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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 235 records · Page 13Linked to original sources
PubMed1999

Transition protein 4 from boar late spermatid nuclei is a topological factor that stimulates DNA-relaxing activity of topoisomerase I.

Transition protein 4 (TP4) from boar late spermatid nuclei, having higher affinity for double-stranded DNA and a local melting activity of DNA, stimulated SV40 DNA-relaxing activity of eukaryotic topoisomerase I at TP4/DNA molar ratios of 6.6-11. A TP4-spermidine mixture stimulated the activity of topoisomerase I much more than spermidine alone, but no more than TP4 alone, and poly-L-arginine did not. These results suggest that TP4 contributes to the chromatin reorganization in the late spermatid nuclei from nucleosomal-type structure with negatively supercoiled DNA to nucleoprotamine structure with no supercoiled DNA.

Animals↗
PubMed1999

Doubling time of serum CA 19-9 in the clinical course of patients with pancreatic cancer and its significant association with prognosis.

BACKGROUND AND OBJECTIVES: Pancreatic cancer is generally a disease with a poor prognosis, and relationship between change of serum CA 19-9 level and progression of this disease was investigated with regard to clinical pace of disease and tumor growth. METHODS: CA 19-9 doubling time was examined in 75 patients with pancreatic cancer, including 41 inoperable cases. Then, its relation with their prognosis and change in tumor was evaluated. RESULTS: The doubling time of CA 19-9 and CEA could be calculated in 90.2% and 58.5% of patients with inoperable pancreatic cancer. CA 19-9 doubling time was clearly associated with survival time in inoperable and palliatively operated cases, but not with sex, age, site of the lesion, or liver metastasis, and was significantly correlated with the tumor volume doubling time. CONCLUSIONS: Examination of CA 19-9 doubling time may be useful in clinical evaluation of the prognosis for patients with pancreatic cancer and could possibly prove valuable in terms of the analysis of the growth process in this disease.

Adult↗
PubMed1999

Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia.

BACKGROUND: Recently, an internal tandem duplication of the FLT3 gene (FLT3/ITD) was found in 20% of adult cases of acute myelogenous leukemia (AML), and this length abnormality was suggested to be associated with leukemic progression. PROCEDURE: We examined the mRNA expression of the FLT3 gene by using reverse transcription-polymerase chain reaction (RT-PCR) in 64 children with AML, and further abnormal transcripts were cloned and sequenced. RESULTS: An unexpected longer product was found in seven patients (11%) by RT-PCR of the FLT3 gene. Sequence analysis of these abnormal products revealed the presence of tandemly duplicated fragments in all seven patients. Three factors were identified to be associated with high incidence of FLT3/ITD; older patients (> or = 10 years) (P = 0.049), high WBC count (> or = 50,000/microl) at presentation (P = 0.002), and M3 in FAB subtypes (P = 0.002). Induction failure was observed in 3 (43%) of 7 patients with FLT3/ITD. Only FLT3/ITD was identified as a significant risk factor for induction failure by univariate analysis (P = 0.013), although it was not significant by multivariate analysis (P = 0.11). The Kaplan-Meier estimate of event-free survival rate at 5 years was 14% for patients with FLT3/ITD, which was significantly lower in comparison with 69% for patients without FLT3/ITD (P = 0.003). This finding was also identified by multivariate analysis (P = 0.01). CONCLUSIONS: In this study, FLT3/ITD was observed in 11% of childhood AML and identified to be associated with poor prognosis. A large prospective study with uniform treatment is necessary to confirm our results.

Adolescent↗
PubMed1999

Fas and Fas ligand interaction induces apoptosis in inflammatory myopathies: CD4+ T cells cause muscle cell injury directly in polymyositis.

OBJECTIVE: To investigate the involvement of the Fas/Fas ligand (Fas/FasL) system in the inflammatory myopathies. METHODS: Frozen muscle sections obtained from 7 patients with polymyositis (PM), 4 patients with dermatomyositis (DM), and 3 controls were studied by immunochemistry. Apoptosis was detected by DNA electrophoresis and in situ labeling using the TUNEL method. RESULTS: Fas was detected on muscle fibers and infiltrating mononuclear cells (MNC) in 6 PM patients and 2 DM patients. FasL was expressed mainly on CD4+ T cells and some CD8+ T cells, and on macrophages surrounding Fas-positive muscles in 4 PM patients and 1 DM patient. In 3 of the 5 patients with FasL-positive MNC, the TUNEL method showed that both invaded myonuclei and MNC underwent apoptosis. Chromosomal DNA from the muscle tissue of these patients showed ladder formation. CONCLUSION: Fas/FasL is involved in muscle cell apoptosis in at least 2 of the inflammatory myopathies, PM and DM. Although CD8+-mediated cytotoxicity is thought to be the main mechanism of muscle injury in PM, our data suggest that CD4+ T cells also directly cause muscle cell damage.

