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Biomedical subjects

N Inaba

Publications and source records attributed to N Inaba.

At least 73 records · Page 4Linked to original sources

[Effects of FRG-8813, a new-type histamine H2-receptor antagonist, on the healing of gastric and duodenal ulcer in rats and spontaneously ulcerative mice].

We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given orally twice a day for 7 days, accelerated the healing of gastric or duodenal ulcer induced by acetic acid injection or application at the non-antisecretory doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813 were more potent than those of famotidine or cimetidine. In W/WV mice, several ulcers spontaneously developed on gastric mucosa during the 8 weeks after the birth. The ulcers were aggravated by several unknown factors after the ulcer generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we suggest that FRG-8813 is able to accelerate the healing of ulcers by antisecretory plus increasing actions on the integrity of the gastric mucosal defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the treatment of gastric or duodenal ulcers in humans.

Acetamides↗

Immunohistochemical and ultrastructural investigation of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in gynecologic neoplasms.

New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated immunohistochemically by avidin-biotin immunoperoxidase technique and immunoelectron microscopy in various gynecologic neoplasms and normal gynecologic tissues. MP2 A and MP2 B were not specific for malignant tumors. MP2 C was present in 67-100% of ovarian carcinomas, 100% of benign dermoid cysts, and 77% of endometrial carcinomas. Except for endocervical adenocarcinomas, MP2 D was hardly detectable in gynecologic malignancies. Although MP2 E was hardly detectable in benign gynecologic tumors, this protein was present in ovarian carcinomas, uterine squamous carcinomas, endocervical adenocarcinomas, and endometrial adenocarcinomas. These results suggest a possible clinical application of these MP2 proteins as a new tumor marker for gynecologic malignancies.

Biomarkers, Tumor↗

A study of adult T-cell leukemia virus (ATLV) infection in the field of obstetrics: its epidemiology, vertical transmission and familial clustering.

Nine hundred and seventy-one healthy individuals in Iwate Prefecture, 659 pregnant women in Ishigaki Island, 487 pregnant women in Chiba Prefecture and 108 familial members of the ATLA-Ab-positive pregnant women (pregnant carrier women) were tested for ATLA-Ab by the PA, EIA and WB tests. 1) The rate of agreement of EIA with the PA test was 88.4% and there were no false negative sera by both examinations. These results indicate the both tests are available for mass screening. 2) In Iwate and Chiba Prefectures, the ATLA-Ab-positive rates of pregnant women were 5.3 and 0.6%, respectively. In addition, the incidences for healthy individuals ranged from 5.3 to 21.1% by age in Iwate Prefecture. Thus, Iwate Prefecture was found to equal Ishigaki Island (7.1%) in ATLA-Ab detection rates. 3) Forty-five (41.7%) out of 108 familial members of 15 pregnant carrier women were found to be seropositive for ATLA-Ab, which confirms a certain familial clustering of ATLV.

Adolescent↗

Effects of antiestrogens on ovarian aldo-keto reductase in relation to ovulation in rats.

The pharmacological effects of antiestrogens on ovarian aldo-keto reductase and ovulation were investigated in rats. The activities of reduction of 13,14-dihydro-15-keto-PGF2 alpha, 4-benzoylpyridine and menadione in ovarian cytosol were significantly decreased by antiestrogen treatments, and the ovulation was completely inhibited. However, administration of luteinizing hormone-releasing hormone at 3:00 p.m. on the day of proestrus restored both enzyme activities and ovulation, which were inhibited by antiestrogens, to control levels. These results indicate that nonsteroidal antiestrogen inhibits the luteinizing hormone surge on the day of proestrus in 4-day cycling rats and that ovarian aldo-keto reductase may be closely involved in the ovulatory process in rats.

Alcohol Oxidoreductases↗

Regulation of ovarian carbonyl reductase mediated by estrogen receptor in immature rats.

