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Biomedical subjects

S Kishimoto

Publications and source records attributed to S Kishimoto.

At least 163 records · Page 9Linked to original sources
PubMed1992

Chemical modification of fumagillin. II. 6-Amino-6-deoxyfumagillol and its derivatives.

6-Amino-6-deoxyfumagillol (5) was synthesized by reductive amination of 6-oxo-6-deoxyfumagillol (4), which was obtained by oxidation of fumagillol (2). The reduction proceeded stereoselectively by the equatorial attack of hydride and 5 was found to have the same stereochemistry as that of 2. Several derivatives of 5 were prepared and most of them showed anti-angiogenic activity comparable to that of fumagillol derivatives.

Animals↗
PubMed1992

Chemical modification of fumagillin. I. 6-O-acyl, 6-O-sulfonyl, 6-O-alkyl, and 6-O-(N-substituted-carbamoyl)fumagillols.

The hydroxy group of fumagillol (3), a degradation product of fumagillin (1), was acylated, sulfonylated, alkylated or carbamoylated, and the anti-angiogenic activity of the resulting products was examined. These compounds inhibited the angiogenesis induced by basic fibroblast growth factor in the rat corneal micropocket assay and the growth of vascular endothelial cells in vitro. Among them, compound 2 (AGM-1470) was found to show the most potent inhibitory effect on the growth of vascular endothelial cells and was selected from this series as a candidate for further development.

Animals↗
PubMed1992

Facial nerve to facial canal cross-sectional area ratio in children.

The incidence of facial palsy among children is lower than that among adults, and the recovery rate after facial palsy among children is higher than that of adults. To investigate these differences, we compared the cross-sectional area ratio of the facial nerve to that of the facial canal in 26 pediatric temporal bone specimens with that of 10 adult temporal bone specimens. The ratios were 0.31 +/- 0.08, 0.35 +/- 0.10, and 0.18 +/- 0.12, respectively, in the labyrinthine, horizontal, and mastoid segments of pediatric specimens. The ratios for adult specimens were 0.46 +/- 0.07, 0.52 +/- 0.17, and 0.37 +/- 0.04, respectively, in the labyrinthine, horizontal, and mastoid segments. These ratios were all significantly smaller than those for the corresponding segments of the adult specimens (P < .01). The results indicate that in children there is less possibility for entrapment of the facial nerve in the facial canal, and that children require facial nerve decompression less often than adults.

Adult↗
PubMed1992

A raised level of soluble CD8 in bronchoalveolar lavage fluid in summer-type hypersensitivity pneumonitis in Japan.

We used ELISA to measure soluble CD8 (sCD8) in the bronchoalveolar lavage fluid (BALF) and serum of patients with summer-type hypersensitivity pneumonitis (HP). The sCD8 levels in BALF were significantly higher in the patients with summer-type HP, surpassing those found in sarcoidosis and the other pulmonary diseases studied; however, the sCD8 levels in the serum of patients with summer-type HP did not differ from the levels of the healthy controls. The numbers of CD8+ T cells were increased in the BALF of the patients with summer-type HP, and there was a correlation between the sCD8 levels and the concentrations of CD8+ T cells. Gel filtration and polyacrylamide gel electrophoresis of the fluid revealed that the anti-CD8 monoclonal antibody-reactive components in the BALF of patients with pneumonitis corresponded to a protein with a molecular weight of between 52 and 54 kDa. Soluble CD8-rich fraction purified from the BALF of patients with summer-type HP augmented in vitro lymphocytes' proliferative responses stimulated with Cryptococcus neoformans, one of the causative agents for summer-type HP. Our result suggests that soluble CD8 in the BALF may play an important role in the pathogenesis of summer-type HP.

Adult↗
PubMed1992

Acquired T cell specific deficiency other than acquired immunodeficiency syndrome (AIDS).

