Search PubMed⌕ Search

Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 253 records · Page 14Linked to original sources

Genotype distribution in Nagoya and new genotype (genotype 3a) in Japanese patients with hepatitis C virus.

We evaluated hepatitis C virus (HCV) genotype distribution among Japanese patients in the city of Nagoya and the possible existence of any other genotype not determined by Okamoto's method. Eighty-five of 93 (91.4%) anti-HCV-positive patients had detectable HCV RNA. The genotype of the HCV isolate was determined in 84 of 85 (98.8%) of these HCV RNA-positive patients by Okamoto's method but determination was not possible in one (1.2%). Genotype 1b was detected in 58 of the 85 patients (68.2%), genotype 2a in 20 (23.5%), genotype 2b in 3 (3.5%), and genotype 1b + 2a in 3 (3.5%). In the remaining 1 patient in whom the genotype could not be determined, we determined the nucleotide sequence of the core region in HCV RNA extracted from this patient and evaluated it by molecular evolutionary analysis. This HCV isolate was then classified as genotype 3a. These results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japanese isolates, we should take more care because genotype 3a is not determined by current typing systems.

Amino Acid Sequence↗

Detection of decay-accelerating factor in stool specimens of patients with colorectal cancer.

BACKGROUND & AIMS: Colorectal cancers have an increased expression of decay-accelerating factor (DAF). The aim of this study was to determine whether stool specimens of patients with colorectal cancer contain increased amounts of DAF. METHODS: DAF was measured using an immunoassay in the stool specimens of 40 persons with colorectal cancer, 18 with colorectal adenomatous polyps, 13 with upper gastrointestinal cancer, and 41 without gastrointestinal disease. RESULTS: Stool DAF concentrations in patients with colorectal cancer (0-9.8 ng/g stool; median, 1.6 ng/g) were significantly higher than those in patients with adenoma (0-6.4 ng/g; median, 0 ng/g) (P < 0.05), patients with upper gastrointestinal cancer (0-3.1 ng/g; median, 0 ng/g) (P < 0.05), and subjects without gastrointestinal disease (0-3.4 ng/g; median, 0 ng/g) (P < 0.01). Resection of colorectal cancers caused a marked decrease in stool DAF concentrations. The stool DAF test was positive in a substantial portion of patients with colorectal cancer whose tumors were small ( < 2 cm), at an early TNM stage, or unassociated with fecal occult blood positivity. The sensitivity of the test for colorectal cancer was 55%, and the specificity was 85%. CONCLUSIONS: The measurement of stood DAF deserves evaluation as a test for detection of colorectal cancer.

Adenomatous Polyposis Coli↗

Flow cytometric analysis of the DNA content in colorectal adenomas with focal cancers.

BACKGROUND & AIMS: Variable results have been reported on the nuclear DNA content of colorectal polyps. The significance of DNA aneuploidy in the malignant transformation of colorectal polyps was evaluated. METHODS: We analyzed by flow cytometry the nuclear DNA content of freshly frozen samples of 50 colorectal adenomas with or without focal cancers, analyzing separately the adenomatous and cancerous regions of the polyps. RESULTS: In the adenomatous regions of the 50 polyps, the DNA was diploid in 43 and aneuploid in 7; the adenomas with DNA aneuploidy in the adenomatous regions were more frequently accompanied by focal cancers than were the DNA-diploid adenomas (P < 0.01). In 60% of the polyps with DNA aneuploidy in the cancerous regions, the DNA was also aneuploid in the adenomatous region and had similar DNA indices; this result suggests that the DNA aneuploidy had already occurred during the adenomatous stage, which lends support to the concept of the adenoma-carcinoma sequence. DNA aneuploidy in the adenomatous region was significantly correlated with the size of colorectal polyps (P < 0.05). CONCLUSIONS: DNA aneuploidy may be an important indicator for the early diagnosis of malignant transformation of colorectal polyps.

Adenoma↗

Virion-like structures in HeLa G cells transfected with the full-length sequence of the hepatitis C virus genome.

