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S Nozawa

Publications and source records attributed to S Nozawa.

At least 19 recordsLinked to original sources
PubMed2001

Expression of an isoform of the testis-specific estrogen sulfotransferase in the murine placenta during the late gestational period.

Cytosolic sulfotransferases play essential roles in regulating the activities and transfer of steroids. To evaluate their biological significance in the murine uterus and placenta during the course of gestation, we determined their activities with several steroids as substrates. Activated estrogen sulfotransferase (EST) was found in the placenta and uterus during the late gestational period. Reverse-transcribed cDNA of murine placental EST (mpEST) was isolated from mouse placenta at 18 days of gestation and its expression in the tissue coincided with a change in its enzyme activity. The open-reading frame of mpEST encodes a protein composed of 296 amino acids with a predicted molecular mass of 35.5 kDa and was revealed to be an isoform of the murine testis-specific EST gene (99.7%). Also, the amino acid sequence of mpEST showed 49.6 and 77.9% homology with human placental and endometrial EST, respectively, showing that it corresponds to human endometrial EST. COS-7 cells transfected with mpEST exhibited sulfotransferase activity with the phenolic hydroxy groups of steroids and artificial substrates. The best acceptor substrate was estrogen.

Animals↗
PubMed2001

Analysis of E6 variants of human papillomavirus type 33, 52 and 58 in Japanese women with cervical intraepithelial neoplasia/cervical cancer in relation to their oncogenic potential.

The variation of the E6 region of human papillomavirus type 16 (HPV16) is associated with a high risk for cervical carcinogenesis. To see whether the same is the case with HPV33, 52 and 58, known to have high homology with HPV16, we analyzed the E6 sequence variation of these HPVs in 107 Japanese women with cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC): 20 HPV33-positive, 46 HPV52-positive and 41 HPV58-positive cases. HPV33 variants were more frequently observed in CINs I/II than in CIN III/ICCs (71% (5/7) versus 15% (2/13), P=0.02). In HPV52-positive cases, a single E6 variant was detected in 98% of the cases, whereas the prototype accounted for 98% of HPV58-positive cases. In summary, the distribution of E6 variants is different among HPV types tested, suggesting a link between E6 variation and oncogenic potential being type-specific.

Female↗
PubMed2001

Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse.

BACKGROUND: Natural antibodies that react with galactose-alpha(1,3)galactose [galalpha(1,3)gal] carbohydrate epitopes exist in humans and Old World primates because of the inactivation of the alpha1,3-galactosyltransferase (alpha1,3GT) gene in these species and the subsequent production of antibodies to environmental microbes that express the galalpha(1,3)gal antigen. The Gal knockout (Gal o/o) mouse, produced by homologous disruption of the alpha1,3GT gene, spontaneously makes anti-galalpha(1,3)gal antibodies and can be used to study the genetic control of humoral immune responses to this carbohydrate epitope. METHODS: Six hybridomas that produce monoclonal antibodies (mAbs) to galalpha(1,3)gal were generated in Gal o/o mice. The mAbs were tested to characterize the binding activity with flow cytometry using pig aortic endothelial cells and ELISA with galalpha(1,3)gal carbohydrates. The VH and VK genes of these hybridomas were cloned, sequenced, and analyzed. RESULTS: The mAbs showed distinct patterns of antibody binding to galalpha(1,3)gal antigens. The VH genes that encode the mAb binding activity were restricted to a small number of genes expressed in their germline configuration. Four of six clones used closely related progeny of the same VH germline gene (VH441). Comparison of the mouse gene VH441 to the human gene IGHV3-11, a gene that encodes antibody activity to galalpha(1,3)gal in humans, demonstrates that these two genes share a nonrandom distribution of amino acids used at canonical binding sites within the variable regions (complimentary determining regions 1 and 2) of their immunoglobulin VH genes. CONCLUSIONS: These results demonstrate the similarity of the Gal o/o mice and humans in their immune response to galalpha(1,3)gal epitopes. Gal o/o mouse can serve as a useful model for examining the genetic control of antibody/antigen interactions associated with the humoral response to pig xenografts in humans.

Amino Acid Sequence↗
PubMed2001

Combination of inflammatory cytokines increases nitrite and nitrate levels in the paraventricular nucleus of conscious rats.

