Mucosal immunity in the female genital tract

Immunoglobulin (Ig)-producing cells in mucosal tissues represent quantitatively the most important humoral immune system of the body. All exocrine tissue sites contain immunocytes (B-cell blasts and plasma cells) that mainly synthesize dimers and larger polymers of IgA (collectively called pIgA) with incorporated J chain. Such pIgA is actively transported to external secretions as secretory IgA (SIgA) by the polymeric Ig receptor (pIgR), a transmembrane epithelial glycoprotein also called the secretory component (SC). The same transport mechanism includes pentameric IgM to generate SIgM. Although the most active SIgA system occurs in the gut, secretory immunity also operates in the female genital tract, with considerable pIgA production in the cervical mucosa and fallopian tubes. The origin of these local IgA immunocytes remains undefined. In mice, both lymphoid tissue in the large bowel (GALT) and nasopharynx (NALT) have been suggested as inductive sites for B cells homing to the urogenital tract. It is well established that integrin alpha 4 beta 7 is used by primed lymphoid cells to enter the intestinal lamina propria through interactions with mucosal addressin cell adhesion molecule (MAdCAM)-1 expressed on venule endothelium. However, alpha 4 beta 7 does not appear to be an important homing molecule in the airways, and the same might be true for the urogenital tract; this could explain that high levels of IgA antibodies occur in cervicovaginal secretions of mice after nasal immunization. The endometrium can likewise perform pIgR-mediated external translocation of pIgA that in this tissue appears to be mainly derived from serum, partly under hormonal regulation. In addition, paracellular diffusion of serum-derived and locally produced IgG through epithelia is an important part of humoral immunity in the female genital tract.     

Antibacterial effects of levofloxacin, erythromycin, and rifampin in a human monocyte system against Legionella pneumophila

Recently few cases as to female genital tuberculosis were reported, therefore it is considered that the incidence of the female genital tuberculosis was decreased. However it is important to make a right diagnosis of tuberculosis, because the tuberculosis in the female sexual organs is one of the factors of female sterility. The diagnosis is needed to examine bacteriologically or pathologically. The diagnosed genital tract or pelvic tuberculosis was treated by anti-tuberculosis chemotherapy firthtly and by surgical procedures in case of necessity.     

Detection of human immunodeficiency virus type 1 and type 2 in the female genital tract: implications for the understanding of virus transmission

Risk of perinatal or female to male sexual transmission of HIV is likely to be associated with whether, and at what concentration, the virus is present in the cervical and vaginal secretions of the HIV-infected woman. Examining correlates of cervical and vaginal HIV shedding is, therefore, essential for the development of strategies to interrupt HIV transmission. This article presents the rationale for using detection of HIV in the female genital tract as a marker of infectivity, and briefly describes methods for detecting HIV-1 and HIV-2 in cervical or vaginal fluids. Findings from studies incorporating the measurement of HIV in the female genital tract are reviewed, placing particular emphasis on issues relevant to epidemiological studies of HIV transmission.     

The prognosis of female genital sarcomas of the adult woman with special reference to sarcomas of the uterine corpus (author's transl)]

Report on 88 cases of sarcomas of the female genital organs. The sarcomas were confined to the uterine body in 72 cases. The prognosis of this disease depends primarily on the adequacy of the treatment. The treatment consists of as radical an operation as possible followed by external radiation and intra-vaginal application of radium. The microscopic type of the sarcoma of the uterus is of secondary importance. Patients who survived for 3 years following this treatment have a good prognosis for a 5 year or a 10 year cure. Other sarcomas of the female genital tract are mentioned.     

Effect of subtotal thyroidectomy on natural history of ophthalmopathy in Graves'' disease

Metastases to the vagina from breast carcinoma are uncommon, and are most often detected during autopsies of patients who have died from a breast cancer or from metastases to the genital tract. A case of symptomatic vaginal metastasis secondary to bilateral breast carcinoma is reported. The potential routes of dissemination include lymphatic and vascular spread. Their respective frequencies vary in the literature. Lymphatic spread in this case is suggested by demonstrable ovarian, myometrial, and lymph node involvement associated with massive submucosal vaginal involvement. This observation of concomitant visceral and lymphatic spread improves our knowledge of metastatic spread from breast cancer to the female genital tract by the lymphatic route.     

