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Characterization of human papillomavirus type 45, a new type 18-related virus of the genital tract.

DNA of human papillomavirus (HPV) type 45, a new HPV type 18-related papillomavirus of the genital tract, was cloned from a recurrent cervical lesion displaying mild to moderate dysplasia with koilocytosis. HPV-45 DNA was identified in paraffin sections of biopsies of both the initial and recurrent lesions of the patient, taken 7 months apart. HPV-45 DNA hybridized efficiently to that of many different HPV types under low and moderate stringency conditions (Tm - 37 degrees C to Tm - 25 degrees C) but with only HPV-18 DNA under high stringency conditions (Tm - 17 degrees C). HPV-45 DNA was distinguished from HPV-18 DNA by (i) differences in restriction enzyme digest patterns, (ii) lack of hybridization at Tm - 17 degrees C between HPV-18 and some fragments of HPV-45, (iii) a value of 25% in liquid reassociation kinetics between HPV-18 and HPV-45 and (iv) differences in intensities of hybridization with selected tissue DNAs. The prevalence of HPV-45 infection in the genital tract was low. In tests of over 600 tissue DNAs from female genital tract lesions, HPV-45 sequences were detected in three additional tissues, one each of invasive cervical carcinoma, condyloma, and normal cervical epithelium. HPV-45 is a newly recognized papillomavirus which rarely infects the genital tract and is associated with lesions across a wide histological spectrum.

Chromosome Mapping↗

Clinical and serological outcome of genital herpes simplex virus (HSV) type 2 inoculation following oral HSV type 1 infection in guinea-pigs.

The clinical and serological outcome of genital herpes simplex virus type 2 (HSV-2) inoculation in animals previously orally infected with HSV type 1 was evaluated. A prior HSV-1 oral infection modified the genital HSV-2 infection so that only four of 18 (22%) animals were initially symptomatic although all but one animal shed HSV-2 from the cervicovaginal area for at least 5 days following inoculation. Three of four animals with symptomatic initial disease also developed recurrences, as did an additional six animals that did not manifest acute genital disease. Anti-glycoprotein gG-1 antibody was found in 17 of 18 animals with only an HSV-1 infection and anti-gG-2 antibody in all of nine animals with only an HSV-2 infection. Anti-gG-2 antibody was detected in eight of 17 animals with a prior HSV-1 infection following HSV-2 inoculation and one had an indeterminate response. Eight of these nine animals developed recurrent genital disease compared to one of eight that did not respond to gG-2 (P less than 0.006). Thus a prior oral HSV-1 infection modified both the initial presentation of HSV-2 infection and the HSV type-specific serological response.

Animals↗

Differential roles of B cells and IFN-gamma-secreting CD4(+) T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice.

The role of B, CD4(+) T and CD8(+) T cells in both primary genital infection with attenuated herpes simplex virus type 2 (HSV-2) and development of protective immunity to a later challenge with virulent HSV-2 using lymphocyte-deficient mice has been elucidated. Following primary inoculation with attenuated thymidine kinase-deficient (TK(-)) HSV-2, B cell-deficient (microMT) mice developed a local viraemia and transient genital inflammation, suggesting a role for B cells in the innate control of local infection and inflammation. Natural antibodies are implicated in this process, as passive transfer of normal serum into microMT mice significantly reduced HSV-2 TK(-) shedding in the vaginal lumen, although it did not affect subsequent inflammation. Protection against lethal HSV-2 challenge was noted in HSV-2-vaccinated wild-type, CD8(+) T cell-deficient and microMT mice and was characterized by strong virus-specific IFN-gamma responses in vitro and delayed type hypersensitivity (DTH) responses in vivo. In contrast, CD4(+) T cell-deficient (CD4(-/-)) mice had impaired HSV-2-specific IFN-gamma production and DTH responses and succumbed rapidly to genital HSV-2 challenge. However, protective responses to HSV-2 could be induced in HSV-2-vaccinated CD4(-/-) mice by treatment with recombinant IFN-gamma. Taken together, these results suggest that CD4(+) T cells secreting IFN-gamma are critical for immune protection against lethal genital HSV-2 re-infection, whereas B cells/natural antibodies have anti-viral and -inflammatory effects in the innate control of a primary infection.

