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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transgenic mice containing the complete human immunodeficiency virus (HIV) coding sequences fused to the mouse mammary tumor virus long terminal repeat were generated. They were found to produce high levels of authentic gag and env HIV proteins in several tissues known to support mouse mammary tumor virus-driven transcription. HIV proteins were also detected in serum and in body fluids (milk and epididymal secretions) known to be natural sites of retrovirus, and specifically of HIV, production. These results indicate that primary mouse cells from different tissues have the capacity to produce HIV proteins. These mice represent a novel animal model for HIV infection.
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PMID:Efficient production of human immunodeficiency virus proteins in transgenic mice. 131 90

Mechanisms underlying human immunodeficiency virus type 1 (HIV-1) infection of the male reproductive tract and the sexual transmission of HIV-1 through semen are poorly understood. To address these issues, the authors performed morphologic and immunocytochemical analyses of reproductive tissues obtained at autopsy from 43 male acquired immune deficiency syndrome (AIDS) patients. Monoclonal antibodies recognizing different subpopulations of white blood cells were used to detect leukocyte infiltration and map the location of potential lymphocytic/monocytic HIV-1 host cells and immunocytochemistry and in situ hybridization techniques were used to detect HIV-1-infected cells in the testis, excurrent ducts, and prostate. Distinct pathologic changes were observed in a majority of testes of AIDS patients that included azoospermia, hyalinization of the boundary wall of seminiferous tubules, and lymphocytic infiltration of the interstitium. The reproductive excurrent ducts and prostate appeared morphologically normal except for the presence of focal accumulations of white blood cells in the connective tissue stroma. In the testis many white blood cells were shown to be CD4+, indicating the presence of abundant host cells (T-helper/inducer lymphocytes and macrophages) for HIV-1. Furthermore macrophages and cells of lymphocytic morphology were observed migrating across the boundary walls of hyalinized seminiferous in tubules to enter the lumen. In 9 of the 23 cases tested for HIV-1 protein expression by immunocytochemistry. HIV-1 + cells of lymphocytic/monocytic morphology were found in the seminiferous tubules and interstitium of the testis, epididymal epithelium, and connective tissue of the epididymis and prostate. One patient with epididymal blockage had accumulations of HIV-1-antigen-positive cells of macrophages morphology in the distended lumen of the efferent ducts. There was no evidence of active HIV-1 infection in germ cells or Sertoli cells of the seminiferous tubules or other epithelial cells lining the excurrent ducts or prostatic glands.
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PMID:Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome. 185 30

Human immunodeficiency virus (HIV) was detected by assay of reverse transcriptase activity in a "virus pellet" obtained by differential sucrose density centrifugation of cell-free semen from three patients with the acquired immune deficiency syndrome (AIDS), one individual with AIDS-related complex (ARC), and in an asymptomatic homosexual male. Reverse transcriptase assays indicated virus concentrations in the range of 10(8) particles/ml of semen, an accumulation substantiated by electron microscopic visualization of cell-free virus. This is the first description of cell-free retrovirus in seminal fluid and at a greater concentration than reported for blood or other body fluids or tissues. These results suggest that the male reproductive tract of humans may be a reservoir of HIV expression, and raises the possibility that the cells lining the epididymal lumen could be chronically infected with HIV. These are important considerations in formulating treatment and preventive strategies.
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PMID:Detection of human immunodeficiency virus in cell-free seminal fluid. 263 53

The main purpose of this research was (i) to perform a comparative study of sperm parameters in human immunodeficiency virus (HIV) seropositive and high risk subjects in order to identify any possible alterations in the semen which specifically result from HIV infection and (ii) to study the p24 antigen as an early diagnostic marker of infection in high risk subjects. HIV seropositive subjects showed no significant variations regarding sperm densities, motility and viscosity compared to high risk subjects and controls. On the other hand, these HIV seropositive subjects showed (a) a significantly higher percentage of cytoplasmic droplet forms and immature germ cells, perhaps caused by an early failure of epididymal function and/or by a condition of stress affecting spermatogenesis after HIV infection and (b) a significantly higher level of spermiophage cells, suggesting that HIV activates mechanisms that increase spermiophagy. In addition, HIV seropositive men showed a significant positive correlation between blood CD4+ and sperm motility as well as a significant inverse correlation between CD4+ and sperm abnormalities. This is perhaps due to a decrease in testosteronaemia leading to defective epididymal sperm maturation. To date, p24 has not been found in the serum or seminal plasma of high risk subjects. The longitudinal study in progress should provide further information on this point.
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PMID:Semen analysis in HIV seropositive men and in subjects at high risk for HIV infection. 867 25