Antibodies and antibody-secreting cells in the female genital tract after vaginal or intranasal immunization with cholera toxin B subunit or conjugates

We studied the antibody response including antibody-secreting cells (ASC) in the female genital tract of mice after mucosal immunizations with the recombinant B subunit of cholera toxin (rCTB) perorally, intraperitoneally, vaginally, and intranasally (i.n.). The strongest genital antibody responses as measured with a novel perfusion-extraction method were induced after vaginal and i.n. immunizations, and these routes also gave rise to specific immunoglobulin A (IgA) and IgG ASC in the genital mucosa. Specific ASC in the iliac lymph nodes, which drain the female genital tract, were seen only after vaginal immunization. Progesterone treatment increased the ASC response in the genital tissue after all mucosal immunizations but most markedly after vaginal immunization. We also tested rCTB as a carrier for human gamma globulin (HGG) and the effect of adding cholera toxin (CT) as an adjuvant for the induction of systemic and genital antibody responses to HGG after vaginal and i.n. immunizations. Vaginal immunizations with HGG conjugated to rCTB resulted in high levels of genital anti-HGG antibodies whether or not CT was added, while after i.n. immunization the strongest antibody response was seen with the conjugate together with CT. In summary, vaginal and i.n. immunization give rise to a specific mucosal immune response including ASC in the genital tissue, and vaginal immunization also elicits ASC in the iliac lymph nodes. We have also shown that rCTB can act as an efficient carrier for a conjugated antigen for induction of a specific antibody response in the genital tract of mice after vaginal or i.n. immunization.     

Endoscopic removal of a complex foreign body from the bladder

Metastatic lesions of the umbilicus are more common than primary malignancies and are commonly referred to as Sister Mary Joseph nodules. Most arise from the stomach or the female genital tract. We describe an unusual case of renal cell carcinoma with peritoneal implants producing a Sister Mary Joseph nodule diagnosed by CT. To our knowledge, no report of a urinary tract malignancy with umbilical involvement has been described in the radiological literature.     

Ineffectiveness of heparin treatment in burn shock in the guinea pig

Homogenates of tissue from the female genital tract contain isoamylases which are, to a certain extent, electrophoretically distinguishable from the pancreatic and salivary isoamylases. In healthy nonpregnant women, high levels of activity of genital isoamylases were found in tissue homogenates of cervical and Fallopian tube mucosa, whereas activity was weak or absent in homogenates of endometrium. The isoamylases of the cervical mucosa had an electrophoretic migration rate toward the anode identical to that of the salivary main fraction, whereas the isoamylases of the Fallopian tube migrated faster. Specific genital isoamylase activities were also demonstrable in peritoneal fluid collected from the cul-de-sac. During the menstrual cycle, these activities showed a midcycle peak. In pregnant women, the levels of activity of the genital isoamylases in peritoneal fluid were lower than in nonpregnant women. In homogenates of the male accessory genital glands, the isoamylases specific for the genital tract were present in minute amounts. The isoamylases specific for the genital tract were not detectable in serum in either sex.     

