Biomedical subjects

N Inaba

Publications and source records attributed to N Inaba.

At least 55 records · Page 3Linked to original sources

PubMed1994

Immunolocalization of complement C1s and matrix metalloproteinase 9 (92kDa gelatinase/type IV collagenase) in the primary ossification center of the human femur.

The first component of complement C1s has been shown to degrade type I and type II collagens (Yamaguchi et al. 1990), the latter of which is a major constituent of the cartilage matrix. In order to understand the physiological roles of C1s in cartilage resorption, the expression of C1s was examined by immunohistochemistry in the primary ossification center where the matrix is removed and replaced by bone marrow. Hypertrophic chondrocytes, endothelium and hematogenous elements in the capillary buds were intensely stained by a monoclonal antibody against C1s. Matrix metalloproteinase 9 (MMP-9, 92kDa gelatinase/type IV collagenase) was also immunolocalized in hypertrophic chondrocytes, mesenchymal cells in the primitive bone marrow and the cartilage matrix adjacent to the marrow. In addition, C1s was found to activate the zymogen of MMP-9. These observations suggest that C1s and MMP-9 coordinately participate in matrix degradation in cartilage.

Antibodies, Monoclonal↗

PubMed1993

Gastric antisecretory effect of FRG-8813, a new histamine H2 receptor antagonist, in rats and dogs.

FRG-8813, a new histamine H2 receptor antagonist, was examined for antisecretory effects and compared with famotidine and cimetidine in rats and dogs. In pylorus-ligated and lumen-perfused rats, FRG-8813 given i.v. reduced basal gastric acid secretion and the acid secretion evoked by histamine, tetragastrin, bethanechol, and 2-deoxy-D-glucose in a dose-dependent manner. The i.v. antisecretory activity of FRG-8813 was equivalent to or slightly less than that of famotidine and the intraduodenal (i.d.) activity was greater than that of cimetidine. The duration of action of FRG-8813 was substantially longer than that of farmotidine and cimetidine for both i.v. and i.d. routes. The i.v. ED40 values for the histamine- and tetragastrin-evoked responses and the i.v. ED30 value for the bethanechol-evoked response were 0.15, 0.09 and 0.43 mg2kg, respectively. In Heidenhain pouch dogs, when the three H2 antagonists were given i.v. or orally, the relative antisecretory potency of the compounds was similar to that in rats. The long-lasting antisecretory effect of FRG-8813 was also observed, and the i.v. ED50 values for histamine-, tetragastrin- and bethanechol-evoked responses were 0.1, 0.24 and 1.0 mg/kg, respectively. Comparison of the parenteral and enteral potencies indicated that FRG-8813 has a lower bioavailability than famotidine and cimetidine in rats and dogs. These data suggest that FRG-8813 has a potent and long-lasting antisecretory effect with a far greater potency than cimetidine and with a slightly lower potency than famotidine.

Acetamides↗

PubMed1993

The development of an enzyme immunoassay for placental tissue protein 17 (PP17) and its clinical significance.

We developed an enzyme immunoassay (EIA) for placental protein 17 (PP17) using avidin biotin binding, and measured the serum-PP17 levels of 37 healthy men, 103 nonpregnant women, 48 pregnant women, and 86 patients with gynecologic malignancies. The mean level was 12.8 ng/ml in healthy men and 44.2 ng/ml in nonpregnant women (p < 0.05). The calculated upper limit of normal was 97.8 ng/ml (mean + 2 sigma). The serum PP17 concentration was remarkedly reduced postmenopausally. Pregnant women showed a mean serum level of 19.2 ng/ml, which was significantly lower than that of nonpregnant women. Immunoserological results strongly suggest that PP17 is produced far more in the normal endometrium than in the placentae and decidua. Patients with gynecologic malignancies had obviously lower mean serum PP17 levels (8.3-19.9 ng/ml) than those found in healthy nonpregnant women. Measurement of the serum PP17 concentration might be useful in distinguishing gynecologic malignancies from various normal conditions.