In the present study, the enhancing effect of synthetic estrogen on ovarian carbonyl reductase, a new prostaglandin (PG)-metabolizing enzyme, was investigated, and the antagonistic effect of antiestrogen on this enhancement was examined in immature rats. Ovarian carbonyl reductase activity towards 13,14-dihydro-15-keto-PGF2 alpha (15KD-PGF2 alpha), 4-benzoylpyridine (4BP) and menadione was determined photometrically and radiochemically, and quantitation of ovarian carbonyl reductase content was performed by Western blot analysis. Diethylstilbestrol (DES) and hexestrol (HX) enhanced the increasing effect of human chorionic gonadotropin (hCG) on ovarian carbonyl reductase activity and content when these synthetic estrogens (0.2 mg/kg) were administered for 3 days from 26 days of age, before hCG treatment. On the other hand, tamoxifen, which inhibits the binding of estradiol to the estrogen receptor, significantly prevented estradiol (E2) from enhancing the effect of hCG on ovarian carbonyl reductase. Furthermore, the ovarian carbonyl reductase activities towards the three substrates correlated well with the ovarian carbonyl reductase content. These results indicate that ovarian carbonyl reductase in immature rats may be regulated by a specific increase in the ovarian response to luteinizing hormone mediated by estrogen receptor.

Alcohol Oxidoreductases↗

Serum placental alkaline phosphatase (PLAP) in gynecologic malignancies--with special reference to the combination of PLAP and CA54/61 assay.

Serum placental alkaline phosphatase (PLAP) levels in patients with gynecological tumors were measured by two kinds of enzyme-antigen immunoassay kits provided by Innogenetics (PLAP-I) and Sangtec Medical (PLAP-S), and the combination assays for PLAP with other tumor markers were studied. None of the healthy women studied were PLAP positive, and the positive rate in patients with benign ovarian tumors was less than 6%. The positive rate in patients with ovarian cancers was about 35%, which was higher than the rates for other cancers. It was significantly higher in patients with ovarian serous cystadenocarcinoma (60%). Remarkably high PLAP-I values were observed in patients with dysgerminoma. By the combination assay for PLAP with CA54/61 antigen in ovarian cancers, the diagnostic efficiency increased compared with that for PLAP and CA125. We conclude that PLAP is useful in the diagnosis of ovarian serous cystadenocarcinoma and dysgerminoma and that CA54/61 is the better partner for the combination assay.

Alkaline Phosphatase↗

Enzyme immunoassay for placental protein 4 (PP4) and its possible diagnostic significance in patients with genital tract cancer.

We have established an enzyme immunoassay for placental protein 4 (PP4), by using avidin-biotin binding reaction, and set its normal range below 10.9 ng/ml (mean + 2 sigma). Throughout the menstrual cycle, the serum PP4 profile was similar to that of serum progesterone. In the follicular and ovulatory phase, PP4 remained relatively low, with the mean levels of 1.5 ng/ml and 1.8 ng/ml, respectively. In the luteal phase, the mean level was 3.2 ng/ml. In normal pregnancy, serum PP4 levels were low irrespective of gestational age, with a mean level of 3.0 ng/ml. There was only one case in which the serum PP4 level over 10.9 ng/ml. Mean serum PP4 levels and the frequencies of elevated serum PP4 levels were respectively 6.3 ng/ml and 11% in patients with benign ovarian neoplasms, 4.7 ng/ml and 6% in patients with endometriosis, and 5.5 ng/ml and 18% in patients with uterine myomata. The frequency of raised PP4 levels was 48% and the mean value was 13.3 ng/ml in patients with endometrial carcinoma, and the values were 44% and 13.4 ng/ml respectively in patients with cervical carcinoma. In patients with ovarian malignancy, the respective values were 15% and 7.0 ng/ml. The results did not relate to clinical stages of disease (FIGO), while the frequencies of elevated serum PP4 in patients with uterine carcinoma was over 40% in stage I diseases. Compared with other tumor markers such as carcino-embryonic antigen (CEA), tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125), PP4 seems to be more promising as a marker of endometrial carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Annexin A5↗

Immunohistochemical localization and physiological regulation of carbonyl reductase in immature rat ovary.

