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Biomedical subjects

H Komori

Publications and source records attributed to H Komori.

At least 19 recordsLinked to original sources
PubMed2006

Identification of novel E2F1 target genes regulated in cell cycle-dependent and independent manners.

The transcription factor E2F mediates cell cycle-dependent expression of genes important for cell proliferation in response to growth stimulation. To further understand the role of E2F, we utilized a sensitive subtraction method to explore new E2F1 targets, which are expressed at low levels and might have been unrecognized in previous studies. We identified 33 new E2F1-inducible genes, including checkpoint genes Claspin and Rad51ap1, and four genes with unknown function required for cell cycle progression. Moreover, we found three groups of E2F1-inducible genes that were not induced by growth stimulation. At least, two groups of genes were directly induced by E2F1, indicating that E2F1 can regulate expression of genes not induced during the cell cycle. One included Neogenin, WASF1 and SGEF genes, which may have a role in differentiation or development. The other was the cyclin-dependent kinase inhibitor p27(Kip1), which was involved in suppression of inappropriate cell cycle progression induced by deregulated E2F. E2F1-responsive regions of these genes were located more upstream than those of typical E2F targets and did not have typical E2F sites. These results indicate that there are groups of E2F1 targets, which are regulated in a distinct manner from that of typical E2F targets.

Animals↗
PubMed2005

An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus.

OBJECTIVE: To identify the genetic loci regulating the incidence and severity of renal autoimmune vasculitis developed in murine lupus. METHODS: Vasculitis of renal arteries was histopathologically evaluated in MRL/Mp-Fas(lpr) (MRL/lpr), C57BL/6-Fas(lpr) (B6/lpr), (MRL/lpr x B6/lpr) F1, and MRL/lpr x (MRL/lpr x B6/lpr) F1 backcross mice. Using genomic DNA samples of the backcross mice, genome-wide scans, association studies, and linkage analyses were carried out based on genotypes of polymorphic microsatellite markers. Correlations of vasculitis grade and levels of various autoantibodies were also evaluated. RESULTS: Two recessive susceptibility loci of the MRL allele were identified on chromosomes 4 and 1, which had previously been defined as the autoimmune related loci termed Arvm1 and Sle-1/Nba2, respectively. The former was epistatic to the latter in a female specific manner. The titre of antinuclear autoantibody (ANA) in IgG class, but not ANA in IgM class or anti-dsDNA in either IgG or IgM class, correlated significantly with vasculitis grade. CONCLUSIONS: The present loci have been reported in previous studies using a different set of murine strains, suggesting that they are of importance in the development of autoimmune vasculitis in murine models. The concomitance of autoimmune vasculitis and IgG ANA suggests a shared genetic factor regulating these traits.

Animals↗
PubMed2001

Crystal structure of thermostable DNA photolyase: pyrimidine-dimer recognition mechanism.

DNA photolyase is a pyrimidine-dimer repair enzyme that uses visible light. Photolyase generally contains two chromophore cofactors. One is a catalytic cofactor directly contributing to the repair of a pyrimidine-dimer. The other is a light-harvesting cofactor, which absorbs visible light and transfers energy to the catalytic cofactor. Photolyases are classified according to their second cofactor into either a folate- or deazaflavin-type. The native structures of both types of photolyases have already been determined, but the mechanism of substrate recognition remains largely unclear because of the lack of structural information regarding the photolyase-substrate complex. Photolyase from Thermus thermophilus, the first thermostable class I photolyase found, is favorable for function analysis, but even the type of the second cofactor has not been identified. Here, we report the crystal structures of T. thermophilus photolyase in both forms of the native enzyme and the complex along with a part of its substrate, thymine. A structural comparison with other photolyases suggests that T. thermophilus photolyase has structural features allowing for thermostability and that its light-harvesting cofactor binding site bears a close resemblance to a deazaflavin-type photolyase. One thymine base is found at the hole, a putative substrate-binding site near the catalytic cofactor in the complex form. This structural data for the photolyase-thymine complex allow us to propose a detailed model for the pyrimidine-dimer recognition mechanism.

