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Ontogeny of androgen receptor and disruption of its mRNA expression by exogenous estrogens during morphogenesis of the genital tubercle.

PURPOSE: The ontogeny of androgen receptor expression in male and female mouse genital tubercles, and the effects of in utero ethinyl estradiol exposure on androgen receptor mRNA expression in the hypospadias model were studied. MATERIALS AND METHODS: Androgen receptor mRNA expression was measured in mouse genital tubercles from fetuses and pups collected on gestational days 12, 14, 16 and 18, and from newborns using immunohistochemistry and real-time quantitative polymerase chain reaction. Pregnant dams were exposed to ethinyl estradiol or corn oil as controls from gestational days 12 to 17. Genital tubercles of gestational day 19 fetuses were then examined by further quantitative polymerase chain reaction analysis after identification of the seam area using a dissecting microscope to diagnose hypospadias in males. RESULTS: Androgen receptor protein was detected in genital tubercles by gestational day 14. Androgen receptor mRNA expression increased gradually in each sex during normal development. However, female genital tubercles expressed a higher level of androgen receptor mRNA throughout development compared to male genital tubercles (p <0.0001). In utero ethinyl estradiol exposure led to a 5.4 and 4.5-fold increase in androgen receptor mRNA in the genital tubercles of female and male embryos (p = 0.004 and 0.001, respectively). Hypospadiac male genital tubercles showed increased androgen receptor mRNA expression compared to control males (p = 0.006). Levels in hypospadiac males did not differ from those in control females but they were less than those in ethinyl estradiol treated females (p >0.05 and 0.01, respectively). CONCLUSIONS: Androgen receptor protein is expressed abundantly in male and female genital tubercles. Androgen receptor mRNA levels are higher in female than in male genital tubercles through development and they increase in response to in utero ethinyl estradiol exposure with ethinyl estradiol treated females having the highest levels of expression, followed by ethinyl estradiol treated hypospadiac males. We infer that higher estrogen in genital tubercles results in a physiological response of increased androgen receptor mRNA expression. We found no direct association between changes in androgen receptor mRNA expression and the presence or absence of hypospadias in males, suggesting that alterations in the expression of proteins other than or in addition to androgen receptor result in anomalous urethral development. This finding supports the idea that the etiology of hypospadias is multifactorial in origin.

Animals↗

Poor correlation between genital lesions and detection of herpes simplex virus in women in labor.

OBJECTIVE: To estimate the accuracy of clinical diagnosis of genital herpes for herpes simplex virus (HSV) detection among women in labor. METHODS: Viral detection by culture and HSV DNA polymerase chain reaction (PCR) among women who underwent cesarean delivery for genital herpes was compared with women without HSV symptoms in labor who had genital swabs collected for HSV culture and to a subset of these women who had genital specimens available for PCR analysis, regardless of culture results. RESULTS: From 1989 to 1999, 126 of 19,568 (0.6%) women underwent cesarean delivery for HSV. Twenty-six percent of 110 of these women had HSV detected by culture from at least 1 genital specimen and 46% of 70 of these women had HSV detected by PCR. During the same period, 61 of 12,623 (0.5%) asymptomatic women had HSV detected by culture. Between 1995 and 1996, 57 of 2,109 (2.7%) asymptomatic women had HSV detected by PCR. Thus, the presence of genital lesions had a sensitivity for HSV detection of 37% by culture and 41% by PCR. The amount of HSV present in asymptomatic women with HSV detected in genital secretions by PCR was often as high as those with genital lesions, although the median amount of HSV DNA detected was greater in women with lesions. CONCLUSION: Clinical diagnosis of genital herpes at the time of labor correlates relatively poorly with HSV detection from genital sites or lesions by culture or PCR and fails to identify asymptomatic women who have HSV in their genital secretions at the time of labor.

Adolescent↗

Male genital hygiene beliefs and practices in Nairobi, Kenya.