Evidence of an acquired T cell-specific deficiency distinct from acquired immunodeficiency syndrome (AIDS) in a 63-yr-old Japanese female is provided. Recently, this patients suffered from primary invasive pulmonary aspergillosis. Skin tests to purified protein derivative of tuberculin (PPD) and Aspergillus antigens were negative. Upon admission to our hospital, her lymphocytes were exclusively unresponsive to T cell mitogens (concanavalin A, phytohemagglutinin, and OKT 3). The level of cells defined by monoclonal antibodies (CD1, CD2, CD3, CD4, WT31, and CD5) was less than 3%. In contrast, no decrease in the number of red blood cells, platelets, neutrophils or B cells was apparent. Five years ago, the patient had a normal white blood cell and lymphocyte count. However, over the following 4 yr, she developed lymphopenia. With medication, her pulmonary disease recovered, while lymphopenia still continued. The levels of immunoglobulins, complements and enzyme activities (adenosine deaminase and purine nucleoside phosphorylase) were normal. Moreover, several tests for HIV (ELISA and Western bolt) were negative suggesting that the T cell-specific deficiency was not a congenital immunodeficiency or AIDS but rather a new type of acquired immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Therapeutic effects of oral rebamipide and in combination with cimetidine on experimental gastritis in rats.

The present study evaluated the therapeutic effects of rebamipide alone and in combination with cimetidine on experimental gastritis established by the administration of 5 mM sodium taurocholate (TCA) for 6 months in rats. Morphological and biochemical analyses were performed to determine the effects of rebamipide, administered alone or in combination with cimetidine, on chronic, atrophic and erosive gastritis. Rebamipide and cimetidine were administered to rats as a dietary admixture for 4 weeks after withdrawal of TCA. Rebamipide dose-dependently reduced the total length of the erosion, normalized the mucosal thickness and increased the number of parietal and total cells, and tended to reduce interstitial infiltration of inflammatory cells and proliferation of collagenous fibers. Moreover, histochemical and biochemical studies also showed rebamipide to be effective. Rebamipide increased the PAS-positive mucus and normalized the reduced gastric mucosal SOD activity. The therapeutic effect of rebamipide on the experimental gastritis was enhanced by the combined use of cimetidine. These results suggest that rebamipide has a therapeutic effect on chronic atrophic erosive gastritis induced by TCA, and that the mechanism of the therapeutic effect is partially due to the increase in PAS-positive mucus and gastric mucosal SOD activity. Furthermore, the enhanced effect of the combination therapy of rebamipide with cimetidine was considered to be due to the actions of both cimetidine and rebamipide.

Administration, Oral↗
PubMed1992

Hormonal regulation of vitamin D-binding protein production by a human hepatoma cell line.

Regulation of vitamin D-binding protein production by various hormones was studied in an established human hepatoma cell line, HuH-7. Among all the hormones studied, the maximal production of the binding protein was obtained by an extra-cellular addition of triamcinolone or epidermal growth factor. Cell numbers were not so changed except for the addition of insulin or glucagon. Our data indicate that the protein production may be regulated by insulin, estradiol, triamcinolone, dihydrotestosterone or epidermal growth factor.

Carcinoma, Hepatocellular↗
PubMed1991

Molecular heterogeneity of e antigen polypeptides in sera from carriers of hepatitis B virus.

Hepatitis B e Ag (HBeAg) was isolated from pooled sera of carriers, without abnormalities in liver function, by affinity column chromatography with mAb against HBeAg. HBeAg polypeptide with an estimated molecular size of 20,000 Da (p20e) was detected, in addition to regular HBeAg polypeptides (p17e/p18e). p20e, as well as p17e/p18e, did not bind with mAb against the carboxyl-terminal domain of the C-gene product. p20e disclosed an N-terminal sequence of MQLFHLXLII- (X unknown), whereas p17e had that of SKLXLGXLXGMDIDPXKEFG- (X's unknown). By comparing them with the amino acid sequence encoded by the precore region and C gene of hepatitis B virus DNA, p20e was deduced to possess amino acids 1 to 19 of the precore-region product at the N-terminus, which contains signal sequence and usually removed before the secretion of HBeAg. p17e had amino acids 20 to 29 of the precore-region product that continued to the C-gene product. Inasmuch as p20e was invariably detected in HBeAg preparations from carriers without evidence for liver disease, it would not have been released into the circulation from destructed hepatocytes. HBeAg polypeptide bearing an uncleaved signal sequence would help in further understanding the mechanism of HBeAg secretion.