Inflammatory cytokines stimulate glial cells in vitro to produce nitric oxide (NO) from inducible NO synthase (iNOS). Whether the stimulation with cytokines produces NO derived from iNOS has not hitherto been demonstrated in the vivo brain. Nitrite and nitrate (NOx(-)) levels in the rat paraventricular nucleus (PVN) were measured before and after intraparenchymal microinjection of cytokines with a microdialysis technique. The cytokines, tumor necrosis factor (TNF)-alpha (10 ng), interleukin (IL)-1 beta (2 ng), and interferon (IFN)-gamma (2 ng) were microinjected. None of the cytokines alone had any effect on the NOx(-) levels for 8 h. But a combination of TNF-alpha and IFN-gamma gradually increased NOx(-) levels beginning at 140 min after the microinjection, and NOx(-) levels reached 1.8 times the basal level at 380 min. A combination of TNF-alpha and IL-1 beta increased NOx(-) beginning at 340 min, reaching 1.7 times the basal level at 440 min, whereas a combination of IL-1 beta and IFN-gamma had no effect. Microinjection of a mixture of all three cytokines increased NOx(-) levels beginning at 120 min, reaching 3.3 times the basal level at 400 min. Aminoguanidine, which is a selective inhibitor of iNOS, reduced NOx(-) levels induced by the mixed cytokine treatment. Semi-quantitative RT-PCR for iNOS mRNA was done. The intensity of the iNOS mRNA band for the cytokine-treated PVN was stronger than that for the vehicle-treated PVN. These results suggest that the increased NOx(-) after the treatment with mixed cytokines were dependent on iNOS activity. This is the first report to indicate that only cytokines induce NOS in vivo in the brain.

Animals↗
PubMed2001

Prediction of the potentially fertile period by urinary hormone measurements using a new home-use monitor: comparison with laboratory hormone analyses.

BACKGROUND: The study compared a new urinary hormone monitoring system, Clearview Primera Fertility Monitor (CPFM), with laboratory hormone analyses in the prediction of the potentially fertile period. METHODS: Thirty healthy female volunteers provided blood and early morning urine samples for one cycle. Serum oestradiol, progesterone and luteinizing hormone (LH), and urinary LH and oestrone-3-glucuronide (E3G) were measured. The fertility status of volunteers; Low, High or Peak, was collected from monitors and compared with the hormone measurements. RESULTS: There was agreement between the first day of peak fertility and the urinary LH peak day in 65.6% of cycles and detection 1 or 2 days before the urinary LH peak day in 24.1 and 6.9% of cycles respectively. In 58.6% of cycles the system detected up to 5 days of increased fertility prior to the urinary LH peak day. Warning days of the urinary LH peak were similarly determined using defined thresholds of E3G and oestradiol providing up to 5 days warning in 82.8 and 96.6% of cycles respectively. CONCLUSIONS: The system can provide couples attempting to conceive with information about the potentially fertile days in the cycle in order that they may time intercourse. It also has potential for use in evaluation and treatment of infertile couples.

Adult↗
PubMed2001

Effects of counseling on climacteric symptoms in Japanese postmenopausal women.

OBJECTIVES: We objectively assessed the effects of counseling on climacteric symptoms in Japanese postmenopausal women. METHODS: Symptoms in 44 women (age, 51.4 +/- 3.4 years; period after menopause, 3.6 +/- 3.4 years) treated with counseling were evaluated according to the Keio modified menopause index. The response to counseling was compared with that to hormone replacement therapy (HRT). RESULTS: Forty cases (90.9%) showed an improvement in index score. There were no significant relationships between improvement and age, the period after menopause, or the severity or type of symptoms before counseling. The most improved symptom was headache, followed by palpitation and insomnia. Physical symptoms accounted for most of the common symptoms. The pattern of improvement with counseling was markedly different from that with HRT. CONCLUSIONS: We suggest that counseling is effective for treating climacteric symptoms, since it improves not only psychological symptoms, but also physical ones. Counseling may deserve evaluation as a complementary treatment to HRT.

Arrhythmias, Cardiac↗
PubMed2001

[Dose finding study of paclitaxel and carboplatin for ovarian cancer (JKTB)].

