Biomedical subjects

C Takahashi

Publications and source records attributed to C Takahashi.

At least 73 records · Page 4Linked to original sources

PubMed1993

Cytokine regulation of cell-to-cell interactions in lymphokine-activated killer cell cytotoxicity in vitro.

The permanent pancreas carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on pancreas carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon gamma (IFN gamma) and tumour necrosis factor alpha. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1 beta treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFN gamma in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells, but not of LAK cells, with IFN gamma or other cytokines resulted in a decrease of susceptibility for LAK cell cytotoxicity. The decreased susceptibility inversely correlated with HLA-ABC expression on the PCI cells. The collective evidence indicates that, although LAK cell attachment to pancreas carcinoma cells through the LFA-1/ICAM-1 molecule is augmented by IFN gamma, IFN gamma treatment of pancreas carcinoma cells reduces LAK cell cytotoxicity possibly through an increase in HLA-ABC or a regulation of molecules closely associated to HLA-ABC expression.

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PubMed1993

Susceptibility of renal tubular cells to lymphokine-activated killer (LAK) cells: application of culture system using a collagen gel matrix.

Monolayer cultures of renal tubular (hKEC) cells were established. These cells formed empty spheroids after 2-3 weeks of culture in a collagen gel matrix. A subcellular polarity from the apex to basement was induced in these "spheroidal" hKEC cells. The weak expression of laminin at the outer surface was evident on spheroidal but not on monolayered hKEC cells. The regulation of HLA-ABC, DR, and intercellular adhesion molecule-1 (ICAM-1) antigens on hKEC cells in the gel matrix was investigated utilizing digestion of gel matrix by collagenase. Enzymatic digestion of the collagen gel did not significantly affect the surface expression of HLA-ABC and ICAM-1, but reduced HLA-DR expression as shown by flow cytometry. The MHC and ICAM-1 molecules on both spheroid-forming and monolayered hKEC cells were upregulated by adding a supernatant of mixed lymphocyte reaction (MLR) and recombinant human interferon (IFN)-gamma. HLA-DR antigen expression was inconsistently induced on the hKEC cells cultured in collagen gel without MLR supernatant or IFN-gamma. In contrast, no HLA-DR expression was found on monolayered hKEC cells in the absence of MLR supernatant or IFN-gamma. Spheroid-forming hKEC cells, when dispersed by enzymatic digestion, were more susceptible to cytolysis by lymphokine-activated killer (LAK) cells than were the enzymatically dispersed, monolayered cells in the 51Cr-release assay. The LAK cells were seen to migrate into the collagen gel and kill the hKEC cells. Thus, LAK cells may function to favor the acceleration of graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Surface↗

PubMed1993

A case of nodular cutaneous amyloidosis. Amyloid production by infiltrating plasma cells.

We report a solitary nodular form of primary cutaneous amyloidosis due to locally infiltrating plasma cells. An 81-year-old Japanese women presented with a scarlet, dome-shaped 1.5-cm nodule with an irregular surface. Histology showed thick deposits of eosinophilic, oval, and homogeneous bodies in the dermis with mild infiltrates of mononuclear cells. The homogeneous bodies stained positively with periodic acid-Schiff, Congo red, and Yanagihara's Dylon stain, and immunohistochemically with anti-human lambda light-chain antibody. Methylgreen pyronine staining revealed that approximately half of the cellular infiltrates around the vessels were plasma cells. Electron microscopy demonstrated the homogeneous bodies to be amyloid masses, a part of which were in the cytoplasm of the plasma cells. Laboratory examination showed a slight elevation of IgG but no obvious findings suspicious for systemic amyloidosis or gammopathy.

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PubMed1993

A case of xeroderma pigmentosum complementation group F with neurological abnormalities.

We report a 48-year-old Japanese man suffering from xeroderma pigmentosum associated with mental retardation, cerebral atrophy and cerebellar ataxia. Cultured fibroblasts from an unexposed area of skin had reduced DNA repair capacity after UV irradiation, with higher sensitivity to UV than normal cells in colony-forming ability and host cell reactivation using herpes simplex virus. Genetic complementation tests by cell fusion with polyethylene glycol revealed that the patient belonged to group F. He died of bile duct cancer at the age of 50. This is the first report of an XP-F patient with neurological abnormalities.

