Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 91 records · Page 5Linked to original sources

PubMed2001

Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais.

Adhesion molecules on endothelial cells are known to be important ligands for malaria infected red blood cells (PRBC) [Mol Biochem Parasitol, 76, (1996) 1], and may be involved in the pathogenic process of cerebral malaria (CM) which is the most serious complication of falciparum malaria, through enhancing micro embolism or sequestration in the capillaries of the brain. PECAM-1/CD31 is one of these candidate ligands and is coded by a polymorphic gene. Two hundred and ten Thai malaria patients (43 cerebral, 89 severe and 78 uncomplicated) were analyzed for their genetic polymorphism of CD31 to examine the clinical relationship between the disease and specific genotypes. Four alleles were defined 125 valine (V)-563 asparagine (N); 125V-563 serine (S); 125 leucine (L)-563N; and 125L-563S. We found that the frequency of the 125 V/V 563 N/N genotype was significantly high in CM patients as compared with severe cases without CM (P<0.01, OR=2.92), suggesting that this genotype is one of the risk factors for CM.

Adult↗

PubMed2001

Secoiridoid glycosides from Gentiana scabra.

Two new secoiridoid glycosides, 4'-O-beta-D-glucopyranosylgentiopicroside (1) and 6'-O-beta-D-glucopyranosylgentiopicroside (2), have been isolated from the rhizomes and roots of Gentiana scabra together with three known compounds, olivieroside, 1-O-beta-D-glucopyranosylamplexine, and benzyl alcohol O-alpha-L-arabinopyranosyl (1 --> 6)-beta-D-glucopyranoside. The structures of 1 and 2 were elucidated using chemical and physicochemical (MS and NMR) studies.

China↗

PubMed2001

Excretion into gastrointestinal tract of irinotecan lactone and carboxylate forms and their pharmacodynamics in rodents.

PURPOSE: To investigate the excretion of irinotecan hydrochloride (CPT-11) and its active metabolite, SN-38, into the gastrointestinal lumen via the biliary and/or intestinal membrane route after dosing with lactone and carboxylate forms of CPT-11, and to evaluate the toxic and antitumor effects of the two forms. METHODS: The excretions of CPT-11 and SN-38 were investigated by the in situ perfusion technique using rats. The incidence of delayed diarrhea was evaluated after i.v. dosing (60 mg/kg) with CPT-11 lactone and carboxylate forms for 4 days. Antitumor activity and changes in body weight were investigated in mice with Meth A tumors. RESULTS: The excretion of CPT-11 into bile was greater in dosing with CPT-11 carboxylate than that with its lactone form, whereas the exsorption across intestinal membrane was greater in dosing with CPT-11 lactone than that with its carboxylate form. Dosing with CPT-11 lactone dose-dependently inhibited the increase in tumor weights in Meth A tumor mice, whereas the dosing with its carboxylate form reduced the antitumor effect. CONCLUSIONS: The decreased antitumor effect caused by dosing with the CPT-11 carboxylate form could be due to less accumulation in the tissue including tumor cells resulting from the rapid elimination of the form in the body.

Animals↗

PubMed2001

Strong association of a tumor necrosis factor-alpha promoter allele with cerebral malaria in Myanmar.

To investigate the host genetic factors affecting the clinical course of falciparum malaria, polymorphism of the tumor necrosis factor-alpha (TNF-alpha) promoter region was analyzed in patients with cerebral malaria. Two hundred and forty-three Myanmar patients with falciparum malaria at Mae Sot Malaria clinic and Mae Sot General Hospital located at the border between Thailand and Myanmar, were included in this study. Among the patients (128 from Karen, 115 from Burma), 200 were uncomplicated and 43 had cerebral malaria. The TNF-alpha 5'- flanking region showed biallelic polymorphic sites at -238, -308, -857, -863, -1031, and there were 7 alleles (TNFP-A, B, C, D, M1, M4, M7) found in the patients from Myanmar. We found that the TNFP-D allele was significantly associated with cerebral malaria in the populations from Karen (Pc<0.0001, OR=124.86) and Burma (Pc<0.0001, OR=34.50). TNFP-D showed no significant linkage disequilibrium with any alleles of HLA-B or HLA-DRB1, suggesting that TNFP-D was primarily associated with cerebral malaria in Myanmar.