OBJECTIVES: Attitudes and practices concerning genital hygiene may influence topical microbicide use by men. This study examines knowledge and behaviours related to hygiene, genital hygiene, circumcision and hygiene, and to genital hygiene before and after sex among men in Nairobi, Kenya. METHODS: We conducted 463 interviews of men recruited by respondent driven sampling techniques and 10 focus group discussions with a subsample of 100 volunteers from this group. Men were asked individual quantitative survey and qualitative group discussion questions about general hygiene behaviours, genital hygiene, and the temporal relation of genital hygiene behaviours to sexual encounters. RESULTS: Bathing once daily was associated with education, income, and inside tap water. Genital washing aside from regular bathing and washing before sex ever were negatively associated with bathroom crowding. Genital hygiene before the most recent sexual encounter was uncommon and negatively associated with HIV risk perception, bathroom crowding, and ethnicity. Men believed genital hygiene before sex would arouse suspicions of infidelity or cool sexual ardour. Genital hygiene after sex was associated with education, religion, and having inside tap water. Genital hygiene after the most recent sexual encounter was associated with age, income, and with men having at least one child. CONCLUSIONS: Genital hygiene behaviours were associated with resource access factors and group discussions suggest that they are modulated by interactions in sexual partnerships. Topical microbicides may improve hygiene before and after sex.

Adult↗

Decreased expression of IGF-II and its binding protein, IGF-binding protein-2, in genital skin fibroblasts of patients with complete androgen insensitivity syndrome compared with normally virilized males.

The action of androgen by way of the AR is required for the development of male gonads and external genitalia. The interplay between androgens and the somatotropic axis, in particular the IGFs in sexual development, is currently under thorough investigation. The IGF system is thought to mediate the androgen action in androgen-responsive cells. To investigate the interaction of androgens with the IGF system, we compared the expression of IGFs and IGF-binding proteins in cultured genital skin fibroblasts from nine patients with the syndrome of complete androgen insensitivity with that in genital skin fibroblasts from 10 normally virilized males. Mutations in the AR gene and/or abnormalities of the AR protein in the immunoblot were detected in all complete androgen insensitivity genital skin fibroblast strains. They caused a complete failure of DHT binding. RIA and RT-PCR demonstrated that the genital skin fibroblast strains expressed IGF-II, IGF-binding protein-2, and IGF-binding protein-3, but no IGF-I. Most strikingly, complete androgen insensitivity genital skin fibroblast strains produced significantly lower IGF-II (P < 0.001; 42.2 +/- 9.7 vs. 106.9 +/- 11.8 ng/mg protein) and IGF-II mRNA (P < 0.01, by RT-PCR) than control genital skin fibroblast strains. The production of IGF-binding protein-2 was also decreased (P < 0.03) in complete androgen insensitivity genital skin fibroblasts, whereas that of IGF-binding protein-3 did not differ. Furthermore, high levels of IGF-binding protein-5 mRNA were detected in all genital skin fibroblast strains, whereby the 28-kDa band in the ligand blot, probably representing IGF-binding protein-5, was more abundant in complete androgen insensitivity genital skin fibroblasts. Exposure of the genital skin fibroblasts to T (5 x 10(-8) M) had only weak effects on the expression of IGFs and IGF-binding proteins. In conclusion, although the mechanism underlying these differences requires further study, it is conceivable that in addition to the endocrine actions of IGF-I, IGF-II and IGF-binding protein-2, as local growth factors, are involved in the mediation of androgen action and growth of genital tissues.

Androgen-Insensitivity Syndrome↗

Natural history and epidemiological features of genital HPV infection.

