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Biomedical subjects

M Ishii

Publications and source records attributed to M Ishii.

At least 145 records · Page 8Linked to original sources
PubMed2000

Effects of collateral vessel occlusion on oral glucose tolerance test in liver cirrhosis.

Alterations in carbohydrate metabolism associated with liver cirrhosis are characterized by a high serum insulin level and prolonged hyperglycemia on oral glucose tolerance test (OGTT). We measured plasma glucose, immunoreactive insulin (IRI), and C-peptide immunoreactivity (CPR) levels during a 75-g OGTT before and after varices obliteration in 10 cirrhotic patients with gastric varices. After obliteration, the indocyanine green retention rate was decreased and the portal flow velocity was increased. A significant decline in plasma glucose and IRI levels was also noted on OGTT. Moreover, the plasma glucose and IRI levels declined at 90 and 120 min in OGTT while they increased progressively by 120 min before obliteration. The levels of CPR were similar before and after treatment. These results indicate that decreased portal flow due to extrahepatic shunt and consequent impairment of insulin metabolism play a role in glucose intolerance observed in cirrhotic patients and that shunt occlusion improves glucose metabolism.

Adult↗
PubMed2000

Granulomatous slack skin: successful treatment with recombinant interferon-gamma.

Granulomatous slack skin is a rare variant of indolent cutaneous lymphoma, characterized by a cutis laxa-like clinical appearance and widespread granulomatous infiltration. A 25-year-old man had suffered from slowly progressive infiltrative, scaly and atrophic plaques and flaccid nodules with deep induration in the axillae, trunk and thighs. Histopathologically, dense lymphoid cell infiltration with numerous multinucleated giant cells (MGC) throughout the dermis to the subcutaneous tissue was observed. T-cell receptor gene rearrangement was detected in the skin lesions. Granulomatous infiltration with MGC was found in enlarged lymph nodes and the liver. Acute exacerbation was successfully treated with systemic recombinant interferon-gamma.

Adult↗
PubMed2000

Interleukin 4 receptor alpha chain polymorphism Gln551Arg is associated with adult atopic dermatitis in Japan.

Localization of a locus for atopy to chromosome 16p12-p11 and reported associations of Ile50Val and Gln551Arg polymorphisms in interleukin-4 receptor alpha chain (IL 4R gene) with atopy prompted us to sequence the gene in 27 adult atopic dermatitis (AD) and 29 non-atopic (non-AD) subjects. Among six known polymorphisms, Gln551Arg was significantly associated with AD (P = 0.01). This polymorphism was found to be heterozygous in six of 27 patients with AD but none of the 28 non-AD controls. Ile50Val, which was previously reported to be associated with atopic asthma in Japan, showed no association with AD in our group. Glu375Ala and Cys406Arg also showed no association with AD. The IL 4R gene should thus be considered a compelling candidate gene for AD.

Adolescent↗
PubMed2000

Combined cutaneous hamartoma encompassing benign melanocytic naevus, vellus hair cyst and epidermoid cyst.

We describe a combined cutaneous hamartoma in a 57-year-old man, which comprised a vellus hair cyst, an epidermoid cyst and an intradermal melanocytic naevus in a single facial tumour. The vellus hair cyst was filled with keratinous material with unusual slit-like lacunae. While numerous cases of epidermoid cyst have been reported in association with an intradermal melanocytic naevus, our case is a rare example of a lesion combining several hamartomatous elements.

Cysts↗
PubMed2000

Chemotherapy-induced acral erythema: report of a case and immunohistochemical findings.

Chemotherapy-induced acral erythema (CAE) is an uncommon and distinct reaction seen in patients receiving high-dose chemotherapy. The exact pathogenic mechanisms of this disorder are still unknown. We report a 27-year-old woman who presented with red, swollen and painful macules on both palms, clinically consistent with this disease. Histological examination demonstrated vacuolar degeneration of the basal cell layer and spongiotic blisters in the epidermis, especially in the atrophied eccrine ducts and papillary oedema with mild perivascular infiltration of mononuclear and hypersegmented neutrophils. Immunohistochemistry showed that the infiltrating mononuclear cells were CD3-CD16+CD56+ leucocyte function antigen-1+, possibly natural killer cells. The eccrine ducts expressed HLA-DR and intracellular adhesion molecule-1 (ICAM-1). Our findings suggest that cell-to-cell interaction between NK cells and keratinocytes in the eccrine apparatus may induce CAE and may be involved in the pathogenesis of the skin reaction in our patient and possibly in this disease.