Gene Frequency↗

PubMed2001

Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with schizophrenia in Japanese samples.

In our search for candidate genes for affective disorder on the short arm of chromosome 18, we cloned IMPA2, a previously unreported myo-inositol monophosphatase gene, that maps to 18p11.2. We determined its genomic structure and detected three new single nucleotide polymorphisms (SNPs). In the present study, we screened the gene further to search for additional polymorphisms in Japanese samples and identified seven other SNPs, including a novel missense mutation. These polymorphisms clustered into three regions of the gene. Three relatively informative SNPs, 58G>A, IVS1--15G>A and 800C>T from clusters 1, 2 and 3, respectively, were selected for association tests using a case-control design. The Japanese cohort included 302 schizophrenics, 205 patients with affective disorder and 308 controls. Genotyping was done either by melting curve analysis on the LightCycler or by sequencing. All three SNPs showed significant genotypic association (nominal P = 0.031--0.0001) with schizophrenia, but not with affective disorder. These findings increase the relevance of 18p11.2 to schizophrenia susceptibility because GNAL, which has been shown previously to be implicated in schizophrenia in an independent study, is in close physical proximity to IMPA2. Our findings suggest that IMPA2 or a gene nearby may contribute to the overall genetic risk for schizophrenia among Japanese.

Adult↗

PubMed2001

Expression of RCAS1 and FasL in human trophoblasts and uterine glands during pregnancy: the possible role in immune privilege.

Pregnancy is an immunological balancing act. Trophoblasts do not express MHC class I or II, except HLA-C and G, but express Fas ligand (FasL), which confers immune privilege. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) has recently been recognized to play a role in immune evasion of the tumour cells. We therefore studied the involvement of RCAS1 and FasL in the infiltration of NK cells by examining the curettaged uterine contents of 20 cases of early stage of pregnancy. The cases were clinically divided into two groups; curettage was performed (A) due to the absence of foetal heart beats, and (B) due to spontaneous uterine bleeding and abortion. In group A, RCAS1 was expressed in the uterine glands and extravillous cytotrophoblasts, as was FasL. Infiltration of NK cells around the uterine glands was scarcely detected. In contrast, in group B, expression of both RCAS1 and FasL was strikingly decreased in both the level of expression and the numbers of RCAS1/FasL-positive cells and massive infiltration of NK cells was frequently detected around the uterine glands. These findings suggest that a reduction in RCAS1 and FasL expression seems to be closely associated with activation and infiltration of maternal NK cells and destruction of uterine glands, resulting in rejection of the foetus. Thus, expression of RCAS1 and FasL in the uterine glands and cytotrophoblasts may play a role in the downregulation of the maternal immune response, thereby maintaining pregnancy at early stage.

Abortion, Spontaneous↗

PubMed2001

High expression of MDR-1 gene and P-glycoprotein in initial and re-biopsy specimens of relapsed B-cell lymphoma.

AIMS: Multidrug resistance (MDR) is a major obstacle in the treatment of lymphoma. The expression of MDR-1 mRNA and P-glycoprotein (MDR-1/P-gp) has been linked to MDR. We aimed to investigate the expression of MDR-1/P-gp in B-cell lymphoma. METHODS AND RESULTS: Samples at diagnosis and relapse from 10 patients with B-cell lymphoma were obtained. We also obtained 14 unselected control cases of B-cell lymphoma at diagnosis. The expression of mRNA and protein were determined semiquantitatively by RT-PCR and immunohistochemistry. High MDR-1 and P-gp expressions were found in seven and seven of 10 samples obtained at diagnosis, eight and eight of 10 samples obtained at relapse, and three and four of 14 control cases at diagnosis, respectively. The results of RT-PCR paralleled those of immunohistochemistry. Concordance of high MDR-1/P-gp expression was noted in 27 of 34 samples (r = 0.73, P = 0.001). There were no significant changes in MDR-1/P-gp expression in all cases at relapse and during the clinical course following chemotherapy. In the 14 control cases, the average survival time was 12.7 months in MDR-1/P-gp positive cases and 29.0 months in the MDR-1/P-gp negative cases (P = 0.20). CONCLUSIONS: Our results showed that at least some B-cell lymphomas express MDR-1/P-gp, which could be detected by different methods, and suggested that high MDR-1/P-gp expression in tumour cells may be associated with a high probability of relapse and poor prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Interleukin-13 and interleukin-13 receptor in Hodgkin's disease: possible autocrine mechanism and involvement in fibrosis.