BACKGROUND & AIMS: The process and the site of hepatitis C virus (HCV) particle formation in cells after infection remain unknown. The aim of this study was to create an in vitro model for the study of HCV particle formation. METHODS: HeLa G cells were transfected with the full-length sequence of the HCV genome. Viral protein expression was analyzed using immunoblotting. The cells were examined using immunoelectron and conventional electron microscopy. RESULTS: Core, E2, NS3, NS5a, and NS5b proteins were identified using immunoblotting. Immunoelectron microscopy showed that the core antigen was located along the membrane of the endoplasmic reticulum (ER) and occasionally in its cisternae. Core antigen-positive particles of 30 nm in diameter were found in the cytosol and in the cisternae of the ER. The particles in the cisternae were coated with an outer membrane that was connected to the ER membrane. Conventional electron microscopy revealed particles of 45 nm in diameter with electron-dense cores in the cisternae of the ER. The outer membrane of the particles was occasionally connected to the ER membrane. CONCLUSIONS: The findings suggest that HCV core proteins are synthesized and assembled into particles in the cytosol and that they bud into the cisternae of the ER to form coated particles.

Base Sequence↗

Pathogenic significance of interleukin-6 in a patient with antiglomerular basement membrane antibody-induced glomerulonephritis with multinucleated giant cells.

We report a patient with anti-glomerular basement membrane disease who developed renal failure associated with systemic manifestations, including acute-phase inflammatory reactions and plasmacytosis. Renal tissue obtained by an open surgical biopsy showed circumferential cellular crescents, multinucleated giant cells, and exudation of fibrin in all glomeruli. Immunofluorescence microscopy demonstrated deposition of immunoglobulin G, C3, and membrane attack complex along glomerular capillary walls. Multinucleated giant cells were suggested to be macrophage-monocyte lineage because they were CD68 positive. Bone marrow aspiration showed an increase of plasma cells. Immunostaining showed intensive expression of interleukin-6 (IL-6) in practically every part of the renal sites involving multinucleated cells, crescents, tubules, and infiltrating cells, suggesting that one of the sources of systemically elevated IL-6 was the kidney. Serum IL-6, anti-glomerular basement membrane antibody, and acute-phase proteins were markedly elevated, and returned dramatically to the normal level after corticosteroid therapy and plasmapheresis. We believe that IL-6 played an important role in the development of many symptoms in the present case.

Aged↗

Changes of intracellular electrolyte contents in rat skeletal muscle during body suspension.

The CNS-mediated inhibition of active Na(+)-K+ transport in both "type S" muscle, soleus (SOL), and "type FF" muscle, extensor digitorum longus (EDL) was investigated in rats suspended horizontally. Plasma Na+ and K+ contents did not change during the suspension period. The relative wet weight of SOL decreased more than that of EDL by suspension. There was significant intracellular Na+ accumulation and K+ loss in both SOL and diaphragm of suspended rats. However, cerebrum, cerebellum, medulla oblongate, ventricle, liver, pancreas, kidney, intestine, aorta and EDL were spared from the intracellular Na+ accumulation and K+ loss. Sciatic nerve sectioning or cervical spinal cord transection recovered the Na+ and K+ contents in the SOL of suspended rats. The results indicate the existence of neural inhibition of the active Na(+)-K+ transport in skeletal muscle of the suspended rats.

Animals↗

Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury.

