Search PubMed⌕ Search

Biomedical subjects

R Kudo

Publications and source records attributed to R Kudo.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of granisetron and its combination with dexamethasone on cisplatin-induced delayed emesis in the ferret.

1. Granisetron and its combination with dexamethasone for the treatment of delayed emesis following cisplatin (CDDP) administration were investigated using ferrets. 2. CDDP-induced emesis was significantly inhibited in both the granisetron group and the combined granisetron and dexamethasone group during the acute and delayed phase in terms of total emesis, latency to first emesis and duration of emesis. 3. Food and water consumption in the combined group of ferrets was significantly increased as compared with the CDDP control group. 4. 5-Hydroxytryptamine (5-HT) level was increased in the ileum and the 5-hydroxyindole acetic acid (5-HIAA) level was increased in the area postrema of ferrets after 3 days of CDDP administration. It is suggested that the antiemetic activity of granisetron and/or dexamethasone is not related to 5-HT levels in delayed emesis. 5. Both granisetron and its combination with dexamethasone are effective in CDDP-induced emesis, but combination treatment is more effective than granisetron alone for the duration of emesis in the delayed phase.

Animals↗
PubMed1998

Mechanism of endothelin-1 release from endothelial cells in pregnancy-induced hypertension.

We investigated the mechanism of vasoconstrictor-induced endothelin-1 (ET-1) release from human umbilical vein endothelial cells (HUVECs) in serum from women with pregnancy-induced hypertension (PIH). We obtained serum samples from seven women with PIH, seven healthy nonpregnant women (NP), and seven normal pregnant women (NPIH). ET-1 and inositol 1,4,5-trisphosphate (IP3) were assayed by ET-1 ELISA and an IP3 3H assay system, respectively. ET-1 release from HUVECs incubated with 10% serum (NP, NPIH, and PIH) was greater than that without human serum. Angiotensin II (Ang II)- and epinephrine (Epi)-induced ET-1 release were significantly increased by PIH serum. IP3 production in HUVECs incubated with 10% serum (NP, NPIH, and PIH) was greater than that without human serum. Ang II- or Epi-induced IP3 production in HUVECs incubated with PIH serum was increased but not significantly compared to that with other sera. Our results suggest that increased ET-1 release from HUVECs incubated with human serum may be mediated by IP3 production, but that Ang II- or Epi-induced ET-1 release from HUVECs incubated with PIH serum may be mediated by another mechanism.

Endothelin-1↗
PubMed1998

A case of a malignant mixed tumor in the vagina.

Malignant mixed tumors in the vagina are extremely rare. We experienced a case of a malignant mixed tumor (synovioid variant). Surgical treatment was performed, followed by 3 courses of chemotherapy. Up to the present time, 4 years after the first treatment, no signs of recurrence have been observed.

Biopsy↗
PubMed1998

Body fat distribution and uterine leiomyomas.

PURPOSE: Investigation of the etiological relationship between body fat and uterine leiomyomas. SETTINGS: This was a case-control study. Percent body fat was measured bioelectrically with a body fat analyzer. SUBJECTS: In Sapporo City, Japan, 100 women with uterine leiomyomas (pathologically diagnosed) and 200 controls who were confirmed to have no uterine leiomyomas by clinical examination. RESULTS: Among the four types classified by BMI (over/under 24.0) and percent body fat (over/under 30%), the occult obesity type (BMI < 24.0 and percent body fat > or = 30%) had the highest risk. There were no patients of muscular type (BMI > or = 24.0 and percent body fat < 30%). Women with more than 0.80 of waist-to-hip ratio were also at significantly higher risk. CONCLUSIONS: Occult obesity and upper body fat distribution may lead to the development of uterine leiomyomas.

Adipose Tissue↗
PubMed1998

Effects of estradiol and an aromatase inhibitor on progesterone production in human cultured luteal cells.

The human corpus luteum produces both estradiol and progesterone. It is well known that there are both autocrine and paracrine systems for the regulation of the corpus luteum and that estradiol regulates the progesterone production of the corpora lutea of some other species. To assess the direct effects of estrogen on human luteal function, we performed cell culture experiments. A low concentration of estradiol, almost equal to the amount of estradiol produced by human cultured luteal cells, directly stimulated progesterone production. 4-Cyclohexylaniline, an aromatase inhibitor, significantly reduced both progesterone production and estradiol production. Levels of estradiol higher than the levels that cultured human luteal cells themselves produced significantly reduced basal progesterone production and also significantly reduced human chorionic gonadotropin (hCG), forskolin and dibutyryl-cyclic AMP-stimulated progesterone production. According to these data, high doses of estradiol produced a luteolytic action which widely inhibited the steroidogenesis process. In conclusion, our results indicated that estradiol in part regulates progesterone production physiologically and blocks progesterone production in a pharmacological or pathological state in the human corpus luteum.

