Biomedical subjects
Publications and source records attributed to M Isobe.
VRK1 is a novel human putative serine/threonine kinase, and is located on chromosome 14 at band q32 where an autosomal recessive congenital microphthalmia (CMIC) is mapped. We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human VRK1 gene. This polymorphism will be useful in genetic studies of disorders localized at the 14q32 region, such as CMIC.
We report the chromosomal localization of the gene for human poly(A) polymerase (PAP) and the characterization of a newly isolated CA repeat near the PAP locus. By fluorescence in situ hybridization and polymerase chain reaction (PCR)-based analysis with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel, this gene was mapped on the q32.1-q32.2 region of chromosome 14. From a genomic clone containing the human PAP locus, we have isolated a polymorphic dinucleotide (CA) sequence. High heterozygosity (0.81) makes this polymorphism a useful marker in the genetic study of disorders localized at the 14q32 region, such as autosomal recessive congenital microphthalmia (CMIC).
Comparative genomic hybridization was used to identify chromosomal imbalances in eight cell lines and 12 blood samples from patients with adult T-cell leukemia/lymphoma (ATL). The chromosomes most often over-represented in the cell lines were 2p (6 cases), 7q (4 cases), and 14q (4 cases), with minimal common regions at 2p16-22, 7q21-36, and 14q32, respectively. Distinct imbalances were detected in only 7 of the clinical samples. Chromosomes 14q32 and 2p16-22 harbor TCL1 and a transcription factor, HTLF (human T-cell leukemia virus enhancer factor), respectively. FISH analysis revealed that TCL1 did not juxtapose to TCRA, and we detected no expression of TCL1 in any of the ATL cell lines despite the 14q32 amplifications. Moreover, expression of HTLF was not elevated in the ATL cell lines bearing multiplication of 2p. These results suggest that chromosomal regions 2p16-22 and 14q32 harbor genes other than HTLF and TCL1 that are involved in cellular immortalization or in the pathogenesis of ATL.
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Previous allelotyping studies on colorectal carcinoma suggest that loss of heterozygosity (LOH) on chromosome 14q may be a common genetic alteration in this tumor type. The purpose of this study was to determine precise frequency of LOH at 14q32 region in colorectal carcinomas and to define a minimal region of LOH. LOH at 14q32 in 66 primary colorectal carcinomas were analyzed by polymerase chain reaction-based deletion mapping using six highly polymorphic microsatellites. The average rate of informative data was 68.2% in all cases of colorectal carcinoma analyzed. The average rate of LOH at 14q32 was 44.1%, with the highest frequency of 50.0% at D14S267 locus in the informative cases. The minimal region of LOH was defined by markers D14S65 and D14S250 at 14q32. The present data provide useful information for the isolation of tumor suppressor genes from this region.
PURPOSE: This study examines the effect of polymer capsules containing recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone regeneration in a large segmental bone defect in the rat. MATERIALS AND METHODS: Poly(DL-lactide-co-glycolide) (PLGA) capsules containing 3 microg of rhBMP-2 were implanted in a 5-mm segmental femoral defect in rats, and the femurs were harvested at 4 and 8 weeks after implantation and observed by radiographically and microscopically. RESULTS: At 8 weeks after implantation, union of bone was found radiographically and histologically in the femoral defects implanted with the rhBMP-2/PLGA capsules. In contrast, the control animals did not show bridging of the defect. CONCLUSIONS: This study provides evidence that use of rhBMP-2/PLGA capsules is a promising delivery system to regenerate bone.
Administration of anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody (mAb) plus anti-lymphocyte function associated antigen (LFA)-1 mAb induces tolerance in murine cardiac transplantation, while anti-vascular cell adhesion molecule (VCAM)-1 mAb plus anti-very late antigen (VLA)-4 mAb administration prolongs graft survival, but leads to tolerance only in some cases. BALB/c mice hearts were transplanted into C3H/He recipients. Each combination of anti-VCAM-1 plus anti-VLA-4 mAbs (100 microg each/day, i.p.) or anti-ICAM-1 plus anti-LFA-1 mAbs (50 microg each/day, i.p.) was administered for 5 days. For control study, third group mice received daily with FK506 administration (1 mg/kg/day). The cardiac allografts and recipients' spleens were harvested on day 7; the expression of cytokines were detected using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR. Th2 cytokines (IL-4 and IL-10) were markedly enhanced and Th1 cytokines (IFN-gamma and IL-2) were suppressed in recipients treated with anti-ICAM-1 mAb plus anti-LFA-1 mAb, while poor Th2 cytokine expression allowed persistent Th1 cytokine expression in recipient mice with anti-VCAM-1 mAb plus anti-VLA-4 mAb treatment. Both Th1 and Th2 cytokine expression was suppressed in FK506-treated mice. It is concluded that immunological tolerance and prolonged graft survival induced by blocking cell adhesion is regulated by different cytokine expression.