The spectrum of genital HPV infections comprises clinical, subclinical, and latent disease in addition to HPV-associated neoplasia. The definition of subclinical and latent HPV infection is still incomplete and awaits clarification by highly sensitive HPV detection systems that preserve the morphology of the tissue. Genital HPVs infect the human body mainly by sexual transmission, but other pathways of HPV transmission may be possible as suggested by (a) high prevalences of antibody reactivity in children; (b) lack of association of HPV seropositivity with sexual activity; (c) presence of HPV DNA in oral cavity scrapings of children and adults; and (d) development of recurrent respiratory papillomatosis among children exposed to HPV 6 or 11 during birth. Successful infection depends on the infection site and the immunological state of the host: susceptibility to genital HPVs seems highest for the squamous epithelium of the lower genital tract. HPV DNA is also present in extragenital sites but this is rarely accompanied by clinical or subclinical lesions. The molecular basis for this specific tropism is unknown. The immune response in HPV-infected tissues is characterized by depletion of T helper/inducer cells or Langerhans cells and an impaired immunological function of natural killer cells or the infected keratinocyte. Epidemiological studies indicate that individuals with cell-mediated immunodeficiencies are at increased risk for genital HPV infections. Data about the biological course of genital HPV infections are just beginning to emerge. Regression or persistence of subclinical and latent genital HPV infections as analysed in longitudinal investigations show a constant come-and-go of HPV presence. In an infected individual, complete clearing of the virus seems rather exceptional. With respect to progression, the biological potential of cervical HPV infections is characterized by an increased risk for development of HPV-associated neoplasia, especially in lesions infected with high-risk HPV types (e.g., HPV 16 and 18). Demographic data of genital HPV infections are very variable due to differences in the HPV detection assays used and in the populations examined; the prevalence of subclinical and latent genital HPV infections appears to be at least three times higher compared with clinical HPV infections. This rate increases by a further 3-5-fold when patients are examined several times. Seroreactivity against genital HPV types may be due to an active infection or the result of contact with HPV earlier in life.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Langerhans cell histiocytosis of the female genital tract.

Langerhans cell histiocytosis (LCH) of the female genital tract is rare. Four new cases are reported, and there is a review of the 38 cases in the literature. This disease may involve the vulva, vagina, cervix, endometrium, and ovary. Four distinct patient groups, segregated on the basis of initial presentation and subsequent anatomic extent of disease, were categorized as follows: (1) "pure" genital LCH, (2) genital LCH with subsequent multi-organ involvement, (3) oral or cutaneous LCH with subsequent genital and multi-organ involvement, and (4) diabetes insipidus with subsequent genital and multi-organ disease. Although involvement of the genital tract can occur at any age, it is most common in young adulthood. Clinically, LCH may mimic either primary neoplasia or various inflammatory lesions; the major pathologic differential diagnosis is venereal and other inflammatory diseases. The pure genital form may have a distinct nosologic position in the spectrum of LCH similar to the "pure," self-limited cutaneous histiocytosis seen in infants. There is no correlation between histologic findings and the outcome of the genital lesions. There is also no correlation between clinical presentation and/or the extent of involvement and outcome of genital lesions; complete regression, partial improvement, persistent lesions, and recurrences were seen in all four groups of patients. The treatment of genital LCH is not well defined and is highly individualized. Therapy has included surgery, radiation, topical corticosteroids, topical nitrogen mustard, systemic chemotherapy, and combination therapy; mixed results were obtained with all treatment modalities. Although no modality has been shown to yield a superior outcome, complete surgical excision is advocated as initial therapy.

Adult↗

Genital ulcer disease among STD clinic attenders in Nairobi: association with HIV-1 and circumcision status.

In previous studies, genital ulcers in men have been found to be associated with increased risk of HIV-1 seroconversion. To further explore this association male patients attending a sexually transmitted disease (STD) clinic in Nairobi for either urethritis (controls, n = 276) or a genital ulcer (cases, n = 607) were compared with respect to sexual behaviour, presence of HIV-1 antibody and circumcision status. Patients were followed to study risk factors for incident genital ulcers and HIV-1 seroconversion. At entry, being married was associated with higher prevalence of HIV-1 (OR = 1.76) and genital ulcers (OR = 1.42). Lack of circumcision was associated with both HIV-1 infection (OR = 4.67) and the presence of a genital ulcer (OR = 2.23). Genital ulcers were also associated with HIV-1 infection (OR = 1.87) independent of circumcision status. On follow-up, HIV-1 seropositivity was associated with incident genital ulcers. It is argued that the association between genital ulcers and HIV-1 infection may be more complex than ulcers simply being a risk factor for HIV-1 infection, and that HIV-1 infection may either increase the risk of acquiring a genital ulcer, or HIV-1 infection and genital ulcers may have some unknown risk factor in common.

Adult↗

Use and function of genital contacts among female bonobos.