In the kidneys of anti-glomerular basement membrane (anti-GBM) antibody disease, binding of antibodies to tubular basement membrane (TBM) is often observed. The present work was performed to explore the mechanisms of binding of anti-GBM antibodies to TBM in vivo with special reference to 5I2Ag, a rat membrane inhibitor of complement which regulates complement activation at C3 convertase level. To suppress functions of renal 5I2Ag, F(ab')2 fragment of 5I2 (a neutralizing mAb against 5I2Ag) was perfused in the left kidney and then blood circulation was restored. Mild proteinuria ( < 10 mg/16 hr) was observed during first several days. Five days later, there were tubulointerstitial injuries defined by tubular vimentin staining and leukocyte infiltration. Significant deposition of C3 was observed in the capillaries and in TBM. In rats intravenously injected with rabbit anti-rat GBM antibodies five minutes after kidney perfusion with 5I2, strong binding of rabbit IgG to TBM was observed at one and five days after injection. Although these rats showed mild proteinuria comparable to those perfused with 5I2 and those injected with normal rabbit serum, tubulointerstitial injury was significantly enhanced at Day 5. In contrast, rats perfused with irrelevant mAb and injected with anti-GBM antibodies did not show any significant binding of antibodies to TBM nor tubulointerstitial injury. Furthermore, rats which were made proteinuric by puromycin aminonucleoside and injected with anti-GBM antibodies did not show any significant binding of rabbit IgG to TBM. These results indicate that 5I2Ag, a rat membrane inhibitor of complement at the C3 convertase level, regulates vascular permeability in the living kidney, and that dysfunction or decreased expression of this molecule leads to increased accessibility of anti-GBM antibodies to TBM.

Albuminuria↗

Functional masticatory evaluation in hemifacial microsomia.

The features of hemifacial microsomia with unilateral condylar hypoplasia in a 9-year-old female patient were analysed in a multidisciplinary fashion. Cephalometric roentgenograms revealed malformation of the mandible, with the right condylar process being smaller than the left. In addition, the right maxillary alveolar process was underdeveloped. Closed view radiography with oblique lateral transcranial projection (by modified Schüller's method) of the temporomandibular joint revealed an anterior dislocation of the condyle on the unaffected side. Computed tomography (CT) of the masticatory muscles demonstrated that the medial pterygoid muscle on the affected side, unlike the other muscles, was larger than that on the unaffected side. The surface electromyographic activities of the temporal and masseter muscles and reduction of the maximum bite force on the affected side during clenching corresponded with the CT findings. The hypertrophy of the medial pterygoid muscle on the affected side was considered likely to be a compensatory adjustment to keep the mandible centred. A three-dimensional study of the movement of the mandible revealed that the condyle on the affected side moved vertically and that the rotational centre was located antero-inferior to the condylar process during maximum jaw opening and closing movements. These findings suggested lack of articular guidance. Moreover, the unaffected condylar process showed considerable backward movement during retrusion and ipsilateral excursion of the mandible. The mandibular head on the unaffected side showed obvious protraction during all jaw movements, which might have induced the overgrowth of the condylar head on the unaffected side in this growing child.

Alveolar Process↗

Therapeutic effects of lansoprazole on peptic ulcers in elderly patients.

We studied the effects of lansoprazole on ulcer healing and Helicobacter pylori infection in elderly patients with peptic ulcers. In a group of 24 patients with gastric ulcers, the H. pylori infection rate was 100%. In the course of gastric ulcer healing with famotidine or lansoprazole alone, the H. pylori infection showed no signs of decline. The ulcer healing rates after 8 weeks were similar between the H2-receptor antagonist famotidine (73%), and the proton pump inhibitor lansoprazole (82%). When eradication of H. pylori infection was attempted by concomitant administration of lansoprazole and amoxicillin 500 mg b.i.d. for 2 weeks, the eradication rate was 33% in the group given lansoprazole 30 mg q.d. plus ampicillin 500 mg b.i.d., whereas it was 77% in the group given lansoprazole 30 mg b.i.d. plus ampicillin 500 mg b.i.d. Lansoprazole is considered to be a useful agent for the treatment of patients with peptic ulcers and H. pylori infection and its effectiveness in H. pylori eradication is improved by b.i.d. administration along with ampicillin.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Complete nucleotide sequence of a skin element excised by DNA rearrangement during sporulation in Bacillus subtilis.