Animals↗

Heterotypic protection of mice against chlamydial salpingitis and colonization of the lower genital tract with a human serovar F isolate of Chlamydia trachomatis by prior immunization with recombinant serovar L1 major outer-membrane protein.

Intrauterine infection of mice with a human genital tract isolate of Chlamydia trachomatis (serovar F) resulted in salpingitis. In some cases, oviduct damage was sufficient to cause infertility due to lumenal blockage. Parenteral immunization with a purified, heterologous, recombinant major outer-membrane (rMOMP) preparation reduced the proportion of animals developing severe salpingitis by 77% compared with mock-immunized controls, but failed to reduce chlamydial colonization of the lower genital tract. In contrast, mice immunized with rMOMP directly into the Peyer's patches to stimulate mucosal immunity shed fewer chlamydiae from the vagina than controls, but showed little reduction in oviduct damage. No consistent correlation was observed between antibody levels to rMOMP in immunized mice and reduced lower genital tract colonization. Immunization with rMOMP via the presacral space, a route previously shown to stimulate mucosal immunity in the genital tract, produced high levels of circulating anti-rMOMP IgG but only traces of anti-rMOMP IgA in vaginal secretions. There was no difference in the severity of salpingitis in these animals compared with mock-immunized controls. Immunization with rMOMP conferred no protection against infertility resulting from direct inoculation of chlamydiae into the oviducts.

Animals↗

Human genital melanocytes as androgen target cells.

As some parts of human skin - such as genital and areolar skin - become pigmented after puberty, melanocytes in these regions are thought to be sex hormone target cells. We immunohistochemically localized androgen receptors in the nuclei of cultured human genital melanocytes by monoclonal and polyclonal antibodies. When these cells were incubated with [1,2-3H]-testosterone, the major metabolite in the medium was dihydrotestosterone and 5alpha-reduction predominated over 17beta-oxidation. Androgen receptor and type I 5alpha-reductase mRNAs could be detected in genital melanocytes by reverse transcriptase polymerase chain reaction. The tyrosinase activity was stimulated by the addition of androgen. This stimulation was antagonized by cyproterone acetate, whereas tyrosinase mRNA expression was not affected by androgen. These results indicate that human genital melanocytes are androgen target cells, and that androgen plays a role for pigmentation in the specific regional skin after puberty.

17-Hydroxysteroid Dehydrogenases↗

The development of the genital peritoneum in domestic mammals. An analysis of the literature and nomenclature.

This review presents and discusses the reasons for the currently employed anatomical terminology relating to the genital peritoneum of various domestic species, based upon its prenatal development. When reviewing the development of genital organs, attention must be paid to changes in the related peritoneum in order to define currently used terminology more clearly. The relevance of some terms such as Caudal genital ligament, Plica gubernaculi, Plica iguinalis and genital fold is considered. A system of serosal folds, the Plica gonadoinguinalis or genitoinguinalis, seems to be a useful term to be added to the Nomina Embryologica Veterinaria.

Animals↗

Outcomes of infants whose mothers are positive for human herpesvirus-6 DNA within the genital tract in early gestation.