Three coumarins were isolated as siginificant inhibitors of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus (EBV) activation in Raji cells from the peel of lemon fruit. They were identified as 8-geranyloxypsolaren (LE-1), 5-geranyloxypsolaren (bergamottin, LE-2), and 5-geranyloxy-7-methoxycoumarin (LE-3), respectively, by spectroscopic analysis. Three isolates had no potential O(2)-scavenging and markedly suppressed TPA-induced superoxide (O(2)(-)) generation in differentiated human promyelocytic HL-60 cells. Furthermore, LE-1 and LE-3 reduced both lypopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-induced nitric oxide (NO) generation in mouse macrophage RAW 264.7 cells. Similarly, they were found to be NO generation inhibitors rather than scavengers by measuring the extracellular L-citrulline levels. The occurrence of these coumarins in a lemon fruit was abundant in the flavedo of the peel based on quantitative analysis using high-performance liquid chromatography (HPLC). The present study suggests that the coumarins in lemon fruit are promising chemopreventive agents by inhibiting radical generation.
OBJECTIVE AND IMPORTANCE: Compression of the medulla oblongata by a tortuous vertebral artery is rare. We report two patients with this lesion who were treated with vascular decompression of the vertebral artery. CLINICAL PRESENTATION: A 36-year-old man developed right hemiparesis with lower cranial nerve deficits, and a 47-year-old man developed left lower cranial nerve deficits and left cerebellar dysfunction. In both patients, magnetic resonance imaging revealed a tortuous vertebral artery compressing the medulla oblongata. INTERVENTION: In both patients, the compressed medulla oblongata was treated by detaching the vertebral artery from the medulla oblongata, shifting it, and anchoring it to the nearby dura mater. Postoperatively, both patients are asymptomatic and have returned to their previous jobs. CONCLUSION: Although compression of the medulla oblongata by a tortuous vertebral artery is rare, it can cause brainstem dysfunction. Magnetic resonance imaging clearly revealed the vascular compression in these patients. Surgical treatment was effective. The symptoms related to a tortuous vertebral artery and some techniques for surgical treatment are discussed. Awareness of this rare lesion is necessary to ensure appropriate treatment.
Cereulide is the causative toxin of the emetic type of food-borne illness caused by Bacillus cereus. This toxin was previously shown to be associated with fulminant liver failure in a human case. Mice were injected i.p. with synthetic cereulide and the development of histopathological changes was examined. Hepatocytes showed mitochondrial swelling with loss of cristae, and dose-dependent increase of small fatty droplets. These microsteatotic hepatocytes were distributed mainly in the pericentral area. At higher cereulide doses, massive degeneration of hepatocytes occurred. The serum values of hepatic enzymes were highest on days 2-3 after the inoculation of cereulide, and rapidly decreased thereafter. General recovery from the pathological changes and regeneration of hepatocytes was observed after 4 weeks.
OBJECTIVE: To determine the clinical and prognostic value of identifying metabolic abnormalities of myocardial fatty acid metabolism in idiopathic dilated cardiomyopathy using iodine-123 beta-methyl-iodophenyl pentadecanoic acid (123I BMIPP). SETTING: Cardiac care division in national hospital. PATIENTS: 32 consecutive patients with idiopathic dilated cardiomyopathy in whom both 123I BMIPP and thallium-201 myocardial single photon emission computed tomography were performed. METHODS: The uptake of each tracer was scored visually from 0 (normal) to 3 (defect) in 17 segments (eight basal, eight midventricular, and one apical). A total score for all 17 segments was compared with clinicopathological variables. Prognostic value of mismatches between the two tracers were also evaluated. RESULTS: The 123I BMIPP total score was correlated with pulmonary capillary wedge pressure (r = 0.68, p < 0.001), left ventricular end diastolic pressure (r = 0.65, p < 0.001), percentage fractional shortening at six months' follow up (r = -0.58, p = 0. 001), myocyte diameter (r = 0.66, p < 0.001), and percentage area of interstitial fibrosis (r = 0.69, p < 0.001) measured by morphometry in the biopsy specimens. During a mean (SD) follow up of 20 (11) months, deterioration of the New York Heart Association functional class was observed in 11 of the 32 patients; four of these died. Segments with a greater decrease in 123I BMIPP than thallium-201 uptake (type B mismatching) were often observed in patients with deterioration (88/187, 29% v 58/357, 16%; p < 0.001). CONCLUSIONS: The extent of the abnormality of myocardial fatty acid metabolism in idiopathic dilated cardiomyopathy reflects the severity of haemodynamic deterioration and histopathological changes. Type B mismatching is one of the important prognostic indicators in idiopathic dilated cardiomyopathy.
