Antisperm antibody: a monkey wrench in conception / magic bullet of contraception?

Antisperm antibodies can cause infertility by interacting with spermatozoa through immunoglobulin binding protein thereby blocking their penetrance of cervical mucus and / or by interfering with sperm-egg interaction. However, these antibodies appear not to be cytotoxic to embryos since a high implantation rate and consequently high pregnancy rate were achieved by IVF-ET treatment of women with antisperm antibodies. Also the finding that these antibodies do not appear to cause any deleterious clinical symptoms and have yet be associated with infertility suggested that sperm antigens are promising candidates in the development of immunocontraceptives. Some synthetic peptides corresponding to segments of human sperm antigens have effectively induced infertility in female rats when administered as an immunogen. Different peptides, adjuvants and routes of administration should be studied to determine the optimum conditions for inducing high antisperm antibody titers in the host. Moreover, identification of various steps and factors that are involved in regulating the production of antisperm antibodies such as immunoglobulin binding factor may open new paths in the treatment of immunological infertility and at the same time lead to a more effective immunocontraceptive

Immunological functions of adult T cell leukemia cells of a patient complicated with synchronous double primary gynecologic cancer

A patient with triple malignancies is reported, who presented cervical cancer, vulvar cancer and adult T cell leukemia (ATL). ATL was diagnosed as a smouldering type, because antibody to human T cell leukemia virus associated antigen (ATLA) was positive with a titer of 1 : 160. Although her malignant cells had an OKT 4+8-3+Tac+ phenotype, the cells did not display helper T cell functions. Namely they showed no response to Phytohemagglutinin (PHA) and Interleukin 2 (IL-2) and suppressed the PWM driven IgG synthesis of B cells obtained from healthy donor. They did not produce IL-2 by stimulation with PHA and phorbol myristate acetate (PMA). Furthermore, these ATL cells were producing IL-2 inhibitor like factors. As synchronous triple malignancies are extremely rare, two gynecologic cancers seem to ascribe to the suppressing state of the immunosurveillance mechanism by viral infection

Galectin-1はヒト口腔扁平上皮癌細胞のアノイキスを抑制する

In order to determine the factors that relate to anoikis of the human oral squamous cell carcinoma (hOSCC) cells, we tried to search the proteins using the HSC-3 cell with metastaticity and the HSC-2 cells without metastaticity. The HSC cells were cultured in a dish coated with poly-HEMA to prevent cell adhesion, and then the degree of cell death was examined. The ratio of cell death for HSC-2 cells was significantly higher than that for HSC-3 cells, and the result of TUNEL staining showed that the cell death was apoptosis. The level of anoikis in HSC-2 cells was notably higher than that in HSC-3 cells. The expression level of TrkB, caveolin-1, and galectin-3 genes that are known as factors related to anoikis was investigated by RT-PCR. There was no significant difference in the gene expression between HSC-2 and HSC-3 cells. Galectin-1 was found by the proteome analysis and the protein was expressed more strongly in the HSC-3 cells as compared with the HSC-2 cells. A similar result was obtained in the amount of the mRNA expression. The anoikis of HSC-3 cells was caused strongly by the addition of lactose that inhibits the binding of galectin-1 to the cell membrane. When recombinant-galectin-1 was added to the medium, the level of anoikis in HSC-2 cells was decreased significantly. From these results, it was suggested that galectin-1 is the factor that suppresses anoikis in hOSCC cells

Effect of Cetraxate, a Mucosal Protective Agent, on Gastric Mucosal Blood Flow and Gastric Clarithromycin Concentration in Nicotine-treated Rats

Our previous study demonstrated that combination treatment with cetraxate plus omeprazole, amoxicillin, and clarithromycin is effective for the eradication of Helicobacter pylon in smokers. To evaluate the effect of cetraxate on gastric mucosal blood flow (GMBF) and the gastric concentration of clarithromycin in nicotine-treated rats, 10 rats were divided into two groups given nicotine with or without cetraxate, and GMBF was measured by laser Doppler blood flowmetry. Another 36 rats were divided into three groups (control, nicotine, and nicotine + cetraxate). Clarithromycin was administered intraduodenally and nicotine was administered after 30 minutes, with cetraxate being given 30 minutes later. The gastric mucosal clarithromycin concentration was measured. After cetraxate administration, GMBF increased significantly in the nicotine + cetraxate group compared with the nicotine group (p<0.05). The mucosal clarithromycin concentration increased in the nicotine + cetraxate group compared with the nicotine group, but the difference was not significant. Our results indicate that cetraxate increased GMBF in nicotine-treated rats

Effects of raloxifene on the production of cytokines in stimulated whole blood in ex vivo and in vitro studies

Purpose : The aims of this study were to determine the effects of raloxifene therapy on production of cytokines and in vitro effects of raloxifene on production of cytokines by whole blood cultures. Methods :We obtained samples of peripheral blood from 6 postmenopausal women with osteopenia at baseline and after 3 and 6 months of raloxifene therapy and 10 postmenopausal women who did not receive raloxifene therapy. Whole blood from raloxifene-treated women was stimulated with lipopolysaccharide (LPS) or phytohemeagglutinin (PHA). Whole blood from postmenopausal women who were not treated with raloxifene was preincubated with raloxifene at concentrations of 10-10-10-7 M and then stimulated with LPS or PHA. Concentrations of IL-1β, IL-4, IL-6, IL-12p40, IL-12p70, TNF-α and IFN-γ in the supernatant were measured by respective ELISAs. Results : In ex vivo cultures, raloxifene therapy inhibited LPS-stimulated production of IL-1β, IL-6, IL-12p40, IL-12p70 and TNF-α, but not PHA-stimulated production of IL-4 and IFN-γ. In in vitro cultures, raloxifene at a concentration (10-9 M) inhibited LPS-stimulated production of IL-1β, IL-6 and IL-12p40 and PHA-stimulated production of IFN-γ. Conclusions : Raloxifene therapy decreases the production of IL-1β, IL-6, IL-12 and TNF-α but not that of IL-4 and IFN-γ, suggesting that modulation of cytokines could play a role in the mechanisms of the osteoprotective effect of raloxifene

High Incidence of Micronuclei in Lymphocytes from Residents of the Area near the Semipalatinsk Nuclear Explosion Test Site

The Semipalatinsk area is highly contaminated with radioactive fallout from 40 years of continuous nuclear testing. The biological effects on human health in this area have not been studied. Significant remaining radioactivities include long-lived radioisotopes of ^, ^, ^Pu, ^Cs and ^Sr. To evaluate the long-term biological effects of the radioactive fallout, the incidence of micronuclei in lymphocytes from residents of the area was observed. Blood was obtained from 10 residents (5 females and 5 males, aged 47 to 55 years old) from each of the 3 areas of Znamenka, Dolon and Semipalatinsk, which are about 50-150 km from the nuclear explosion test site. For micronucleus assay, PHA-stimulated lymphocytes were cultured for 72 h and cytochalasin B was added at 44 h for detecting binuclear lymphocytes. Five thousand binuclear lymphocytes in each resident were scored. The means of micronucleus counts in 1,000 lymphocytes in residents of Semipalatinsk, Dolon and Znamenka were 16.3, 12.6, and 7.80, respectively, which were higher than those of the normal Japanese persons (4.66). These values were equivalent to the results obtained from 0.187-0.47 Gy of chronic exposure to γ-rays at a dose rate of 0.02 cGy/min. The high incidence of micronuclei in residents of the Semipalatinsk nuclear test site area was mainly caused by internal exposure rather than external exposure received for the past 40 years