As part of the Bacillus subtilis genome sequencing project, we have determined the complete nucleotide sequence of a skin element which is located between spoIVCB and spoIIIC. The entire sequence of this element is 48,032 bp in length, and contains 57 ORFs with putative ribosome-binding sites. Two of them correspond to previously sequenced and characterized genes, cwIA and spoIVCA. Furthermore, seven ORF products identified in this element show interesting similarities with known proteins present in data banks, including the phi 105 immunity repressor, the phi 105 Cro-like protein and the SPP1 terminase. These results indicate the possibility that the skin element is a cryptic remnant of an ancestral temperate phage.

Amino Acid Sequence↗

Reinforced cytotoxicity of lymphokine-activated killer cells toward glioma cells by transfection of the killer cells with the gamma-interferon gene.

Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human gamma-interferon (HuIFN-gamma) gene by means of liposomes having a positive charge on their surface. The cells secreted significant amounts of HuIFN-gamma (reaching more than 5 U/ml) into the culture medium. The HuIFN-gamma produced by the cells induced intercellular adhesion molecule-1 (ICAM-1) and enhanced the expression of Fas antigen on the surface of human glioma cells. Also, LAK cells transfected with HuIFN-gamma gene exhibited reinforcement of cytotoxicity toward human glioma cell lines (U251-MG and SK-MG-1). Furthermore, the reinforcement was significantly quenched by anti-ICAM-1 and/or anti-TNF-alpha monoclonal antibody.

Antibodies, Monoclonal↗

Decreased expression of the very low density lipoprotein receptor mRNA in the cardiac ventricle of spontaneously hypertensive rats.

1. To elucidate the functional implication of very low density lipoprotein (VLDL) receptor, we studied the gene expression of VLDL receptor in rats. The VLDL receptor mRNA was highly expressed in the cardiac ventricle and skeletal muscle. Intermediate amounts of VLDL receptor mRNA were detected in adipose tissue, adrenal gland, brain and lung. Thus the tissue distribution of VLDL receptor mRNA in rats was similar to that reported previously in rabbits. 2. We studied the gene expression of the VLDL receptor in the heart of stroke-prone spontaneously hypertensive rats (SHRSP), an animal model for hypertension-induced cardiac hypertrophy. RNase protection assay showed that the level of ventricular VLDL receptor mRNA was already decreased to one half when hypertension was not fully developed, and further diminished to one fifth when cardiac hypertrophy was established. 3. It is reported that energy utilization in SHRSP hypertrophied myocardium is impaired. Our results suggest that inactive fatty acid metabolism in the ventricle of SHRSP is related to the lowered expression of the VLDL receptor which is postulated as a gate for triglyceride-rich lipoprotein particle.

Animals↗

Surgical treatment for Crohn's disease.

The medical records of 16 consecutive patients with Crohn's disease surgically treated in our department from 1978 to 1993 were retrospectively reviewed. The indication for surgery was obstructive symptoms due to Crohn's strictures that were unresponsive to conservative therapy. The types of operations performed were classified into five categories. Nine patients (56.3%) had small bowel resection only, 4 (25.0%) underwent an ileocolonic resection, 1 (6.3%) had a total colectomy, 1 (6.3%) had Mile's operation and 1 (6.3%) had subtotal gastrectomy with gastrojejunostomy and antral mucosectomy. Of these 16 patients, 13 (81.3%) had resection with a single anastomosis and strictureplasty was concomitantly performed in only 2 cases (12.5%). Crohn's disease recurred in 3 patients (18.8%), 1 of whom required a second operation.

Adult↗

Expression of ICAM-I on M cells covering isolated lymphoid follicles of the human colon.

To clarify the immunological function of 'M' (microfold or membranous) cells in the large intestine, we examined the expression of intercellular adhesion molecule-1 (ICAM-1) and HLA-class II antigens immunohistochemically in M cells and follicle-associated epithelia (FAE) covering isolated lymphoid follicles of the human colon in comparison with their expression in Peyer's patches of the small intestine. In Peyer's patches of the small intestine, ICAM-1 was not expressed on the epithelial cells covering the lymphoid follicles, but their cell surfaces were stained positively for HLA-DR. In contrast, colonic M cells expressed ICAM-1 on their cell surfaces but were negative for HLA class II antigens. By immunoelectron microscopy, ICAM-1 was seen to be distributed on the surface of microfolds, on the membranes of apical vesicles and on part of the basolateral plasma membranes of M cells, but was not expressed on adjacent FAE. These findings imply that the M cells in the colon and in Peyer's patches have different immunological roles. In addition, identification of ICAM-1 expression on the colonic M cells should help elucidate the pathogenesis of some inflammatory colonic diseases which appear to start in the lymphoid follicles of the colonic mucosa.