The present study was performed to clarify the role of the ovarian carbonyl reductase (OCR) in ovarian function in immature rats. The OCR activities towards three specific substrates, 13,14-dihydro-PGF2 alpha, 4-benzoylpyridine and menadione, were photometrically and radiochemically determined in the 9,000 x g supernatants of ovaries, and OCR content was measured by Western-blot-peroxidase anti-peroxidase (PAP) analysis. Immunohistochemical localization of the enzyme in the ovary was performed by the avidin-biotin-complex (ABC) method for paraffin sections. Positive immunoreactivity with OCR antibody was observed for the theca cells and interstitial gland cells at 72 hr after pregnant mare serum gonadotropin (PMSG) treatment when ovulation was confirmed, and the granulosa cells were consistently negatively stained. The OCR activity was significantly increased by PMSG, human chorionic gonadotropin (hCG) and PMSG-hCG treatments, but estradiol and tamoxifen overcame the effect of PMSG on the enzyme activity. Moreover, estradiol enhanced the effect of hCG, but tamoxifen did not. Changes in the OCR activity well-correlated with those in the OCR content. These findings indicate that the OCR is regulated by gonadotropin and estrogen and that metabolites formed by the enzyme could be closely involved in ovarian cell function.

Alcohol Oxidoreductases↗

Incidence of antibodies against human immunodeficiency virus, human T-cell lymphotropic virus type 1, hepatitis B virus, hemorrhagic fever with renal syndrome virus and Chlamydia in Tonga and western Samoa.

Among the populations of Tonga and Western Samoa, serum antibodies against human immunodeficiency virus or hemorrhagic fever with renal syndrome virus were not detected (0/904 and 0/192). No serum samples were considered to be positive for antibody against human T-cell lymphotropic virus type 1 (0/527). Hepatitis B antigen and antibody were found in 4% (8/192) and 47% (90/192), respectively. Chlamydia trachomatis IgG and C. psittaci IgG antibodies were detected in 39% (75/192) and 47% (91/192), respectively. The possibilities of the spread of human immunodeficiency virus and hemorrhagic fever with renal syndrome virus on the islands when the viruses invade from abroad were discussed.

Adolescent↗

[Diagnosis: tumor marker].

We have reviewed the clinical usefulness of tumor markers in gynecologic malignancy. In cervical squamous cell carcinoma. SCC and CEA showed increase in frequency of elevated cases according to the clinical stages (FIGO), and the frequency was significantly higher in recurrent cases than in patients with no evidence of disease. In endometrial carcinoma, presently, no specific tumor marker has been found. The diagnostic efficiency of CA 125, CA 19-9 and TPA were 25.2, 23.8 and 32.6, respectively. Further investigation must be necessary to establish markers sensitive enough. In primary ovarian malignancy, combination assay might be much more useful than single assay. The most effective combinations were TPA/CA 125/Ferritin in serous cystadenocarcinoma, and CEA/CA 19-9/TPA in mucinous cystadenocarcinoma. In the monitoring of the disease, it seems to be essential to select suitable combination of markers in each case. In addition, recently, multivariate analysis systems, such as CAMPAS (computer-aided multivariate and pattern analysis system), have become available.

Biomarkers, Tumor↗

[The treatment of refractory choriocarcinoma].

The choriocarcinoma was one of the most curable malignant neoplasms. This is chiefly because the effective chemotherapy was introduced and the sensitivity of hCG was improved. But about 10-20% cases with choriocarcinoma were drug resistant or recurrent cases. And now, the treatment of these refractory choriocarcinomas were one of the most important clinical problems. We describe a new combination chemotherapy for these refractory choriocarcinomas in this paper. This high dose 5-FU + Act-D protocol was effective for drug resistant cases with MEA protocol.

