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Biomedical subjects

N Ishikawa

Publications and source records attributed to N Ishikawa.

At least 109 records · Page 6Linked to original sources
PubMed2000

Regulation of cellular functions by nucleoside diphosphate kinases in mammals.

The role of nucleoside diphosphate (NDP) kinases in cell growth, differentiation, and tumor metastasis in relation to signal transduction was investigated. The essential role of NDP kinase in cell growth was validated by coupling between reduced NDP kinase levels, induced by antisense oligonucleotides, and the suppression of proliferative activity of a cultured cell line. In addition, because NDP kinase levels are often enhanced with development and differentiation, as has been demonstrated in postmitotic cells and tissues, such as the heart and brain, we further examined this possibility using the bone tissue (osteoblasts) and a cultured cell line PC12D. The enhanced NDP kinase accumulation was demonstrated in the matured osteoblasts in vivo and in vitro by immunohistochemistry. In PC12D cells, neurite outgrowth took place in NDP kinase beta-transfected clones without differentiation inducers, which was accompanied by prolongation of doubling time. Neurite outgrowth, triggered by nerve growth factor and a cyclic AMP analog, was down-regulated upon forced expression of inactive mutant NDP kinase by virtue of a dominant negative effect. NDP kinase alpha-transfected rat mammary adenocarcinoma cells (MTLn3) and nm23-H2-transfected human oral squamous cell carcinoma cells (LMF4) manifested reduced metastatic potential and were associated with an altered sensitivity to environmental factors, such as motility and growth factors. NDP kinase alpha, compared to NDP kinase beta, was involved in a wide variety of the cellular phenomena examined. Taken together, NDP kinase isoforms appear to elicit both their own respective and common effects. They may have an ability to lead cells to both proliferative and differentiated states by modulating responsiveness to environmental factors, but their fate seems to depend on their surrounding milieu.

Amino Acid Sequence↗
PubMed2000

CD4+ T cell-mediated cytotoxicity toward thyrocytes: the importance of Fas/Fas ligand interaction inducing apoptosis of thyrocytes and the inhibitory effect of thyroid-stimulating hormone.

The accumulation of activated CD4+ T cells and antigen (Ag)-dependent cellular interactions between thyrocytes and CD4+ T cells have been determined in thyroid gland from patients with Graves' disease. The Fas/Fas ligand (FasL) interaction between antigen-presenting cells and T cells regulates the apoptosis of the former cells triggered by the latter cells. The inhibition of Fas-mediated apoptosis in thyrocytes could be a underlying mechanism of hyperplasia of thyrocytes in patients with Graves' disease. We investigated the potential role of Fas/FasL interaction between thyrocytes and CD4+ T cells in the induction of Fas-mediated apoptosis of the former cells induced by the latter cells. The presence of only a few specific T cells responsive to a putative autoantigen has hampered the investigation of specific T cell activation toward antigen-presenting cells (APCs). Therefore, we used a superantigen, staphylococcal enterotoxin B (SEB), to examine specific T cell activation toward thyrocytes in vitro since it stimulates a large proportion of T cells with particular Vbeta elements. Spontaneous apoptosis of thyrocytes in culture was not found even in the presence of various kinds of cytokines. In contrast, a clear induction of Fas-mediated apoptosis by anti-Fas IgM was determined in interferon-gamma (IFN-gamma)-stimulated thyrocytes. In addition, a significant cytotoxicity of purified CD4+ T cells toward IFN-gamma-stimulated thyrocytes in the presence of SEB was induced, and the addition of anti-HLA-DR and -DQ monoclonal antibodies (mAbs) or blockade of the Fas/FasL interaction reduced this cytotoxicity. FasL expression of CD4+ T cells cocultured with IFN-gamma-stimulated thyrocytes in the presence of SEB was clearly induced. Furthermore, the addition of mAbs against CD54 and CD58 inhibited both cytotoxicity and FasL expression of CD4+ T cells. The cytotoxicity of CD4+ T cells toward IFN-gamma-stimulated, SEB-pulsed thyrocytes was markedly inhibited when we used thyrocytes cultured with IFN-gamma in the presence of thyroid-stimulating hormone (TSH) as target cells. Our results suggest that 1) CD4+ T cells were activated by thyrocytes expressing MHC class II molecules in an SEB-dependent manner and then expressed FasL. 2) These activated FasL+ CD4+ T cells killed thyrocytes by interacting with Fas on thyrocytes and FasL on activated CD4+ T cells. The presence of costimulating molecules such as CD54 and CD58 on thyrocytes was also necessary to generate activated FasL+ CD4+ T cells. 3) Since the actions of thyroid stimulating antibody (TSAb) toward thyrocytes are similar to those of TSH, one goitrogenic activity of TSAb may, in part, be due to the inhibitory effect on Fas-mediated apoptosis of thyrocytes triggered by activated CD4+ T cells.