Amino Acid Sequence↗
PubMed1991

Distribution of neurokinin A-like and neurokinin B-like immunoreactivity in human peripheral tissues.

Using specific radioimmunoassay and immunocytochemistry for neurokinin A (NKA) and neurokinin B (NKB), distribution and localization of the two peptides in human peripheral tissues were studied. Both NKA-like immunoreactivity (NKA-LI) and NKB-like immunoreactivity (NKB-LI) were present in the walls of the gut and gall bladder and in the pancreas. In the gut, the values for NKA-LI were 0.56-35.73 pmol/g wet weight, while those in pancreas and gall bladder were 0.64-0.68 and 0.36 pmol/g wet weight, respectively. The values of NKB-LI were 0.45-2.66 pmol/g wet weight in the gut, 0.93-1.65 pmol/g wet weight in the pancreas, and 0.30 pmol/g wet weight in the gall bladder. The immunocytochemical reactivity to both peptides was localized to ganglia of the submucosal and myenteric nerve plexuses in the gut wall, and to neurons in the muscle layer and mucosa of the gut wall. Weak but positive NKA-LI appeared in nerve cells of the pancreas, while NKB-LI was not detectable in the pancreas. Conversely, in the gall bladder wall, NKA-LI was undetectable while a very faint NKB-LI was found in the muscle layer. The localization of NKA corresponded closely to that of NKB in the tissues although the relative concentrations of the peptides varied from organ to organ.

Digestive System↗
PubMed1991

A comparative trial of LC9018 plus doxorubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer.

The efficacy and safety of intrapleural LC9018 (Yakult Co. Ltd., Tokyo, Japan) with or without doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) were evaluated in a randomized, controlled trial performed in 95 patients with malignant pleural effusions secondary to lung cancer. Seventy-six patients were eligible for the assessment of efficacy. The response rate for treatment with intrapleural doxorubicin plus LC9018 (38 patients) was 73.7%, which was significantly higher than the response rate of 39.5% for the control group treated with doxorubicin alone (38 patients) (P less than 0.01). The LC9018 group also showed a significantly greater improvement in performance status (PS) and symptoms (chest pain, chest discomfort, and anorexia) than the control group (P less than 0.05). A significant prolongation of survival was noticed in the LC9018 group (P less than 0.05). The main side effects of LC9018 were fever and transient hepatic dysfunction, but there were no serious adverse reactions. These results suggest that the intrapleural instillation of LC9018 can be recommended for the treatment of malignant pleural effusions.

Adjuvants, Immunologic↗
PubMed1991

Target-specific innervation by autonomic and sensory nerve fibers in hairy fetal skin transplanted into the anterior eye chamber of adult rat.

Pieces of hairy skin tissue of fetal rat were transplanted into the anterior eye chamber of adult rats. The ability of autonomic and sensory nerve fibers from the host iris to innervate the grafted skin tissue was immunohistochemically and enzyme-histochemically examined using antisera against tyrosine hydroxylase (TH), substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP), and a reaction medium for acetylcholinesterase (AchE). The grafted tissue was successfully implanted and connected with the host iris. Epidermis, dermis, subcutaneous tissue, hairs, hair follicles, sebaceous glands, and piloerector muscles developed in the graft. Two weeks after transplantation, TH-, SP-, and CGRP-immunoreactive fibers were observed in association with the blood vessels in the graft. Four weeks after transplantation, TH-immunoreactive fibers were distributed in the piloerector muscles, whereas SP- and CGRP-immunoreactive fibers were present around the hair follicles. VIP-immunoreactive and AchE-positive fibers were restricted to the host iris at all survival times. These results suggest that the outgrowth of autonomic and sensory nerve fibers from the host iris show target specificity for the grafted skin tissue.

Animals↗
PubMed1991

Restorative effect of neurotropin on maturation of bone marrow cells to IL-2-producing T-cells in aging BALB/c mice.