Apoptosis↗
PubMed1999

C-myc antisense oligodeoxynucleotides can induce apoptosis and down-regulate Fas expression in rheumatoid synoviocytes.

OBJECTIVE: To investigate the role of c-myc in the pathogenesis of rheumatoid arthritis (RA) and the mechanism of synovial apoptosis. METHODS: Using cultured human synoviocytes from patients with RA and c-myc antisense oligodeoxynucleotides (AS ODN), we examined the inhibition of cell proliferation by the MTT assay and the induction of apoptosis with TUNEL staining and fluorescence microscopy. In addition, the effect of c-myc on down-regulation of Fas expression was analyzed by flow cytometry, cytotoxicity assay, and reverse transcriptase-polymerase chain reaction. RESULTS: Treatment with c-myc AS ODN induced inhibition of cell proliferation, along with down-regulation of c-Myc protein and c-myc messenger RNA (mRNA) expression. The morphologic changes of synovial cell death were typical of apoptosis. In addition, c-myc AS ODN treatment down-regulated expression of Fas mRNA but not Fas antigen. Analysis of the involvement of the caspase cascade revealed that the cytotoxic activity of c-myc AS ODN was completely blocked by inhibitors of both caspase 1 (YVAD-FMK) and caspase 3 (DEVD-FMK). CONCLUSION: Our results strongly suggest that c-myc AS ODN might be a useful therapeutic tool in RA and clarify that cell death by c-myc AS ODN is induced through the caspase cascade, similar to Fas-induced apoptosis. In addition, combination therapy with anti-Fas antibody and c-myc AS ODN reduced Fas-dependent cytotoxicity.

Aged↗
PubMed1999

Characteristics of the production of active oxygen species from adherent and non-adherent neutrophils.

Our objective was to evaluate the characteristics of the production of AOS from the neutrophils that had adhered to the endothelial cells, fibronectin or polystyrene, using the method of electron paramagnetic resonance (EPR) spin trapping. Neutrophils and endothelial cells were isolated from human venous blood and umbilical veins, respectively. AOS production from neutrophils was not elicited only by adhesion. The stimulation of adherent neutrophils with phorbol myristate acetate (PMA) induced the production of AOS. The production of AOS from adherent neutrophils to endothelial cells, but not to fibronectin or polystyrene, decreased with the interval time between the adhesion and the stimulation by PMA. The amount of AOS produced by the neutrophils adherent to fibronectin or polystyrene was maintained for one hour after stimulation with PMA, whereas that by suspended neutrophils gradually decreased with the time after stimulation. Results indicate that adherent and non-adherent neutrophils exhibit differing time course of AOS production.

Cell Adhesion↗
PubMed1999

Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells.

We evaluated the effects of alpha-Toc on surface expression of CD11b/CD18 on polymorphonuclear leukocytes (PMN) stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and oxidized low-density lipoprotein (oxLDL). Incubation of PMN with fMLP (1 microM) or oxLDL (100 microg/mL) increased CD11b/CD18 expression; pretreatment with alpha-Toc reduced in a dose-dependent manner. PMN obtained from healthy adults ingesting 600 mg alpha-Toc per day for 10 days were similarly incubated with fMLP or oxLDL; the surface level of CD11b/CD18 was inversely correlated with serum alpha-Toc concentrations. Adherence of PMN to human umbilical vein endothelial cells was increased by fMLP or oxLDL stimulation but reduced by alpha-Toc pretreatment or anti-CD18 monoclonal antibodies. cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) activity in PMN was also assayed. A PKC inhibitor, but not a PKA inhibitor, suppressed CD11b/CD18 up-regulation, and alpha-Toc slightly decreased fMLP- and oxLDL-induced activation of PKC. These results suggest that alpha-Toc may prevent inflammation by both reducing CD11b/ CD18 up-regulation and decreasing PMN-dependent adherence to EC.

CD18 Antigens↗
PubMed1999

Biochemical effect of intra-articular injections of high molecular weight hyaluronate in rheumatoid arthritis patients.