Chlamydial infection in inducible nitric oxide synthase knockout mice

Type 1 CD4+-T-cell-mediated immunity is crucial for the resolution of chlamydial infection of the murine female genital tract. Previous studies demonstrating a correlation between CD4+-T-cell-mediated inhibition of chlamydial growth and gamma interferon (IFN-gamma)-mediated induction of nitric oxide synthase suggested a potential role for the nitric oxide (NO) effector pathway in the clearance of Chlamydia from genital epithelial cells by the immune system. To clarify the role of this pathway, the growth levels of Chlamydia trachomatis organisms in normal (iNOS+/+) mice and in genetically engineered mice lacking the inducible nitric oxide synthase (iNOS) gene (iNOS-/- mice) were compared. There was no significant difference in the course of genital chlamydial infections in iNOS+/+ and iNOS-/- mice as determined by recovery of Chlamydia organisms shed from genital epithelial cells. Dissemination of Chlamydia to the spleen and lungs occurred to a greater extent in iNOS-/- than in iNOS+/+ mice, which correlated with a marginal increase in the susceptibility of macrophages from iNOS-/- mice to chlamydial infection in vitro. However, infections were rapidly cleared from all affected tissues, with no clinical signs of disease. The finding of minimal dissemination in iNOS-/- mice suggested that activation of the iNOS effector pathway was not the primary target of IFN-gamma during CD4+-T-cell-mediated control of chlamydial growth in macrophages because previous reports demonstrated extensive and often fatal dissemination of Chlamydia in mice lacking IFN-gamma. In summary, these results indicate that the iNOS effector pathway is not required for elimination of Chlamydia from epithelial cells lining the female genital tract of mice although it may contribute to the control of dissemination of C. trachomatis by infected macrophages.     

The role of echography in the evaluation of gynecological neoplasia

Physiological and pathological echograms of the female genital tract are examined. Following a rapid review of the literature, the role of echography in gynecology is evaluated on their decennial experience.     

The DNA/RNA-binding protein, TB-RBP, moves from the nucleus to the cytoplasm and through intercellular bridges in male germ cells

In male infants, traumatic ablation of the penis, with or without loss of the testicles may occur as a sequel to mutilatory violence, accidental injury, or circumcision error. Post-traumatically, one program of case management is surgical sex reassignment to live as a girl, with female hormonal therapy at the age of puberty. The other program is genital reconstructive surgery to live as a boy, with male hormonal therapy at puberty if the testicles are missing. In both programs, the long term outcome is less than perfect and is contingent on intervening variables that include societal ideology; surgical technology; juvenile and adolescent timing and frequency of hospital admissions construed by the child as nosocomial abuse; development of body image; health and sex education; fertility versus sterility; coitus and orgasm; possible lesbian orientation if living as a girl; and long-term cost accounting, including the psychic cost of being a pawn in possible malpractice litigation on whose disability a very large fortune in compensation may devolve. There is, as yet, no unanimously endorsed set of guidelines for the treatment of genital trauma and mutilation in infancy, and no provision for a statistical depository for outcome data.     

Abnormal female reproductive function

Sex differentiation may be seen as a sequence of gonadal determination, gonadal differentiation, genital differentiation. Malfunction of this causes abnormal female reproductive function. SRY (sex-determining region Y) has been show to induce testis which is needed to bring about development of the other male sex organs. Absence or point or frame shift mutation in the SRY causes XY females. Secondary sex determination depends on testosterone produced by Leydig cells. Testicular feminization syndrome typically lack the normal androgen receptor protein and therefore, they are distinctly female phenotype. Rokitansky syndrome is a type of aplasia vaginae and is a malformation of the Mullerian duct. They all present primary amenorrhea. Secondary amenorrhea is a common type of abnormal female reproductive function and differential diagnosis depends on hormonal analysis. One of the topics includes polycystic ovarian syndrome which is recently treated by laparoscopic surgery.     

Comparison of the oral, rectal, and vaginal immunization routes for induction of antibodies in rectal and genital tract secretions of women

To determine which mucosal immunization routes may be optimal for induction of antibodies in the rectum and female genital tract, groups of women were immunized a total of three times either orally, rectally, or vaginally with a cholera vaccine containing killed Vibrio cholerae cells and the recombinant cholera toxin B (CTB) subunit. Systemic and mucosal antibody responses were assessed at 2-week intervals by quantitation of CTB-specific antibodies in serum and in secretions collected directly from mucosal surfaces of the oral cavity, rectum, cervix, and vagina with absorbent wicks. The three immunization routes increased levels of specific immunoglobulin G (IgG) in serum and specific IgA in saliva to similar extents. Rectal immunization was superior to other routes for inducing high levels of specific IgA and IgG in rectal secretions but was least effective for generating antibodies in female genital tract secretions. Only vaginal immunization significantly increased both specific IgA and specific IgG in both the cervix and the vagina. In addition, local production of CTB-specific IgG in the genital tract could be demonstrated only in vaginally immunized women. Vaginal immunization did not generate antibodies in the rectum, however. Thus, generation of optimal immune responses to sexually transmitted organisms in both the rectal and the genital mucosae of women may require local immunization at both of these sites.     