Detergent-based vaginal microbicides, in addition to their high contraceptive failure rates, cause mucosal erosion and local inflammation that might increase the risk of heterosexual human immunodeficiency virus (HIV) transmission. In a systematic effort to identify a microbicide contraceptive potentially capable of preventing the sexual transmission of HIV as well as providing fertility control, a series of novel aryl phosphate derivatives of 5-bromo-6-methoxy-3'-azido-3'-deoxythymidine (AZT; zidovudine) were synthesized and examined for dual anti-HIV and sperm-immobilizing activity (SIA). Whereas AZT displayed potent anti-HIV activity (IC50 = 0.006 microM) but lacked SIA (EC50 > 300 microM), two 5-bromo-6-methoxy-aryl phosphate derivatives of AZT, compounds WHI-05 and WHI-07, exhibited potent anti-HIV activity as well as SIA. The IC50 (HIV) and EC50 (SIA) values for WHI-07 were 439-fold and 13.5-fold lower, respectively, than those for the detergent-based virucidal spermicide, nonoxynol-9 (N-9). Sperm motion kinematics using computer-assisted sperm motion analysis combined with confocal laser scanning microscopy, high-resolution low-voltage scanning, and transmission electron microscopy demonstrated that both WHI-05 and WHI-07 cause a complete and irreversible loss of sperm motility in a concentration- and time-dependent fashion without concomitantly affecting the sperm acrosomal membrane integrity. In experiments designed to assess the fertilizing capacity of treated sperm, preincubation of sperm with either compound resulted in a concentration-dependent loss of the ability to adhere to and penetrate zona-free hamster eggs as well as inhibition of binding to human zona. WHI-07 applied intravaginally prior to artificial insemination of epididymal sperm drastically reduced fertility in hormonally primed CD-1 mice. Unlike the intravaginal application of N-9, repetitive intravaginal application of WHI-07 did not damage the vaginal epithelium or cause local inflammation. Structure-function relationship analyses showed that the addition of bromo-methoxy functional groups to AZT was essential for, and the aryl phosphate derivatization contributory to, the SIA of both compounds. Compounds WHI-05 and WHI-07 may be useful as dual-function vaginal contraceptives for women who are at high risk for acquiring HIV/acquired immunodeficiency virus syndrome by heterosexual vaginal transmission.
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PMID:Aryl phosphate derivatives of bromo-methoxy-azidothymidine are dual-function spermicides with potent anti-human immunodeficiency virus. 971 47

Human immunodeficiency virus (HIV) protease inhibitors (PI) may alter lipid metabolism in patients with acquired immunodeficiency syndrome (AIDS). However, the influence of dietary fat on the metabolic effects of PI therapy remains unknown. AKR/J mice were fed high or low fat diets and treated with the PI indinavir (IDV), nelfinavir (NFV), saquinavir (SQV) or amprenavir (APV) by subcutaneous delivery for 2 wk. Serum concentrations of glucose, insulin, triglyceride, free fatty acid, glycerol, pancreatic lipase, bilirubin, alkaline phosphatase, blood urea nitrogen and PI, and interscapular and epididymal fat weights were determined. Some metabolic effects of PI were dependent on diet. IDV- and NFV-treated mice had greater serum glucose concentration and body weight; IDV-treated mice had lower serum insulin; NFV-treated mice had greater interscapular fat mass; and SQV treated mice had lower serum triglyceride concentration than control mice fed the low but not the high fat diet. In contrast, NFV- and IDV-treated mice had greater triglyceride concentration and blood urea nitrogen, and SQV treated mice had greater serum cholesterol than control mice fed the high but not the low fat diet. The serum concentration of SQV was lower in mice fed the high fat compared with the low fat diet. Other effects were not dependent on diet. IDV- and NFV-treated mice had greater fatty acids, and IDV-treated mice had greater pancreatic lipase, bilirubin and alkaline phosphatase than control mice fed either diet. APV treatment had little effect on these serum measurements. Thus, changes in dietary fat can influence some but not all of the effects of PI on metabolism. Furthermore, each PI produces different effects in vivo, indicating that various PI affect distinct metabolic pathways.
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PMID:Dietary fat alters HIV protease inhibitor-induced metabolic changes in mice. 1095 36