AIMS: Hodgkin's disease (HD) is characterized by the presence of Hodgkin and Reed-Sternberg (H-RS) cells against a hyperplastic background of reactive cells such as lymphocytes, histiocytes, plasma cells, eosinophils, neutrophils, and stromal cells. There is ample evidence to suggest that proliferation and survival of HD-derived cells is due to cytokine signalling. Recently, high expression of interleukin (IL)-13 was described in HD-derived cell lines. Here we investigated the possible involvement of IL-13 in the pathophysiology, especially autocrine pathways of H-RS cells. METHODS AND RESULTS: The expression of IL-13 and IL-13 receptor (IL-13R) was determined by immunostaining and reverse transcriptase-polymerase chain reaction in 39 cases of HD, including 17 cases with nodular sclerosis (NS) type, 19 cases with mixed cellularity (MC), and three cases with lymphocyte predominance (LP) type. Expression of IL-13 was confined to H-RS cells and a few lymphocytes. IL-13R was expressed in H-RS cells, lymphocytes, histiocytes, fibroblasts, and endothelial cells. H-RS cells of MC and NS types frequently expressed both IL-13 and IL-13R. However, the number of IL-13-positive H-RS cells was statistically higher in NS-type than in MC-type, but the number of IL-13R was similar. IL-13R-positive fibroblasts were frequently encountered in NS-type. H-RS cells of LP type rarely expressed IL-13. CONCLUSIONS: Our results suggest that IL-13 might be involved in autocrine pathways of H-RS cells and fibrosis at least in NS-type. Our results also indicated that in addition to the morphological and phenotypic differences, the neoplastic cells of LP type might be functionally different from H-RS cells of MC- and NS-types.

Adolescent↗

PubMed2001

CD10 and Bcl10 expression in diffuse large B-cell lymphoma: CD10 is a marker of improved prognosis.

AIMS: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically and pathologically heterogeneous. The Bcl10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosa-associated lymphoid tissue (MALT) lymphomas, and is considered to be an apoptosis-associated gene. CD10 is considered to be a marker of follicular centre B-cell differentiation. To assess the clinical significance and roles of CD10 and Bcl10 in DLBCL, we analysed 138 cases, using immunohistochemical methods. METHODS AND RESULTS: CD10 expression was limited to the cytoplasm, whereas Bcl10 expression was detected in the cytoplasm and/or nuclei. CD10 expression was detected in 39 of 138 cases (28.2%), cytoplasmic Bcl10 in 68 cases (49.2%), and nuclear Bcl10 in 34 cases (24.6%). Nuclear Bcl10 was detected in 14 of 28 cases (50%) of extranodal DLBCL, but only 20 of 110 cases (18.2%) of nodal DLBCL. Cytoplasmic Bcl10 was detected in 19 of 28 cases (67.8%) of extranodal DLBCL and 49 of 110 cases (44.5%) of nodal DLBCL. CD10 expression closely correlated with improved survival (68% overall survival (OS) vs. 48% OS), but not with site of disease. A high International Prognostic Index (IPI) was considered to be a poor prognostic factor associated with a shorter OS. CD10 expression was detected in 27 of 84 cases (32.1%) with low-risk IPIs, and in 12 of 54 cases (22.2%) with high-risk IPIs. In the low-risk group, cases expressing CD10 carried a better prognosis than CD10- cases (93% OS vs. 71% OS), whereas this was not the case in the high-risk group (25% vs. 20%). CONCLUSIONS: Bcl10 expression was associated with extranodal DLBCL, but not with prognosis. CD10 expression was closely associated with improved survival, but not with risk as predicted by IPI. Overall, our results suggest that CD10 expression may be useful, in combination with clinical parameters, for determining the prognosis of DLBCL.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Evidence for local immunosuppression and demonstration of c-myc amplification in pyothorax-associated lymphoma.