Brain Diseases↗

PubMed1992

Phosphorylation of the Rex protein of human T-cell leukemia virus type I.

Rex protein, the posttranscriptional regulator of human T-cell leukemia virus type I (HTLV-I), is required for the control of viral structural protein expression and virus replication. Rex is a phosphoprotein found predominantly in the cell nucleolus, whose function is thought to be regulated by its nucleolar localization and phosphorylation. Therefore, we investigated the in vivo phosphorylation of Rex protein in more detail. Phosphorylation of Rex occurred in all HTLV-I-infected cell lines examined in vivo, primarily at serine residues and to a very small extent at threonine residues. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) led to significant but transient enhancement of the incorporation of [32P]orthophosphate into Rex protein. N-terminal truncation of Rex protein abolished TPA-dependent phosphorylation. Chymotryptic digestion of phosphorylated Rex yielded two phosphopeptides. In vivo phosphorylation sites were identified as serine residues 70 and 177 and threonine residue 174. Serine 70 was a TPA-dependent phosphorylation site within a regulatory domain. We have already shown that the protein kinase C inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) specifically blocked accumulation of viral unspliced gag-pol mRNA. Therefore, the phosphorylation at serine 70 may be involved in the regulation of Rex function in response to extracellular stimuli.

Amino Acid Sequence↗

PubMed1992

The antitumor activity and immunosuppressive effects of 5-fluorouracil suppositories in rectal cancer patients.

The antitumor activity and immunological effects of the local administration of 5FU were investigated by determining the tissue concentration of 5FU, histological appearance of the primary tumor, and lymphocyte subsets of the regional lymph nodes in 23 rectal cancer patients. Twelve patients were treated with 5FU suppositories preoperatively, being the 5FU group, while 11 patients were given no preoperative treatment, being the control group. The 5FU concentrations in the primary tumors were higher than those in the regional lymph nodes and appeared to remain high for an extended period. No histological changes peculiar to the 5FU group were observed in the primary tumors. An analysis of the lymphocyte subsets in the pararectal nodes revealed that Leu2a+15- cells, or cytotoxic T lymphocytes, were significantly decreased in numbers in the 5FU group compared to the control group. These results suggest that the local use of 5FU may not only exert an antitumor effect against rectal cancer, but can also cause the suppression of antitumor immunity in the regional lymph nodes.

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PubMed1992

The alterations of norepinephrine and acetylcholine concentrations in immature rat urinary bladder caused by streptozotocin-induced diabetes.

The concentrations of norepinephrine (NE) and acetylcholine (ACh) in the body and base of the bladder were investigated two, four and eight weeks after the administration of streptozotocin to four-week-old rats. At four and eight weeks after following dosage, NE concentrations in the base of the bladder of the diabetic rats were significantly higher than those of control rats. At the two-week diabetic condition, ACh concentrations in both the body and base of the bladder diabetic rats were about two-fold higher than in the respective control levels and remained constant for eight weeks. However, the control rats showed dramatic increase in ACh concentration from two to four weeks after dosage. There was no significant difference in the response of bladder muscle strips to phenylephrine, isoproterenol and ACh in the diabetic vs. control rats throughout the experiment. These observations suggest that the alteration of autonomic nervous system may occur at an early stage of diabetes mellitus in immature rats and that the high concentration of NE in the diabetic bladder base may reflect an adaptive overfunction of the adrenergic system probably to maintain continence. Furthermore, the lack of change in ACh concentration with age in diabetic rats may suggest an impaired development of the cholinergic system.

Acetylcholine↗

PubMed1992

Accelerated rejection of allografted rat liver perfused with anti-ICAM-1 monoclonal antibody.

Infusion of mouse anti-rat ICAM-1 into the portal vein of ACI rat liver graft before transplantation resulted in accelerated rejection by LEW recipients (2.9 +/- 2.5 days), when compared to the ACI liver grafts perfused with either Lactate-Ringer's solution (9.8 +/- 1.3) or anti-human ICAM-1 mAb (9.8 +/- 3.1). Histologic features of anti-rat ICAM-1 perfused grafts were spotty ischemic necrosis, whereas those of control grafts were marked cellular infiltration. These combined survival and histologic data suggest that the accelerated rejection may be mediated by vascular deterioration.