Aniline Compounds↗
PubMed1998

[Mobilization of peripheral blood stem cells in advanced ovarian cancer].

High-dose chemotherapy with hematopoietic support has been expected to improve the survival of advanced ovarian cancer patients in recent years. An essential component of such treatment has been the ability to collect and reinfuse a large number of peripheral blood stem cells (PBSCs) following high dose therapy. This study was designed to determine which clinical and hematological factors would be better indicators to collect the proper volume of PBSCs. Thirteen patients received a total of 24 courses of induction chemotherapy and 69 of apheresis. We usually mobilized stem cells using CEP chemotherapy (cisplatin 50-70 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 1.5 g/m2) with G-CSF and CEE regimen (cyclophosphamide 2.0 g/m2, epirubicin 50 mg/m2, and etoposide 50 mg/m2) as a salvage for mobilization. We obtained an average 5 x 10(6)/kg of CD34+ cells for 3 days as one course. The number of CD34+ cells collected significantly depended on the platelets and reticulocytes on the first day of apheresis, but not a nadir of WBCs. It is concluded that apheresis should be started on recovery of WBCs to 5,000-10,000/microliters, of immature granulocytes to > or = 10% and of reticulocytes to > or = 20%. This study confirmed the feasibility of collecting enough PBSCs to use standard chemotherapy of ovarian cancer patients.

Adult↗
PubMed1998

[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group].

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.

Administration, Oral↗
PubMed1997

Co-ordinated expression of connexins 26 and 32 in human endometrial glandular epithelium during the reproductive cycle and the influence of hormone replacement therapy.

Hormones are involved in the regulation of intercellular communication, and gap junction intercellular communication may play an important role in the prevention of endometrial cancer. We have investigated changes in the expression of the gap junction proteins connexin 26 (Cx26) and Cx32 in human endometrial glandular epithelium during the reproductive cycle as well as the influence of hormone replacement therapy. Frozen sections from 71 endometrial tissue samples (53 taken from women who had undergone hysterectomy during the menstrual cycle, 3 early pregnancy deciduae and 15 from menopausal women, some of whom were receiving estrogen alone or estrogen plus progesterone) were analyzed by immunofluorescence and confocal laser scanning microscopy. Cx26 and Cx32 were expressed weakly in the proliferative phase, markedly during ovulation and most strongly in the mid-secretory phase; by the late secretory phase, they decreased drastically. Cx26 and Cx32 also were expressed in early pregnancy. Women who had received estrogen and progesterone expressed the Cxs, but those who had received estrogen only or no therapy did not. These results were confirmed by Western blot analysis. They indicate that expression of Cx26 and Cx32 is correlated with cell differentiation and with the glandular function of the endometrial epithelium and suggest that expression of Cxs is controlled by serum progesterone.

Blotting, Western↗
PubMed1997

Proliferation-associated regulation of telomerase activity in human endometrium and its potential implication in early cancer diagnosis.

Telomerase activity was detected in normal endometrium in association with proliferation and regulated during the menstrual cycle in a hormone-dependent manner. The activity was maximal at the late-proliferative phase to mid-secreting phase, and was absent or extremely low at early-proliferative phase and late-secreting phase. Activity was also detected in all endometrial simple hyperplasias tested (16 of 16) and in most cancers (28 of 30), but none was detected in endometrium of either pregnant or postmenopausal women in the absence of hyperplasia. Our data provide evidence that the telomerase activity in postmenopausal endometrium reflects a hyperproliferative condition. Therefore, we conclude that telomerase can provide a novel marker for early endometrial cancer diagnosis. Hormone-dependent regulation of telomerase suggests the possibility of therapeutic and preventive strategies for endometrial cancers through the management of ovarian steroid hormones or other agents that regulate telomerase activity.

Adenocarcinoma↗
PubMed1997

Long survival of patients with unresectable cervical carcinoma after radiotherapy.

We report our experience with radiotherapy for three patients with cervical carcinoma in whom surgery had been downgraded to the performance of exploratory laparotomy only, because of extensive primary tumor or nodal invasion to the surrounding organs and vessels. Tumor invasion to the bladder, side wall invasion or unresectable nodal disease at the time of exploration prevented definitive surgery in our case series. After laparotomy, we carried out radiation therapy consisting of external irradiation to the pelvis and intracavitary irradiation with high dose rate 60Co or low dose rate 137Cs sources. Local and regional control was obtained in all three patients, and there was no locoregional recurrence during > 5 years of follow-up. One patient died of paraaortic lymph node metastases, but she had no pelvic recurrence. Several authors have reported an increased risk of small bowel obstruction in patients who undergo laparotomy before radiotherapy. None of our patients developed small bowel obstruction, although one had anal bleeding which was cured by conservative therapy. Radiotherapy was effective for locoregional control in all three patients with unresectable cervical carcinoma.