AIMS: Pyothorax-associated lymphoma (PAL) develops in the pleural cavity of patients with a long history of pyothorax. Epstein-Barr virus (EBV) is also involved in PAL, similar to lymphomas in immunodeficient patients. Here we examined T-lymphocyte subsets as well as c-myc and REL gene amplification in PAL tissues. METHODS AND RESULTS: We determined the number and distribution of CD4+ and CD8+ T-lymphocytes, to evaluate T-cells in the host immune reaction in seven cases of PAL. As controls, we also studied 10 cases of extranodal diffuse large B-cell lymphoma (DLBL) and 10 cases of nodal DLBL. Chromosomal imbalances in PAL were determined by using comparative genomic hybridization (CGH) analysis. The mean numbers of CD4+ and CD8+ and their ratio were significantly lower in PAL than in nodal DLBL. CGH analysis of PAL showed amplification of the 8q24 chromosomal region. In addition, c-myc amplification was found in four cases of PAL by Southern blot analysis. CONCLUSIONS: Our results suggest that the development of PAL may involve a local immunosuppressive environment and that amplification of c-myc might promote tumour progression, as has been described in the development of Burkitt's lymphoma.

Aged↗

PubMed2001

Comparison of Ricketts analysis and Downs-Northwestern analysis for the evaluation of obstructive sleep apnea cephalograms.

To determine which analysis is suitable to examine the dentofacial skeletal pattern characteristics of the obstructive sleep apnea syndrome (OSAS), we took lateral cephalograms of 44 Japanese OSAS patients and 34 Japanese non-OSAS controls. By Ricketts analysis, we found significant differences between OSAS patients and non-OSAS controls on facial axis, lower facial height and total facial height, which showed that Japanese OSAS patients have dolico facial patterns. However, by Downs-Northwestern analysis, we did not find any significant difference between OSAS patients and non-OSAS controls using the same cephalograms as the Ricketts analysis.

Adult↗

PubMed2001

Five-year survival of older people with anemia: variation with hemoglobin concentration.

OBJECTIVES: To investigate the significance of low hemoglobin concentration and longevity in older people. DESIGN: Randomized prospective study. SETTING: Nursing home and geriatric hospital ward in a metropolitan welfare center. PARTICIPANTS: Apparently stable older residents from 1990 to 1996. MEASUREMENTS: Survival rates were estimated by statistical analysis. Sixty-three older subjects with low hemoglobin (Hb<11 g/dl) and age/sex-matched normal controls (Hb> or =11 g/dl) were observed for 60 months. Scores of activities of daily living (ADLs) did not significantly differ between the two groups. Cerebrovascular disease was the main complication in both, and malignant neoplasms were not apparent initially. RESULTS: After 60 months, the 5-year survival rate (FSR) of normal controls was significantly higher than that of cases with anemia (P =.0078). FSR was 67% in normal controls and 48% in anemic individuals age 70 to 79. The figures for individuals age 80 to 89 were 62% and 41%, respectively, and for individuals age 90 to 99 were 25% and 13%, respectively, the survival rate significantly decreasing with age in both groups (P <.001). FSR with severe anemia (Hb< or = 8.9 g/dl) was 0% in males, and 27% in females. Values for moderate anemia (9.0 g/dl to 10.9 g/dl) were 25% and 51%, respectively, for normal hemoglobin (11.0 g/dl to 12.9 g/dl) were 44% and 61%, respectively, and for high hemoglobin (13.0 g/dl< or =Hb) were 50% and 70%, respectively. Advanced carcinomas were often detected at autopsy in anemic individuals. No death by cancer occurred in normal controls. CONCLUSION: Low hemoglobin concentration predicts early death in nursing home residents. Anemia-associated conditions that might be life-threatening risks in older people require further investigation.