Sexually transmitted diseases (STDs) affect the physiology of male/female reproduction. Chronic bacterial infection of semen is uncommon, but may be a cause of male infertility. Antibacterial treatment results in improvement in sperm quality, once the infection is eradicated. Little is known about how infection with Mycoplasma hominis affects semen quality, but treatment with antibiotics improves motility and decreases the percentage of coiled tails. Chlamydia trachomatis is not frequently isolated from the urethral cultures of normal men, but is a major cause of nongonococcal urethritis and epididymitis. Chlamydia is an important cause of epididymal and oviductal obstruction. Trichomonas vaginalis most frequently colonizes the vagina and cervix of women and the anterior urethra of the male sexual partners. The highest prevalence is in sexually active men and women and Trichomoniasis may well be the most common STD. Syphilis may be an important cofactor in facilitating transmission of the human immunodeficiency virus (HIV). A history of syphilis or a positive serologic test for syphilis is associated with HIV seropositivity in men. In South Africa, the seropositivity in pregnant black women ranges from 11-20%. Ga-Rankuwa Hospital is the referral center for 40 peripheral hospitals and over 4 million people. Since the inception of the Andrology Laboratory in June 1985, more than 5300 semen analyses have been performed on 2000 patients.
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PMID:Sexually transmitted diseases (STD) in infertile males attending the andrology clinic at Ga-Rankuwa Hospital. 1228 85

Since the basic domain of human immunodeficiency virus type I (HIV-1) transactivator of transcription (TAT) protein was reported to possess the ability to traverse biological membranes efficiently, various therapeutic proteins have been attached to TAT for the purpose of therapy. In this study, the tripeptide GKH (glycine-lysine-histidine) derived from parathyroid hormone (PTH), known as lipolytic peptide, was attached to 9-poly lysine (TAT) to be used as a cosmetic ingredient in slimming products. TAT-GKH at 10(-5) M induced approximately 37.6% and 41.5% maximal lipolytic effects in cultured 3T3-L1 differentiated adipocytes and in epididymal adipocytes isolated from rats, respectively, compared with basal lipolysis. The lipolytic effect of GKH was not changed by TAT-GKH fusion. In cytotoxicity tests, there was no cytotoxicity in any dose concentration of TAT-GKH. We confirmed that TAT-GKH induced lipolytic activity by GKH without cytotoxicity and with the possibility of its use as a safe cosmetic ingredient. TAT-GKH elevated penetration into excised hairless mice skin 36 times more efficiently than GKH. TAT-GKH can be used as a cosmetic ingredient in slimming products, with both penetration enhancement and lipolytic effect without cytotoxicity.
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PMID:Penetration enhancement in mouse skin and lipolysis in adipocytes by TAT-GKH, a new cosmetic ingredient. 1460 89

Highly active antiretroviral therapy (HAART) of human immunodeficiency virus-infected patients is associated with adverse effects, such as lipodystrophy and hyperlipidemia. The lipodystrophic syndrome is characterized by a peripheral lipoatrophy and/or fat accumulation in the abdomen and neck. In order to get insights into the physiopathological mechanisms underlying this syndrome, we treated mice with protease inhibitors (PIs) over a long period of time. Although atazanavir-treated mice presented the same circulating triglyceride concentration as control mice, lopinavir-ritonavir-treated mice rapidly became hypertriglyceridemic, with triglyceride levels of 200 mg/dl, whereas control and atazanavir-treated animals had triglyceride levels of 80 mg/dl. These results obtained with mice reproduce the metabolic disorder observed in humans. White adipose tissue (WAT) was analyzed after 8 weeks of treatment. Compared to the control or atazanavir treatment, lopinavir-ritonavir treatment induced a significant 25% weight reduction in the peripheral inguinal WAT depot. By contrast, the profound epididymal WAT depot was not affected. This effect was associated with a 5.5-fold increase in SREBP-1c gene expression only in the inguinal depot. Our results demonstrate that the long-term treatment of mice with PIs constitutes an interesting experimental model with which some aspects of the lipoatrophy induced by HAART in humans may be studied.
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PMID:Long-term treatment with lopinavir-ritonavir induces a reduction in peripheral adipose depots in mice. 1700 Jul 48

Pyrimethamine is known to have antimalarial activities and used clinically in the therapy of toxoplasmosis and human immunodeficiency virus-associated pneumonia. In this study we aimed to test the effects of pyrimethamine on spermatogenesis in mice. For this aim, animals were given pyrimethamine as a single application and the doses were 5, 10, 20, and 40 mg/kg. For the spermatogenic effects, the sperm shape abnormality, epididymal sperm counts, and testes weights were evaluated at the end of days 7, 14, 21, 28, and 35 after single pyrimethamine injection at the first day. Pyrimethamine increased the frequency of abnormal sperm shape for all studied weeks except the first week and its germ cell stage-specific effects correspond to spermatozoa, spermatids, and spermatocytes. It also decreased the epididymal sperm counts at the end of days 28 and 35, which corresponds to the spermatocyte stage of mouse spermatogenesis.
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PMID:In vivo evaluation of the toxic effects of pyrimethamine on spermatogenesis in male mice. 1910 34


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