Amino Acid Sequence↗
PubMed2001

Functional recovery and regeneration of descending tracts in rats after spinal cord transection in infancy.

STUDY DESIGN: The functional recovery of rats that underwent spinal cord transection in infancy was evaluated by multimodal examination (functional tests, electrophysiologic evaluation, tract-tracing) to determine the basis for the recovery. OBJECTIVES: To determine whether the hind limb function in rats that underwent spinal cord transection in infancy is regained completely, which descending tracts regenerate after the transection, and whether the functional recovery is correlated with axonal reconnection. SUMMARY OF BACKGROUND DATA: It is widely accepted that a newborn rat recovers its hind limb function after spinal cord transection even without any specific treatments. This functional recovery might be attributed to possible regeneration of some descending pathways, although there is a counterargument that well-trained spinal cord reflexes may bring about functional compensation. METHODS: The thoracic spinal cord of infant rats was completely transected at Th10 when they were 2 weeks of age. Multimodal functional tests and electrophysiologic studies were performed 5 weeks later. Some recovered rats (i.e., those able to walk after the transection) underwent spinal cord retransection, with subsequent reevaluation of locomotion and muscle-evoked potentials. At 6 weeks after the initial transection, tract-tracing studies were performed in some animals. RESULTS: A motor performance score detected the functional differences between the control and the recovered rats. Muscle-evoked potentials of hind limbs after electrical stimulation to the brain were recorded in some of the recovered rats, but never in the unrecovered rats. Moreover, the muscle-evoked potentials of the recovered rats disappeared after spinal cord retransection that resulted in loss of voluntary movement. Morphologic studies in two rats provided evidence that reconnection of rubrospinal, vestibulospinal, and reticulospinal tracts had occurred, whereas corticospinal regeneration was not detected. CONCLUSIONS: It can be concluded that the hind limb function of rats that underwent spinal cord transection in infancy was partially regained; that axonal regeneration of the rubrospinal, vestibulospinal, or reticulospinal tracts was demonstrated, whereas the reconnection of the corticospinal tract was not observed; and that the axonal regeneration of these tracts is involved in the functional recovery.

Animals↗
PubMed2001

Initial and long-term results of directional coronary atherectomy in unprotected left main coronary artery.

Angioplasty in the unprotected left main coronary artery (LMCA) has been controversial. Recently, several studies have suggested that new procedures and devices such as directional coronary atherectomy (DCA) and stents may change this situation. Although there are many reports of unprotected LMCA stenting, there are few reports of DCA of this lesion. Therefore, initial and long-term results were evaluated in 101 patients who underwent DCA for unprotected LMCA in our hospital. Emergency procedures were performed in 15 patients and electively in 86 patients. Scheduled angiographic follow-up was routinely performed, and all patients were clinically followed for >4 months after DCA. Technical success was achieved in 99%, and in-hospital outcomes were cardiac death (2%), noncardiac death (4%), Q-wave myocardial infarction (1%), non-Q-wave myocardial infarction (8.9%), coronary artery bypass grafting (0%), and repeat angioplasty (4%). In-hospital results varied considerably, depending on presentation. In-hospital mortality was significantly higher in the emergency, left ventricular ejection fraction < or =35%, and high-risk surgical subgroups. The angiographic restenosis rate was 20.4% at follow-up, and its predictor was postminimal lumen diameter by multivariate analysis. Mean clinical follow-up was 2.8 years; estimated 1- and 3-year survival rates were 87% and 80.7%, respectively. The cardiac survival rate of the low-risk surgical subgroup was significantly higher than that of the high-risk surgical subgroup (p <0.05). Thus, our data show that DCA can be performed safely and effectively in unprotected LMCA with an acceptable low restenosis rate and high survival rate.

Adult↗
PubMed2001

Requirement of nitric oxide for murine oocyte maturation, embryo development, and trophoblast outgrowth in vitro.