Adrenal Cortex Hormones↗
PubMed2000

Suppressive effects of cyclosporin A and FK-506 on superoxide generation in human polymorphonuclear leukocytes primed by tumor necrosis factor alpha.

Most previous studies have found no effects of cyclosporin A and FK-506 on active oxygen generation in human polymorphonuclear leukocytes. Recently various differences in biologic properties have been reported between unprimed peripheral blood human polymorphonuclear leukocytes and tissue or primed human polymorphonuclear leukocytes. In this study, we investigated the effects of cyclosporin A and FK-506 on superoxide (O(2)(-)) generation induced by the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine in human peripheral blood polymorphonuclear leukocytes primed or unprimed with tumor necrosis factor alpha. Neither cyclosporin A nor FK-506 suppressed N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced O(2)(-) generation in unprimed human polymorphonuclear leukocytes at concentrations between 0.1 nM and 10 microM, as in previous studies. Only at 1 microM of cyclosporin A and 100 nM of FK-506 were marginal suppressive effects observed. On the other hand, cyclosporin A and FK-506 both suppressed N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced O(2)(-) generation in tumor-necrosis-factor-alpha-primed human polymorphonuclear leukocytes, strongly and dose dependently, at concentrations between 1 nM and 1 microM. Neither cyclosporin A nor FK-506 influenced tyrosyl phosphorylation of 115 kDa protein, which is inducible during the priming process, suggesting that neither cyclosporin A nor FK-506 influenced the tumor-necrosis-factor-alpha-induced priming process itself, and instead modified the biologic response of primed human polymorphonuclear leukocytes.

Cyclosporine↗
PubMed2000

Fas-mediated cholangiopathy in the murine model of graft versus host disease.

Bile-duct injury observed in hepatic graft versus host disease (GVHD) is regarded as an immune-mediated injury, although its precise mechanism is unclear. However, recent studies have suggested the involvement of Fas-mediated cell death in this immune-mediated cholangiopathy. In this study, we first showed the constitutive expression of Fas receptor by cholangiocytes in situ from normal BALB/c mice, which was upregulated in GVHD mice. Also, we confirmed the Fas protein expression in the isolated cholangiocytes from normal BALB/c mice by immunocytochemistry and immunoblotting. Furthermore, the addition of agonistic Fas antibody-(Jo2)-induced cholangiocyte apoptosis confirmed by DNA-ladder formation and annexin V staining. Cholangiocytes from Fas-deficient mice (MRL lpr/lpr) did not show Jo2-induced apoptosis. Interferon-gamma augmented Fas expression and Fas-mediated cell death, respectively. Following these observations, experimental GVHD was induced by transfer of splenocytes from B10.D2 mice to irradiated (800 rad) BALB/c mice. Liver-infiltrating lymphocytes from the recipient showed dose-dependent cytotoxicity against (51)Cr-labeled cholangiocytes isolated from BALB/c mice. Moreover, the addition of blocking Fas-Fc fusion protein reduced this cytotoxicity to 44.7%. Finally, administration of this Fas-Fc protein to the BALB/c mice, which had been adoptively transferred with splenocytes of B10.D2 mice, prevented the development of hepatic GVHD in vivo. These results showed the involvement of Fas-mediated cell death in cholangiopathy observed in GVHD, and a soluble Fas-Fc protein may have a therapeutic potential for hepatic GVHD.

Animals↗
PubMed2000

Incidence of cleft lip or palate in 303738 Japanese babies born between 1994 and 1995.

To investigate the incidence of cleft lip or palate or both (CLP) in Japan, 303738 babies born in 1532 institutions between 1994 and 1995 were examined and 437 (0.14%) were found to have abnormalities. Of these babies, 32.1% had cleft lip, 43.3% had cleft lip and palate, and 24.8% had cleft palate (Table 2). These results show that the incidence of cleft lip and palate has declined compared with the period from 1981 to 1982.