It has been reported that HHV-6 (human herpesvirus-6) DNA has been identified within the female genital tract. However, the clinical significance of this finding has been unclear. The clinical outcome of the presence of HHV-6 DNA in the genital tract of pregnant women on their infants was evaluated in the present study. One hundred and ten pregnant women were enrolled. Vaginal swabs were collected between 4 and 8 weeks of gestation and the presence or absence of HHV-6 DNA was evaluated by nested polymerase chain reaction (nPCR). The swabs were cultured to isolate the virus. The women were divided into two groups: HHV-6 DNA-positive, and negative. The outcome variables of the infants of these two groups were statistically estimated at birth and at 1 month of age. Saliva and blood cells were collected from the infants at birth and at 1 month of age and were also evaluated by nPCR. HHV-6 DNA was detected in the vaginal swabs of 28 pregnant women (25.5%), but was not detected in any other samples, including saliva and blood cells from their infants. Virus could not be isolated from any vaginal samples. Any outcome variables were not significantly different between the two groups. The presence of HHV-6 DNA within the genital tract of pregnant women did not affect the health of their infants. It is suggested that HHV-6 transmission to infants through the genital tract of their mothers during pregnancy does not occur, or only very rarely.

Adult↗

Surgical repair of genital fistulae.

OBJECTIVE: Genital fistula is one of the serious childbirth injuries that can occur among women in the developing countries. Complex fistulae still represent a challenging management problem. We report our experience of managing genital fistulae at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. METHODS: Eighty-seven women with genital fistulae were managed between January 1988 and December 2002. Sixty-eight cases were urogenital and 19 were rectovaginal fistulae. Three women had concomitant urogenital and rectovaginal fistulae. The position of patients for surgery and the route of repair were individualized according to the appropriate access to the fistulae. RESULTS: Of the 68 cases of urogenital fistulae, 54 were successfully repaired at first attempt. Three patients were cured at second repair. A success rate of 83.8% was achieved. Four patient with ureterosigmoid anastomosis and seven patients who were lost to follow-up, were considered as failures. All of the 19 rectovaginal fistulae (100%) closed after single repair. CONCLUSION: With an experienced uro-gynecologic team using conventional approach and meticulous repair, a high percentage of patients with genital fistulae can be rendered dry and continent.

Adolescent↗

Concurrent genital and rectal prolapse: two pathologies--one joint operation.

This study is a prospective assessment of a joint operation to repair concomitant genital and rectal prolapse, including 10 women treated for concomitant genital and rectal prolapse from 1991 to 1995. Joel-Cohen vaginal hysterectomy was used to correct the genital prolapse, followed by the Altemeier procedure (transperineal rectosigmoidectomy) to correct the rectal prolapse. The post-operative course was uneventful in all cases and there were no recurrences of prolapse in the three year follow up period. Improvement of sphincteric tone was shown in all cases by transrectal manometry, and bladder and rectal continence was maintained. The combined surgical procedure for concurrent genital and rectal prolapse is easy to perform and safe and efficient in terms of recurrence and continence. It is hoped this report will increase multidisciplinary awareness of an effective solution for a potentially debilitating problem.

Aged↗

The use of intrapartum defibulation in women with female genital mutilation.

OBJECTIVE: To assess the use of intrapartum defibulation for women who have had female genital mutilation. DESIGN: A retrospective case analysis. SETTING: King Abdulaziz University Hospital, a teaching hospital in Jeddah, Saudi Arabia. SAMPLE: Two hundred and thirty-three Sudanese and 92 Somali women who were delivered at the hospital between January 1996 and December 1999. METHODS: The outcome of labour of women with female genital mutilation who needed intrapartum defibulation were compared with the outcome of labour of women without female genital mutilation who did not need intrapartum defibulation. RESULTS: One hundred and fifty-eight (48.6%) women had infibulation and needed intrapartum defibulation to deliver vaginally, 116 women (35.7%) did not have infibulation and gave birth vaginally without defibulation, and 51 (15.7%) women were delivered by caesarean section. There were no statistically significant differences, between women who underwent intrapartum defibulation and those who did not, in the duration of labour, rates of episiotomy and vaginal laceration, APGAR scores, blood loss and maternal stay in hospital. The surgical technique of intrapartum defibulation was easy and no intraoperative complications occurred. CONCLUSIONS: Intrapartum defibulation is simple and safe, but sensitivity to the cultural issues involved is essential. In the longer term, continuing efforts should be directed towards abandoning female genital mutilation altogether.