Aged↗
PubMed1997

[A randomized cross-over comparative study of granisetron alone and combination of granisetron, methylprednisolone and droperidol as antiemetic prophilaxis in CDDP-based chemotherapy for gynecologic cancer].

A cross-over clinical trial was carried out to compare the efficacy and safety of granisetron alone (40 micrograms/kg) as a "single" group, with that of granisetron, methylprednisolone (250 mg/ body) and droperidol (0.5 ml/body) as a "cocktail" group for control of emesis and vomiting induced by CDDP-based chemotherapy in 68 courses of 34 patients with gynecologic malignancies. At the first course, "single" or "cocktail" drugs were administered at day 1, 2, and 3 of chemotherapy, and at the second course, "cocktail" or "single" drugs in as cross-over fashion. We examined the degree of nausea and frequency of vomiting during the first 7 days of chemotherapy. As for the severity of nausea, the "single" group showed prominent nausea immediately after CDDP and the most severe level at the 3rd or 4th day. The "cocktail" group showed mild symptoms from the next day and it lasted for several days. Vomiting started 12 hours later in the "single" group and the most frequent peak was the 2nd day, whereas the "cocktail" group showed less than one vomiting at the 2nd or 3rd day throughout the treatment. Clinical response (extremely good, good) in the current series of 68 courses of chemotherapy was also evaluated to be 45% and 35% in the "single" group, respectively, against 75% and 20% in the "cocktail" group, respectively. There was no clinical toxicity or side effects in either treatment group. We conclude that the cocktail treatment is very useful for not only acute, but also late emesis in CDDP-based chemotherapy in gynecologic malignancies.

Adolescent↗
PubMed1997

Vascular reactivity to endothelium-derived relaxing factor in human umbilical artery at term pregnancy.

It has been reported that human umbilical artery (HUA) at term pregnancy released endothelium-derived relaxing factor (EDRF), using a superfusion bioassay system. However, other reports showed that endothelium-dependent relaxation was not observed in isometric tension studies using HUA ring with intact endothelium. Thus, we intended to clarify whether vascular smooth muscle of HUA at term is sensitive to EDRF. HUA was obtained after normal vaginal delivery or cesarean section at term. Isometric tension studies were performed in normal Krebs solution, using HUA rings or strips, which were prepared in calcium-free Krebs solution. Sodium nitroprusside (SNP), a nitric oxide (NO) donor drug, relaxed HUA rings precontracted with 0.1 microM 5-hydroxytryptamine (5HT) in a dose-dependent manner (1 nM-10 microM). Histamine, substance P, carbachol, or the calcium ionophore A23187, which are considered to be EDRF-releasing agents, did not relax the HUA rings. By immunohistochemical study, it was confirmed that endothelial cells were present in the luminal surface of the HUA rings after the isometric tension recording. In a co-axial bioassay system involving HUA strips denuded of endothelium and rabbit aorta with intact endothelium, HUA strips precontracted with 0.1 microM 5HT were relaxed in response to 1 microM SNP but not 1 microM carbachol, which released EDRF from the endothelium of rabbit aorta. These findings suggest that HUA at term is sensitive to NO but not EDRF.

Animals↗
PubMed1996

Definition of a commonly deleted region in ovarian cancers to a 300-kb segment of chromosome 6q27.

Allelic deletions of chromosome 6q that occur frequently in ovarian cancers imply the presence of a putative tumor suppressor gene in this chromosomal vicinity. We analyzed DNA from 32 patients with ovarian carcinomas for loss of heterozygosity at loci on the distal portion of chromosome 6q and constructed a detailed deletion map. The map indicated a commonly deleted region between loci D6S149 (defined by CI6-24) and A2, which are estimated to be 300 kb apart on the basis of our cosmid contig map. By means of exon trapping, we found that the human AF-6 gene, which is disrupted in acute myeloid leukemia cells that carry a (6;11)(q27;q23) translocation, is located within the commonly deleted region. Subsequent screening of the AF-6 gene in ovarian carcinomas revealed no mutations. However, our mapping results, which narrowed the region containing the putative tumor suppressor gene to a 300-kb segment of 6q27, will facilitate further efforts to identify a gene associated with ovarian cancer.

