Condylomata acuminata in the neovagina after male-to-female reassignment treated with CO2 laser and imiquimod.

Condylomata acuminata are frequently occurring genital warts, but little is known about clinical features of the genital warts in transsexuals and their incidence. We report a case of condylomata acuminata arising on the neourethral meatus and the transplanted skin of the neovagina in a male-to-female transsexual, which was successfully treated with CO2 laser irradiation followed by topical application of imiquimod cream on the residual warts. This is a first report of using imiquimod cream for condylomata acuminata arising on the neovagina in a male-to-female transsexual.

Actinic lichen planus in a Japanese man: first case in the East Asian population.

Actinic lichen planus (ALP) is a rare variant of lichen planus in which lichen planus develops on the light-exposed areas of the skin. ALP is reported to occur in the African, Middle Eastern,and Indian populations, with very few cases reported in Caucasians. Here, we report a case of ALP in a Japanese man; to the best of our knowledge, this is the first reported occurrence of ALP in the East Asian population. A 52-year-old Japanese man developed recurrent painful annular erythema on the face and hands. Histopathological examination of his skin biopsy revealed lichenoid-type infiltrates of lymphocytes and histiocytes. We established a diagnosis of ALP on the basis of the distribution of eruptions only on the sunlight-exposed areas and histological findings. Oral administration of systemic steroids proved effective in improving his condition. Lichen planus is known to be induced by an irritant (Koebner phenomenon);we believe that our patient is genetically susceptible to sunlight exposure and that sunlight acted as an irritant stimulating the development of ALP.

Primary gastrointestinal stromal tumor in the retroperitoneum.

Gastrointestinal stromal tumor (GIST) is the most frequent non-epithelial neoplasm in the gastrointestinal tract. GIST has received much attention both for its clinical significance and biological nature, while the retroperitoneal condition identical to GIST has been rarely described. Presented herein is a case of GIST arising from the retroperitoneum in a 67-year-old man. The solid tumor measuring 4 cm was uncovered in the retroperitoneum, between the abdominal aorta and inferior vena cava, on computed tomography. The patient underwent surgical excision of the tumor. Histological examination showed proliferating spindle cells in the clearly demarcated tumor; immunoreactivity for Kit and CD34 in tumor cells confirmed the diagnosis of GIST. The histological origin of GIST is suggested to be gastrointestinal pacemaker cells, because they share specific immunoreactivity for CD117/Kit, which is also relevant to pathogenesis of GIST. The present case was a rare primary GIST in the retroperitoneum with typical immunopathological features.

Accelerated impairment of spermatogenic cells in SOD1-knockout mice under heat stress.

For normal spermatogenesis, the temperature of the scrotum is lower than that of the body. The mechanism by which mammalian testes undergoes cell death as the result of exposure to heat continues to be a matter of debate. Since generation of reactive oxygen species (ROS) during heat stress and involvement in spermatogenic cell damage are postulated, we induced experimental cryptorchidism in the testes of SOD1-knockout mice and examined effects of the gene deficiency. The cleavage of DNA in testicular cells, as judged by TUNEL staining, were elevated in SOD1-knockout mice at an earlier stage than in the wild-type mice. To confirm responsiveness of SOD1 for this high susceptibility to heat stress, spermatogenic cells were isolated from SOD1-knockout and wild-type mice and cultured at 32.5 and 37 degrees C. The cells isolated from SOD1-knockout were more vulnerable at both temperatures than those from wild-type mice. The exposure of cultured rat spermatogenic cells to ROS induced the release of cytochrome c from mitochondria, while Sertoli cells were more resistant under the same conditions. Tiron, a superoxide scavenger, suppressed the heat-induced release of cytochrome c from mitochondria. Collectively, these data suggest that ROS are generated during heat stress and cause spermatogenic cell death. Alternatively, since even a short exposure triggers harmful damage to spermatogenic cells, generated ROS may function as a type of signal for cell death rather than directly causing oxidative damage to cells.

Carbonyl stress and detoxification ability in the male genital tract and testis of rats.

Carbonyl compounds, which are naturally produced and augmented under oxidative stress, have deleterious effects on the reproductive system. The aldo-keto reductase (AKR) family of enzymes catalyze the reductive detoxification of various carbonyl compounds in an NADPH-dependent manner. To elucidate involvement of AKR in detoxification of endogenously produced carbonyls in the male reproductive system, we investigated the differential expression and tissue localization of aldehyde reductase (ALR) and protein adducts produced by reaction with lipid peroxidation products. A strong immunoreactivity to an anti-ALR antibody was observed in the epithelia of the epididymis, vas deferens, seminal vesicle, and prostate gland. Virtually the same cells were stained with a monoclonal antibody (mAb) 5F6, raised against an acrolein-modified protein. In the testis, however, mAb5F6 specifically stained the nuclei of somatic cells and less differentiated spermatogenic cells. While acrolein inactivated glutathione reductase, an enzyme involved in recycling oxidized glutathione, AKR activity was affected at the high concentration only. The colocalization of lipid peroxidation products and AKR in the epithelia of the male genital tract indicates that these tissues are exposed to oxidative stress and possess a protective system coordinately.

Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline.