Adult↗

Abnormal genital bleeding and secondary amenorrhea. Common gynecological problems.

Abnormal genital bleeding and secondary amenorrhea (cessation of menses) are common gynecologic complaints that can indicate serious physical problems. Abnormal genital bleeding is the most common reason for a gynecological office visit and a leading indication for dilatation of the cervix and curettage of the uterus. One of four women with abnormal genital bleeding may have serious physical problems. Although pregnancy is the most common cause of secondary amenorrhea, other conditions related to abnormal pregnancy, functional disorders, physiological changes, or pathology also must be considered. Procedures for evaluating abnormal genital bleeding and secondary amenorrhea are discussed. Information is provided to assist nurses in collecting and assessing data and planning interventions to promote the health of women with these common problems.

Adolescent↗

Skin potentials (SP) recorded from the extremities and genital regions in normal and impotent subjects.

Skin potentials (SP) were evoked by peripheral nerve stimulation from the hands and feet of 41 and from the genital skin of 28 male, controls. The same methods were also applied in 10 functionally impotent cases, 32 diabetic impotent and 8 diabetic normopotent cases. The SP was easily obtained from all 3 sites in all normal subjects and in 10 functionally impotent cases. The SP recorded from the genital skin was either absent or abnormal in 53% of diabetic impotent cases with or without polyneuropathy, while the incidence of abnormalities encountered in the hand and/or foot recordings was 28%. In 8 diabetic normopotent cases the SP recorded from the genital and extremity skin were completely normal. SP recorded from the genital skin is a useful method of evaluating the autonomic-sympathetic dysfunction causing impotence, especially in patients who may have autonomic disorders either located in lumbosacral spinal cord and its efferents, or generalized autonomic-peripheral dysfunction.

Adolescent↗

Mucosal immunity in the genital tract: prospects for vaccines against sexually transmitted diseases--a review.

PROBLEM: Consistent with the absence of protective immunity resulting from previous infection with Neisseria gonorrhoeae, the genital mucosal immune response in human gonorrhea is weak: only low levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies are detectable against gonococci, and inflammatory cytokine responses are poor. METHOD OF STUDY: Mucosal immunization strategies designed to induce persisting genital antibody responses might afford protection against infection, if appropriate conserved antigens can also be identified. RESULTS: Intragastric or intranasal immunization with bacterial antigens expressed as recombinant chimeric proteins with cholera toxin A2/B subunits induced persisting IgA antibodies in genital and other secretions, and circulating IgG antibodies. CONCLUSION: Although gonococci may avoid inducing or even suppress immune responses during natural infection, alternative approaches to vaccine development may be successful. However, inadequate understanding of the origins of antibodies in the genital tract, and their effector mechanisms, will need to be rectified to make this possible.

Bacterial Vaccines↗

Immunologic uniqueness of the genital tract: challenge for vaccine development.

Although the genital tract is considered to be a component of the mucosal immune system, it displays several distinct features not shared by other typical mucosal tissues and external secretions. Both male and female genital tract tissues lack inductive mucosal sites analogous to intestinal Peyer's patches. Consequently, local humoral and cellular immune responses stimulated by infections [with e.g. Neisseria gonorrhoeae, Chlamydia trachomatis, papilloma virus, and human immunodeficiency virus (HIV-1)] are weak or absent, and repeated local intravaginal immunizations result in minimal humoral responses. In contrast to typical external secretions such as intestinal fluid that contain secretory immunoglobulin A (S-IgA) as the dominant isotype, semen and cervico-vaginal fluid contain more IgG than IgA. Furthermore, irrespective of the route of infection, humoral immune responses to HIV-1 are dominated by specific IgG and low or absent IgA antibodies in all external secretions. Because a significant proportion of IgG in genital tract secretions is derived from the circulation, systemic immunization may provide protective IgG antibody-mediated immunity in the genital tract. Furthermore, combined systemic and mucosal (oral, rectal, and especially intranasal) immunization may induce protective humoral responses in both the systemic and mucosal compartments of the immune system.