Actuarial Analysis↗

PubMed2001

Oral-cavity hair growth after free-flap transfer: case report.

It sometimes happens that hair will grow well after a free-flap transfer. But this is a report of an experience of excessive hair growth after reconstruction of a middle pharyngeal defect, using a free, vascularized, radial, forearm flap. This is a relatively rare occurrence.

Adult↗

PubMed2001

A study of induction of nerve regeneration using bioabsorbable tubes.

A silicone tube (S-tube) was packed with CPLA (copolymer of poly-L-lactide) fibers (S-tube+CPLA) or collagen fibers (S-tube+fiber). Two types of tube were prepared from a collagen sheet (Col-tube) and a bioabsorbable atelocollagen membrane for guided tissue regeneration (GTR-tube). They were packed with collagen fibers or films (Col-tube+fiber, GTR-tube+fiber and GTR-tube+film). Bridge grafting (15 mm in length) was performed with these tubes in a rat sciatic nerve model. Specimens were harvested after 8 weeks. Minifascicles were formed in the open space between the CPLA fibers in the S-tube+CPLA group. Regenerated axons were also formed in the degenerated collagen fibers in the S-tube+Col group. Immunocytochemistry evaluation revealed that Schwann cells invaded the space in the absorbing collagen fibers. Histologic analysis of the regenerated axons in the groups with Col-tubes or GTR-tubes revealed that both the Col-tube and the GTR-tube packed with collagen fibers were effective in providing a scaffold for regenerating nerve tissue.

Animals↗

PubMed2001

Low power diode laser treatment using indocyanine green for eradication of esophageal varices.

BACKGROUND AND STUDY AIMS: Endoscopic variceal ligation (EVL) is an alternative to sclerotherapy for the treatment of esophageal varices, but is associated with higher rates of recurrence and subsequent bleeding than sclerotherapy. To prevent recurrence of varices after EVL, we have developed a low-dose diode laser therapy combined with the injection of indocyanine green, which allows enhanced tissue absorption of the laser beam selectively around varices. In this study we investigated the efficacy and safety of this technique. PATIENTS AND METHODS: Eight patients with F2 or F3 esophageal varices were enrolled. At 1 week after EVL, indocyanine green solution (1 mg/ml) was injected submucosally around the remaining varices. A diode laser (power 10 watts) was applied to the surface from the esophagogastric junction to 5 cm above it. The spot size was kept to 5 mm in diameter. RESULTS: Laser irradiation was performed safely, without bleeding from the varices, or perforation. There were no major complications. Endoscopy 1 month later showed F0 forms in seven patients, F1 in one patient, and no red color sign in any patient. No recurrence of varices has been observed in any of the patients during the follow-up period of at least 12 months. CONCLUSION: This technique may provide a simple, safe and effective procedure, as an additional treatment to EVL, for the prevention of recurrence of esophageal varices.

Adult↗

PubMed2001

Inhibition of factor Xa suppresses the expression of tissue factor in human monocytes and lipopolysaccharide-induced endotoxemia in rats.

BACKGROUND: Activated factor X (FXa) is involved in hemostasis, thrombogenesis, inflammation, and cellular immune response. Tissue factor (TF) is an initiator of blood coagulation. We investigated whether FXa induces TF expression in human peripheral monocytes and whether treatment with FXa inhibitor reduces TF expression in an experimental model of rat endotoxemia. METHODS: Human peripheral mononuclear cells were used to determine TF expression induced by FXa. Experimental rat endotoxemia was induced by intravenous bolus injection of lipopolysaccharide (LPS). A specific FXa inhibitor, DX-9065a, was administered subcutaneously immediately after LPS injection. RESULTS: FXa induced TF expression in monocytes without intervention of thrombin and the expression was suppressed by FXa inhibitor. In the experimental model of rat endotoxemia, TF and TF mRNA expression levels in the liver were reduced by DX-9065a. Moreover, administration of DX-9065a suppressed the rise in plasma concentrations of thrombin-antithrombin III complex (TAT) and monocyte chemoattractant protein-1 (MCP-1). CONCLUSIONS: Our results indicated that FXa can induce TF expression in human peripheral monocytes and that inhibition of FXa reduces TF expression in the liver of rat endotoxemia. These results suggest that FXa is an important factor for TF expression in sepsis.