OBJECTIVE: The purpose of this study was to analyze the biochemical characteristics of synovial fluids after treatment of patients with rheumatoid arthritis (RA) with intra-articularly injected hyaluronate (HA). TREATMENT: In a double-blind study, 13 patients received intra-articular injections of 1% HA in phosphate buffered saline (PBS) while 13 other patients were injected 0.01% HA in PBS, as the control group. Injections were administered once a week for five weeks. METHODS: Clinical efficacy and characteristics of synovial fluid were compared between groups. RESULTS: Significant clinical improvement was observed in the HA-treated group compared to the control group. The viscosity of retained synovial fluid increased. Stringing and HA concentration increased significantly whereas the concentrations of protein and chondroitin sulfate 4 and 6 decreased significantly. The HA molecular weight remained the same in both groups. CONCLUSION: Intra-articular HA injection altered the properties of synovial fluid and proved efficacious for patients with RA.

Arthritis, Rheumatoid↗
PubMed1999

Mea2/Golga3 gene is disrupted in a line of transgenic mice with a reciprocal translocation between Chromosomes 5 and 19 and is responsible for a defective spermatogenesis in homozygotes.

A line of transgenic mouse T604 transmitted a transgene to progeny together with a set of chromosomes with a reciprocal translocation. The transgene was integrated at a single site in the translocated chromosomes, as revealed by fluorescence in situ hybridization. The transgenic hemizygous males, also heterozygous for the translocation of chromosomes, showed apparently normal spermatogenesis, while the males homozygous for the transgene as well as for the translocated chromosomes showed a defect in spermatogenesis. Considering that the genetic rearrangement by either insertion of the transgene or the chromosome translocation in the T604 mouse line might have caused a recessive mutation in a gene indispensable for spermatogenesis, we have mapped the transgene integration site and the translocation breakpoints in mouse chromosomes. Linkage analysis with SSLP markers showed that the loci for the transgene and the translocation breakpoints were closely located to D5Mit24 on Chromosome (Chr) 5, and to a region between D19Mit19 and D19Jpk2 on Chr 19. Mea2 gene, mapped only 2 cM from D5Mit24 and known to show male-specific enhanced expression in the testis, was analyzed as a candidate for the gene disrupted in T604 transgenic mice. Southern blot analysis revealed that Mea2 gene was indeed disrupted in T604 mice, and Northern blot analysis of the testis RNA showed that the expression of Mea2 was annihilated in the testis of T604 transgenic homozygotes.

Animals↗
PubMed1999

Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus.

The BAT2 gene lies within the class III region of the major histocompatibility complex. We investigated the frequency of the BAT2 microsatellite alleles (BAT2) in 74 young-onset insulin-dependent diabetes mellitus (IDDM) patients, 51 adult-onset IDDM patients, and 85 normal control subjects, and assessed the associations among these BAT2 alleles, TNFa microsatellite alleles (TNFa), and HLA-DRB1 alleles. The frequency of the BAT2.9 allele was significantly increased in the young-onset IDDM patients (12.8 vs 4.1%, Pc=0.04896), whereas the frequency of BAT2.12 allele was significantly decreased in young-onset IDDM patients (0.0 vs 11.8%, Pc=0.00002) compared with control subjects. The BAT2.9 allele was strongly associated with TNFa9 in the young-onset IDDM patients, although no association was found between the BAT2.9 and HLA-DRB1 alleles. The BAT2.12 allele was strongly associated with TNFa13, and with DRB1*1502 in control subjects. These results suggest that the BAT2 microsatellite polymorphism is associated with the age-at-onset of IDDM and possibly with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. However, this association is not independent of TNFa polymorphisms.

Adolescent↗
PubMed1999

Abnormal focal macular electroretinograms in eyes with idiopathic epimacular membrane.

PURPOSE: To study the functional state of the retina beneath an epimacular membrane by means of focal macular electroretinography. METHODS: Focal macular electroretinograms of 30 consecutive patients (age 25 to 75 years) with unilateral idiopathic epimacular membrane were recorded prospectively. The amplitudes and implicit times of the a and b waves and the oscillatory potentials (O1, O2, O3) recorded from the eye with idiopathic epimacular membrane were compared with those of the normal fellow eye. RESULTS: There was a statistically significant reduction in the amplitude of the a wave (P < .001), the b wave (P < .001), and the oscillatory potentials (O1 + O2 + O3; P < .001) of the affected eyes. The reduction of the b-wave amplitude was significantly greater than that of the a wave, resulting in a lower b/a wave ratio (P = .003) in the affected eyes. The reduction in the amplitude of the oscillatory potentials was significantly greater than that of the other two components (P < .001). The implicit times were significantly prolonged for the a wave (P < .001), the b wave (P = .004), and 03 (P < .001). There was a significant correlation between relative b-wave amplitude (affected/normal fellow eye) and the visual acuity (r = -0.50, P = .007). These findings were similar to those we reported for eyes with aphakic cystoid macular edema. CONCLUSIONS: The focal macular electroretinograms in eyes with epimacular membrane disclosed abnormalities that were similar to those of eyes with cystoid macular edema. This suggests that the epimacular membrane probably induced damage to the neurons in the inner retinal layers. Dysfunction of these neurons is one possible cause of visual impairment in this disease.