Adult↗

[Cell biological characteristics of a human embryonal carcinoma cell line].

We examined the cell biological characteristics of a human embryonal carcinoma cell line. NEC 14, derived from a male germ cell tumor of testis origin. The following results were obtained. 1) The morphological characteristics of NEC 14 cells were small size, an increase in the N/C ratio and poor development of organelle and desmosome-like cell-cell junctions. The NEC 14 cells proliferated rapidly and the population doubling time in vitro was 17 hours. 2) The functional characteristics of NEC 14 cells were the localization of intermediate filaments such as keratin and vimentin, hCG secretion and tissue plasminogen activator and laminin synthesis and expression of cell surface antigens such as stage-specific embryonic antigen-3, trophoblast antigen and neuron cell surface antigen. 3) The mode of chromosome number was 58 and many abnormal and undetermined chromosomes were found in the NEC 14 cells. 4) Differentiation was observed in vitro and in the tumor tissues xenotransplanted into nude mice.

Antigens, Surface↗

[A fundamental and clinical investigation of cancer antigen 130 (CA 130) in the field of obstetrics and gynecology].

Two murine monoclonal antibodies designated 130-22 and 145-9 have been recently established by immunizing mice with a pulmonary carcinoma cell line (PC-9). With use of these monoclonal antibodies a sensitive sandwich immunoradiometric assay (IRMA) for cancer antigen 130 (CA130) was developed in Daiichi Radioisotope Laboratories (Tokyo). Applying this IRMA kit CA130 concentrations were measured in various body fluids with special reference to obstetrics and gynecology. The results are as follows; 1) A CA130-IRMA showed excellent sensitivity, specificity, reproducibility and analytical recovery. The standard dose-response curve covered the range from 10 to 500 U/ml. 2) Serum CA130 levels measured by this assay system were closely correlated with serum CA125 levels, demonstrating quite a high correlation coefficient (r = 0.965). 3) In pregnancy maternal CA130 levels increased moderately (less than 300 U/ml) in the first trimester, and thereafter fell rapidly under normal upper limit (less than 35 U/ml). Immediately after deliveries maternal CA130 levels showed a rapid increase, reaching 269 U/ml (mean levels). In amniotic fluids CA130 concentrations were greatly elevated (3,236 U/ml mean levels), while the levels were almost within normal limit in the umbilical arterial and venous blood. Accordingly it is necessary to measure Schwangerschaftsprotein 1 or human chorionic gonadotropin simultaneously with CA130 to rule out possible pregnancy. 4) CA130 was clearly localized in the amniotic epithelium and umbilical sheath and other placental tissue components remained negative for this antigen. Taking the lower CA130 levels in the umbilical sera into consideration, these immunohistochemical results suggest CA130 is not oncofetal but oncoplacental. 5) Serum CA130 levels increased pretherapeutically beyond 35 U/ml in 87% of ovarian malignancies, and in 56% of endometrial carcinoma. The mean levels of serum CA130 reached 931 and 143 U/ml, respectively. These data indicate clinical usefulness of CA130 as a tumor marker for those diseases. By contrast serum CA130 levels were lower, and very few cases showed serum CA130 levels over 35 U/ml in cervical cancer. 6) In endometriosis 88% of the cases demonstrated increased serum CA130 levels, indicating its usefulness for monitoring therapeutic courses, just like CA125. In benign gynecologic diseases over 80% of cases showed increased serum CA130 levels while only slight increase in serum CA130 was found (mean levels less than 84.0 U/ml). This disadvantage could be lessened by a combination assay with CA72-4 and others whose serum levels were very low in the benign diseases.