Animals↗

PubMed2001

Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with surgical applications.

BACKGROUND: In various surgical cases, effective tissue adhesives are required for both hemostasis (eg, intraoperative bleeding) and air sealing (eg, thoracic surgery). We have designed a chitosan molecule (Az-CH-LA) that can be photocrosslinked by ultraviolet (UV) light irradiation, thereby forming a hydrogel. The purpose of this work was to evaluate the effectiveness and safety of the photocrosslinkable chitosan hydrogel as an adhesive with surgical applications. METHODS: The sealing ability of the chitosan hydrogel, determined as a bursting pressure, was assessed with removed thoracic aorta, trachea, and lung of farm pigs and in a rabbit model. The carotid artery and lung of rabbits were punctured with a needle, and the chitosan hydrogel was applied to, respectively, stop the bleeding and the air leakage. In vivo chitosan degradability and biologic responses were histologically assessed in animal models. RESULTS: The bursting pressure of chitosan hydrogel (30 mg/mL) and fibrin glue, respectively, was 225 +/- 25 mm Hg (mean +/- SD) and 80 +/- 20 mm Hg in the thoracic aorta; 77 +/- 29 mm Hg and 48 +/- 21 mm Hg in the trachea; and in the lung, 51 +/- 11 mm Hg (chitosan hydrogel), 62 +/- 4 mm Hg (fibrin glue, rubbing method), and 12 +/- 2 mm Hg (fibrin glue, layer method). The sealing ability of the chitosan hydrogel was stronger than that of fibrin glue. All rabbits with a carotid artery (n = 8) or lung (n = 8) that was punctured with a needle and then sealed with chitosan hydrogel survived the 1-month observation period without any bleeding or air leakage from the puncture sites. Histologic examinations demonstrated that 30 days after application, a fraction of the chitosan hydrogel was phagocytosed by macrophages, had partially degraded, and had induced the formation of fibrous tissues around the hydrogel. CONCLUSIONS: A newly developed photocrosslinkable chitosan has demonstrated strong sealing ability and a great potential for use as an adhesive in surgical operations.

Animals↗

PubMed2001

Tumoral calcium pyrophosphate dihydrate crystal deposition disease. A clinicopathologic analysis of five cases.

We describe five cases of tumoral calcium pyrophosphate dihydrate crystal deposition disease (CPPDCD) and discuss the clinical, radiological and pathological features. Patients included 4 males and 1 female, ranging in age from 49 to 70 years (median, 63 yrs). The wrist was involved in two patients. The thumb, palmar aspect of the proximal phalanx of the middle finger and dorsum of the carpal bone of the hand were involved in one patient each. In one patient, a preoperative diagnosis of chondrosarcoma had been made. Macroscopically, the lesion was a circumscribed whitish-gray mass with a more or less chalky appearance, measuring between 1.0 to 6.2 cm (median, 2.5 cm). Histologically, all five lesions contained areas of calcification with crystal deposits and chondroid metaplasia. The majority of crystals were rhomboid in shape, characteristic of CPPD, but some needle-shaped crystals were also identified, which resembled urate crystals. A review of the 54 reported cases of tumoral CPPDCD including our series indicated that they could be divided into two categories based on anatomic location: central (head and neck) type (n = 33) and distal (extremity) type (n = 21). Patients of these two groups were not different with respect to age and gender, but those with the central type often presented with a painful mass (15 patients, 46%), or neurological disturbances (11 patients, 33%). Patients with the distal type presented with a painless mass or swelling (12 patients, 57%), but none had neurological signs, although 8 (38.1%) presented with acute attack similar to tophaceous gout. Tumoral CP-PDCD should be differentiated from tophaceous gout, tumoral calcinosis, and malignant or benign tumors.

Aged↗