Biomarkers, Tumor↗

PubMed1993

Immunohistochemical and immunoelectron microscopic study of cytochrome P-450 of human fetal livers (P-450HFLa): implications for an onco-feto-placental enzyme.

Cytochrome P-450 of human fetal livers (P-450HFLa) was demonstrated by the avidin-biotin immunoperoxidase technique in tissue samples as follows: human fetal organs, adult livers, human and cynomolgus placenta, and gynecologic organs which were obtained from 40 patients with gynecologic malignancies and 32 patients with benign diseases. P-450HFLa was clearly localized in the cytoplasm and membranes of the hepatocytes, and the fact was confirmed by an immunoelectron microscopic examination. In addition, a semiquantitative assay of staining intensity demonstrated that this enzyme tended to decrease with advancing age. These findings suggest that hepatic P-450HFLa synthesis is inversely proportional to age, and that this enzyme is one of the differentiation antigens. P-450HFLa was also detected immunohistochemically in other fetal organs. The present study thus confirms that P-450HFLa is not specific to the liver and is ubiquitous even in the fetus. Marked positive staining for P-450HFLa was demonstrated in villous syncytiotrophoblasts. In contrast, no positive staining was found in the cynomolgus-monkey placenta, unlike the case for many other placental antigens. These findings lead to the tentative conclusion that P-450HFLa is a feto-placental enzyme peculiar to humans. P-450HFLa was demonstrated to occur very frequently in gynecologic malignancies. The mean positivity rate for all gynecologic malignancies was 85%, while the rate was below 25% for benign gynecologic diseases, indicating that P-450HFLa is one of the onco-feto-placental enzymes. The present study thus suggests that this enzyme could be a promising new tumor marker for gynecologic malignancies.

Animals↗

PubMed1993

The application of immunotargeting into cancer chemotherapy with carboplatin: in vitro and in vivo studies.

Anti-tumor effects of the following 2 cis-diammin (1, 1-cyclobutandicarboxylato) platin II (carboplatin, Bristol-Myers-Squibb) conjugates were evaluated through both in vitro and in vivo experiments: (1) carboplatin coupled with anti-cytokeratin monoclonal antibody (MAb), TS1 via carboxymethyl dextran (carboplatin-carboxymethyl dextran-TS1), and (2) carboplatin-carboxymethyl dextran-avidin targeted to biotinylated TS1. Using 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide and N-hydroxysuccinimide, carboplatin was conjugated to carboxymethyl dextran, TS1, or avidin, at high molar ratios. The staining positivity of carboplatin-carboxymethyl dextran-TS1 in indirect immunofluorescence was almost identical to that of the original MAb. The average dose of carboplatin given in each treatment was about 60% of a clinical dose. Regarding cytotoxicity, the free drug showed the strongest effect and the best dose-dependency in cell lines: HeLa and ZR-75-1. An in vivo study giving carboplatin-MAb conjugates or free drug to HeLa tumor bearing nude rats proved that the efficacy of carboplatin-carboxymethyl dextran-TS1 in HeLa tumor was not greater than that of the free carboplatin.

Animals↗

PubMed1993

Immunoradiometrical measurement of tissue polypeptide specific antigen (TPS) in normal, healthy, nonpregnant and pregnant Japanese women.