Adult↗

Neuro-otological and neuropathological findings in two cases with Machado-Joseph disease.

We report chronological changes of neuro-otological findings and associated neuropathological findings in 2 patients. Concerning gaze limitation, upward gaze was primarily disturbed, followed by downward gaze and abduction. Adduction tended to be preserved although convergence was disturbed at the early stage. And, upward gaze limitation was followed by loss of oculocephalic responses (OCRs). Bell's phenomenon was preserved until the late stage of the disease. Caloric nystagmus was absent at the early stage. One patient showed dissociation between nystagmus and vestibulo-collic reflex in the caloric test at the early stage of the disease. Neuropathological examination revealed gliosis in the interstitial nucleus of Cajal and the MLF as well as neuronal loss and gliosis in the oculomotor nuclei. The vestibular nuclei also showed gliosis and atrophy of nerve cells.

Brain Stem↗

Two distinctive BMP-carriers induce zonal chondrogenesis and membranous ossification, respectively; geometrical factors of matrices for cell-differentiation.

A partially purified BMP preparation was combined with a fibrous glass membrane (FGM) or porous particles of hydroxyapatite (PPHAP), and then implanted subcutaneously into the backs of rats. As a control of these new carriers, a conventional carrier of insoluble bone matrix (IBM) was also used. These new geometrically different solid-state carriers induced tissues in quite different manners. FGM/BMP implants induced cartilage formation within the entire inner area of the membrane accompanied by a small amount of bone formation on the surface of the membrane. In contrast, PPHAP/BMP implants induced only bone within the pores of PPHAP without any detectable cartilage formation. Enzyme-linked immunosorbent assay revealed that the type II collagen content in FGM/BMP was six times higher than that in IBM/BMP, while there was no detectable type II collagen in PPHAP/BMP. The results were explained by the geometric properties of the two distinctive carriers.

Animals↗

Enhanced expression of decay accelerating factor and CD59/homologous restriction factor 20 on the colonic epithelium of ulcerative colitis.

BACKGROUND: The complement system is thought to be one of the factors involved in damaging the colonic mucosa in the pathogenesis of ulcerative colitis (UC). Several membrane-bound factors that regulate complement activation have been identified. EXPERIMENTAL DESIGN: To elucidate alteration(s) of the complement regulatory proteins and to add to the understanding of the role of the complement-related immune responses in the pathogenesis of UC, we immunohistochemically examined the distribution of decay accelerating factor (DAF), CD59/homologous restriction factor 20 (HRF20), and membrane cofactor protein (MCP) in colonic mucosa with UC and compared it with that in normal and inflammatory control mucosae. RESULTS: In normal colonic epithelia, the cell surface distribution of DAF and CD59/HRF20 was confined to the apical domain, whereas MCP was present on the basolateral surface. Although MCP expression in active UC was not significantly different from normal mucosa, DAF and CD59/HRF20 expression on epithelial cells of UC was markedly enhanced in relation to the severity of mucosal inflammation. In the colonic epithelia of active UC, DAF and CD59/HRF20 were not only overexpressed on the apical surface but also were distributed to the basolateral membrane. The altered cell surface distribution of these molecules was also confirmed by immunoelectron microscopy. The enhanced expression of DAF and CD59/HRF20 was not specific to UC but was observed in colonic mucosa of inflammatory controls, such as ischemic colitis. CONCLUSIONS: Our results indicate that altered regulation of complement activation is present in UC mucosa, but whether it may play a causal role in the immunologic disorders leading to UC remains to be elucidated.

Adult↗