Female bonobos, Pan paniscus, show a mounting behaviour that differs physically from that in other primate species. They embrace each other ventroventrally and rub their genital swellings against each other. We investigated five hypotheses on the function of ventroventral mounting (genital contacts) that derive from previous studies of both primate and nonprimate species: (1) reconciliation; (2) mate attraction; (3) tension regulation; (4) expression of social status; and (5) social bonding. We collected data in six field seasons (1993-1998) from members of a habituated, unprovisioned community of wild bonobos at Lomako, Democratic Republic of Congo. No single hypothesis could account for the use of genital contacts, which appeared to be multifunctional. We found support for hypotheses 1 and 3. Rates of postconflict genital contacts exceeded preconflict rates suggesting that the display is used in the context of reconciliation. Rates of genital contacts were high when food could be monopolized and tension was high. However, genital contacts also occurred independently of agonistic encounters. Our study shows rank-related asymmetries in initiation and performance of genital contacts supporting the social status hypothesis: low-ranking females solicited genital contacts more often than high-ranking females while the latter were more often mounter than mountee. Although subordinates took more initiative to achieve genital contact, dominants mostly responded to the solicitation (ventral presentation) with mounting, indicating that the performance benefits both individuals. We suggest that genital contacts can be used to investigate both quality and dynamics of dyadic social relationships among female bonobos. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗

Sex-specific control of growth and differentiation in the Drosophila genital disc, studied using a temperature-sensitive transformer-2 mutation.

Mutations of the transformer-2 (tra-2) locus of Drosophila melanogaster cause chromosomally female (XX) animals to develop as males, but have no effect on the development of chromosomally male (XY) animals. In the female genital disc, such mutations cause repression of growth and inhibition of differentiation in the female genital primordium, while allowing growth and differentiation of the otherwise repressed male genital primordium. We used a temperature-sensitive mutation of this locus (tra-2ts1) to switch development from one sexual pathway to the other. Following development at the male-determining temperature (29 degrees C), subsequent culture of the XX;tra-2ts1 genital disc in vivo at the female-determining temperature (16 degrees C) allowed the previously repressed female genital primordium to develop and form female genital structures, whereas the formation of male genital elements was grossly disturbed. Conversely, following development at the female-determining temperature, subsequent culture in vivo at the male-determining temperature allowed the formerly repressed male genital primordium to grow and produce male genital structures, and repressed the formation of female elements from the already fully developed female genital primordium. The experiments indicate that the tra-2 product has to operate during the culture period in order to maintain the female state of sex determination, i.e., to promote the development of female structures, as well as to repress that of male structures. The experimental treatments, as well as the results of temperature shifts on developing larvae, resulted in sexual transformation of the anal plates, and clarified the sexual homologies of these structures. In both genitalia and analia, a switch from the female to the male developmental pathway was accomplished more rapidly and effectively than the reverse change.

Animals↗

Frequency and reactivation of nongenital lesions among patients with genital herpes simplex virus.

OBJECTIVE: To determine the frequency, recurrence patterns, and host factors associated with nongenital herpes simplex virus lesions. PATIENTS AND METHODS: In this cohort study at a referral clinic, 457 patients with first episodes of genital herpes were prospectively observed to evaluate the anatomic sites of herpetic lesions at the first and subsequent visits. Of these patients, 73 had primary genital herpes simplex virus (HSV) type 1, 326 had primary first episode genital HSV-2, and 58 had HSV-1 infection prior to acquisition of genital HSV-2. The median follow-up was 63 weeks. RESULTS: Nongenital lesions at the time of acquisition of genital herpes were observed in 25%, 9%, and 2% of patients with primary HSV-1, primary HSV-2, and nonprimary HSV-2, respectively. Half of the patients with concurrent genital and nongenital lesions subsequently had recurrences at a nongenital site. Twenty patients (6.5%) whose primary genital HSV-2 infection involved only the genitalia subsequently developed nongenital recurrences, primarily on the buttocks (12) and legs (4). Nongenital recurrences, especially buttock recurrences, tended to be less frequent but of longer duration than genital recurrences. CONCLUSIONS: Overall, 21% of patients with primary genital herpes will have or will subsequently develop a nongenital recurrence. Among patients with HSV-1, nongenital lesions tended to occur more often on the hand and face, whereas HSV-2 lesions appeared more often on the buttocks. Buttock lesions due to HSV recur less frequently but last longer than genital lesions.