Using a monoclonal immunoradiometrical assay, we measured the concentrations of the specific epitope M3 of tissue polypeptide antigen (TPA), namely, tissue polypeptide specific antigen (TPS), in serum and amniotic fluid obtained from normal, healthy, nonpregnant and pregnant Japanese women (NHNJW and NHPJW). The cut-off value of the serum TPS level was set at 130 U/l, based on the mean +2 standard deviations in the NHNJW. The serial measurement of serum TPS levels demonstrated the significant temporal elevation of TPS level near the time of ovulation (+/- 3 days) in the ovulatory women. In the NHPJW, the mean serum TPS level and the positivity rate (> 130 U/l) increased with the advance of gestation, reaching 183.7 U/l and 66.7%, respectively, in the third trimester. Maternal serum levels were much elevated just before (mean: 982.3 U/l) and after (mean: 824.6 U/l) delivery, and were reduced to about one-fourth by 3 days. In addition, markedly high TPS concentrations were found in the retroplacental blood (one case: 9,076 U/l) and the amniotic fluid (mean: 11,650 U/l). The serum TPS level correlated well (r = 0.871) with the serum TPA level in the TPS range of 2-2,000 U/l, while a poor correlation (r = 0.273) was found in the TPS range of 2-500 U/l. The present study thus obtained fundamental data on TPS in Japanese women. The fluctuation and change of serum TPS levels during the menstrual cycle and in pregnancy should be taken into consideration when we apply TPS as a tumor marker for women.

Adolescent↗

PubMed1993

[Crossed inhibition of lateral pterygoid motoneurons in guinea pig].

The effects of stimulation of the lateral pterygoid (LP) nerve on the contralateral LP motoneurons (Mns) were investigated in the decerebrate guinea pig. 1. Stimulation of the LP nerve induced a hyperpolarizing potential (HP) in the contralateral LP Mn. The onset and peak latency of this HP were 2.14 ms and 4.10 ms in 11 LP Mns on the average, respectively. The HP was reversed to a depolarizing potential after intracellular Cl- injection, indicating that it mainly consisted of IPSPs. 2. The antidromically evoked field potential (AFP) in the LP Mn pool was depressed by the stimulation of the contralateral LP nerve. The threshold intensity was about 1.2 times the LP nerve threshold. 3. The crossed depression of AFP was significantly diminished after the destruction of the caudal part of the contralateral trigeminal mesencephalic nucleus, but not by the lesion of the trigeminal spinal tract. 4. The most rostral level in the trigeminal spinal tract nucleus, where the HRP-labelled axon terminals were found after its injection into the LP muscle, was located caudally to the lesion of the spinal tract. It is concluded that the muscle spindle afferents from the LP muscle are involved in the crossed inhibition of the LP Mns evoked by the stimulation of the LP nerve.

Animals↗

PubMed1993

[Vertical transmission human T-cell lymphotropic virus type-I (HTLV-I)--genetic diagnosis and assessment of the probable routes of HTLV-I infection].

Human T-cell lymphotropic virus type-I (HTLV-I) provirus DNA from peripheral lymphocyte of 39 infants delivered by 26 pregnant carriers was detected by the nested double polymerase chain reaction (PCR) method to identify vertical transmission (VT) of HTLV-I. The 39 infants included 12 breast-fed and 27 bottle-fed infants. Particle agglutination (PA) assay and indirect immunofluorescence (IF) test with 467 cells were performed to detect anti-HTLV-I antibody. In breast-fed infants, two (16.7%) cases were both seropositive and PCR-positive and others were both negative, so there was perfect agreement between seropositivity and PCR-positivity. In bottle-fed infants, two (7.4%) cases were seropositive but PCR-negative. This seropositivity was supposed to be due to the transplacental maternal anti-HTLV-I antibody. In 25 seronegative bottle-fed infants, 4 (14.8%) cases were PCR-positive. No significant difference was found in the PCR-positivity rate between the breast-fed and bottle-fed groups. Our study showed the usefulness of the PCR method in identifying VT, the existence of silent carriers especially in bottle-fed infants and the possibility of transplacental or birth canal routes of HTLV-I infection.

Adult↗

PubMed1993

[A study of first and second line chemotherapies in gestational choriocarcinoma].

