genital tract occurs. More attention to cultural factors should increase the potential for prevention at both levels.

Female↗

Risk factors for condyloma acuminatum in women.

We interviewed 49 women who had a history of condyloma acuminatum and 196 age-matched controls. For women who had ever smoked, the risk of developing condyloma was 3.7 times that of women who had never smoked (95% confidence interval, 1.8-7.6). The relative risk associated with long-term use (five or more years) of oral contraceptives was 9.8 (95% confidence interval, 1.5-65.6). Condyloma acuminatum is caused by infection with human papilloma virus (HPV), usually types 6 or 11. Infection with HPV, most commonly of other types, is associated with an increased risk of cervical neoplasia. If smoking and oral contraceptives increase the risk of infection with these other types of HPV as they do with types 6 and 11, this factor could be the means by which smoking and long-term use of oral contraceptives increase the incidence of cervical neoplasia.

Adolescent↗

Condom use prevents genital ulcers in women working as prostitutes. Influence of human immunodeficiency virus infection.

Control of genital ulcer disease (GUD) is a proposed intervention to slow the dissemination of human immunodeficiency virus (HIV) infection. Programs for the control of sexually transmitted diseases (STD) should focus on groups of high-frequency transmitters, such as prostitutes and their clientele. This study illustrates the interaction between the prevalence of chancroid, use of barrier prophylaxis against STDs, and HIV infection in a population of female prostitutes in Nairobi. Four hundred and twenty three women were evaluated. Despite the increased use of condoms, the prevalence of genital ulcers remained constant between 1986-87 and 1987-88. Genital ulcer disease was simultaneously associated with HIV infection (adjusted odds ratio: 3.7, P less than .01) whereas it was independently and inversely associated with more consistent condom use (P less than .01). The authors conclude that genital ulcer disease can be controlled in these populations but concurrent HIV infection increases the difficulty of this intervention.

Chancroid↗

Contraceptive research projects were awarded $1.5 mil. by Ford Foundation.

The Population Council received a $700,000 grant for a contraceptive leads program carried out by the International Committee for Contraceptive Research. The program, a multicountry effort, will test the effectiveness of an under-the-skin contraceptive implant, a vaginal contraceptive ring, an antipregnancy vaccine, and other products. The Program for the Introduction and Adaptation of Contraceptive Technology received $262,000 to modify contraceptive devices to fit the needs of different cultures around the world. 10 universities and research labs in 6 countries received $544,932 for basic research and training in reproductive biology. The University of California received $21,500 to study endocrine-immunological relationships during pregnancy; The University of Dublin received $95,000 to study implantation; the Institute of Biology and Experimental Medicine (Argentina) received $48,000 for research on sperm maturation; Mahidol University (Thailand) received $78,430 for research on the structure of nuclear proteins in mammalian sperm; the Clinical Research Institute of Montreal received $31,000 to study testicular factors affecting hormonal secretion; and the University of Rochester received $34,000 to study the pineal gland and reproduction. The University of Texas received 2 grants totaling $151,000 for research and training in reproductive biology; The University of Toronto received $56,000 for research on male and female reproductive tissues, and the Zoological Society of London received $30,000 to study epididymal protein secretions in the rabbit. The Ford Foundation has committed more than $225 million over the past 25 years to programs aimed at limiting fertility.

Economics↗

The role of infection in the etiology of preterm birth.

The hypothesis that infection induces or is a precursor to preterm birth or premature rupture of the membranes was examined in a prospective study of 193 randomly selected pregnant women. We investigated the prognostic significance of factors that suggest infection of the uterine cavity before pregnancy, such as a history of pelvic inflammatory disease, a history of intrauterine contraceptive device (IUD) use, multiple sex partners, and the presence of antisperm antibodies, in relation to premature rupture of the membranes and preterm birth. Sexual activity, a potential vehicle for bacterial exchange, was also charted throughout pregnancy via monthly interviews. We performed immunologic tests on each patient and obtained cultures of the cervix for aerobic and anaerobic bacteria and chlamydia at the first visit, occurring at six to 14 weeks' gestation, and again at 36 weeks. The results suggest that infection may indeed play a causative role in premature rupture of the membranes or preterm birth. A strong correlation was found between preterm birth and both a history of pelvic inflammatory disease (P = .004) and a history of IUD use (P = .0015). Amnionitis was associated with the presence of immunoglobulin G (IgG) antisperm antibodies (P = .02), as well as with a history of pelvic inflammatory disease (P = .0006). There was also a correlation between premature rupture of the membranes and a history of multiple sex partners (P = .02). This collective evidence implicates preexisting infection of the uterine cavity as a predisposing factor in premature rupture of the membranes, preterm delivery, and amnionitis.

Chorioamnionitis↗

[Detection of early pregnancy factor in the sera of conceived women before nidation].

In order to apply the early pregnancy factor (EPF) to early diagnosis of fertilization, the establishment of optimal conditions for assay of EPF was attempted, and then EPF in the sera of contracepted and conceived women 4 to 6 days after ovulation were measured. For assay of EPF, 0.25 ml of 1:2 step diluted anti-human lymphocyte serum (ALS), 0.05ml of guinea pig serum as complement and 0.1ml of lymphocytes suspension (1 X 10(7)/ml) pretreated with test serum were mixed and then incubated at 37 degrees C for 90 min. To this mixture 0.1ml of sheep red blood cell suspension (2 X 10(9)/ml) was added and the rosette formation was counted after centrifugation. The rosette inhibition titer (RIT) was expressed as reciprocal of ALS dilutions which resulted in less than 75% of rosette formation as compared with the control. RITs of the conceived women who were assayed on the 5 th day after ovulation were in the range from 16 to 32 X 10(3), while that of the control contraceptive women who were assayed on the same day was in the range from 2 to 4 X 10(3). The sterile women who received AIH but failed to conceive all showed less than 4 X 10(3) as RIT. These results suggest that the assay of EPF is valuable in detecting the early stage of fertilization and possibly may help to differentiate the impairment of embryo implantation from non-fertilization of the ovum as a cause of sterility.

