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Biomedical subjects

T Kitagawa

Publications and source records attributed to T Kitagawa.

At least 451 records · Page 25Linked to original sources
PubMed1988

External ATP-induced passive permeability change and cell lysis of cultured transformed cells: action in serum-containing growth media.

External ATP causes a marked increase in the passive permeability to phosphorylated metabolites in several types of transformed cells in alkaline medium containing low concentrations of Ca2+, but not in untransformed cells. Such increased membrane permeability with external ATP was also observed in B16 melanoma cells at pH 7.4-7.5 in both Tris-buffered saline and a growth medium containing 10% calf serum and divalent ions at normal concentrations, although a higher concentration of ATP was required. The permeability change in the growth medium was significantly enhanced by calmodulin-interacting drugs, such as trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) and chlorpromazine (CPZ). As expected, prolonged exposure of the cells to ATP in the serum-containing medium led to cell lysis. This ATP-dependent cell lysis was observed only in several transformed cell lines, and not in untransformed mouse fibroblasts. These results indicate that the effect of ATP on the membrane permeability in transformed cells is elicited under the physiological conditions and this would be useful in some limited way for cancer chemotherapy management.

Adenosine Triphosphate↗
PubMed1988

The use of N-[beta-(4-diazophenyl)ethyl]maleimide as a coupling agent in the preparation of enzyme-antibody conjugates.

The present study was undertaken to develop a novel method for the enzyme labeling of antibodies. Goat anti-rabbit IgG was used as a prototype and coupled to beta-D-galactosidase (Gal) with a new heterobifunctional cross-linking agent N-[beta-(4-diazophenyl)ethyl]maleimide (DPEM). The antibody was first azo-coupled with DPEM to introduce the maleimide groups into the molecule; excess reagent was removed by gel filtration and then the activated antibodies were crosslinked to the thiol groups of Gal. The conjugates were purified by DEAE-cellulose column chromatography, being completely separated from non-reacted antibodies but remaining mixed with free Gal, and showing approximately 30% enzyme activity bound to antibody. This method is simple, reproducible and so mild that almost full enzyme and antibody activity can be retained. The conjugates were used as a label in an immunoassay and were able to detect first antibody at concentrations as low as 2 ng/tube. Furthermore, the present method was compared with the method using N-(gamma-maleimidobutyryloxy)succinimide (GMBS), and it was found that both conjugates produced comparable results.

Animals↗
PubMed1988

Immunohistochemical distribution of S-100 protein in tumors and tumor-like lesions of bone and cartilage.

Various tumors and tumor-like lesions of bone and cartilage were examined for S-100 protein using the avidine-biotin-peroxidase complex (ABC) immunostaining method. The most intense reactivity for S-100 protein was found in well-differentiated chondrocytes of enchondromas, osteochondromas and chondrosarcomas, and in normal epiphyseal cartilage. S-100 protein was positive in both polygonal stromal cells and chondrocytes of chondroblastomas and in chondrocytes of mesenchymal chondrosarcoma. In osteosarcomas not only chondroblastic areas but also osteoblastic areas showed positive cells. Reticulum histiocytic cells of eosinophilic granulomas and chordoma cells were positive for S-100 protein. The study yielded three main conclusions: (1) S-100 protein could be the marker for tumors of cartilaginous origin and differentiation, notochord origin, and T-zone histiocyte origin; (2) chondroblastoma can be distinguished from other histologically confusing giant cell lesions by using ABC to detect S-100 protein; and (3) S-100 protein has some relationship with tumoral calcification not only in cartilaginous tumors but also in osteosarcoma.

Bone Diseases↗
PubMed1988

Lessons learned from the Japanese nephritis screening study.

A program of urine screening for asymptomatic hematuria and proteinuria in school children has been conducted since 1973 by the Ministry of Education in Japan with great success in the early detection of asymptomatic renal disease. In order to know whether this nationwide program during 13 years has contributed to understanding of the epidemiology of chronic glomerular disease in Japan, a multicenter survey of the patients was conducted. Between 70% and 80% of IgA and non-IgA mesangial proliferative glomerulonephritis and 65%-80% of membrano-proliferative glomerulonephritis (MPGN) were detected by mass urine screening at school. Severe glomerular lesions were more frequently observed in children with chance proteinuria and hematuria, as well as IgA and non-IgA mesangial proliferative glomerulonephritis with significant proteinuria. Mild glomerular change was more frequent in patients with MPGN, IgA and non-IgA mesangial proliferative nephritis with minimal proteinuria who were detected by our screening program, rather than those seen with some of the nephritic signs and symptoms at diagnosis. The above evidence suggests that a screening program may open the way for the early management of these diseases, especially where treatment is already established.