Twenty-eight patients with choriocarcinoma have received the three kinds of combination chemotherapy since 1983 at our department, i.e., MOA consisting of moderate dose methotrexate (MTX), actinomycin-D (Act-D) and vincristine, MEA (moderate dose MTX, Act-D and etoposide) and FA (high dose 5-Fluorouracil and Act-D). The clinical and laboratory data obtained in the 28 patients were summarized as follows; 1. The MOA regimen was administered to 4 patients primarily and to 2 secondarily. All of the 6 patients attained remission, but finally two (33.3%) developed relapse. 2. The MEA regimen was administered to 12 patients primarily and to 12 secondarily. Of the 24 patients, five (20.8%) were found to be resistant to the MEA regimen. Nineteen patients (79.2%) attained remission, but 2 (10.5%) developed recurrence. 3. The FA regimen was attempted in one patient primarily and in 6 secondarily. Although one patient died, the remaining 6 achieved remission and one relapse has been observed in the 6 cases. 4. By applying the above mentioned 3 combination chemotherapy regimens, the overall survival rate was pushed up from 64% to 90% in choriocarcinoma patients. 5. Three patients finally died of the disease but not from the side effects of the combination chemotherapies. The major adverse effects were alopecia, nausea, vomiting and myelosuppression. In particular, serious myelosuppression was caused by the MEA or FA regimen in 5-7% of all chemotherapy courses.

Adult↗

PubMed1993

[The present situation of the computer system for the clinical laboratory in Japan].

We report the present situation of the computer system utilization for the Clinical Laboratory in Japan. For this studies, the data were calculated to our purpose from the materials for statistics published by the Ministry of Health and Welfare, Japan Society of Medical Technologist, and so on. The results were as follows, 1) computer systems were used on the 85% of all hospitals, and the most of them were used for the medical office work included the payment office. At clinical laboratory, there was very few use the computer systems, which account for 25%. 2) In the field of the clinical laboratory, there was mostly used at clinical chemistry, next field was hematology, serology, urinalysis, and microbiology, respectively. 3) Total system for the hospital, including ordering system were used only 0.06% (208 cases) of all hospitals in Japan. We calculated the number of beds with a hundred thousand population, the spread of the computer system, the number of the out-patients, in-patients, and the utilization ratio of beds, then we compared with that data for all of the prefecture included Tokyo, Osaka and Kyoto. As a result of the calculation, the prefecture which the number of bed with a hundred thousand population was much more than another zone were the utilization ratio of beds was less than another area, and there was worth at the spread of computer system. We think there areas had the smaller hospitals than that of having highly spread of computer system.

Clinical Laboratory Information Systems↗

PubMed1993

[Slow virus infection in the field of obstetrics and gynecology--with special reference to HBV, HTLV-1 and HCV].

The slow virus infection (SVI) established by Gajdusek DC in 1964 has been known to involve not only Kuru or Creutzfeldt-Jakob disease but also hepatitis B virus (HBV) infection and very recently human T-cell lymphotropic virus type 1 (HTLV-1) or hepatitis C virus (HCV) infection. These all viruses potentially develop serious, irreversible disease, ie, hepatoma or adult T-cell leukemia, after long latent periods. HBV, HTLV-1 and HCV can be transmitted vertically from carrier mothers to their offspring, and therefore, are serious SVIs in the field of obstetrics. HB immunoglobulin (HBIG) and HB vaccine have been used clinically for the prevention of HBV vertical transmission (VT) under the guidance of the Ministry of Public Welfare in Japan. This nation-wide trial has much contributed to reducing the development of new carriers. However, the protocol recommended by the Ministry is a bit noncost-effective and troublesome for the patients and physicians. To solve the problem we newly designed our own regimen based on the natural history of HBV VT, the neonatal immune response to the recombinant vaccine and cost-effectiveness, and compared it with the Ministry one. It is not doubt that breast feeding is the most important route for HTLV-1 VT. However, other infectious routes, ie, intrauterine or transvaginal infection, have been recently worth noticing.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Feeding↗

PubMed1993

[The effect of etoposide on ovarian function in patients with gestational trophoblastic disease].