We investigated the extent to which NO participates in the developmental competence (oocyte maturation, fertilization and embryo development to blastocyst) using an in vitro culture system adding sodium nitroprusside (SNP), NO donor, and NOS inhibitor (N-omega-nitro-L-arginine methyl ester, L-NAME). We also assessed the effects of NO/NOS system on blastocyst implantation using an in vitro trophoblast outgrowth assay. The treatment of low concentrations of SNP (10(-7) M) significantly stimulated meiotic maturation to metaphase II stages in cumulus enclosed oocytes. In contrast, 10(-3) and 10(-5) M L-NAME demonstrated a significant suppression in resumption of meiosis. This inhibition was reversed by the addition of SNP. No development beyond the four-cell stage was observed by the addition of high concentration of SNP (10(-3) M). Inhibition of embryo development, especially the conversion of morulae to blastocysts, was also observed in the treatment of lower doses of SNP (10(-5) and 10(-7) M). Similarly, inhibition of NO by NOS inhibitor resulted in the dose-dependent inhibition of embryo development and hatching rates, but the concomitant addition of SNP with L-NAME reversed the inhibitory effect by each SNP or L-NAME treatment. Furthermore, low concentration of SNP (10(-7) M) but not high concentration of SNP (10(-3) M) significantly stimulated trophoblast outgrowth, whereas the addition of L-NAME suppressed the spreading of blastocysts in a dose-dependent manner. These results suggest that NO may have crucial roles in oocyte maturation and embryogenesis including the process of implantation. The observed differences in required amount of NO and the sensitivity to cytotoxicity of NO in each developmental stage embryos may also suggest that NO/NOS system is tightly regulated in developmental stage specific manner.

Animals↗
PubMed2001

Budd-Chiari syndrome and extrahepatic portal obstruction associated with congenital antithrombin III deficiency.

We report a patient with Budd-Chiari syndrome (BCS) and extrahepatic portal obstruction (EHO) associated with congenital antithrombin (AT) III deficiency. A 35-year-old man was admitted to Nishi Kobe Medical Center for evaluation of abnormal intrahepatic veins. By various imaging modalities, BCS and EHO were diagnosed. Laboratory data revealed parallel decreases in activity and antigen concentration of AT III despite normal liver function. Taken together, the etiology of both BCS and EHO was considered to be thrombosis, associated with congenital AT III deficiency. Two years after beginning warfarin therapy, the patient has no symptoms and his liver function remains normal. Anticoagulant therapy is considered useful for preventing progression of the disease.

Adult↗
PubMed2001

A case of localized primary sclerosing cholangitis mimicking intrahepatic bile duct cancer.

A 75-year-old woman with chronic hepatitis was regularly followed-up in our hospital. A computed tomography (CT) scan revealed an obviously enlarged intrahepatic bile duct in the posterior branch of the left lateral segment. Percutaneous cholangiography revealed an enlarged posterior branch of the left lateral segment and a narrow stenotic region at the root of this branch. We diagnosed her as having intrahepatic bile duct cancer, and a left lateral segmentectomy of the liver was performed. However, microscopic examination of the resected specimens revealed peribiliary fibrosis in the stenotic bile duct and other areas of the intrahepatic bile duct with no malignant cells. Thus, the final diagnosis was made to be primary sclerosing cholangitis. We must consider primary sclerosing cholangitis in the differential diagnosis of localized stenosis of the intrahepatic bile duct.

Journal Article↗
PubMed2001

Vascularity of advanced gastric carcinoma: evaluation by using power Doppler imaging.

BACKGROUND: We investigated the vascularity of advanced gastric adenocarcinomas by using percutaneous power Doppler imaging. METHODS: Seventeen patients with gastric cancer and 10 without a gastric tumor, but with a slightly thick gastric wall in the B-mode ultrasound, were investigated with the use of power Doppler imaging. The color signals of the gastric lesion were graded as follows: 1, no color signals or the same as the surroundings; 2, color signals were slightly increasing; and 3, color signals were obviously increasing. RESULTS: The color signals of three patients were graded 1, those of eight patients were graded 2 and those of six patients were graded 3 in the gastric cancer group. The color signals of all 10 patients without a gastric tumor were grade 1. This difference was statistically significant (P = 0.0002). CONCLUSIONS: Power Doppler imaging showed vascularity of gastric cancer increasing in the majority of patients (14 of 17: 82%). Thus, power Doppler imaging might be a good screening examination method for gastric cancer.