Herpes Genitalis↗

Stress as a predictor of symptomatic genital herpes virus recurrence in women with human immunodeficiency virus.

OBJECTIVE: Genital herpes (Herpes Simplex Virus Type 2, HSV-2) is a significant public health problem for HIV+ women, who have high rates of HSV-2 seropositivity and elevated risk for HSV-2 associated morbidity and mortality. Life stress has been identified as a co-factor in genital herpes recurrence. However, no research has evaluated the relationship between stress and genital herpes recurrences in HIV+ women. The purpose of this study was to determine whether stress was associated with symptomatic genital herpes recurrences in women seropositive for HIV and HSV-2. METHODS: Thirty-four HIV-infected African-American and Caribbean-American women underwent a psychosocial interview, blood draw and gynecologic examination to assess gynecologic symptoms (including genital herpes) at study entry. Life stress was measured using a 10-item modified version of the Life Experiences Survey (LES). Genital herpes recurrence over 1-year follow-up was abstracted using medical chart review. RESULTS: Using hierarchical linear regression analysis, life stress at study entry was significantly associated with number of genital herpes recurrences during 1-year follow-up (beta=.38, P=.03) after controlling for HIV disease variables and relevant behavioral factors. Recent life stress, in particular, was highly predictive of genital herpes recurrence during follow-up (beta=.57, P=.002). The relationship between life stress and genital herpes recurrence persisted after controlling for HSV-2 viral reactivation (i.e., HSV-2 IgG titers) at study entry. CONCLUSION: These findings suggest that stress may be a significant predictor of genital herpes recurrence in women with HIV and HSV-2. Stress management interventions may buffer HSV-related morbidity and mortality in women with HIV.

Adolescent↗

The urethral plate--does it grow into the genital tubercle or within it?

OBJECTIVE: To determine whether the urethral plate grows into the genital tubercle or develops within it. MATERIALS AND METHODS: Sprague-Dawley rat embryos were examined at 11-21 days of gestation and compared with available human embryo sections. Rat embryos were examined by a combination of light microscopy, dissection, serial histological section and immunohistochemistry. RESULTS: In rat embryos the urethral plate extended to the tip of the genital tubercle from the earliest stages of genital tubercle development. The plate formed from adherence in the sagittal plane of the inner walls of the primitive cloacal cavity. The urethral plate continued to extend to the tip of the genital tubercle throughout penile development in the male and developed a lumen ahead of the advancing perineal mesenchyme. In the female the perineal side of the urethral plate disintegrated by massive apoptosis. This loss of perineal substance allowed the genital tubercle to collapse on itself and left the urogenital opening at the base of the genital tubercle. Human embryos also showed the presence of the urethral plate at the tip of the genital tubercle throughout genital tubercle development. CONCLUSION: The urethral plate forms ab initio within the genital tubercle and extends to the tip; it does not grow into the genital tubercle as is often described. The contribution of ectodermal ingrowth to urethral development at the tip of the penis is minimal.

Animals↗

Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons.

BACKGROUND: Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection. METHODS: We conducted a prospective study to investigate genital shedding of HSV among 53 subjects who had antibodies to HSV-2 but who reported having no history of genital herpes, and we compared their patterns of viral shedding with those in a similar cohort of 90 subjects with symptomatic HSV-2 infection. Genital secretions of the subjects in both groups were sampled daily and cultured for HSV for a median of 94 days. RESULTS: HSV was isolated from the genital mucosa in 38 of the 53 HSV-2-seropositive subjects (72 percent) who reported no history of genital herpes, and HSV DNA was detected by the polymerase-chain-reaction assay in cultures prepared from genital mucosal swabs in 6 additional subjects. The rate of subclinical shedding of HSV in the subjects with no reported history of genital herpes was similar to that in the subjects with such a history (3.0 percent vs. 2.7 percent). Of the 53 subjects who had no reported history of genital herpes, 33 (62 percent) subsequently reported having typical herpetic lesions; the duration of their recurrences in these subjects was shorter (median, three days vs. five days; P<0.001) and the frequency lower (median, 3.0 per year vs. 8.2 per year; P<0.001) than in the 90 subjects with previously diagnosed symptomatic infection. Only 1 of these 53 subjects had no clinical or virologic evidence of HSV infection. CONCLUSIONS: Seropositivity for HSV-2 is associated with viral shedding in the genital tract, even in subjects with no reported history of genital herpes.