Thirty-four patients with low risk gestational trophoblastic disease were treated with etoposide alone. Within 60 days after treatment, synthetic luteinizing hormone releasing hormone (LH-RH: 100 micrograms) was injected intravenously. The serum concentrations of LH, follicle-stimulating hormone (FSH) before and 30, 60, 120 minutes after LH-RH administration, estradiol (E2) and progesterone were measured. In addition, the basal body temperature (BBT) was taken continuously to evaluate ovulation. (1) The patients aged 40 or more in whom serum LH and FSH levels were higher before LH-RH administration, showed excessive response to LH-RH. These excessive responses were 45.5% and 7.1% in patients in their thirties and twenties, respectively. (2) Serum E2 and progesterone levels decreased with advanced age, which was not affected by total doses of etoposide. (3) Seven (77.8%) patients over 40 years were found to have anovulatory cycles, based on their BBT, and ovulation was confirmed in all the patients under 40 years. (4) Eleven pregnancies were confirmed. Nine delivered apparently healthy infants. The influence of etoposide on ovarian function was transient except for patients over 40 years old.

Adult↗

PubMed1992

Dipyridamole enhances an anti-proliferative effect of interferon in various types of human tumor cells.

The anti-proliferative activity of human interferon (HuIFN) was enhanced by dipyridamole, 2,6-bis-(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]-py rimidine, when tested against various human tumor cell lines, including KT (breast carcinoma), PLC/PRF/5 (hepatoma), MGC-I, U251-SP and T98 (glioma), HAC-2 and SHIN-3 (ovarian carcinoma), and MM-ICB (melanoma). The enhancement occurred irrespective of the kind of HuIFN used (alpha, beta or gamma) and the original degree of susceptibility of the cells to HuIFN. Even low doses down to 0.01 microM of dipyridamole that had no intrinsic anti-proliferative activity could enhance the effect of HuIFN. The enhancement of HuIFN effects seems not to be caused by induction of HuIFN production, because neither anti-viral activity nor HuIFN antigens were detected in culture medium in cells treated with dipyridamole. Mopidamole, a derivative of dipyridamole lacking one piperidine residue, produced little enhancement of the effects of HuIFN. Among ovarian cancer cell lines tested, the enhancement of the activity of HuIFN by dipyridamole for HAC-2 and SHIN-3 cells was equivalent to or greater than that for 3 chemotherapy agents (adriamycin, vincristine, and a camptothecin derivative). However, neither HOC-21 ovarian cancer cells nor HEC-1 endometrial adenocarcinoma cells were susceptible to any combinations. When MGC-1, U251-SP, and HAC-2 cells were injected into nude mice, the growth of tumors was more markedly inhibited by the subcutaneous administration of HuIFN in combination with oral administration of dipyridamole than by the HuIFN alone. Thus, this combination therapy seems to be worth trying for human cancer, although the enhancement of the effects of HuIFN by dipyridamole varied among the cell lines examined.

Animals↗

PubMed1992

CA54/61 as a marker for epithelial ovarian cancer.

Using a new one-step, double-determinant enzyme immunoassay, we performed quantitative measurements of a mucin-type glycoprotein antigen (CA54/61) that we recently detected in sera of ovarian carcinoma patients. When the cutoff value was set at 12 units/ml, at which a high diagnostic efficiency was demonstrated [or at 20 units/ml (mean + 3 SD of healthy females)], the positive rates of ovarian serous, mucinous, clear cell, and endometrioid carcinomas were 76% (or 63%), 63% (or 55%), 57% (or 52%), and 50% (or 38%), respectively. Even in mucinous cystadenocarcinoma, more than one-half of the cases were positive, indicating the potential utility of the assay in the diagnosis of mucinous tumors. In sera from patients with benign ovarian tumors, only 9% (or 4%) of the cases were positive, indicating the quite high specificity of this test for ovarian carcinomas. To make a comparison between CA54/61 and CA125, we set the cutoff level of CA125 at 110 units/ml, at which value a high diagnostic efficiency was demonstrated [or at 35 units/ml (mean + 3 SD of healthy females)]. When both CA54/61 and CA125 were assessed in sera from 36 patients with mucinous cystadenocarcinoma, the positive rates of CA54/61 and CA125 were 64% (or 56%) and 36% (or 56%), respectively, suggesting that CA54/61 is of clinical value as a new tumor marker for ovarian cancers, including mucinous tumors.