Prenatal exposure to diethylstilbestrol in mice: toxicological studies

The effect of prenatal exposure to diethylstilbestrol (DES) on the postnatal development of male and female genital tract function was studied. The placental transfer or radiolabeled (3H or 14C) DES was studied in pregnant mice. DES-associated radioactivity in the fetal plasma approximated that in maternal plasma 1/2 hr after intravenous administration of [3H]DES; 3H activity corresponding to DES in the fetal genital tract was about threefold higher. The decrease in reproductive capacity of female offspring from mice treated with DES during gestation was dose-related; a low incidence (10% or less) of cancer of the vagina, cervix, and/or uterus was also observed in these mice. Male offspring exposed prenatally to the highest dose (100 microng/kg) of DES in this study also had lower reproductive capacities. Lesions in the genital tract of these mice included epididymal cysts, inflammation, cryptorchidism, and nodular masses in the seminal vesicles and/or prostate gland. Such lesions and sterility were not observed at the lower DES doses. Histological studies with neonatal mice raise the possibility that Müllerian duct tissue may represent a site for the transplacental toxicity of DES in both the male and female fetus.     

"HPV effect" in the female lower genital tract. A community study

OBJECTIVE: To determine the distribution of "human papillomavirus (HPV) effect" and intraepithelial neoplasia in the lower female genital tract in one community with a prospective study. STUDY DESIGN: In a family practice setting, colposcopy was offered to all women presenting for a routine cervical cytologic smear. Directed biopsies were taken from areas staining abnormally with acetic acid or iodine. RESULTS: This study of 224 women showed a high incidence of HPV effect in the lower genital tract (68%), including 18% on the vulva. The age distribution suggests a coital influence. A five-year review showed persistence of HPV effect on the vulva or vagina in only one patient. One other woman developed cervical intraepithelial neoplasia (CIN) 1. CONCLUSION: HPV effect is common in the lower genital tract of women under the age of 30 years. Colposcopic study suggested that HPV effect on the vulva and vagina is transient. The relatively high incidence of HPV effect on the vulva may explain why cervical HPV and CIN generally appear only after coitarche, as a consequence of physical transfer. This may help explain why women with a single lifetime sexual partner are not exempt from the risk of cervical cancer or its precursors.     

Neuropeptide Y1 receptors in the rat genital tract

Using in situ hybridization and immunohistochemistry, the expression of type 1 neuropeptide Y (NPY) receptors (Y1-Rs) has been demonstrated in the rat genital tract. In the male Y1-R mRNA and Y1-R-like immunoreactivity (LI) were found in smooth muscles of predominantly arterioles and small arteries inside testis. Fibers showing NPY-LI could not be detected within testis but only in the tunica albuginea. These Y1-Rs are suggested to mediate vasoconstriction, possibly activated by NPY released from nerves in the tunica albuginea. In the female rat Y1-R mRNA, but not Y1-R-LI was found in vascular smooth muscles of arteries in the ovary and oviduct. In the oviduct Y1-R mRNA was also detected in the non-vascular smooth muscle layer. Fibers showing NPY-LI were found around blood vessels both in the ovary and oviduct. In the female genital tract also Y1-Rs may thus be involved in regulatory mechanisms mediating, for example, vasoconstriction.     

Lower genital tract neoplasia in women with HIV infection

Women who are infected with human immunodeficiency virus (HIV) are at greater risk for the development of lower genital tract neoplasia than are HIV-negative women. Among HIV-positive women, those who are more severely immunosuppressed appear to be at higher risk for cervical intraepithelial neoplasia (CIN), also known as squamous intraepithelial lesions (SILs). Women who are HIV-positive also are more likely than HIV-negative women to have multifocal lower genital tract neoplasia. Cervical cancer is one of the most important acquired immune deficiency syndrome (AIDS)--related malignancies in women. Cancer and intraepithelial neoplasia of the lower genital tract can be persistent, progressive, recurrent, and difficult to treat in HIV-positive women. The most effective method for treating SILs has not been determined. Regular performance of Pap smears in HIV-positive women is of critical importance, as is careful examination of the entire lower genital tract. Also, women with high-grade intraepithelial or cervical cancer should be tested for HIV.     