Cleft Lip↗
PubMed2000

Synchronous development of disseminated superficial porokeratosis and hepatitis C virus-related hepatocellular carcinoma.

Immunosuppression and transplantation have been reported to induce porokeratosis (PK), especially its variant, disseminated superficial PK (DSP). On the other hand, there is ample evidence of a relationship between hepatitis C virus (HCV) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). We report 3 cases of DSP in which the outbreak of DSP was suspected to have occurred during the development of HCC in patients with HCV-positive LC. The patients had undergone ultrasonographic study regularly, and no signs of malignancy had been found before the development of DSP. Their outbreaks of DSP were very acute, and the period between the development of DSP and diagnosis of HCC ranged from 2 to 6 months. The association of HCV-related HCC and DSP has never been previously reported. HCV-induced immunomodulation or its effect on the p53 system may be the basis for this type of association. It is necessary to consider development of HCC whenever DSP is found in HCV-positive patients. DSP may be a new paraneoplastic dermadrome.

Aged↗
PubMed2000

Catheter interventional treatment in Kawasaki disease: A report from the Japanese Pediatric Interventional Cardiology Investigation group.

OBJECTIVE: To assess the current status of catheter intervention in Kawasaki disease and to evaluate its efficacy and outcome. STUDY DESIGN: A questionnaire was sent to 55 major institutions in Japan. RESULTS: A total of 58 procedures in 57 patients were reported. The median age at the time of intervention was 12.1 years. The procedures included percutaneous transluminal coronary angioplasty (PTCA; n = 34), percutaneous transluminal coronary rotational ablation (PTCRA; n = 13), directional coronary atherectomy (DCA; n = 4), and stent implantation (n = 7). The immediate success rate was 74% for PTCA, 100% for PTCRA, 100% for DCA, and 86% for stents. The interval from the onset of disease to intervention in successful PTCA (n = 25) was significantly shorter than that in unsuccessful PTCA (n = 9). Restenosis after PTCA was observed in 24%. Development of new coronary aneurysms was reported in 3 patients for PTCA, 2 for PTCRA, 3 for DCA, and 1 for stents. Except for the DCA, all new aneurysms were associated with the use of high-pressure balloon inflation. Two deaths were reported as acute complications. CONCLUSIONS: Catheter intervention is a promising therapeutic strategy in the management of coronary stenosis caused by Kawasaki disease. Care should be paid to avoid acute coronary arterial complications and the development of new coronary aneurysms.

Adolescent↗
PubMed2000

Growth inhibitory effect of a new camptothecin analog, DX-8951f, on various drug-resistant sublines including BCRP-mediated camptothecin derivative-resistant variants derived from the human lung cancer cell line PC-6.

DX-8951f, a new water-soluble camptothecin (CPT) derivative, has been reported to show potent antitumor effects against various tumors in vitro and in vivo. We further evaluated the cytotoxic effect of DX-8951f against eight drug-resistant sublines derived by stepwise exposure of human oat cell carcinoma PC-6 to various drugs. In paclitaxel-, adriamycin-, vincristine- and etoposide-resistant cells, overexpression of P-glycoprotein (P-gp) and a correlative reduction in drug accumulation and typical drug-sensitivity pattern were confirmed. The etoposide-resistant line with the highest P-gp level was cross-resistant also to SN-38, CPT-11 and topotecan (TPT), but not to 9-aminocamptothecin (9-AC), CPT and DX-8951f. SN-38- and CPT-11-resistant cells, of which topoisomerase I activities and levels were similar to those of the parent cells, showed cross-resistance clearly to TPT, 9-AC and mitoxantrone, but hardly to DX-8951f. In these two resistant sublines, the intracellular topotecan level was significantly lower than that in parental PC-6 and the reduced accumulation was found to be mediated by breast cancer resistant protein (BCRP). The cisplatin-resistant variant, which had a 2-fold increase in glutathione content, showed no cross-resistance and the 5-fluorouracil-resistant variant, which had a 50% decrease in glutathione content, exhibited collateral sensitivity to most of the other anticancer agents including DX-8951f. We concluded that DX-8951f showed a potent cytotoxic effect on various types of drug-resistant cells.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. South Tohoku District Study Group.