We conducted a dose-finding study for combination therapy of paclitaxel (Taxol; TXL) and carboplatin (Paraplatin; CBDCA). TXL is a novel plant-derived anticancer agent that is a diterpene derivative possessing the taxane ring. The subjects were patients with ovarian carcinoma, who were evaluated by a modified Fibonacci method. The dosage of TXL was 150 to 180 mg/m2. CBDCA was administered by dose escalation from AUC = 4 to 7. The administration schedule was as follows. Pre-medication was administered before TXL was given. TXL was then administered by intravenous infusion over 3 hours, followed by CBDCA. The dose of CBDCA was determined using the Calvert formula: [AUCX (GFR + 25)]. GFR was calculated with the Jelliffe equation. The non-hematological toxicities observed in 15 eligible cases were mainly grade 1, with no grade 3 or above, and no increase in severity was observed with stepping up. The hematological toxicities were grade 3 leukopenia in 5 of 15 cases, neutropenia in 5 cases and thrombocytopenia in 0 cases. No grade 4 toxicity was observed. The lowest counts of leukocytes and neutrophils were reached after 10.8 and 11.7 days, respectively. The toxicities were reversible in most cases with subsequent recovery. The above findings indicate that the recommended dosages for TJ therapy for Japanese ovarian cancer patients should be TXL 180 mg/m2 and CBDCA at a target of AUC = 6.

Adolescent↗
PubMed2001

[Hormonal therapy for endometrial adenocarcinoma].

Recently, the number of cases of endometrial cancer has increased in Japan. Most of the increase are accounted for by premenopausal cases, which are frequently positive for ER or PR. Hormonal treatment using progestins such as MPA has been widely applied to endometrial cancer patients under 40 years old under the conditions of grade 1 well-differentiated endometrioid adenocarcinoma without myometrial invasion. In our hospital, we applied high-dose (600 mg/day) MPA for over 8 weeks in 14 cases of endometrial cancer, of which adenocarcinoma disappeared in 12 cases (86%), followed by cyclic administrations of low-dose MPA, with 7 subsequent recurrences. We think that a protocol for improving ovarian function, such as active induction of ovulation, should be established to induce intrinsic progesterone sufficient for the prevention of the recurrence of endometrial cancers. In the 2 cases, in which adenocarcinoma remained even after long administrations of MPA, myometrial invasion was noted in the surgically resected specimens. For advanced or recurrent endometrial cancers, MPA has been reported to be effective in an average of 26% in several reports, and effective in 42% cases when applied with combination chemotherapy, such as CAP, by virtue of the "chemical modulator" effect, which can delay the acquired resistance against ADM or CDDP. Furthermore, MPA has resulted in a significant improvement of 5-year disease-free survival rate when used as adjuvant therapy after complete operations and whole pelvic irradiation, compared with administrations of 5-FU in a randomized controlled study in Japan. Thus, in the future, we consider that hormonal therapy will play a more important role in endometrial cancer treatment.

Adenocarcinoma↗
PubMed2000

Current status of reproductive function in Japanese fertile men: international collaborative project on a study of partners of pregnant women.

The data on reproductive function in 255 Japanese fertile men resident in the Kawasaki/Yokohama area in Japan were described. The sperm concentration was 107.9 +/- 97.4 x 106/mL. The semen volume was 3.2 +/- 1.5 mL and percentage motile spermatozoa (grade A + B in WHO criteria) was 56.8% +/- 14.7%. The evidence for secular changes in semen quality and other changes in male reproductive health is inconclusive, although regional differences would appear to be stronger. The present study is the first large-scaled prospective survey on the reproductive function of Japanese normal men proven fertility, which was planned as an international comparative study.

Adult↗
PubMed2000

Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats.

BACKGROUND AND AIMS: The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury. METHODS: Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy. RESULTS: Anti-neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase: alanine aminotransferase ratio, a marker of non-parenchymal cell injury, was increased in cholestatic-hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic-hepatectomized rats, but was not found in the antirat neutrophil serum-treated rats. CONCLUSION: These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage.

Alanine Transaminase↗
PubMed2000

Gonadotropin-releasing hormone analogue therapy for peritoneal inclusion cysts after gynecological surgery.