Adenocarcinoma↗
PubMed2001

The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene.

It has been suggested that matrix metalloproteinase-3 (MMP-3, stromelysin-1) has an important role in the degeneration of intervertebral discs (IVDs). A human MMP-3 promoter 5A/6A polymorphism was reported to be involved in the regulation of MMP-3 gene expression. We suggest that IVD degeneration is associated with 5A/6A polymorphism. We studied 54 young and 49 elderly Japanese subjects. Degeneration of the lumbar discs was graded using MRI in the younger group and by radiography in the elderly. 5A/6A polymorphism was determined by polymerase-chain reaction-based assays. We found that the 5A5A and 5A6A genotype in the elderly was associated with a significantly larger number of degenerative IVDs than the 6A6A (p < 0.05), but there was no significant difference in the young. In the elderly, the IVD degenerative scores were also distributed more highly in the 5A5A and 5A6A genotypes (p = 0.0029). Our findings indicate that the 5A allele is a possible risk factor for the acceleration of degenerative changes in the lumbar disc in the elderly.

Adolescent↗
PubMed2001

[A case of giant dumbbell shaped schwannoma with massive pleural effusion].

A 58-year-old female was admitted to the hospital complaining of dyspnea. The chest roentgenogram and CT scan revealed a large mediastinum tumor and massive pleural effusion in the right hemithorax. The diagnosis of lung cancer with carcinomatous pleulitis was performed through thoracocentesis an treatment of chemotherapy was chosen. After 6 years, she was admitted again to the hospital complaining of dull pain in the right leg. Chest CT scan and MRI showed a giant dumbbell shaped mass connected to the spinal canal. The tumor was larger than that of six years ago and diagnosed as schwannoma by CT-guided pericutaneous needle biopsy. At operation, hemilaminectomy of Th 1-3 was done first, and total tumor resection was performed through posterolateral thoracotomy. Intrathoracic adhesion was severe and it was difficult to control air leakage from the lung, thoracoplasty was performed.

Female↗
PubMed2001

[A case of polyarteritis nodosa limited to both calves with a low titer of MPO-ANCA].

A-57-year-old woman had suffered from high fever, general malaise, and loss of weight (6 kg) since January, 2000. She was admitted to our hospital in May, 2000, because of gait disturbance following to swelling of bilateral calves with severe pain beside the above symptoms. Laboratory data showed leukocytosis (WBC 10,000/microliter), high ESR (98 mm/hr), positive CRP (3.43 mg/dl), positive ANA (x160), high titer of RA (266 IU/l), and a low titer of MPO-ANCA (18 EU). T 2-weighted magnetic resonance image (MRI) showed intensity area of the M. gastrocnemius. Skin biopsy specimens of the right leg demonstrated necrotizing arteritis of small-sized arteries. These findings supported the diagnosis of limited type of polyarteritis nodosa (PN). In this report, we demonstrate a rare case of PN limited to both calves with characteristic MRI findings and a low titer of MPO-ANCA.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

[Role of new devices for angioplasty in the unprotected left main coronary artery].

OBJECTIVES: Angioplasty for the unprotected left main trunk remains controversial, but new procedures and devices such as directional coronary atherectomy and stenting have improved the results. We compared the results of angioplasty with the inflexible balloon and new devices. METHODS: The procedures were performed in 239 consecutive lesions in 160 patients between April 1986 and March 2000. This study excluded emergency cases and repeat angioplasty cases, and included 120 initial and elective cases. Initial and long-term results were compared between the balloon group (n = 29) and the new device group (n = 91). RESULTS: Lesion success rate was lower in the balloon group (90% vs 100%, p < 0.05), but there were no significant differences in in-hospital results including cardiac death (0% vs 0%), noncardiac death (0% vs 3.3%), Q-wave myocardial infarction (0% vs 2.2%), non-Q wave myocardial infarction (3.4% vs 6.6%), bypass surgery (0% vs 0%) and repeat angioplasty (6.9% vs 1.1%). Quantitative angiography showed significant improvements in minimal lumen diameter (mean 2.17 vs 3.16 mm, p < 0.001) and percentage diameter stenosis (mean 31% vs 13%, p < 0.001) in the new device group after the procedures. The minimum lumen diameter remained larger at 3 (p < 0.001) and 6 months (p < 0.05) in the new device group. Therefore, angiographic restenosis rate was higher in the balloon group (55% vs 21%, p < 0.005). Five-year survival rate showed no significant difference between the groups (75.0% vs 83.8%). CONCLUSIONS: New devices significantly improved the minimal lumen diameter after angioplasty for unprotected left main trunk disease, and lead to significant improvement of restenosis rate at follow-up.