Antigens, Tumor-Associated, Carbohydrate↗

Detection of the human papillomavirus 6b E2 gene product in genital condyloma and laryngeal papilloma tissues.

We have previously reported that the E2 open reading frame of human papillomavirus type 6b (HPV6b) was expressed in Bombyx mori cell line Bm-N as a fusion protein with baculovirus polyhedrin. Here we show that antibody against this E2-polyhedrin fusion protein recognized a putative gene product as a 49-kDa protein in some genital condyloma and laryngeal papilloma tissues, which were associated with HPV6 and HPV11, by immunoblotting analysis. The antibody reacted also with antigens in the nucleus of cells in the middle and upper layers of these papilloma tissues.

Animals↗

Clinical significance of a solid-phase immunoradiometrical assay for sialyl SSEA-1 antigen in obstetrics and gynecology.

The clinical usefulness of sialyl SSEA-1 antigen was evaluated in obstetrics and gynecology. Serum levels of sialyl SSEA-1 were measured in patients with benign or malignant gynecologic diseases, and in normal pregnant women. Moreover, in 10 cases of full term delivery, samples of maternal sera immediately prior to delivery, soon after delivery and 5-day-puerperium, cord sera from the umbilical artery and vein, and amniotic fluid were taken to measure its concentration. During the course of pregnancy, serum SSEA-1 levels were within the normal range (below 38 U/ml), showing no significant correlation with gestational weeks. Of patients with gynecologic diseases, those with malignant ovarian neoplasms, uterine cervical carcinoma and benign ovarian neoplasms exhibited elevated (over 38 U/ml) levels in 26%, 15% and 6% of all cases, respectively. In cases of full term delivery, the concentrations of sialyl SSEA-1 in the maternal and cord sera were within the normal range. Concentrations were extremely high, however, in the amniotic fluid.

Amniotic Fluid↗

Immunochemical measurement and immunohistochemical detection of membrane-associated placental tissue protein 1.

Using the avidin-biotin binding system, an enzyme immunoassay procedure was developed to measure the membrane-associated placental tissue protein 1 (MP1) in serum. The standard curve covered the range from 10 to 1000 ng/ml of MP1. The intra- and inter-assay coefficient of variations (C.Vs) were less than 5 and 10%, respectively. Recoveries of MP1 added to serum ranged between about 96 and 101%. The MP1 serum level was over 10 and under 112 ng/ml in non-pathological men, and under 240 ng/ml in non-pathological women. The MP1 level in the ovulatory phase was higher than in other phases of the menstrual cycle. In pregnancies during 6-39 weeks, the MP1 level ranged from 10 to 540 ng/ml, and it increased during the third trimester of gestational age. In benign gynecologic diseases, the MP1 concentration in serum ranged from 10 to 215 ng/ml. The MP1 levels in benign diseases were compared with those in ovarian malignancies, in endometrial carcinoma, and in uterine cervical cancer. The immunohistochemical location of MP1 was detected in the cell membrane of ovarian cystadenocarcinoma.

Female↗

[Resistance to anticancer drugs in relation to cytochrome P-450].

Cytochrome p-450 is a product of a multigene family, and catalyzes the activation and the detoxication of a wide variety of exogenous as well as endogenous compounds. Recent studies have the purified forms of cytochrome p-450 and provided evidence that some anticancer agents are metabolically activated by the cytochrome. In general, cancer cells express lower amounts of cytochrome p-450 as compared to normal liver cells. We recently succeeded in purifying P-450 HFLa, a form of cytochrome P-450 in human fetal livers. Examinations using antibodies to P-450 HFLa, however, showed that proteins cross-reactive with antibodies to P-450 HFLa existed in gynecologic malignancies. Development of multiple drug resistance is usually associated with a decrease in the content of cytochrome P-450, which is in contrast with glutathione S-transferase and a few other enzymes. The mechanisms responsible for such altered enzyme activity by multiple drug resistance are unclear as yet.

Animals↗