What information can change the attitude of teachers toward the human papillomavirus vaccine?

AIM: We conducted a self-administered survey on the perception of teachers toward human papillomavirus (HPV) vaccine to determine the ways to increase their willingness to encourage its use. METHODS: Answers were obtained both prior to and after having the teachers read five brief information articles: (i) cervical cancer knowledge, (ii) vaccine knowledge, (iii) result of a survey in Nagoya, (iv) news report of the World Health Organization statement and (v) articles written by Dr Muranaka, a journalist. RESULTS: Most of the respondents (180/247) did not know about the natural history of cervical cancer. Only 36% knew that HPV is the cause of cervical cancer, although 63% knew that HPV vaccine would prevent cervical cancer. Few respondents had knowledge regarding adverse events following immunization and the survey results from Nagoya. Among those who were initially negative for the HPV vaccine, only 43% revealed that they fully understood its safety and only 29% reversed their opinion to recommend vaccination to their daughters and/or students, even after reading our informational material. The most useful information for changing their attitudes was to increase their understanding of vaccines and informing them about Nagoya city survey results. They mostly wanted a proof of the preventive effects of the vaccine on cervical cancer in Japan. CONCLUSION: Gynecologists and pediatricians must proactively communicate accurate scientific information to the government and the media to spread awareness among people in Japan. Also, we must try to demonstrate the capabilities of this vaccine to prevent cervical cancer and/or its precancerous lesions.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition.

Gynecology in the office setting is developing worldwide. Clinical guidelines for office gynecology were first published by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011. These guidelines include a total of 72 clinical questions covering four areas (Infectious disease, Malignancies and benign tumors, Endocrinology and infertility, and Healthcare for women). These clinical questions were followed by several answers, backgrounds, explanations and references covering common problems and questions encountered in office gynecology. Each answer with a recommendation level of A, B or C has been prepared based principally on evidence or consensus among Japanese gynecologists.These guidelines would promote a better understanding of the current standard care practices for gynecologic outpatients in Japan.

A case of placental polyp treated with an intraoperative injection of prostaglandin F2α followed by hysteroscopic resection.

A 27-year-old woman had massive genital bleeding after an artificial abortion. Color Doppler ultrasonography showed a hypervascular mass. Hysteroscopy revealed a placental polyp. Serum hemoglobin level was decreased to 7.7 g/dl. Although uterine artery embolization (UAE) followed by hysteroscopic resection has been used for treatment of a placental polyp, UAE may not be an ideal option for patients with intent for future pregnancy because of the risk of ovarian function failure. This report presents a case of a placental polyp managed successfully with intracervical injection of prostaglandin F2α, as an alternative UAE, followed by hysteroscopic resection.

The role of blood in early endometrial-peritoneal interactions in a syngeneic mouse model of endometriosis.

PURPOSE: The aim of this study was to clarify the role of blood in the early stage of development of endometriotic lesions by developing a syngeneic transplantation model using immunocompetent mice. METHODS: Endometriotic lesions were induced in C57BL/6 mice by an intraperitoneal injection of endometrial fragments plus saline or endometrial fragments plus blood. Some endometrial fragments plus blood were injected with heparin, hirudin or tissue plasminogen activator (tPA). Endometriotic lesions on days 1, 3 and 5 were evaluated by gross and microscopic findings. RESULTS: The areas of endometriotic lesions in the blood group (6.4 ± 1.7 mm2) were significantly larger than those in the saline group (0.5 ± 0.3 mm2). The areas of endometriotic lesions were significantly reduced by the addition of heparin, hirudin or tPA. On day 1, endometriotic lesions in the blood group were observed on the peritoneum in five of the six mice. Endometriotic lesions on days 3 and 5 were significantly larger than those on day 1. On day 5, endometriotic lesions appeared cystic in all the mice. CONCLUSIONS: Blood accelerates the early stage of development of endometriotic lesions when endometrial fragments plus blood are injected. Blood property might be involved in early endometrial-peritoneal interactions.

Effectiveness of human papillomavirus vaccination in young Japanese women: a retrospective multi-municipality study.

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017.We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

The impact of systematic para-aortic and pelvic lymphadenectomy on survival in patients with optimally debulked ovarian cancer.