Adult↗

PubMed1992

Human chorionic gonadotropin causes an estrogen-mediated induction of rat ovarian carbonyl reductase.

We earlier reported that human chorionic gonadotropin (hCG) stimulates rat ovarian carbonyl reductase (CR) activity and content, and that estrogen enhances the stimulatory effect. The present study was performed to determine the mode of action of the gonadotropin. Cycloheximide (CHX) and actinomycin D (AD) were given to estradiol-pretreated immature rats 6 h before hCG treatment. The enzyme activity was measured with three substrates, and the enzyme content was determined by the method of Western-blot analysis using anti-rat ovarian CR anti-serum as the first antibody. Both protein inhibitors significantly prevented hCG from increasing the enzyme activity and content in estradiol-pretreated ovary. These results indicate that rat ovarian CR is induced by LH via the action of estrogen.

Alcohol Oxidoreductases↗

PubMed1992

The immunohistochemical localization of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in human and cynomolgus monkey placentae.

New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated by avidin-biotin immunoperoxidase technique in the human and cynomolgus monkey placentae, decidua and umbilical cords. In human early placentae, MP2 A, B, C, and E were localized mainly in the membrane of villous syncytiotrophoblasts and cytotrophoblasts. Histiocytes in the villous stroma were positive for MP2 A, B, D, and E. In human term placentae, obvious positive staining for MP2 A, B, C, and E was observed in the membrane of villous syncytiotrophoblasts, in the amniotic epithelium, and in the umbilical cord sheath. Histiocytes in the villous stroma were positive for MP2 A, B, C, E, and especially for MP2 D. Importantly, MP2 A, C, and E were positive in polymorphonuclear neutrophils, since most of these common antigens are also carcinoma-associated, suggesting clinical usage of MP2 proteins as a new tumor marker. In the cynomolgus monkey placentae, similar immuno-staining results were obtained. The monkey can thus serve as a experimental model for the investigation of the placental proteins.

Amnion↗

PubMed1992

[Limonoids in Phellodendron amurense (Kihada)].

Limonoids and their glucosides in the seeds and barks of Phellondendron amurense (Kihada) were analyzed. The seeds contained limonin (1950 ppm), obakunone (20 ppm), limonin 17-beta-D-glucopyranoside (820 ppm) and obakunone 17-beta-D-glucopyranoside (1360 ppm). The barks contained limonin (6760 ppm), obakunone (1240 ppm) and nomilin (270 ppm).

Chromatography, High Pressure Liquid↗

PubMed1992

[Effects of FRG-8813, a new type histamine H2-receptor antagonist, on various experimental gastric and duodenal lesions in rats].

We examined the anti-ulcer effects of FRG-8813, a new type histamine H2-receptor antagonist, on various experimental gastric and duodenal lesions in rats. FRG-8813, administered orally, inhibited the formation of lesions dose-dependently in experimental models with the exception of the Shay ulcer model. The anti-ulcer potency of FRG-8813 was 4 approximately 10 times greater than that of cimetidine when the ED50 values of both compounds were compared. Famotidine and cimetidine inhibited lesion formation at higher doses than the anti-secretory doses. The anti-ulcer action of FRG-8813, however, appeared at even lower doses than those of anti-secretory action. These results suggest that FRG-8813 is able to prevent lesion formation with anti-secretory action plus other mechanisms unlike typical histamine H2-receptor antagonists.

Acetamides↗