Adult↗

Association of genital shedding of herpes simplex virus type 2 and HIV-1 among sex workers in rural Zimbabwe.

INTRODUCTION: Herpes simplex virus type 2 (HSV-2) facilitates sexual acquisition of HIV-1 but data on transmission are less clear. In this study the interaction between genital shedding of HIV-1 and HSV-2 was explored among Zimbabwean sex workers. METHODS: Women (n = 214) were interviewed about genital symptoms. Blood samples were analysed for HIV-1 and HSV-2 antibodies, HIV-1 plasma viral load (PVL) and CD4 lymphocyte count and genital swabs for detection of HIV-1 and HSV-2 genital shedding, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis, and a cervico-vaginal lavage (CVL) for quantitative measurement of HIV-1 shedding. Shedding analyses were undertaken on women co-infected with HSV-2 and HIV-1. RESULTS: A total of 124 women were co-infected with HIV-1 and HSV-2; 58 were infected with HSV-2 alone. Most HIV-1-infected women were co-infected with HSV-2 (95.4%). Genital HIV-1 shedding was detected in 84.3% of co-infected women and was associated with low CD4 cell count and high PVL but not with reported symptoms of genital herpes or genital shedding of HSV-2. There was no difference in HIV-1 shedding among women shedding HSV-2 (79.3%) and women not shedding HSV-2 (83.2%) (P = 0.64). The adjusted odds ratio for HIV-1 shedding between HSV-2 shedders and non-shedders was 0.8 [95% confidence interval (CI), 0.2-3.3]. HIV-1 PVL(log10) and CVL viral load(log10) were correlated (r = 0.38; 95%CI, 0.2-0.5). After adjusting for PVL, genital symptoms and age, HSV-2 shedding had no effect on CVL viral load (P = 0.13). CONCLUSION: Rate and quantity of HIV-1 genital shedding do not appear to be altered by presence of HSV-2 genital shedding.

Adolescent↗

The frequency of scarring after genital ulcers in Behçet's syndrome: a prospective study.

BACKGROUND: Although genital ulceration with or without scar formation is an important manifestation of Behçet's syndrome, formal data on the rate of genital scarring are lacking. OBJECTIVE: To study prospectively the frequency of genital scar formation after genital ulcers in patients with Behçet's syndrome. Methods One hundred and two patients (72 males and 30 females) with fresh genital ulcers presenting at a dedicated Behçet's syndrome outpatient clinic were followed for 6 weeks. The ulcer location, size, and frequency of scar formation were noted. All patients were treated with similar topical therapy. RESULTS: Two hundred and ten genital ulcers were followed in both sexes. The rate of scar formation was 66.2% (102/154) in male patients and 60.7% (34/56) in female patients. When genital ulcers were stratified as a function of size, large genital ulcers (> or = 1 cm in diameter) developed scars more frequently than did smaller ulcers (< 1 cm). The rate of scar formation in male patients with large genital ulcers was 89.4% (59/66) and with small ulcers was 48.9% (43/88) (P < 0.001). In females, all 19 large ulcers healed with scarring, and the same was true for 40.5% (15/37) of the small ulcers (chi(2) = 18.61, P < 0.001). CONCLUSION About two-thirds of genital ulcers in Behçet's syndrome leave scars. The rate of scar formation depends on the ulcer size.

Adult↗

Mouse genital ridges in organ culture: the effects of temperature on maturation and experimental induction of teratocarcinogenesis.