Chaperonin 10↗

Expression of biologically active beta subunit of bovine follicle-stimulating hormone in the methylotrophic yeast Pichia pastoris.

Follicle-stimulating hormone (FSH), a pituitary gonadotropin, is a heterodimer composed of an alpha subunit, which is common to all the glycoprotein hormones, noncovalently associated with the hormone-specific beta subunit. The objective of the present study is to develop a recombinant DNA expression system for the beta subunit of FSH that can be applied to study structure-function relationships while producing large quantities of the hormone subunit for immuno-contraceptive, clinical, and veterinary purposes. We report here the expression of biologically active bovine FSH beta (bFSH beta) in the methylotrophic yeast Pichia pastoris. The Pichia-expressed FSH beta (pFSH beta) was secreted into the culture medium and was found to be immunologically very similar to pituitary-derived ovine FSH beta. Replacement of cognate signal peptide with the yeast alpha mating factor signal peptide increased the level of expression from 230 ng/ml (cognate signal peptide) to 4 micrograms/ml (alpha mating factor signal peptide) of the culture supernatant. pFSH beta His.tag (pFSH beta with six histidine residues at the C terminus) was purified to apparent homogeneity using one-step nickel affinity chromatography. The molecular weight of purified pFSH beta His.tag was approximately 22,000, which was slightly higher than that of the pituitary-derived ovine FSH beta. pFSH beta His.tag could assemble with the alpha subunit to yield a heterodimer capable of binding to the FSH receptors and also elicit biological response. These data show that pFSH beta His.tag is properly folded and biologically active.

Amino Acid Sequence↗

Chapter 1: HPV in the etiology of human cancer.

The causal role of human papillomavirus (HPV) in all cancers of the uterine cervix has been firmly established biologically and epidemiologically. Most cancers of the vagina and anus are likewise caused by HPV, as are a fraction of cancers of the vulva, penis, and oropharynx. HPV-16 and -18 account for about 70% of cancers of the cervix, vagina, and anus and for about 30-40% of cancers of the vulva, penis, and oropharynx. Other cancers causally linked to HPV are non-melanoma skin cancer and cancer of the conjunctiva. Although HPV is a necessary cause of cervical cancer, it is not a sufficient cause. Thus, other cofactors are necessary for progression from cervical HPV infection to cancer. Long-term use of hormonal contraceptives, high parity, tobacco smoking, and co-infection with HIV have been identified as established cofactors; co-infection with Chlamydia trachomatis (CT) and herpes simplex virus type-2 (HSV-2), immunosuppression, and certain dietary deficiencies are other probable cofactors. Genetic and immunological host factors and viral factors other than type, such as variants of type, viral load and viral integration, are likely to be important but have not been clearly identified.

Conjunctival Neoplasms↗

[Sterility of immunologic origin].

Antispermatozoal antibodies in the woman, the man, or both, may be the cause of nonorganic infertility in a small number of couples. The antibodies are most often found in the serum or in the genital fluids. Diagnosis is based on the postcoital test and on various laboratory tests to assess sperm-cervical mucous compatibility and to detect antispermatozoal antibodies. In women the strongest relation between results of laboratory tests and infertility is between the presence of serum antispermatozoal antibodies and infertility of more than 3 years' duration. In men there is a relation between high levels of these antibodies in the semen and infertility. Various treatments have been proposed, but further prospective studies are needed. However, promising results have been reported with homologous intrauterine insemination and with immunosuppression in men.

Adult↗

Risk of HIV infection among Dutch expatriates in sub-Saharan Africa.

In order to study the prevalence of human immunodeficiency virus (HIV) infections and related risk factors, Dutch expatriates returning from sub-Saharan Africa were asked to complete a questionnaire on sexual, occupational and other risk factors, and to donate a sample of blood to test for antibodies against HIV. The 1968 participants were workers of various professions and their family members over 16 years of age posted in sub-Saharan African countries by Dutch governmental, non-governmental and commercial organizations for at least 6 months cumulative time between 1 January 1979 and 1 January 1990. Antibodies against HIV-1 were found among 4 of 1122 men (0.4%) and 1 of 846 women (0.1%). The woman and 3 of the men had had sexual contact with African partners and had been treated for sexually transmitted diseases, 2 of these 3 men also had an African life partner. One man reported occupational exposure only. Of the 1968 participants 89 men (7.9%) and 18 women (2.1%) lived with an African partner; 344 men (30.7%) and 111 women (13.1%) had heterosexual contact with other African partners. Only 22.3% (men) and 18.6% (women) of casual sexual contacts with African partners were always protected by a condom. Two hundred and thirty-two of 408 (56.9%) (para)medics reported needlesticks. Groups at risk of HIV infection through sexual exposure were identified using logistic regression models. In conclusion, the observed prevalence of HIV-1 is low. However, unprotected sexual contact with African partners and needlestick accidents were common. This study underscores the continuous need for health education of expatriates on the risks of transmission of HIV in Africa.

Adolescent↗