Apoptosis↗
PubMed2000

Thyroid function in wholly breast-feeding infants whose mothers take high doses of propylthiouracil.

BACKGROUND: Propylthiouracil (PTU) might theoretically be preferred over methimazole (MMI) during breast-feeding because of its lower milk/serum concentration ratio (0.1 vs. 1.0). The problem is that Graves' disease often relapses during the postpartum period, and high doses of PTU are sometimes needed to control maternal hyperthyroidism) during breast-feeding. However, there are virtually no data on the effects of maternal PTU on thyroid status of infants whose mothers take more than 300 mg PTU daily and who are wholly breast-feeding. OBJECTIVES: To investigate whether mothers can breast-feed without adverse effects on infants' thyroid status while taking 300 mg or more daily of PTU. SUBJECTS AND DESIGN: Eleven infants who were wholly breast-fed while their mothers took PTU 300-750 mg daily for Graves' hyperthyroidism were included in this study. In one of the 11 infants, the mother also took iodine 6 mg daily for a limited period. Thyroid status in these infants was evaluated. MEASUREMENTS: Free T4 (FT4), thyrotrophin (TSH), and TSH binding inhibiting antibody (TBIAb) concentrations were examined at least once in the age range 6 days to 9 months. Maternal blood was also examined for FT4 and TBIAb on the same day, or within a week, of the infants' blood tests. FT4, TSH and TBIAb concentrations at birth were examined, using cord blood, in cases where antithyroid drugs had been continued through delivery. RESULTS: Three of the 11 infants had TSH concentrations higher than the normal range for adults. In one of the three infants, the TSH concentration, which was determined 19 weeks after birth, was just above the normal range. In the remaining two infants whose mothers had taken PTU through delivery, TSH concentrations, determined within 7 days after birth, were distinctly high, but they became normal while maternal PTU doses were the same as or higher than those at the initial examination. Maternal PTU doses or FT4 concentrations were not significantly correlated with infants' TSH concentrations. CONCLUSION: Mothers can breast-feed while taking propylthiouracil at doses as high as 750 mg daily without adverse effects on thyroid status in their infants.

Adult↗
PubMed2000

Plasma levels of granulocyte elastase-alpha1-proteinase inhibitor complex in children with hemolytic uremic syndrome caused by verotoxin-producing Escherichia coli.

BACKGROUND: Activated neutrophils play an important role in the pathogenesis of renal injury in humans and in experimental models of hemolytic uremic syndrome (HUS). To evaluate the clinical significance of the circulating granulocyte elastase-alpha1-proteinase inhibitor complex (GEPIC), which is a marker of neutrophil activation, we investigated the plasma concentrations of GEPIC in children with hemolytic uremic syndrome (HUS) associated with verotoxin-producing Escherichia coli (VTEC), VTEC gastroenteritis without HUS and in normal controls. METHODS: Of 22 children (1-19 years of age; mean age 5.5 years) with VTEC infection, nine were diagnosed with HUS. Plasma GEPIC, soluble thrombomodulin (sTM) and thrombin-antithrombin-III complex (TAT) levels were measured by ELISA. RESULTS: The number of polymorphonuclear leukocytes and the levels of plasma GEPIC in patients with HUS were significantly higher than those in non-HUS (9850+/-5091 vs. 5278+/-3327 /microL, P<0.05; 432.1+/-211.7 vs. 188.3+/-117.0 ng/mL, P<0.01) or control subjects (9850+/-5091 vs. 4728+/-1977 /microL, P<0.05; 432.1+/-211.7 vs. 105.9+/-51.1 ng/mL, P<0.001). Furthermore, plasma GEPIC levels showed a positive correlation with sTM (r = 0.522; P<0.01), a marker of endothelial cell injury, and TAT (r = 0.594; P<0.01), a marker of thrombin activity. CONCLUSIONS: These results suggest that an increase in circulating GEPIC levels in patients with VTEC-associated HUS may be related to endothelial injury, which may possibly lead to a more severe episode of this disease.