Child↗
PubMed1988

Radiation therapy for advanced gastric cancer.

A retrospective study of 75 patients with advanced inoperable gastric cancers, referred to the National Cancer Center Hospital between 1962 and 1982, was performed. According to the Borrmann classification based on X ray findings, Type 1 was found in 3 patients, Type 2 in 5, Type 3 in 40, and Type 4 in 15. Twelve patients could not be classified. The histological type was papillary adenocarcinoma in 7 patients, tubular adenocarcinoma in 23, mucinous carcinoma in 6, poorly differentiated adenocarcinoma in 14, signet ring cell carcinoma in 12 and others in 13. The site of remote metastasis in 19 patients was Virchow's lymph node in 8 patients, Douglas pouch in 3, liver and lung in 2 each and others in 4. All patients were treated by a either telecobalt 60 unit or a linear accelerator using 6 Mv photon and the total dose to primary lesion was 4000 cGy in 5 weeks to 7000 cGy in 8-9 weeks. Complete response (CR) was achieved in 6 patients or 8.0%, partial response (PR) in 46 or 61.3%, and no change (NC) in 23 or 30.7%. The response rate based on the sum of CR and PR was about 70%. The 50% survival period in months was 26.5, 7.3, and 3.2, respectively for patients with CR, PR, and NC. For the response of advanced gastric cancer to chemotherapy in the National Cancer Center Hospital, the combined use of UFT and Mitomycin C gave the highest rate, 46%. As for as local response is concerned, the response rate to radiation was 70%, a better result than that of chemotherapy alone.

Adenocarcinoma↗
PubMed1988

Microleiomyomas of human stomach.

The incidence and distribution of microleiomyomas occurring in human stomachs were investigated in a sample of 286 resected stomachs examined by a whole organ stepwise cutting method. Seventy-two micromyomatous lesions were found in 47 cases (16.4%), without any sexual predilection. Almost all lesions (94.4%) were less than 5 mm in diameter, the rest being in the range of 6 to 10 mm. Multiple lesions were found in 18 cases (38.3%). Histologically they were all benign leiomyomas. All 72 micromyomas were located in the upper half of the stomach; 22 (30.6%) were concentrated at the esophago-gastric junction. The predisposed site for micromyoma development exactly coincided with that area bearing an inner oblique muscle layer. The incidence of microleiomyoma was much lower, 2.2% (26/1,208), when specimens obtained by lower partial gastrectomy were studied for comparison. This indicated that variation in material investigated may be an important factor underlying the large discrepancies noted in previous reports concerning the incidence of microleiomyomas of the stomach.

Age Factors↗
PubMed1988

Distinct antitumor mechanisms of recombinant murine interferon-gamma against two murine tumor models.

The antitumor activity of recombinant murine interferon-gamma (rMuIFN-gamma) against B16 melanoma and EL4 thymoma, which display different sensitivities in in vitro tests, was studied. In antiproliferation tests, B16 cells were highly sensitive to rMuIFN-gamma and growth was markedly inhibited at as low as 10 U/ml, whereas EL4 cells resisted treatment even at concentration as high as 10(4) U/ml. One of these two tumors was inoculated i.d. into C57BL/6 mice and then rMuIFN-gamma (10(4) units) was repeatedly injected s.c. starting 1 day after the tumor inoculation. For the B16-bearing mice, tumor growth was markedly suppressed and the mean survival period was prolonged, but cured mice were not observed. For mice bearing EL4 cells, the therapeutic effects were more pronounced and cured mice were observed. The EL4-cured mice showed in vivo protective immunity against EL4 tumors but not against P815 tumors, indicating tumor specificity. Histologically, a large number of lymphocytes had infiltrated the necrotic tumor mass. These results indicated that rMuIFN-gamma may have not only a direct effect but also an indirect effect in host-mediated murine response on the growth of murine tumor cells under in vivo conditions.

Animals↗
PubMed1988

Differential efficacies of recombinant murine interferon-gamma and recombinant human interleukin 2 against EL4-bearing mice.

The effects of treating tumor-bearing mice with recombinant murine interferon-gamma (rMuIFN-gamma) and recombinant human interleukin-2 (rIL2) were compared using EL4 thymoma with the same mouse model. Successive administration of rMuIFN-gamma (10(4) units) starting 1 day after tumor inoculation was highly effective, while rIL2 (5 x 10(4) Jurkat units) starting 7 days later produced potent suppression of tumor growth leading to complete cure in about 50% of the mice treated with either of two agents. These results showed that the effectiveness of these lymphokines differed depending on the time of their administration. Furthermore, the therapeutic effect of rIL2 against tumor-bearing mouse was poorer in T-cell-deficient nude mice than in B6 mice and NK-cell-deficient beige mice, whereas the effect of rMuIFN-gamma was poorer in beige mice than in B6 and nude mice. These results suggest that the role of NK cells in the tumor regression caused by the treatment of rMuIFN-gamma is much more important than that of other activated lymphocytes, and that the antitumor activity of rIL2 may be due to the generation of T-cell-related lymphocytes. Our results reveal that combination therapy with rMuIFN-gamma and rIL2 can induce a synergistic effect on EL4-bearing mice.