AIM: The objective of this study was to verify the impact of systematic retroperitoneal lymphadenectomy on survival in patients with ovarian cancer. MATERIAL & METHODS: During 2001­2005, clinical records of 118 patients with epithelial ovarian cancer were collected in Tokushima prefecture. From a number of hospitals, patients in one group were treated without systematic lymphadenectomy, and in another group, patients were treated with routine systematic lymphadenectomy. Clinical records were reviewed retrospectively and progression-free survival (PFS) and overall survival (OS) were compared. RESULTS: Sixty-two patients were staged as I­II according to the macroscopic findings at surgery. Forty of these patients received systematic lymphadenectomy and 22 patients did not. The 5-year OS was 100 and 80%, respectively (P = 0.07). The 5-year PFS was 94 and 71%, respectively (P = 0.04). In patients with clear cell adenocarcinoma, 3-year OS and PFS were significantly better in the lymphadenectomy group (P = 0.01, P = 0.046, respectively). The 56 patients staged as III­IV according to the macroscopic findings at surgery were optimally debulked. Twenty-eight of these patients received systematic lymphadenectomy and 28 patients did not. There is no difference in the 5-year OS (65 and 66%, respectively; P = 0.71) or the 5-year PFS (30 and 52%, respectively; P = 0.48). CONCLUSION: This study has demonstrated that the systematic lymphadenectomy had benefit only in patients with ovarian cancer macroscopically confined to the pelvis. In patients with clear cell adenocarcinoma, systematic lymphadenectomy was beneficial. To the contrary, systematic lymphadenectomy had no benefit on OS or PFS in patients with advanced ovarian cancer if optimally debulked.

Changes in serum cytokine concentrations during the menopausal transition.

OBJECTIVE: The purpose of the present study was to clarify the changes in serum concentrations of 17 cytokines in healthy women during the menopausal transition by using a multiplexed cytokine assay and to clarify the associations of these cytokines with serum estradiol concentration. METHODS: Sixteen premenopausal, 54 perimenopausal and 52 postmenopausal women were enrolled in this study. Seventeen cytokines in serum samples were measured simultaneously using a Bio-Plex human cytokine 17-Plex assay. RESULTS: Serum IL-6 concentration showed a weak positive correlation with age (r=0.196, p<0.05). Postmenopausal women for whom less than 5 years had passed since menopause showed significant (p<0.05) increase in serum concentrations of IL-2, GM-CSF and G-CSF, while serum IL-4 concentration was significantly (p<0.05) increased in postmenopausal women for whom more than 5 years had passed since menopause. Serum estradiol concentration showed a significant negative correlation with serum IL-6 concentration and weak negative correlations with serum concentrations of IL-2, IL-8 and GM-CSF. CONCLUSION: We were able to simultaneously measure the levels of 17 cytokines using a highly sensitive cytokine assay, and we found that the changes in serum cytokine concentrations during the menopausal transition differed. We also found that serum IL-6 concentration during the menopausal transition was negatively correlated with serum estradiol concentration.

Myeloid-related protein-8/14 is associated with proinflammatory cytokines in cervical mucus.

Myeloid-related protein-8 (MRP-8), MRP-14, and MRP-8/14 are found in a variety of inflammatory conditions and are involved in the host defense system. The objective of this study was to determine the concentrations of MRP-8, MRP-14, and MRP-8/14 in human cervical mucus and the associations between MRP-8/14 and proinflammatory cytokines. Samples of cervical mucus were obtained using a syringe from sexually active women (n=97) during the preovulatory phase. Samples from seven women were obtained using a swab placed in the cervical canal during the proliferative, preovulatory, and luteal phases. Concentrations of MRP-8, MRP-14, MRP-8/14, IL-1alpha, IL-6, IL-8, and granulocyte elastase were measured using an ELISA. The mean levels of MRP-8, MRP-14, and MRP-8/14 in cervical mucus were 1.87, 0.46, and 23.90microg/ml, respectively. The concentration of MRP-8/14 showed positive correlations with concentrations of IL-1alpha (p<0.0001), IL-8 (p<0.0001), and granulocyte elastase (p<0.0001). However, there were no significant differences in MRP-8/14 levels in the cervical mucus of each patient during the menstrual cycle. MRP-8/14 was mainly detected in human cervical mucus and showed a positive correlation with proinflammatory cytokines. The MRP-8/14 level in cervical mucus may be useful as a marker of inflammation of the uterine cervix.

Sperm-zona pellucida interaction and immunological infertility.