Primary prevention of heart disease and stroke: a simplified approach to estimating risk of events and making drug treatment decisions

We evaluated the ability of mice made genetically deficient for B cells to resolve a primary infection and to develop protective immunity against vaginal challenge with a human isolate of Chlamydia trachomatis bacteria. The B-cell-deficient microMT mice cleared a primary ascending infection with similar or faster kinetics compared with wild-type mice. The presence of chlamydial inclusion bodies and the degree of inflammation in the upper genital tract was comparable and showed similar kinetics in microMT as in wild-type mice. Following resolution of the primary infection the mice were challenged by 100 ID50 of live bacteria and the level of protection and the extent of local inflammation was assessed. Strikingly, all microMT mice, as well as most of the wild-type mice, demonstrated complete immune protection with no bacterial shedding. While high titres of chlamydia-specific antibodies were stimulated locally and systemically in wild-type mice, no antibodies were detected in microMT mice. However, in both strains, immunohistochemical analysis of the upper genital tract demonstrated the presence of large numbers of CD4+ T cells and increased levels of interferon-gamma (IFN-gamma)-producing cells. The results unequivocally demonstrate that antibodies are not required for full protection to develop against ascending infection with a high dose of C. trachomatis in the female genital tract. Our study confirms the notion that cell-mediated immunity, in particular that owing to CD4+ T helper I (Th1)-type cells, is critical for host resistance against C. trachomatis in mice.     

Physiological and sensorial determinism of maternal behavior in mammals]

In mammals, the development of maternal behaviour is generally controlled by neuroendocrine factors followed by sensory factors. Whereas the dynamics of the steroid balance at parturition are of primary importance in non-human mammals, stimulation of the uterine tract during the expulsion of the foetus is the key-factor in ungulates. This induces a cascade of physiological events and particularly the activation of the oxytocinergic system. The increase in prolactin release appears to be important only in rodents. Activation of the opiate system induces inhibitory effects in rodents and facilitatory effects in ungulates and, in rodents, the medial preoptic area is the central key structure of hormonal action. In women, no correlation exists between hormonal levels and maternal attitudes either during pregnancy or in the post-partum period. Physiological factors enhance receptivity to stimuli coming from the neonate and this allows the female to display maternal behaviour beyond this critical period. Odours facilitate the organisation of both maternal and infantile behaviour and are involved in individual recognition for both. Olfaction may also participate in the regulation of mother-young interactions in humans.     

Are estrogens carcinogenic during development of the testes?

Many chemicals in the environment mimic the female sex hormone, estrogen. Exposure to environmental estrogens during early fetal development was proposed by Sharpe & Skakkebaek as a potential risk factor for subsequent testicular disease, including neoplasia and poor semen quality. To understand the mechanisms of action of estrogenic chemicals during differentiation of the male genital tract, we have studied developmental exposure to the synthetic estrogen, diethylstilboestrol (DES). While DES is a much more potent estrogen than most environmental chemicals examined, several of these compounds share some of the same properties as DES, such as a relative lack of binding to serum estrogen carrying proteins. Prenatal exposure to DES is associated with poor semen quality, prostatic disease, cryptorchidism and testicular neoplasia in mice. A rare form of testicular cancer, rete testis carcinoma, was observed in five percent of male mice treated in utero with DES. We also demonstrated altered regulation of an estrogen responsive gene, lactotransferrin (LTF) in the seminal vesicles of treated mice, but not the controls. Likewise, LTF was irreversibly altered in the uteri of developmentally treated females; at the molecular level altered methylation of the gene appears to be involved, thus, providing a potential marker for hormonal effects during development. The induction of permanent or "imprinted" responses during the development of a relatively estrogen-free reproductive tract cell suggests that undifferentiated targets for estrogen action may be sites for subsequent growth and differentiation defects associated with neoplasia.