Animals↗

PubMed1992

Interaction of rat lecithin-cholesterol acyltransferase with rat apolipoprotein A-I and with lecithin-cholesterol vesicles.

The interaction of rat plasma lecithin-cholesterol acyltransferase with lecithin-cholesterol vesicles and with rat apo-A-I was studied in comparison with that of human plasma lecithin-cholesterol acyltransferase to clarify the reaction mechanism of rat plasma lecithin-cholesterol acyltransferase. The interaction of both human and rat lecithin-cholesterol acyltransferase with lecithin-cholesterol vesicles was investigated by gel permeation chromatography on Superose 12. Both enzymes had almost the same affinity to the vesicles. The affinity of rat enzyme to rat apo-A-I was stronger than that of human enzyme to human apo-A-I when estimated on the apo-A-I-Sepharose 4B column. When human apo-A-I was added to the human enzyme/vesicle mixture which contained the enzyme-vesicle complex, the enzyme was effectively dissociated from the complex. But when rat apo-A-I was added to the rat enzyme/vesicle mixture, apo-A-I-enzyme-vesicle complex was still recognized by its elution pattern on gel permeation chromatography. This suggests that the mixture of rat enzyme, rat apo-A-I, and vesicles, which are the major components in the rat lecithin-cholesterol acyltransferase reaction, forms a stronger complex than do the components of the human reaction.

Animals↗

PubMed1992

The role of the seminal vesicles and coagulating glands in fertilization in the rat.

To investigate the role of the seminal vesicles (SV) and coagulating glands (CG) in fertilization in the rat, partial resections of the SV (25%--group B), 50%--group C, and 75%--group D) or bilateral resection of the SV alone (100%--group E), or together with the CG (group F) were undertaken. In other groups, bilateral resection of the CG only (group G), or bilateral resection of the CG with ipsilateral SV resection (group H) were performed. A group of sham-operated rats served as controls (group A). There were no significant differences among groups A, B, C and D in the number of fertile rats post-operatively but significant differences were evident in groups E, F, G, H when compared with the control group (P less than 0.01 for all groups). Only the fertile rats were able to form copulatory plugs (CP) post-operatively. Bilateral ligation of the SV ducts was performed in ten fertile rats. Post-operatively, the proportion of fertile rats was decreased significantly (P less than 0.01). Removal of the ligatures resulted in a significant increase (P less than 0.01) in fertility. It was also demonstrated that the addition of rat seminal vesicular secretions (SVS) to epididymal sperm suspensions resulted in a significant decrease (P less than 0.001) in sperm motility. These results suggest that the SV and CG are necessary for fertility in rats, and that one role of SVS is the formation of a CP and not the maintenance of sperm motility.

Animals↗

PubMed1992

Hepatitis C virus in chronic hemodialysis patients with non-A, non-B hepatitis.

Sixteen of 110 hemodialysis (HD) patients fulfilling criteria of non-A, non B hepatitis (NANBH), i.e. alanine aminotransferase (ALT) greater than 50 U/ml in the absence of both serologic markers for acute HBV and HAV infections and clinical evidence of another cause of hepatitis, were tested for the presence of antibodies against hepatitis C virus (anti-HCV) by enzyme immunoassay (Ortho, Diagnostics). All (100%) were anti-HCV-positive. There were 5 patients with a monophasic (M) rise pattern (1 or 2 ALT rises), and 11 cases demonstrated a polyphasic (P) rise elevation pattern (more than 2). The mean ALT value of the M group was 202.3 +/- 209 U/ml and that of the P group was 116.6 +/- 39.1 U/ml. The patients received a mean of 19.1 +/- 16.2 units of packed red cells during the follow-up period (69.9 months). Only 1 patient received no blood transfusion. Six patients had a past HBV infection and 3 became HIV-infected in the course of this study. The high rate of infection of hemodialysis patients with hepatitis C virus in our setting points to the need for improved control measures.

Adult↗

PubMed1992

Surgical repair versus medical treatment of varicocele in the rat: pharmacological manipulation of the varicocelized testicle.