Immune reactions against gametes appear to be physiologically important for the maintenance of homeostasis in reproduction. In contrast, aberration of the immune homeostasis might give rise to 'immunological infertility'. Antisperm antibodies cause infertility by blocking fertilization. The mechanism can be explained as inhibiting the acrosome reaction of sperm by their blocking effect on capacitation through inhibiting an increase of fluidity of the sperm membrane. Autoantibodies against zona pellucida also cause infertility by blocking sperm-zona pellucida interaction, though the definitive mechanism has not been elucidated. Pretreatment of spermatozoa with D-mannnose completely inhibited sperm penetration through, but not binding to, the zona pellucida. Furthermore, very rapid kinetics between sperm extracts and D-mannnose by a BIAcore apparatus suggest that a D-mannose ligand of the sperm surface is easy to bind to and dissociate from a D-mannose residue in the sperm receptor site on the zona pellucida. Thus, D-mannnose on the human zona pellucida might be an essential molecule acting as a second sperm receptor, through which sperm penetrate into the zona pellucida. Because these antibodies appear to not cause any deleterious clinical symptoms, sperm and zona pellucida antigens are promising candidates in the development of an immunocontraceptive. (Reprod Med Biol 2006; 5: 95-104).

Involvement of carbohydrate molecules on zona pellucida in human fertilization.

Although the involvement of several receptors and ligand molecules in sperm-zona interaction in many species have been proposed, there has been a little analysis of the kinetics between these molecules during the interaction. In the present study, we applied the detection method using surface plasmon resonance (SPR) by a BIAcore apparatus for the analysis of the putative receptor-ligand interaction of sperm-egg binding. Mannose-BSA or [man](5)-[GlcNAc](2)-Asp was immobilized on the surface of a sensor chip. When concanavalin A (Con A) was delivered to each of two different sensor chips to evaluate their usefulness, the resonance signal after sample injection onto a [man](5)-[GlcNAc](2)-Asp-fixed chip decreased rapidly than the mannose-BSA-fixed chip. However, the amount of binding for Con A during the injection onto the [man](5)-[GlcNAc](2)-Asp-fixed chip was high. When acid sperm extracts (acid extracts) and fractions through a CM column, containing protease activity (protease fractions), were delivered to the mannose-BSA-fixed chip, the SPR signal during the injection was not obviously changed compared with that of the control. However, when sperm samples were delivered to the [man](5)-[GlcNAc](2)-Asp-fixed chip, the SPR response during the injection was enormous. These results suggest that the [man](5)-[GlcNAc](2)-Asp-fixed chip is more useful than the mannose-BSA-fixed chip for investigating the interactions with sperm extracts and that the sensitive method using SPR by a BIAcore apparatus is applicable for the analysis of the putative receptor-ligand interaction of sperm-egg binding.

A repertoire of cytokines in human seminal plasma.

The pathophysiological significance of seminal cytokines in sperm function is still controversial. We determined the repertoire of cytokines in seminal plasma obtained from men with or without abnormalities in semen and assessed the pathophysiological significance of seminal cytokines. After conventional analysis of semen samples obtained from 86 men, levels of seminal cytokines (interleukin [IL]-1alpha, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha], interferon-gamma, granulocyte colony-stimulating factor [G-CSF], macrophage CFS [M-CSF]) and granulocyte elastase were measured by an enzyme-linked immunosorbent assay. Leukocytospermia was defined as seminal plasma, which has > or =1000 ng/ml granulocyte elastase. Leukocytospermia was found in nine of 62 of the subjects in the normozoospermic group but in none of the 24 subjects showing abnormal sperm parameters (azoospermia, n=5; oligozoospermia, n=4; asthenozoospermia, n=15). The IL-8 level in the leukocytospermic group was significantly higher than those in the normal and oligozoospermic groups. IL-1alpha and TNF-alpha levels in the leukocytospermic group were significantly higher than those in the normal and asthenozoospermic groups. Although the G-CSF level in the leukocytospermic group was significantly higher than that in the normal group, high levels of M-CSF were detected in all groups. The IL-8 level was strongly correlated with IL-1alpha (r=0.935, P<0.0001) and G-CSF (r=0.916, P<0.0001) levels. Cytokines detected in seminal plasma are associated with the pathogenesis of leukocytospermia but not with the pathogenesis of asthenozoospermia and oligozoospermia.

Sperm-immobilizing antibodies suppress an increase in the plasma membrane fluidity of human spermatozoa.