In a previous paper, we have demonstrated that Neurotropin, a non-protein extract isolated from the inflamed skin of rabbits inoculated with vaccinia virus, restores decreasing immune responses through the recovery of interleukin-2 (IL-2) production in aging BALB/c mice. To clarify the mechanism by which Neurotropin restores IL-2 production, its effect on the recruitment of IL-2-producing T-cells from bone marrow cells was examined using syngenic radiation bone marrow chimeras. Two fundamental lesions in recruiting IL-2-producing T-cells in aging BALB/c mice were demonstrated: (1) a drastic decline of the maturation of bone marrow cells to IL-2-producing T-cells as demonstrated by old----young chimeras; and (2) an environment unable to support bone marrow cell differentiation to IL-2-producing T-cells by young----old chimeras. Neurotropin clearly restored the maturation of bone marrow cells to IL-2-producing T-cells when administered from 13 to 16 month-old mice, whereas the non-complementing environment was not normalized with Neurotropin administration. These results suggest that Neurotropin administration restores IL-2 production through the recovery of the maturation of bone marrow cells to IL-2-producing T-cells, resulting in restoration of in vivo T-cell immune response in aging BALB/c mice.

Adjuvants, Immunologic↗
PubMed1991

Low incidence of Ha-ras oncogene mutations in human epidermal tumors.

Activation of the Ha-ras oncogene by point mutations has been suggested to play a role in animal skin carcinogenesis models. In this study, we investigated the significance of the Ha-ras mutations in human epidermal tumors. DNAs from paraffin-embedded tissues of benign and malignant human epidermal tumors (27 samples from 25 patients) were prepared and examined for point mutations of codons 12, 13 and 61 of Ha-ras gene by polymerase chain reaction and oligonucleotide hybridization. Only one sample of basal cell carcinoma and one sample of keratoacanthoma were found to carry an A to T transversion at the second position of codon 61. This low incidence of Ha-ras mutations suggests that the mutational activation of the gene may not be primarily involved in human epidermal tumorigenesis.

Adult↗
PubMed1991

Anteriorly based pericranial flap: an anatomic study of feeding arteries.

The purpose of this study was to obtain anatomic data on the branching levels of the deep branches of the supraorbital artery (SoA) and of the supratrochlear artery (StA) in pericranial flaps. Ten preserved cadavers were used for this study. Each vessel was identified on 12 sides. The deep branch of the SoA had a larger caliber than that of the StA in seven of nine sides. The branching level of the deep branch of the SoA was cephalad to that of the StA on six of nine sides. The deep branch of the SoA diverged shortly after emerging from the supraorbital foramen or notch. However, there were a few cases in which the branch originated at a distance of a few millimeters before or after the foramen or notch. From a practical standpoint, dissection of this pericranial flap below the level of the supraorbital ridge is not advised, and preservation of both feeding arteries is encouraged in order to establish abundant vascularity for this flap.

Journal Article↗
PubMed1991

Characterization and purification of an immunosuppressive factor produced by a small cell lung cancer cell line.

The present study was undertaken to determine whether small cell lung cancer (SCLC) cell lines produce immunosuppressive factors and, if they do, to characterize the factors. The supernatants of SCLC cell lines, H69 and N857, inhibited not only the blastogenic response of human peripheral blood lymphocytes (PBL) to phytohemagglutinin or concanavalin A, but also the cytotoxic activity of lymphokine-activated killer cells. Neither was inhibited by supernatants from non-SCLC cell lines PC9, QG56, and A549. The immunosuppressive activity of H69 supernatant was stable upon heating to 56 degrees C for 60 min, but labile when heated to 70 degrees C for 10 min. The activity was abolished after dialysis at pH 2.0 or pH 11.0, but not at pH 4.5 or pH 9.0. Digestion with trypsin or proteinase eliminated the immunosuppressive activity, whereas treatment with neuraminidase, mixed glycosidase, DNase or RNase had no effect, suggesting that the immunosuppressive activity in H69 supernatant is due to a protein factor. This H69-derived immunosuppressive factor was isolated by ion exchange chromatography using a gradient of 0.04 to 0.08 M NaCl solution. Gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the factor to have molecular weights of 98 kD and 102 kD, respectively. These results suggest that SCLC cells produce a potent immunosuppressive factor which may account for the immune deficiency in SCLC patients.

Carcinoma, Small Cell↗