OBJECTIVE: We evaluated the measurements of serum alpha-fetoprotein (AFP) and the protein induced by vitamin K absence (PIVKA-II) in 734 patients with chronic hepatitis (CH) and liver cirrhosis (LC) who had been followed-up for the development of hepatocellular carcinoma (HCC). METHODS: Serum AFP and PIVKA-II were measured every month and abdominal ultrasonography was performed every 3 months. Youden's index (sensitivity + specificity -1) was calculated. RESULTS: On an average follow-up period of 374.5 days, HCC was detected in three HBsAg-positive LC patients (10.0%/yr), four anti-HCV-positive CH patients (1.35%/yr), 21 anti-HCV-positive LC patients (7.8%/yr), and one patient with both HBsAg- and anti-HCV-positive LC (22.7%/yr). At the time of HCC detection, the size of HCC was 4.7+/-0.6 (mean +/- SD) cm in HBsAg-positive patients and 2.4+/-1.3 cm in anti-HCV-positive patents. Cut-off values of 20 ng/ml for AFP (Youden's index = 0.422) and 60 mAU/ml for PIVKA-II (Youden's index = 0.316) gave the highest index for each marker. When these two markers were combined, cut-off values of 40 ng/ml for AFP and 80 mAU/ml for PIVKA-II gave the highest index (Youden's index = 0.500, sensitivity = 65.5%, specificity = 85.5%, positive predictable value = 14.8%, negative predictable value = 98.3%). The levels of AFP or PIVKA-II increased within three months before the detection of HCC. CONCLUSIONS: Simultaneous measurements of serum AFP and PIVKA-II levels that are performed every 3 months are useful for detecting a developing HCC. The optimal cut-off values for AFP and PIVKA-II may be 40 ng/ml and 80 mAU/ml, respectively.

Adult↗
PubMed2000

Effects of paternal lymphocyte immunization on peripheral Th1/Th2 balance and TCR V beta and V gamma repertoire usage of patients with recurrent spontaneous abortions.

PROBLEM: The mechanism of immunotherapy for patients with recurrent spontaneous abortions is not well understood. In order to investigate the suppressor mechanism of paternal lymphocyte immunization, we examined peripheral blood lymphocyte subpopulations and the repertoire of T-cell receptor (TCR) gene segments. METHOD OF STUDY: Twelve patients with recurrent miscarriage were treated with immunization with paternal lymphocyte vaccinations three times during 12-14 weeks. Before and 2 weeks after the final inoculation, lymphocyte subsets and intra-cellular interferon (IFN)-gamma and/or interleukin (IL)-4 production were examined by flow cytometry. TCR V beta and V gamma repertoires were examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We found no significant difference in CD4/CD8 ratios, prevalence of CD56+CD3+ or CD57+CD3+ cells (possible extrathymic T cells), gamma(delta)T cells, and CD5+ CD19+ (B-1) cells. However, by in vitro activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, peripheral CD4 cells demonstrated a significant decrease of IFN-gamma-producing T helper 1 (Th1) cells and an increase of IL-4-producing T helper 2 (Th2) cells after immunotherapy. Seven of nine patients who exhibited remarkable decreases in Th1/Th2 ratios became pregnant within 6 months after three courses of immunotherapy, and four women delivered healthy babies, while none of the three patients who exhibited an increased or unchanged Th1/Th2 ratio had full-term pregnancies (chi2 < 0.0001). Further, changes in usage of TCR V beta and V gamma gene segments were observed after immunotherapy in six patients examined. CONCLUSION: Our findings suggest a shift of Th1-dominant to Th2-dominant status by vaccination might play important roles in maintaining successful pregnancies. Induction of some T cells that utilize different TCR repertoires possibly suppresses maternal rejection reactions.

Abortion, Habitual↗
PubMed2000

Expression of functional chemokine receptors of human placental cells.