OBJECTIVE: To clarify the mechanism by which capacitation is blocked by sperm-immobilizing antibodies, changes in the plasma membrane fluidity of human spermatozoa exposed to sperm-immobilizing antibodies were evaluated. DESIGN: In vitro cell culture study using human spermatozoa. SETTING: Department of Obstetrics and Gynecology, School of Medicine, The University of Tokushima. PATIENT(S): Semen samples were obtained from four healthy, fertile volunteers. INTERVENTION(S): The internalization of [3H]lyso-platelet activating factor (lyso-PAF) across the plasma membranes of human spermatozoa, which were exposed to sperm-immobilizing antibodies (antisperm group) or not exposed (control group), was measured at 20 and 60 minutes after the addition of a phospholipid probe using the modified albumin-back extraction method. MAIN OUTCOME MEASURE(S): The percentage of internalization of [3H]lyso-PAF across the plasma membrane of human spermatozoa. RESULT(S): Although the percentages of internalization of [3H]lyso-PAF (mean +/- SE) in the antisperm and control groups 20 minutes after addition of [3H]lyso-PAF were not significantly different (6.6% +/- 1.5% and 9.2% +/- 2.1%, respectively), at 60 minutes after the addition, the percentage in the antisperm group (9.0% +/- 1.3%) was significantly lower than that in the control group (13.4% +/- 1.3%). This inhibitory effect was diminished when spermatozoa exposed to sperm-immobilizing antibodies were incubated in an antibody-free medium. CONCLUSION(S): Sperm-immobilizing antibodies suppress the increase in internalization of an alkyl ester lysophospholipid probe in plasma membranes of human spermatozoa, and this inhibitory effect is reversible. Therefore, sperm-immobilizing antibodies suppress the fluidity of the plasma membranes of human spermatozoa, thus blocking capacitation.

Lysophosphatidic acid stimulates nuclear and cytoplasmic maturation of golden hamster immature oocytes in vitro via cumulus cells.

Lysophosphatidic acid (LPA), a member of the phospholipid autacoid family, is induced in incubated human follicular fluid by lysophospholipase D. It is well known that LPA functions as a growth factor and the hypothesis that LPA in human follicular fluid takes a part in meiosis of oocytes is quite plausible. We studied the effects of LPA on the maturation of golden hamster immature oocytes in vitro. Hamster oocytes with a germinal vesicle were cultured in Tyrode's albumin lactate pyruvate (TALP) medium with 10(-5) M LPA, 10 ng/ml epidermal growth factor (EGF), 30 ng/ml insulin-like growth factor-1, 1 ng/ml tumor growth factor-alpha or 1 ng/ml basic fibroblast growth factor. The nuclear maturation rates in the LPA and EGF groups were significantly higher than in the control group and the other growth factors did not show any stimulatory effect (LPA group; 74.3% [75/101], EGF group; 82.4% [89/108] vs. control group; 60.2% [59/98], p < 0.05, p < 0.01, respectively). When the cells of cumulus were removed, EGF and LPA did not increase the nuclear maturation rates. Cotreatment EGF and LPA did not significantly enhance the stimulatory effect observed with LPA alone on maturation in vitro. The penetration rate determined by the zona-free hamster oocyte test was significantly higher in the LPA group than in the control group (26.7% vs. 13.2%, p < 0.05) and was comparable with that of oocytes matured in vivo. In conclusion, LPA stimulates the nuclear and cytoplasmic maturation of hamster immature oocytes via cumulus cells.

Production of human mast cell chymase in human myometrium and placenta in cases of normal pregnancy and preeclampsia.

OBJECTIVE: To investigate whether the human mast cell chymase-endothelin-1(1-31) system was present in human myometrium, chorion and umbilical cord in normal pregnancy. METHODS: Myometrium, placenta and umbilical cord were obtained from five normal pregnant women and 10 with preeclampsia. Each tissue was stained with antibodies against hMC and ET-1(1-31). RESULTS: Routine cells were located mainly around vessels. The number of hMC-positive cells and production of ET-1(1-31) were significantly higher in myometrium from patients with severe preeclampsia compared to those from normal pregnant women. In contrast, their numbers were significantly lower in placenta and umbilical cord in patients with severe preeclampsia. CONCLUSIONS: These results suggest that the hMC-ET-1(1-31) system is active in normal pregnancy. Overproduction of hMC and ET-1(1-31) in the myometrium may be involved in the pathogenesis of severe preeclampsia, and in such cases some defense mechanism may operate in the fetus to cope with the pathological effect of the hMC-ET-1(1-31) system.

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-1ß, 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-1ß, 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-1ß, IL-6 and IL-12p40 and PHA-stimulated production of IFN-γ. CONCLUSIONS: Raloxifene therapy decreases the production of IL-1ß, 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.

Adenosarcoma of the uterus: magnetic resonance imaging characteristics.