Adolescent↗
PubMed2000

Comparison of the depth of the desiccated zone with selected vaporizing-cutting electrodes: a basic study in animals.

OBJECTIVE: To evaluate in an animal model the haemostatic efficacy of vaporizing-cutting (VC) electrodes recently developed for use in high-energy transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Four VC electrodes were assessed for their haemostatic efficacy in the muscle and liver of pigs (in vitro) and dogs (in vivo). The devices tested were the roller-cutting and Vapor Cut (Karl Storz GmbH, Germany); the Wedge (Boston Scientific Corp., Boston, USA); and the Uroloop (Endocare Inc., Irvine, CA). In each the depth of the desiccated zone was compared with that produced by a standard cutting loop electrode. Each electrode was attached to a scanning system (developed previously) that allowed the electrode pressure on the tissue surface (in 3% sorbitol solution) and the running speed to be adjusted. The same generator was used with all devices. The tissue (muscle or liver) was cut by running the electrode over the surface at 200, 250 or 300 W, with the loop electrode used as the reference. After completing the procedure, the surgical wound and the surrounding tissue were dissected out and the depth of the heat-affected zone (HAZ, defined as the desiccated zone) measured. RESULTS: In pig muscle (stroke speed 5 mm/s) there was no significant difference in the depth of the HAZ between the four VC electrodes and the loop, or among the VC electrodes at any of the power levels tested. In pig liver (stroke speed 5 mm/s), the roller cutting and Vapor Cut electrodes produced a thicker HAZ than the loop at all power levels tested (P < 0.01). The Wedge electrode produced a significantly thicker HAZ than the loop at 200 and 300 W (P < 0.01). There were no significant differences in HAZ among the VC electrodes at any power level. In dog muscle in vivo (stroke speed 10 mm/s), the roller cutting, Vapor Cut and Wedge electrodes produced a significantly thicker HAZ at 250 W than the loop at 150 W (the usual power for TURP) (P < 0.01). There was no significant difference among the VC electrodes. In dog liver in vivo (stroke speed 10 mm/s), the roller cutting electrode produced a significantly thicker HAZ at 250 W than the loop at 150 W (P < 0.01). CONCLUSIONS: The present VC electrodes produced a thicker desiccation zone at higher powers (200-300 W) than the standard loop at the usual power (150 W). The four VC electrodes produced a similar desiccation zone. With pig muscle and liver in vitro, regular loops used at a higher power created a desiccation zone that was 70-80% of the depth created by the VC electrodes.

Animals↗
PubMed2000

Removal of anti-A/B antibodies with plasmapheresis in ABO-incompatible kidney transplantation.

Because of a shortage of cadaver donors in Japan, ABO-incompatible living kidney transplantation has been carried out. Sixty-seven ABO-incompatible living kidney transplantations (LKT) were performed between January 1989 and December 1995 at our institution. In our previous report on the long-term results of ABO-incompatible LKT, graft survival of ABO-incompatible LKT up to 3 years was significantly lower than that of ABO-compatible LKT, but no significant difference was seen from 4 to 8 years. We removed anti-A/B antibodies by immunoadsorption and/or double filtration plasmapheresis before kidney transplantation. There was a significant difference between the anti-A/B antibody titers before and after plasmapheresis. The anti-A/B antibody titers also were well suppressed over the long term after transplantation.

ABO Blood-Group System↗
PubMed2000

Is there a place for the late cardioversion of atrial fibrillation? A long-term follow-up study of patients with post-thyrotoxic atrial fibrillation.