Human chorionic gonadotropin, kallikrein, indomethacin, and hydralazine were administered to different groups of varicocelized rats, while surgical repair of the varicocele was performed in another group of rats. The effects of conservative and surgical treatment on epididymal sperm content and motility, the weights of the testes, epididymis, and male accessory genital glands, and fertility were compared between each group and a sham-treated group of rats. Surgical repair significantly improved all the evaluated parameters and all the conservative regimens, except hydralazine, resulted in a significant improvement in most parameters. Our results indicate that stimulation of the Leydig or/and Sertoli cells of a varicocelized testicle can counteract some of the detrimental consequences of the varicocele itself.

Animals↗

PubMed1991

Phosphorylation and subcellular distribution of calpastatin in human hematopoietic system cells.

Calpastatin is an endogenous inhibitor protein acting specifically on calpain (EC 3.4.22.17; Ca2(+)-dependent cysteine proteinase). The phosphorylation of calpastatin was investigated in human hematopoietic system cell lines. Microheterogeneity of calpastatin was observed, in which 118- and 116-kDa forms were named calpastatin a and b, respectively. The phosphorylation of both calpastatins was identified in all cell lines examined and occurred mainly at serine residues with trace amounts of phosphothreonine in vivo. The incubation of cells with 12-O-tetradecanoylphorbol-13-acetate increased the incorporation of 32P-orthophosphate into calpastatin a. Two-dimensional maps of 32P-labeled phosphopeptide from both calpastatins were identical except for additional minor spots for calpastatin a. [35S]methionine-labeled calpastatins a and b were localized mainly in the cytosol, and only 6% of cellular calpastatins were detected in the membrane fraction. By contrast, more than 30% of the 32P-labeled calpastatins a and b were distributed in the membrane fraction. Thus, the phosphorylation of calpastatin may be involved in regulating the calpain-calpastatin protein kinase system by its subcellular distribution.

Amino Acid Sequence↗

PubMed1991

Cytokine regulation of ICAM-1 expression on human renal tubular epithelial cells in vitro.

Regulation of the intercellular adhesion molecule-1 (ICAM-1) expression on human renal tubular epithelial cells in culture (hKEC-1) was investigated. A large proportion of hKEC-1 cells from the primary cultures expressed the ICAM-1 antigen. Supernatants from mixed lymphocyte reaction (MLR) of both specific and third-party combinations augmented the expression of the ICAM-1 antigen, in a dose-dependent manner. A kinetic study revealed maximal augmentation by MLR supernatant on the first day, with a gradual decrease thereafter. Among several recombinant human cytokines tested, i.e., interferon-gamma, tumor necrosis factor-alpha, interleukin 1 alpha and beta, and IL-4, IFN-gamma, TNF-alpha, and IL-1 alpha/beta were shown to augment the expression of ICAM-1. MLR supernatants and IFN-gamma were more effective in augmenting ICAM expression than TNF-alpha and IL-1 alpha/beta. IFN-gamma upregulated ICAM-1 expression in a dose-dependent manner, and maximal augmentation was achieved on the first day. The MLR supernatants were shown to contain IFN-gamma and TNF-alpha, and the activity of the MLR supernatant was partially inhibited by neutralizing antibody against IFN-gamma. These data suggest that cytokines, especially IFN-gamma, TNF-alpha, and IL-1 alpha/beta, released by T cells and antigen-presenting cells upon recognition of alloantigens upregulate ICAM-1 expression on renal tubular epithelial cells. This may result in an increase in the attachment of graft-infiltrating T cells to the renal tubular cells, by the ICAM-1-LFA-1 interaction.

Antigens, CD↗

PubMed1991

Identification of ICAM-1-positive cells in the nongrafted and transplanted rat kidney--an immunohistochemical and ultrastructural study.