OBJECTIVE: The purpose of this report is to estimate the effectiveness of gonadotropin-releasing hormone analogue (Gn-RHa) therapy for peritoneal inclusion cysts. METHODS: Patients who had cystic masses that developed after gynecological surgery and were strongly suspected of being peritoneal inclusion cysts based on the results of ultrasound, magnetic resonance imaging (MRI), and tumor marker studies, were treated with a Gn-RHa (buserelin acetate or leuprorelin acetate). Buserelin acetate was administered at a dose of 900 microg/day, and leuprorelin acetate at a dose of 3.75 mg/month. Ultrasonography was performed in the outpatient clinic every 2 weeks after the start of administration to measure the diameter of cysts. RESULTS: We treated 8 patients with peritoneal inclusion cysts conservatively with a Gn-RHa. The cysts resolved in 7 of the patients. Two of them developed a recurrence, but further Gn-RHa therapy was followed by complete resolution of the cysts in one patient and we resume Gn-RHa therapy to the other patient. The peritoneal inclusion cysts failed to shrink in only one patient. CONCLUSION: It is suggested that Gn-RHa therapy is effective in some cases of peritoneal inclusion cysts.

Adult↗
PubMed2000

Usefulness of HMG-CoA reductase inhibitor in Japanese hyperlipidemic women within seven years of menopause.

OBJECTIVE: To assess the therapeutic value of treatment with an HMG-CoA reductase inhibitor in women with hypoestrogenic hyperlipidemia caused by menopause. DESIGN: Fifty-six women with total cholesterol (TC) levels of 220 mg/dl or more who were within 7 years of menopause were randomly assigned to receive an HMG-CoA reductase inhibitor (pravastatin 10 mg/day; treated group, 26 patients) or no medical treatment (nontreated group, 30 patients) in this 6-month nonblinded prospective trial. RESULTS: In the treated group, the mean (SD) TC levels decreased significantly from 254.5+/-22.3 mg/dl at baseline to 204.7+/-22.2 mg/dl (19.6%), and the mean low-density lipoprotein cholesterol (LDL-C) level decreased significantly from 146.7+/-30.5 to 104.3+/-22.5 mg/dl (28.9%); the mean arteriosclerotic index decreased significantly from 2.98 to 2.08 (30.2%). There were no significant changes in either triglyceride levels or high-density lipoprotein cholesterol (HDL-C) levels. In the nontreated group, there were no significant changes in the TC, HDL-C, LDL-C, or triglyceride levels; there was also no change in the arteriosclerotic index. After 6 months, the TC level, LDL-C level, and arteriosclerotic index were significantly lower in the treated group compared with the nontreated group (p<0.01). CONCLUSIONS: The results indicate that the HMG-CoA reductase inhibitor lowered TC and LDL-C levels and was useful in the treatment of hypoestrogenic hyperlipidemia for periods of at least 6 months.

Arteriosclerosis↗
PubMed2000

Comparative effects of estrogen and raloxifene on B lymphopoiesis and bone loss induced by sex steroid deficiency in mice.

Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss because of stimulated bone resorption. We have reported that OVX selectively stimulates B lymphopoiesis in mouse bone marrow, which is somehow related to bone resorption. Estrogen prevents both the increased B lymphopoiesis and the bone resorption caused by estrogen deficiency. Raloxifene also has a potent estrogenic activity for bone with minimal estrogenic activity for the uterus. To examine the effects of raloxifene on B lymphopoiesis and bone resorption, OVX mice were given either estrogen or raloxifene subcutaneously for 2-4 weeks using a miniosmotic pump. Reduced uterine weight in OVX mice was restored completely by 17beta-estradiol (E2). Some 300-fold higher doses of raloxifene increased uterine weight of OVX mice, but only slightly. The number of B220- positive pre-B cells was increased markedly in bone marrow after OVX. The increased B lymphopoiesis was prevented not only by E2 but by raloxifene. In OVX mice, the trabecular bone volume (BV) of the femoral distal metaphysis was reduced markedly, when measured by microcomputed tomography (microCT) scanning and dual-energy X-ray absorptiometry. Both E2 and raloxifene similarly restored it. Like estrogen deficiency, androgen deficiency induced by orchidectomy (ORX) also resulted in a marked bone loss and increased B lymphopoiesis. Both E2 and raloxifene prevented the changes in ORX mice. These results indicate that both estrogen deficiency and androgen deficiency similarly stimulate B lymphopoiesis in mouse bone marrow, which accompany bone loss. Raloxifene exhibits estrogenic actions in bone and bone marrow to prevent bone loss and regulate B lymphopoiesis without inducing estrogenic action in the uterus.

Androgens↗
PubMed2000

Imbalanced expression of TAN-1 and human Notch4 in endometrial cancers.