AIMS: As atrial fibrillation is associated with significant mortality and morbidity, restoration of sinus rhythm is desirable. However, previous data suggest that cardioversion should be restricted to patients in whom the fibrillation is of limited duration (<1-2 years) because of high relapse rates. It may be the frequent association with cardiac disease, rather than the duration of fibrillation itself, which determined the high relapse of earlier studies. The aim of this study was to investigate rates of cardioversion, maintenance of sinus rhythm and predictors of subsequent relapse in a homogeneous group of patients without evidence of any co-existent cardiac disease. METHODS AND RESULTS: We report on a retrospective series of 106 patients with thyrotoxicosis-induced fibrillation but no other heart disease: 87% had been in atrial fibrillation for >12 months (median duration 28.5, interquartile range 15-47 months). Cardioversion was attempted using disopyramide and then electric shock. Ninety-eight patients were successfully cardioverted: at late follow-up, 80.6+/-37 months (mean+/-SD), 67% were in sinus rhythm. CONCLUSION: Although a relationship between the duration of fibrillation and maintenance of sinus rhythm was found, the high proportion remaining in sinus rhythm, compared with other series, suggests this influence may be less important than the presence or absence of structural heart disease.

Adult↗
PubMed2000

Immunoregulation by aqueous humor.

PURPOSE: The eye is a classic example of an immune-privileged site. To investigate the local defense system of the eye, the immunosuppressive effects of the aqueous humor on cytokine production was examined. METHODS: Using T cell clones (TCCs) established from infiltrating cells in the aqueous humor of patients with human T lymphotropic virus type 1 (HTLV-1) uveitis as target cells and the aqueous humor of patients with senile cataract obtained during cataract surgery, we examined the effects of the aqueous humor on the production of cytokines by HTLV-1-infected TCCs. RESULTS: HTLV-1-infected TCCs produced large amounts of various cytokines. The aqueous humor inhibited the production of cytokines in a dose-dependent manner. The inhibitory activity was heat labile. First protein liquid chromatography showed at least four major peaks of different molecular size, indicating that the aqueous humor contains multiple immunosuppressive factors. Transforming growth factor-beta, alpha-melanocyte-stimulating hormone, and vasoactive intestinal peptide did not suppress cytokine production. The inhibitory activity was neutralized by monoclonal antibody to Fas ligand. CONCLUSION: These data suggest that soluble Fas ligand is a candidate suppressive factor in the aqueous humor.

Aqueous Humor↗
PubMed2000

A case of superior oblique myokymia observed by an image-analysis system.

Superior oblique myokymia is a microtremor of the eye that causes monocular torsional oscillopsia. A modified Harada-Ito procedure was used to treat a case of the disease in a 20-year-old woman. The authors used video-image analysis pre- and postoperatively to evaluate the effect of the surgery on abnormal torsional eye movements. This analysis revealed that before surgery, the abnormal torsional movement had a very regular cycle (duration of attack, 8.0 +/- 0.5 s; time interval between attacks, 18.7 +/- 3.2 s; n = 9). After the surgery, amplitude of the abnormal torsional eye movement was reduced, and the oscillopsia had subjectively improved, although the movement cycle remained unchanged. The authors' video-image analysis, which used iris striation, proved to be a useful method for clinical measurement of torsional eye movements.

Adult↗
PubMed2000

Comparison of metabolic risk factors in patients with recurrent urolithiasis stratified according to age and gender.

OBJECTIVE: Little is known regarding the metabolic features associated with aging and gender in urolithiais patients. We compared the metabolic characteristics among 3 generations (young, middle-aged and old) with recurrent calcium-containing urinary stones. METHODS: One hundred and eighty-one patients with recurrent calcium-containing stones, including 71 patients aged </=45 years (group 1), 71 patients aged 46-60 years (group 2) and 39 patients aged >/=61 years (group 3), were investigated by metabolic evaluation. The frequencies of metabolic abnormalities, the value of each urinary constituent and the supersaturation index (AP(CaOx) index) were compared among subgroups of the 3 generations, containing both males and females. RESULTS: The number of metabolic abnormalities was the greatest in group 1, followed by group 2 and group 3. Hyperoxaluria was the most common abnormality in each group. Group 1 females showed a lower frequency of hypocitraturia than group 3 females. This was the only characteristic that showed a significant difference between the groups. Urinary calcium excretion was significantly greater in group 1 than in group 3. Urinary citrate excretion and the AP(CaOx) index were significantly higher in group 1 than in group 3 in females. Male patients had a significantly higher number of metabolic abnormalities than female patients, especially in group 1. CONCLUSION: Multiple metabolic abnormalities, particularly a high calcium excretion appear to be crucial factors in the development and recurrence of urolithiasis in young patients. Low urinary citrate excretion could play an important role in the occurrence of urolithiasis in elderly females.