Antibody Formation↗

The impact of female genital cutting on first delivery in southwest Nigeria.

To date, data linking obstetric morbidity to female genital cutting in populations with less severe types of cutting have been limited to case reports and speculation. In this cross-sectional study, 1,107 women at three hospitals in Edo State, Nigeria, reported on their first-delivery experiences. Fifty-six percent of the sample had undergone genital cutting. Although univariate analyses suggest that genital cutting is associated with delivery complications and procedures, multivariate analyses controlling for sociodemographic factors and delivery setting show no difference between cut and noncut women's likelihood of reporting first-delivery complications or procedures. Whereas a clinical association between genital cutting and obstetric morbidity may occur in populations that have undergone more severe forms of cutting, in this setting, apparent associations between cutting and obstetric morbidity appear to reflect confounding by social class and by the conditions under which delivery takes place.

Adolescent↗

Ineffectiveness and toxicity of BCG vaccine for the prevention of recurrent genital herpes.

One hundred fifty-five patients with genital herpes were enrolled in a double-blind, placebo-controlled trial comparing 0.1 ml of intradermal BCG vaccine with placebo for the prevention of recurrent episodes of genital herpes. The mean rate or recurrence over 9 months of prospective follow-up was 0.528 recurrences per month in BCG recipients compared with 0.392 recurrences per month in placebo recipients (not significant). The BCG vaccine also failed to influence the duration of lesions in the first recurrent episode of genital herpes after vaccination. Six patients were given a second inoculation of BCG vaccine, and persistent cutaneous granulomas were noted in three of these six patients. Intradermal inoculation with BCG does not appear to affect the natural history of genital herpes, and repeated inoculations can be toxic.

Adult↗

Posttherapy suppression of genital herpes simplex virus (HSV) recurrences and enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs.

Imiquimod, an immunomodulator with no direct in vitro antiviral activity, has in vivo anti-herpesvirus activity by inducing interferon and enhancing other only partially defined immune responses. Imiquimod treatment of primary genital herpes simplex virus (HSV) infection in guinea pigs reduces the level of genital disease by 90%. We further investigated its utility as suppressive therapy of recurrent disease in animals that had recently recovered from primary genital HSV-2 disease. Imiquimod administered intravaginally once per day for 5 days reduced the number of recurrences only during treatment, while a 21-day regimen reduced the number of recurrences for 8 weeks. For the entire 10 weeks of observation, overall numbers of recurrences were reduced 67% by the 21-day imiquimod treatment (P < 0.0001). Latent HSV in ganglia was not affected by either regimen. Increased circulating alpha interferon activity was observed during therapy with both regimens. Interferon levels rapidly returned to baseline with cessation of treatment. Posttreatment, 5-day imiquimod treatment did not provide clinical benefit or enhancement of cell-mediated or cytokine responses. Twenty-one-day imiquimod treatment reduced both the number of clinical recurrences and levels of HSV antibody for 5 to 6 weeks posttreatment compared with the placebo. Additionally, 21-day imiquimod treatment enhanced HSV antigen-specific interleukin 2 production and proliferative responses by mononuclear cells (P < 0.001) for 4 weeks after treatment. Twenty-one-day imiquimod therapy suppressed recurrent HSV genital disease during and for weeks after therapy, enhanced memory-dependent cytokine and T-cell responses, and reduced the level of antibody responses.

Adjuvants, Immunologic↗

Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes.

Prevention of sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of topical microbicides, and one promising approach is the use of dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new dendrimer products developed to provide stable and cost-efficient microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of genital herpes. From these experiments one product, SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated SPL7013 provided significant protection from genital herpes disease and infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis infection.

Animals↗