Adenosarcoma of the uterus is a rare tumor containing benign glandular epithelial and malignant mesenchymal elements. Typical adenosarcoma is a low-grade tumor, presents as a large polypoid mass occupying the endometrial cavity, and may protrude into the vaginal cavity. The presence of small hyperintense cysts scattered within the mass on T(2)-weighted imaging, reflecting glandular epithelial components, and relatively low signal intensity on high b-value diffusion-weighted imaging, reflecting its low-grade nature, may be characteristic findings.

Evaluation of the potential of synthetic peptides of 80 kDa human sperm antigen (80 kDaHSA) for the development of contraceptive vaccine for male.

80 kDaHSA has been demonstrated to be responsible for inducing immunoinfertility. Synthetic peptides NT, 1, 2 and 4 of 80 kDaHSA are immunogenic and immunobiologically mimic the native protein. Peptides 1 and NT being highly immunogenic their potential for contraceptive vaccine development was evaluated. Active immunization of male rabbits with peptide-1 and -NT induced reversible infertility in 100% and 60% of animals, respectively and subsequently active immunization of non-human primate model, male marmosets with peptide-1 induced reversible infertility in six out of seven high antibody titer animals. The present study suggests the potential of peptide-1 of 80 kDaHSA for the development of contraceptive vaccine.

Antifertility effect of passive administration of antibodies to 80 kDa human sperm antigen and its synthetic peptides in male and female rats.

PROBLEM: A human sperm antigen of molecular size of about 80 kDa (80 kDa HSA) has been reported to be sperm-specific, conserved and responsible for inducing immunological infertility. The partial N-terminal amino acid sequence of 80 kDa HSA (peptide NT) and its peptides obtained by enzymatic digestion with endoproteinase Lys-C (peptides 1-4) and with endoproteinase Glu-C (peptides 5 and 6) did not show sequence homology with any of the proteins of the GenBank. The peptides NT, 1, 2, 3 and 4 were synthesized, conjugated to keyhole limpet hemocyanin and used as an immunogen to raise the antibodies in rabbits. Peptide 3 did not elicit significant antibody titer while peptides NT, 1, 2 and 4 elicited significant antibody titer and immunobiologically mimicked the native protein. METHOD OF STUDY: Effects of passive administration of two injections each of 200 microL of antibodies or 10 and 40 microg purified immunoglobulins to 80 kDa HSA, peptides NT, 1, 2 and 4 on fertility in male and female rats were investigated. RESULTS: Passive administration of antibodies to 80 kDa HSA and its peptides NT, 1, 2 and 4 resulted in agglutination of epididymal spermatozoa with loss of motility but had no effect on sperm count or weights of the reproductive organs. These animals failed to impregnate normal female rats. Passive administration of these antibodies to female rats also resulted in infertility. The presence of antibodies was detected by enzyme-linked immunosorbent assay in uterine secretions of animals treated with antipeptide antibody. The presence of agglutinated spermatozoa was observed in the post-coital vaginal smears of these animals. The immunized females were found to be ovulating normally and the number of corpora lutea were unaltered. Of the four antipeptide antibodies studied, antibodies to peptides NT and 1 were most effective in inhibiting fertility both in male as well as female rats. Hence, the antifertility studies were further confirmed by passive administration of 10 and 40 microg of purified immunoglobulins of antibodies to NT and 1, which resulted in a dose-dependent inhibition of fertility in male and female rats. CONCLUSIONS: The study demonstrated that the synthetic peptides of 80 kDa HSA immunobiologically mimicked the native protein and impaired fertility following passive administration of antipeptide antibodies and hence, suggested the suitability of synthetic peptides of 80 kDa HSA as candidates for development of antifertility vaccine.

The obesity in bilateral ovariectomized rats is related to a decrease in the expression of leptin receptors in the brain.

We investigated the expression levels of leptin receptors in the brain of ovariectomized (OVX) rats. The mean expression level of ob mRNA in adipose tissues of OVX rats was significantly (P < 0.01) lower than that in the SHAM operation group rats, and the mean body weight of OVX rats was significantly (P < 0.01) greater than that in the SHAM group rats. However, there were no differences between serum leptin concentrations in these two groups. The mean level of leptin receptor (OB-R) mRNA expression in the brain tissue and the mean level of long form type OB-R (OB-RL) mRNA expression in the hypothalamus of the OVX rats were significantly (P < 0.05) lower than those in the SHAM group rats. These changes were cancelled by supplementation with 17 beta-estradiol in OVX rats. These results suggested that not only changes in the expression level of ob mRNA in adipose tissue and the serum leptin concentration but also changes in the OB-R mRNA in the brain are involved in the body weight increase in OVX rats and that a decrease in OB-R makes transmission of signals to suppress the amount of food intake difficult, thus leading to an increase in body weight.