Aged↗
PubMed2000

Initial and 6-month results of biodegradable poly-l-lactic acid coronary stents in humans.

BACKGROUND: Although metallic stents are effective in preventing acute occlusion and reducing late restenosis after coronary angioplasty, many concerns still remain. Compared with metallic stents, poly-l-lactic acid (PLLA) stents are biodegradable and can deliver drugs locally. The aim of this study was to evaluate the feasibility, safety, and efficacy of the PLLA stent. METHODS AND RESULTS: Fifteen patients electively underwent PLLA Igaki-Tamai stent implantation for coronary artery stenoses. The Igaki-Tamai stent is made of a PLLA monopolymer, has a thickness of 0.17 mm, and has a zigzag helical coil pattern. A balloon-expandable covered sheath system was used, and the stent expanded by itself to its original size with an adequate temperature. A total of 25 stents were successfully implanted in 19 lesions in 15 patients, and angiographic success was achieved in all procedures. No stent thrombosis and no major cardiac event occurred within 30 days. Coronary angiography and intravascular ultrasound were serially performed 1 day, 3 months, and 6 months after the procedure. Angiographically, both the restenosis rate and target lesion revascularization rate per lesion were 10.5%; the rates per patient were 6.7% at 6 months. Intravascular ultrasound findings revealed no significant stent recoil at 1 day, and they revealed stent expansion at follow-up. No major cardiac event, except for repeat angioplasty, developed within 6 months. CONCLUSIONS: Our preliminary experience suggests that coronary PLLA biodegradable stents are feasible, safe, and effective in humans. Long-term follow-up with more patients will be required to validate the long-term efficacy of PLLA stents.

Adult↗
PubMed2000

Regulation of UDP-glucose:ceramide glucosyltransferase-1 by ceramide.

We report that the expression of mRNA and the activity of UDP-glucose:ceramide (Cer) glucosyltransferase-1 (GlcT-1) of human hepatoma Huh7 and mouse melanoma B16 cells increases after treatment with bacterial sphingomyelinase or upon addition of short-chain Cer. Interestingly, however, GlcT-1 gene transcription was not increased by Cer when GlcT-1 cDNA was introduced with the CMV promoter in GlcT-1-deficient GM95 cells, suggesting that the normal promoter region of GlcT-1 gene is essential for the response. The conversion of C6-Cer to C6-GlcCer occurred much more rapidly in GlcT-1-overexpressing Huh7 cells than in mock transfectants. As a result, GlcT-1-overexpressing cells acquired a greater resistance to C6-Cer-mediated cell death.

Animals↗
PubMed2000

The iteron regions necessary for the RepE-iteron interaction in vivo in mini-F plasmids of Escherichia coli.

We have determined the nucleotide positions of an incC iteron essential for RepE binding by analyzing mutated incC iterons defective in exerting incompatibility towards mini-F plasmids. The mutations affecting this incompatibility occurred mostly at two positions within the incC iteron, i.e. an iteron conserved position and a mini-F specific position. Most of the iterons with a base-change at either of these two positions had lost the binding affinity for RepE. This agrees with the crystallographic structure of the RepE-iteron complex which showed that the N and C terminal domains of RepE interact with the two major grooves on one face of the iteron DNA. These grooves contain the iteron conserved and mini-F specific positions necessary for RepE binding. Thus the binding mode may be common to in the case of mini-F like plasmids.

Bacterial Proteins↗