Spermatogenic cells are susceptible to heat stress and undergo apoptosis. Although a variety of factors appear to be involved in the apoptotic process, the nature of the intracellular signaling pathway is ambiguous. To clarify the process, we chose a simple model in which testes of mice were exposed to mild heating by immersion in hot water at 42 degrees C for 15 min. In situ DNA fragmentation was detected by a TUNEL method. The release of cytochrome c into the cytoplasm was observed by Western blotting both in heat-treated testis and in isolated spermatogenic cells that had been incubated at 42 degrees C for 1h, but not in Sertoli cells. Minocycline, a semisynthetic tetracycline, is known to reach the brain by permeating the blood-brain barrier and suppresses apoptosis in neuronal cells. Since the testis also has a similar barrier, minocycline was examined as a possible agent to inhibit heat stress-induced apoptosis. The results indicate that minocycline suppressed the release of cytochrome c from mitochondria both in vivo and in vitro and significantly decreased the number of TUNEL-positive cells. These findings suggest that heat stress of testes triggers the release of cytochrome c from mitochondria in spermatogenic cells, leading to the activation of an apoptotic pathway.

Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues.

Reactive oxygen species (ROS) are produced under oxidative stress, such as high oxygen concentration and during the metabolic consumption of oxygen molecules. Male reproductive tissues appear to be continuously exposed to ROS produced by active metabolism. In addition, spermatozoa must pass through a high oxygen environment during the mating process. Thus, to maintain viable reproductive ability, a protective mechanism against oxidative stress is of importance. Here, we overview our current understanding of the cooperative function of antioxidative and redox systems that are involved in male fertility. Superoxide dismutase and glutathione peroxidase are major enzymes that scavenge harmful ROS in male reproductive organs. In turn, glutathione and thioredoxin systems constitute the main redox systems that repair oxidized and damaged molecules and also play a role in regulating a variety of cellular functions. While glutathione functions as an antioxidant by donating electrons to glutathione peroxidase and thioredoxin donates electrons to peroxiredoxin as a counterpart of glutathione peroxidase. In addition, aldo-keto reductases, which detoxify carbonyl compounds produced by oxidative stress, are present at high levels in the epithelia of the genital tract and Sertoli cells of the testis. Since these systems are involved in cross-talk, a comprehensive understanding will be required to maintain the physiological functions of male reproductive system.

Concerted changes in the YB2/RYB-a protein and protamine 2 messenger RNA in the mouse testis under heat stress.

Translation of a number of mRNAs is under strict regulation via RNA-binding proteins in the spermatogenic cells of testes. A family of Y-box binding proteins represents promising candidates for these presently uncharacterized RNA-binding proteins. The effects of heat stress on the expression of a Y-box binding protein, YB2/RYB-a, and mouse protamine 2 (mP2) were investigated in cultured spermatogenic cells and mouse testes by immunoblot and Northern blot analyses. Localization and alterations in the expression of the YB2/RYB-a protein and the mP2 mRNA in heat-stressed testes were examined by immunohistochemistry and in situ hybridization, respectively. Levels of the YB2/RYB-a protein in spermatogenic cells decreased rapidly as the result of exposure to higher temperature, 37 degrees C or 43 degrees C, compared with the scrotal temperature, 32.5 degrees C, under the culture conditions used. In experimental cryptorchidism, levels of the YB2/RYB-a protein were decreased after Day 10, while the mRNA levels were affected only slightly. The levels of the mP2 mRNA were also decreased and about comparable with those of the YB2/RYB-a protein. Exposure of the lower abdomen to a high temperature, 43 degrees C for 15 min, also damaged the testis and led to a decrease in YB2/RYB-a protein and the mP2 mRNA levels in a coordinated manner. Because YB2/RYB-a is proposed to function as a stabilizer of mP2 mRNA, the perturbation of YB2/RYB-a by heat stress could account for the decline of the mP2 mRNA in elongated spermatids.

Localization and physiological implication of aldose reductase and sorbitol dehydrogenase in reproductive tracts and spermatozoa of male rats.

The polyol metabolizing pathway, which consists of two enzymes, aldose reductase (AR) and sorbitol dehydrogenase (SDH), converts glucose to fructose. The enzymatic activities, expression, and localization of AR and SDH were studied in reproductive tracts and spermatozoa of male rats by immunohistochemistry, Western blotting, and enzyme assays. Immunoreactivity to an AR antibody was observed mainly in epithelia of epididymis, seminal vesicle, vas deferens, and prostate gland in adult rats. Similar staining profiles were observed for these tissues when an SDH antibody was used. However, in testis, the cells that express these 2 enzymes differed; whereas AR was expressed in Sertoli cells and to lesser extent in spermatogenic cells, SDH was detected in spermatogenic cells of seminiferous tubules. This cell type-specific gene expression was confirmed in primary cultured cells isolated from rat testes. SDH protein levels were higher during spermatid elongation, and large amounts of SDH were carried over to the spermatozoa. Because one of the functions of members of the aldo-keto reductase superfamily is to detoxify harmful carbonyl compounds, an intrinsic function of AR in Sertoli cells may be to catalyze the reduction of cytotoxic metabolites, such as lipid peroxidation products and steroid hormones, which are produced during spermatogenesis. Because uterine fluid and seminal plasma both contain sorbitol, it is likely that SDH in spermatozoa converts sorbitol to fructose for use as an energy source.

Impaired expression of peroxiredoxin 4 in damaged testes by artificial cryptorchidism.

Peroxiredoxins (Prx) are a recently identified family of proteins that have been shown to exhibit peroxidase activity, as well as other divergent functions. Of the six known members of the family, Prx4 is present as a secretable form in most tissues and as a membrane-bound form only in testes. We recently proposed that the unprocessed form may be involved in acrosome formation during spermiogenesis. In the present study, it was found that levels of the unprocessed Prx4 decreased during cryptorchidism and this decrease corresponded to the degree of the defect in spermiogenesis. In contrast, the levels of the secretable Prx4 remained virtually the same during cryptorchidism. These results were consistent with selective expression of the unprocessed form after the spermatid stage, suggesting the existence of a relationship with acrosome formation.