PROBLEM: Chemokine receptors of placental trophoblasts possibly act as co-receptors or alternative receptors of maternal fetal infection by HIV. To clarify their possible expression and the physiological roles of chemokines on human placentae, we studied chemokine chemokine receptor expression and the effects of exogenous chemokines on choriocarcinoma cell lines. MATERIALS AND METHODS: Placental samples were obtained from 13 placentae of various gestational ages. Villous tissue was mechanically dissected from samples. Trophoblasts were enriched by anti-human chorionic gonadotropin (hCG)-coated magnetic beads. Human choriocarcinoma cell lines (JAR, BeWo, JEG-3) were maintained in RPMI 1640 media supplemented with 10% FCS. Expression of chemokine receptors was studied by RT-PCR. The effects of MIP-1alpha, RANTES, MCP-1 on hCG production were estimated by EIA. Effects of chemokines on proliferation of choriocarcinoma cell lines were examined by MTT assay. RESULTS: We observed mRNA expression of CCR-1, 2, 3, 4, 5 and CXCR-1, 2, 4 in 1st trimester placental villi, CCR-I, 2, 4 and CXCR-1, 2. 4 in 2nd trimester placental villi, CCR-1, 2, 4 and CXCR-4 in 3rd trimester placental villi. Using MACS enriched trophoblasts, we observed identical results. A choriocarcinoma cell line BeWo expressed CCR-1, 3, 4 and CXCR-1, 2, 4 while JEG-3 and JAR expressed CCR-1, 3, 4, 5 and CXCR-1, 2, 4. Expression of the CCR-5 and CXCR-4 protein in choriocarcinoma cell lines and MACS-enriched trophoblats were confirmed by flow cytometry. Chemokine MCP-3, MIP-1alpha, RANTES mRNA were expressed by the 1st, 2nd and 3rd trimester placental samples and the three choriocarcinoma cell lines examined. MCP-1 was expressed by 1st and 2nd trimester placental villi. Administration of chemokines up-regulated proliferation (10(-1) - 10 ng/mL) and hCG production (10(-1) - 10(-2)ng/ mL) of the three choriocarcinoma cell lines examined. CONCLUSIONS: Our results suggest possible roles of chemokines/chemokine receptors on placental physiology and their involvement in HIV transmission as alternative receptors.

Chemokines↗
PubMed2000

Long term consequences of regressed coronary aneurysms after Kawasaki disease: vascular wall morphology and function.

OBJECTIVES: To investigate the long term consequences of regressed aneurysms after Kawasaki disease, using follow up coronary angiography; to assess the vascular wall morphology at the site of the aneurysms by intravascular ultrasound imaging; and to evaluate the function of the affected vessels using intracoronary infusions of acetylcholine and isosorbide dinitrate. DESIGN: 33 patients were studied, 27 with previous Kawasaki disease and six with congenital heart disease. All Kawasaki disease patients were followed for more than 10 years from disease onset. The 33 patients comprised four groups: group 1 included 13 Kawasaki disease patients with a total of 23 sites of regressed large sized (>/= 4 mm) coronary aneurysms; group 2 included 13 Kawasaki disease patients with 22 sites of regressed small sized (< 4 mm) coronary aneurysms (four patients had sites of both large and small sized aneurysms); group 3 included a further five Kawasaki disease patients with 25 normal coronary angiography sites in the acute stage of Kawasaki disease; and group 4 comprised the six patients with congenital heart disease as controls, with a total of 27 normal coronary angiography sites. During coronary angiography, 15 microg of acetylcholine and 0.5 mg isosorbide dinitrate were infused into the coronary artery. The luminal diameter at the sites was measured using a cine-videodensitometric analyser, to assess the distensibility of the coronary artery wall. RESULTS: Coronary angiography in all 22 patients in groups 1 and 2 and in all the patients in group 3 was normal, with no stenoses and no irregularity of the arterial wall. However, the intravascular ultrasound imaging in groups 1 and 2 showed various degrees of the intimal thickening. In groups 1 and 2, there was significantly more vascular constriction with acetylcholine, and poorer dilatation with isosorbide dinitrate than in groups 3 or 4 (each p < 0.05, respectively). There was no difference between group 3 and group 4 in response to either acetylcholine or isosorbide dinitrate, CONCLUSIONS: There is evidence of persisting abnormal vascular wall morphology and vascular dysfunction at the site of regressed coronary aneurysms in patients with previous Kawasaki disease. These patients should be counselled to avoid potential risk factors for atherosclerosis, and long term follow up is needed into adult life.

Acetylcholine↗