Cellular localization of intercellular adhesion molecule-1 (ICAM-1) in rat nongrafted intact kidneys and in transplanted kidneys was investigated using monoclonal anti-rat ICAM-1, 1A29. The major ICAM-1-positive cells in the nongrafted and isografted kidneys were endothelial cells in the large vessels and intertubular capillaries, as observed using light microscopy. A weak, but specific expression of ICAM-1 antigen was noted in the glomeruli, but the exact localization and cell type were not clearly discernible. In the allograft, the ICAM-1-positive cells found in the nongrafted and isografted kidneys also expressed ICAM-1 antigen. In addition, tubular epithelial cells at the luminal border and some infiltrating cells in the allograft expressed ICAM-1. In the allograft, some graft-infiltrating cells were shown to be lymphocyte function-associated antigen-1(LFA-1)-positive. As the nature of ICAM-1-positive cells in the infiltrates was unclear, we examined ICAM-1-positive cells using immunoelectron microscopy and the direct immunoperoxidase method. Glomerular endothelial cells, podocytes, and Bowman's capsular epithelial cells expressed ICAM-1 antigen in the nongrafted and transplanted kidneys. Among the infiltrating cells in the allograft, the major ICAM-1 positive cells were macrophagelike tissues, and some blastic lymphocytes also expressed ICAM-1. Only rarely did the proximal tubular cells express ICAM-1 antigen at the luminal surfaces in the intact kidney. In the allograft, the proximal, distal, and collecting ductular epithelial cells expressed ICAM-1 at the luminal surface, and in addition, the ICAM-1 antigen was also localized at the basal surfaces of some of the renal proximal tubular epithelial cells. The upregulated ICAM-1 expression in the allograft may accelerate graft rejection by augmenting adhesiveness of LFA-1-positive graft-infiltrating cells.

Animals↗

PubMed1991

Cytotoxic activity of marine algae and a cytotoxic principle of the brown alga Sargassum tortile.

Partition fractions of hexane, CCl4 and CHCl3 from methanolic extracts of marine algae were each examined for cytotoxic activities against cultured P-388 lymphocytic leukemia cells. Cytotoxic activities were found for partition fractions of 21 species of seaweed. Bioactivity-guided fractionation of the CCl4 partition fraction from Sargassum tortile, exhibiting the most prominent activity, afforded dihydroxysargaquinone (1) and sargatriol (2) previously isolated from this alga. The former was evaluated as a cytotoxic principle, and the latter, showing moderate activity, was suggested to be an artifact derived from 1 during the isolation procedure.

Animals↗

PubMed1991

[Upper gastrointestinal tract lesions in rheumatoid arthritis].

We studied the upper gastrointestinal (GI) tract lesions by endoscopy, and evaluated the relationship between the lesions and clinical characteristics in 154 patients with rheumatoid arthritis (RA). Eighty-six (55.8%) had drug-induced ulcers and/or erosions, which were present mostly at the antrum as multiple lesions. A history of gastric ulcer, positive tests for fecal occult blood and progression of anemia were noticed more frequently in the patients with gastric ulcers and/or erosions, compared to those with normal mucosa. Indomethacin and prednisolone (15mg/day) were also used more frequently in the patients with gastric ulcers. Twelve patients showed amyloid depositions in the gastric mucosa, of which 8 patients had gastric ulcers and/or erosions. These results indicate that the incidence of GI tract lesions is significantly high in RA patients and that the endoscopic examination should be performed during the course of RA treatment.

Adult↗

PubMed1990

Endoscopic and manometric study of the cardia in post-gastrectomy patients.

This study was undertaken to clarify the incidence of hiatus hernia and the functional changes in the cardia of post-gastrectomy patients. One hundred and four post-gastrectomy patients and 399 non-gastrectomy patients were selected for endoscopic study, and the diagnosis of hiatus hernia was made by observing the shape of the cardia inside the stomach. A manometric study was also done on 12 patients with gastric carcinoma and 14 patients with gallstones. Hiatus hernia was observed in 37.5 per cent of the post-gastrectomy patients, this incidence being significantly higher than the 19.3 per cent of the non-gastrectomy patients (p less than 0.01). In the latter group alone the incidence of hernia steadily increased with advancing age. In the post-gastrectomy patients, reflux esophagitis and heartburn were observed in 20.2 per cent and 27.9 per cent, respectively. These incidences tended to be higher in the patients with hernia but there were no significant differences. The manometric study revealed that lower esophageal sphincter pressure was significantly decreased after gastrectomy, but not after cholecystectomy.

Aged↗