Animals↗
PubMed1988

Structural characterization of fibroblast human interferon-beta 1.

The complete amino acid sequence of fibroblast human interferon-beta 1 (IFN-beta 1) was determined, and the higher-order structure of the protein was characterized with Raman spectroscopy. That amino acid sequence was identical to the entire sequence deduced from the cDNA nucleotide sequence, showing there are no proteolytic cleavages of carboxy-terminal residues in contrast to natural human IFN-alpha and natural human IFN-gamma. The N-glycosylation site was confirmed as Asn-80 by the detection of glucosamines in the peptide containing Asn-80. An S-carboxymethyl Cys-17 was detected in the S-carboxymethylated protein, suggesting that Cys-17 is unpaired. Raman spectra indicated a predominance of alpha-helical backbone and three Cys residues in this protein form, one unpaired Cys residue and one disulfide bond. These results provide some evidence for the primary and higher-order structures of natural IFN-beta 1 so far predicted.

Amino Acid Sequence↗
PubMed1988

Intramucosal cysts of the stomach. VIII: Histochemical studies.

Intramucosal cysts of the human stomach have been earlier classified on the basis of their epithelial lining into 1. fundic, 2. foveolar, 3. pyloric, 4. with intestinal metaplasia and 5. with ciliated metaplasia. Four histochemical methods (high iron diamine (HID)-Alcian blue pH 2.5 (AB), PAS, Concanavalin A (ConA), and Grimelius reaction were used. The cells of foveolar cysts contained neutral mucins and sialomucins, and those of pyloric cysts, neutral mucins, sialomucins, mannose-rich glycoprotein and argyrophilic material. The goblet cells in intestinal metaplastic cysts contained neutral mucins and sialomucins as well as sulphated mucins, while ciliated cells in ciliated metaplastic cysts demonstrated mannose-rich glycoproteins and argyrophilic material (although some ciliated cells were negative for both). The cells of fundic gland cysts were negative for all tested methods. The frequency of intramucosal gastric cysts is known to be high in stomachs having adenocarcinoma, and low in stomachs with peptic ulcers. Several reports have demonstrated alterations in the composition of gastric mucins in stomachs harbouring an adenocarcinoma. Consequently, the histochemical stains may prove of value to investigate the true significance of intramucosal cysts in gastric carcinogenesis.

Adenoma↗
PubMed1988

Analysis of blood spot 17 alpha-hydroxyprogesterone concentration in neonates.

Blood spot 17 alpha-hydroxyprogesterone (17-OHP) concentrations were measured in 515 infants aged from the 4th to the 81st day of life, using a fluorescence enzyme immunoassay method, and the values obtained were analyzed with respect to birth weight, gestational age at birth and sampling age, to obtain accurate reference ranges and to decide appropriate cut-off limits in a neonatal mass screening for steroid 21-hydroxylase deficiency. The results obtained indicate that the blood spot 17-OHP values in neonates should be interpreted using several different reference ranges obtained on the basis of the equivalent age of gestation at blood sampling. In the mass screening, therefore, the cut-off limits for recall are decided by these reference ranges as follows: (1) for blood resampling, 120, 30 and 25 nmol/l for the equivalent sampling ages of 31 weeks or less, 32-41 weeks and 42 weeks or more, respectively, and (2) for rapid confirmation of the disease by means of physical and laboratory examinations, 210, 60 and 60 nmol/l, respectively.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Analytical studies on beta-lactam antibiotics. II. Displacement effect of beta-lactam antibiotics on bilirubin bound to human serum albumin.

We established a method for determining the KD value as a measure of the bilirubin-displacing effect for drugs by using bilirubin oxidase, which is produced by Myrothecium verrucaria MT-1. This method makes it possible to conduct measurements of many beta-lactam antibiotics, including those which could not be determined by Brodersen's method. The KD values of latamoxef reported by many investigators based on Brodersen's method were higher than the true value owing to interaction of the drug with peroxidase and H2O2. Our KD value under the new enzyme conditions was 2.6 X 10(3). Little or no interaction of drug with the enzyme system was tentatively confirmed. Flomoxef, a newly developed drug, and 7432-S, under development in our company, had KD values of 0.4 X 10(3) and 2.8 X 10(3), respectively.

Anti-Bacterial Agents↗