The development of cancer is a cellular process that reflects and is partly driven by alterations in cell determination. Mutations in various genes responsible for cell determination have been identified as being oncogenic; however, little is known about the involvement of normal cell fate-determining mechanisms in the oncogenic process. The Notch pathway is an evolutionarily conserved, general cell-interaction mechanism that controls fundamental aspects of cell determination during the development of vertebrates and invertebrates. We have explored the roles of the recently cloned human Notch4 gene, which is a homologue of Drosophila Notch, in endometrial tissue, a cellular environment where cell fate changes take place and neoplastic conditions have been characterized. Northern blot analysis, dot blot analysis, and in situ hybridization were performed on samples of normal endometria at different phases of the menstrual cycle and endometrial cancers. Our results showed that: a) Both human Notch4 and translocation-associated Notch homologue-1 (TAN-1), another human homologue of Drosophila Notch, are expressed in the normal endometrium, mainly in the endometrial glandular cells. b) The level of expression of human Notch4, but not TAN-1, changes during the normal menstrual cycle; i.e., the level of Notch4 expression was significantly lower during the secretory phase than during the proliferative phase. c) Endometrial cancers express a significantly lower level of human Notch4 and a significantly higher level of TAN-1 than normal endometria. These results suggest that human Notch4 and/or TAN-1 are involved in the changes of the endometrium during the menstrual cycle, and also in the development of endometrial cancer.

Adenocarcinoma↗
PubMed2000

[A pilot trial of high dose CEP (cyclophosphamide, epirubicin, cis-platinum) therapy in patients with advanced and recurrent ovarian cancer].

We evaluated the feasibility of high-dose CEP (cyclophosphamide 750 mg/m2, epirubicin 90 mg/m2, cis-platinum 70 mg/m2) therapy, with granulocyte colony-stimulating factor support every 21 days, in 18 patients with advanced and recurrent ovarian cancer. Ten patients (56%) received 6 cycles of this regimen as planned. Toxicities more than grade 3/4 on' the WHO scale of neutropenia and thrombocytopenia were observed in all cases. Nausea, vomiting, mucositis, malaise, alopecia, hepatotoxicity, and fever were common adverse effects. The average relative dose intensity of cyclophosphamide, epirubicin, cis-platinum was 0.77, 0.77, 0.79 respectively, and each RDI decreased in the last two cycles. These data suggest that this regimen could be performed safely with careful consideration on hepatotoxicity and thrombocytopenia.

Adult↗
PubMed2000

[Recent trends in male reproductive disorders].

There is growing concern about the considerable decline in semen quality and the increase of male reproductive disorders such as testicular cancer, hypospadias and cryptorchidism over the past decades. Such trend has also been manifested itself in the form of increasing demand for assisted reproductive technology in recent year. Concerning the above Skakkebaek has been proposed a hypothesis that there may exist common etiological factors for these male reproductive disorders. He presented a new evidence that male reproductive disorders are symptoms of an underlying testicular dysgenesis syndrome at the workshop "Hormones and Endocrine Disruptors in Good and Water: Possible Impact on Human Health" held in Copenhagen, May 27-30, 2000. In this paper, we review several topics presented in this workshop.

Cryptorchidism↗
PubMed1999

Detection of endometrial cancer by flow cytometry using two monoclonal antibodies.

BACKGROUND: To develop a supplementary diagnostic method for endometrial cancer by measuring the reactivity of various endometrial lesions with two monoclonal antibodies. METHODS: We investigated the reactivity of various endometrial lesions with two monoclonal antibodies (MSN-1 and MSN-3) by flow cytometry (one-color and two-color methods). RESULTS: The two-color method appeared to be suitable for use in place of simultaneous performance of the one-color methods with MSN-1 and MSN-3. The positivity rate for normal endometrium was 16.0% with the two-color method, which was lower than the rate of 30.0% obtained with concomitant used of the one-color methods. The positivity rate for endometrial cancer was high, 84.0%, with the two-color method. The positivity rate was 85.7% for well-differentiated endometrial cancer, 71.4% for moderately differentiated cancer, and 100.0% for poorly differentiated cancer; thus, the rate was high irrespective of the cellular differentiation. CONCLUSIONS: The two-color method is more useful than the one-color method as a supplementary diagnostic procedure for endometrial cancer.

Antibodies, Neoplasm↗