Age Factors↗
PubMed2000

Thyrocyte proliferation by cellular adhesion to infiltrating lymphocytes through the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1 pathway in Graves' disease.

Graves' disease (GD) is an autoimmune thyroid disease characterized by infiltration of lymphocytes into the thyroid, and intrathyroid lymphocytes are known to play an important role in the pathogenesis of GD. However, it remains to be understood how lymphocytes adhere to thyrocytes and regulate the thyrocyte function through cellular adhesion. We studied the mechanisms of T cell adhesion to thyrocytes using intrathyroid mononuclear cells (ITMC) and thyrocytes purified from the thyroids of patients with GD. The following novel features of cellular adhesion of ITMC to thyrocytes in the regulation of the thyrocyte function in GD were observed: 1) GD-ITMC expressed lymphocyte function-associated antigen (LFA)-1, which became an active adhesive configuration much higher than peripheral blood mononuclear cells (PBMC) from normal volunteers and GD patients; 2) GD-thyrocytes expressed a high quantity of intercellular adhesion molecule (ICAM)-1; 3) GD-ITMC adhered to GD-thyrocytes, whereas normal PBMC required activation stimuli by phorbol myriacetate, a pharmacological integrin-trigger, to adhere to GD- thyrocytes; 4) monoclonal antibody-blocking studies showed that the adhesion of the activated PBMC and ITMC to thyrocytes was mainly mediated by the LFA-1/ICAM-1 pathway; 5) the adhesion of GD-thyrocytes to the activated-PBMC or ITMC induced the proliferation of the thyrocytes, which was blocked by the addition of ICAM-1 and/or LFA-1 monoclonal antibodies; and 6) in GD thyrocytes of early cultures, ICAM-1 expression on GD-thyrocytes and its adhesion to LFA-1 on phorbol myriacetate-activated PBMC or ITMC were not modulated by the addition of interleukin-1beta or interferon-gamma, and proliferation of thyrocytes by the cellular adhesion via the ICAM-1/LFA-1 pathway was independent of the proliferative response of these cytokines. Taken together, these results suggest that lymphocytes infiltrating GD thyroid induce proliferation of GD-thyrocyte by the cellular adhesion to thyrocytes via ICAM-1/LFA-1, which may lead to the development of a goiter.

Cell Adhesion↗
PubMed2000

4-hydroxynonenal induces a cellular redox status-related activation of the caspase cascade for apoptotic cell death.

4-Hydroxynonenal (HNE), a diffusible product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death. In this study, we partially characterized the mechanism of HNE-mediated cytotoxicity. Incubation of human T lymphoma Jurkat cells with 20-50 microM HNE led to cell death accompanied by DNA fragmentation. Western blot analysis showed that HNE-treatment induced time- and dose-dependent activation of caspase-8, caspase-9 and caspase-3. HNE-induced caspase-3 processing was confirmed by a flow cytometric demonstration of increased catalytic activity on the substrate peptide. HNE treatment also led to remarkable cleavage of poly(ADP-ribose) polymerase (PARP), which was prevented by pretreatment of cells with DEVD-FMK as a caspase-3 inhibitor. The HNE-mediated activation of caspases, cleavage of PARP and DNA fragmentation were blocked by antioxidants cysteine, N-acety-L-cysteine and dithiothreitol, but not by two other HNE-reactive amino acids lysine and histidine, or by cystine, the oxidized form of cysteine. HNE rapidly decreased levels of intracellular reduced glutathione (GSH) and its oxidized form GSSG, and these were also attenuated by the reductants. Coincubation of Jurkat cells with a blocking anti-Fas antibody prevented Fas-induced but not HNE-induced activation of caspase-3. HNE also activated caspase-3 in K562 cells that do not express functional Fas. Our results thereby demonstrate that HNE triggers oxidative stress-linked apoptotic cell death through activation of the caspase cascade. The results also suggest a possible mechanism involving a direct scavenge of intracellular GSH by HNE.

Aldehydes↗