Testicular teratomas can be induced experimentally by grafting genital ridges from male mouse fetuses to the testes of adults. A high incidence of teratomas occurs in genital ridges grafted to scrotal testes, but not in genital ridges grafted to testes maintained at body temperature. Genital ridges were cultured at 32 degrees C or 37 degrees C prior to grafting to the testes to determine the effect of temperature on the incidence of teratomas. Genital ridges cultured at 32 degrees C for two or three days produced a high incidence of teratomas when grafted to the testes, in contrast to genital ridges cultured at 37 degrees C for two or three days which produced a low incidence. Histologically, genital ridges cultured at 32 degrees C contained disorganized testicular tubules and were retarded in development. Genital ridges continued to develop in vitro at 37 degrees C, but were histologically different from genital ridges maturing in the fetus. Genital ridges cultured at 32 degrees C for 10 to 12 days did not develop teratomas in vitro or after grafting to the testes. Further characterization of temperature effects in vitro may lead to a better understanding of teratocarcinogenesis in vivo.

Animals↗

Female genital mutilation: analysis of the first twelve months of a Southeast London specialist clinic.

OBJECTIVES: To analyse the sources and reasons for referral of women who have undergone genital mutilation to a recently established specialist clinic, and to determine the consequences of the genital mutilation procedure. DESIGN: Retrospective descriptive case series. SETTING: The maternity units of Guy's and St. Thomas's Hospital, London. POPULATION: One hundred and sixteen women attending the clinic over a one-year period. MAIN OUTCOME MEASURES: (1) sources and reasons for referral to the specialist clinic; (2) characteristics of the women attending the clinic; (3) acute and chronic complications of the genital mutilation procedure; (4) attitudes towards female genital mutilation. RESULTS: Complete case records were available for 108 women. Of the 86 women who could remember the procedure, 78% were performed by a medically unqualified person, usually at home (71%), at a median age of seven years. Acute and chronic complications were each present in 86% of women with Type III genital mutilation. Most women (82%) were referred by their midwife because they were pregnant, of whom 48% were primigravid. Eighteen non-pregnant women also attended the clinic to request either defibulation or for advice. None of the 89 pregnant women requested re-infibulation after delivery, but almost 6% were seriously considering having their daughter undergo genital mutilation outside the United Kingdom. In addition, fewer than 10% of the women refused to continue the tradition of female genital mutilation. CONCLUSIONS: During its first year, the recently established African Well Woman Clinic has provided specialist care for 116 women with genital mutilation. Such women may attend with a variety of common medical or psychiatric conditions and often do not volunteer that they have undergone the procedure. Doctors and midwives in particular, should enquire specifically about genital mutilation when caring for women from high risk countries, and offer the services of specialist clinics for female genital mutilation.

Adult↗

Vaccine-induced serum immunoglobin contributes to protection from herpes simplex virus type 2 genital infection in the presence of immune T cells.

Herpes simplex type virus 2 (HSV-2) is a sexually transmitted pathogen that causes genital lesions and spreads to the nervous system to establish acute and latent infections. Systemic but not mucosal cellular and humoral immune responses are elicited by immunization of mice with a replication-defective mutant of HSV-2, yet the mice are protected against disease caused by subsequent challenge of the genital mucosa with virulent HSV-2. In this study, we investigated the role of immune serum antibody generated by immunization with a replication-defective HSV-2 vaccine prototype strain in protection of the genital mucosa and the nervous system from HSV-2 infection. Passive transfer of replication-defective virus-immune serum at physiologic concentrations to SCID or B-cell-deficient mice had no effect on replication of challenge virus in the genital mucosa but did significantly reduce the incidence and severity of genital and neurologic disease. In contrast, B-cell-deficient mice immunized with replication-defective HSV-2 were able to control replication of challenge virus in the genital mucosa, but not until 3 days postchallenge, and were not completely protected against genital and neurologic disease. Passive transfer of physiologic amounts of immune serum to immunized, B-cell-deficient mice completely restored their capacity to limit replication of challenge virus in the genital mucosa and prevented signs of genital and systemic disease. In addition, the numbers of viral genomes in the lumbosacral dorsal root ganglia of immunized, B-cell-deficient mice were dramatically reduced by transfer of immune serum prior to challenge. These results suggest that there is an apparent synergism between immune serum antibody and immune T cells in achieving protection and that serum antibody induced by vaccination with replication-defective virus aids in reducing establishment of latent infection after genital infection with HSV-2.

Animals↗