Blotting, Southern↗
PubMed1996

Involvement of peptide antigens in the cytotoxicity between 70-kDa heat shock cognate protein-like molecule and CD3+, CD4-, CD8-, TCR-alpha beta- killer T cells.

We previously reported that the 70-kDa heat shock cognate protein-like molecule (hsc70) is expressed on the cell surface along with the neoplastic transformation of rat fibroblast and that this molecule is recognized by CD3+, CD4-, CD8-, NKR-P1-, and TCR-alphabeta- T (DNT) killer cells in an MHC class I-unrestricted fashion. We investigated the mechanism of interaction between hsc70 and DNT cells. H-ras oncogene-transformed rat fibrosarcoma W31 cells expressed hsc70 on the cell surface in almost the same density when the cells were growing in a conventional 5% FCS (5% W31) as when the cell growth was inhibited in the cultivation with 1% FCS (1% W31). However, DNT cells lysed only 5% W31, but not 1% W31. Since these observations suggest that certain peptide Ags of the fast growing W31 cells may play a role in the interaction between hsc70 and DNT cells, we pulsed 1% W31 cells with trifluoroacetic acid (TFA)-extracted fast growing W31 tumor Ags of less than 3000 Da in molecular size. We also pulsed 1% W31 with TFA-extracted Ags from moderate growing W14 tumors and whole fetus tissues. Our data indicated that DNT cells were clearly cytotoxic to 1% W31 pulsed only with TFA-extracted Ags from W31 tumors. Anti-rat hsc70 mAb completely blocked this cytotoxicity. In addition, pronase K treatment of Ags clearly inhibited the cytotoxicity by DNT cells. Taken together, these data suggest that the complex of peptide Ag and hsc70 is involved in the cytotoxic mechanism between hsc70 and DNT cells.

Animals↗
PubMed1996

Expression of component desmosomal proteins in uterine endometrial carcinoma and their relation to cellular differentiation.

BACKGROUND: While the assessment of the malignancy of neoplasms is based on morphologic studies of cells and tissues, use of objective molecular markers is leading to a better understanding and more biologically meaningful classification of neoplasms. In recent years, changes in the expression of cell adhesion molecules, especially E-cadherin, catenin, and adenomatous polyposis coli (APC), in carcinomas have attracted the attention of researchers. However, little is known about desmosomes in the uterine endometrium or in endometrial carcinomas. In this study, we semiquantified the desmosomal components desmoplakin I and II and desmoglein, in tissue sections using confocal laser scanning microscopy (LSM), and examined their relationship to the pathological type, the occurrence of lymph node metastases, and the extent of myometrial invasion. METHOD: Frozen sections of 31 specimens of normal endometrium, 5 specimens of atypical hyperplasia, and 41 specimens of endometrial carcinoma were stained by the immunofluorescence method using antidesmoplakin I and II and antidesmoglein, and these markers were then semiquantified in tissue sections by LSM. RESULTS: The expression and location of desmoplakin I and II and desmoglein were similar, and their expression decreased with loss of differentiation. The expression was lower in cases of lymph node metastasis than in negative cases and was lower in the cases with > one-half myometrial invasion than in cases with < one-half myometrial invasion. CONCLUSIONS: Reduction of desmoplakin I and II and desmoglein expression may play an important role in the invasiveness and metastatic activity of human endometrial carcinoma. They can therefore be used as differentiation markers for endometrial carcinoma.

Biomarkers, Tumor↗
PubMed1996

Mutational analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial carcinomas with microsatellite instability.

Microsatellite instability, monitored by replication error (RER), has been observed in both sporadic and hereditary types of endometrial carcinoma. In the hereditary tumors, this instability is considered to be caused by a germline defect in the DNA mismatch-repair system. We previously reported that nearly one-quarter of sporadic endometrial carcinomas examined revealed an RER-positive phenotype at multiple microsatellite loci. To investigate the role of genetic alterations of DNA mismatch-repair genes in sporadic endometrial carcinomas, we screened 18 RER(+) endometrial carcinomas for mutations of hMLH1 and hMSH2. Although we found no germline mutations, we detected two somatic mutations of hMLH1 in a single endometrial cancer; these two mutations had occurred on different alleles, suggesting that two separate mutational events had affected both copies of hMLH1 in this particular tumor. These data implied that mutations of hMLH1 or hMSH2 play limited roles in the development of sporadic endometrial carcinomas, and that the tumors with genetic instability might have alterations of other mismatch-repair genes, such as hPMS1 and hPMS2, or of unknown genes related to the mismatch-repair system.

Adaptor Proteins, Signal Transducing↗