BACKGROUND: L-selectin (CD62L) and Mac-1 (CD11b/CD18) play a crucial role in the infiltration of eosinophils. However, changes in CD62L and CD11b expression on eosinophils after stimulation with cytokines were little studied. METHODS: Eosinophils in peripheral blood of healthy volunteers were purified and cultured with interleukin-5 (IL-5), granulocyte/macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma). After up to 24 h incubation, CD62L and CD11b expression were examined using flow cytometry. The effects of dexamethasone (Dex), cycloheximide (CHX) or theophylline on CD62L expression on IFN-gamma-stimulated eosinophils were also studied. RESULTS: IL-5 or GM-CSF downregulated CD62L and upregulated CD11b expression on eosinophils after 30 min stimulation. Conversely, IFN-gamma upregulated CD62L after 12 h stimulation in a time- and dose-dependent manner, and had no effect on CD11b expression. Dex, CHX or theophylline dose-dependently decreased CD62L expression on IFN-gamma-stimulated eosinophils. CONCLUSIONS: IFN-gamma is a particular cytokine which can increase CD62L expression on circulating or infiltrated human eosinophils. It is suggested that protein synthesis and intracellular cAMP participate in the increase in L-selectin expression on IFN-gamma-stimulated eosinophils.
N-Oxidation of benzydamine (BZY) mediated by flavin-containing monooxygenase (FMO) was evaluated by microdialysis in vivo in different regions of rat brain and liver. The probe was implanted into local regions of the brain, such as the olfactory bulb, cerebral cortex, corpus striatum, hippocampus and cerebellum, or the hepatic lobe. By perfusing BZY via the probe, BZY N-oxide was identified in the dialysate. The estimated concentrations of BZY N-oxide in extracellular fluid were almost the same as those in the olfactory bulb, hippocampus and cerebral cortex, half the concentration in the hepatic lobe; however, the concentration in the corpus striatum was lower and that in the cerebellum was higher than in the other regions. These results demonstrate that the extracellular concentration of BZY N-oxide formed in vivo was unexpectedly high in every brain region.
Right ventricular thrombus is a very rare manifestation of cardiovascular Behcet's disease. A 25-year-old man was admitted to hospital due to cough and fever of unknown origin. He experienced repetitive pulmonary embolism due to a right ventricular thrombus, which was surgically removed. A diagnosis of Behcet's disease was made based on his clinical course and the histological findings of the right ventricular wall and the skin lesion. He was quickly relieved of his symptoms after warfarinization and cyclosporine therapy.
We report a case of IgM-lambda type monoclonal gammopathy of undetermined significance showing non-specific anti-streptolysin O activity of extremely high level. An 83-year-old man developed high grade fever, cough and sputum. He was admitted to our hospital under a diagnosis of acute pneumonia by chest X-ray. He showed anti-streptolysin O (ASO) activity in extremely high level measured by a latex immunoaggregation method (LA-method). Although antibiotics cured the acute pneumonia, the ASO activity had remained in high level. Serum protein electrophoresis disclosed existence of M-protein and the M-protein was found to be IgM, lambda class by immunoelectrophoresis. The ASO activity measured by the LA method was ascribed to the M-protein because the level of M-component shown by the electrophoresis was decreased by absorption of the serum with streptolysin O-coated latex beads that were used in the LA-method. However, ASO activity measured by Rantzs-Randall method was in normal level. The ASO activity measured by the LA-method was absorbed with bovine serum albumin coated latex beads without streptolysin O. Therefore, it was concluded that the M-protein was not reacted with streptplysin O itself but was reacted with bovine serum albumin coated latex beads. The ASO activity of extremely high level in our case was non-specific reaction caused by the M-protein.
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