Adult↗
PubMed1999

Discrimination of liver cirrhosis from chronic hepatitis by measuring the ratio of Aleuria aurantia lectin-reactive serum cholinesterase to immunoreactive protein.

We have previously reported that Aleuria aurantia lectin (AAL)-reactive serum cholinesterase (ChE) activity increases in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) compared with chronic hepatitis (CH) and normal controls (NC), and measurement of AAL-reactive ChE activity is useful in discriminating LC from CH. In the present study, we have demonstrated that the measurement of the ratio of AAL-reactive ChE to immuno-reactive ChE protein (AAL/ChE) is superior to the measurement of only AAL-reactive ChE for differentiating LC from CH. At a cut-off value of 4.0 arbitrary units of AAL/ChE, the diagnostic accuracy was 87.7%. This diagnostic accuracy is similar to that of serum hyaluronan, 88.8%. We also examined whether the AAL/ChE measurement is useful for differentiating Child's stage A LC from chronic active hepatitis (CAH) 2B. When mean + 2SD of AAL/ChE in patients with CAH2B was used as a cut-off value for the specific diagnosis of LC, the diagnostic accuracy was 70.2%. These results demonstrate that measurement of AAL/ChE is useful for discriminating LC from CH.

Cholinesterases↗
PubMed1999

A splicing mutation in the hydroxymethylbilane synthase gene in a Japanese family with acute intermittent porphyria.

OBJECTIVES: Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease caused by a decreased activity of hydroxymethylbilane synthase (HMBS). As far as the gene abnormalities of the HMBS, many different mutations have been reported. In this work, we investigated the presence of mutations in a Japanese family with AIP. DESIGN AND METHODS: A 44-year-old Japanese male and nine members of his family were investigated. All of them were screened by traditional biochemical markers. Mutational analysis was performed using polymerase chain reaction-single strand conformation polymorphism method followed by DNA sequencing. A reliable restriction enzyme cleavage assay was established for the pedigree analysis. RESULTS: The mutation was a splicing mutation, a C to G transversion at position -3 of the acceptor site of intron 11 of the HMBS gene, resulting in the exon 12 skipping. The patient is heterozygous for the mutation, and his father appeared to be the source of the mutant allele. This mutation created a new cleavage site of the Nla III restriction enzyme and could be screened by a amplified fragment from genomic DNA with digestion. Using this cleavage assay, an asymptomatic carrier in the family was definitively identified. CONCLUSIONS: This mutation was first found among Japanese AIP patients, but happened to be the same as reported previously from Europe. A similarity of gene abnormality may suggest that those European and Japanese AIP families have a common ancestor. Molecular investigations on the family members should be applied not only for more accurate diagnosis, but also for understanding the molecular genetic heterogeneity underlying this dominantly inherited enzymopathy.

Adult↗
PubMed1999

Nitric oxide increases hepatic arterial blood flow in rats with carbon tetrachloride-induced acute hepatic injury.

BACKGROUND & AIMS: Little is known about the changes in hepatic blood flow associated with acute hepatic injury. The aim of this study was to investigate the effect of nitric oxide (NO) on hepatic blood flow and the severity of hepatic injury in rats with carbon tetrachloride (CCl4)-induced acute hepatic injury. METHODS: Rats were pretreated with CCl4 to induce acute hepatic injury. Hepatic blood flow was measured using a radioactive microsphere method. The role of NO in the regulation of hepatic blood flow and the severity of hepatic injury was investigated by administering NG-nitro-L-arginine (L-NNA) and aminoguanidine (AG). Plasma nitrite/nitrate levels, hepatic NO synthase (NOS) activity, and expression of hepatic NOS messenger RNA (mRNA) were measured, and histological examinations were performed. RESULTS: Hepatic arterial and portal venous blood flow was increased significantly by CCl4, without any change in mean arterial pressure or cardiac output. L-NNA and AG dose-dependently decreased hepatic arterial blood flow, with the highest dose resulting in complete blockade of hepatic arterial dilation, but failed to change portal venous blood flow. Histologically, administration of AG aggravated the hepatic injury in CCl4-treated rats. Plasma nitrite/nitrate levels and hepatic NOS activity were increased significantly by CCl4 treatment. Inducible NOS mRNA was detected in CCl4-treated rats but not in the controls. CONCLUSIONS: The results of this study suggest that the increased hepatic arterial blood flow in CCl4-induced acute hepatic injury is mediated by excessive NO production and up-regulated by inducible NOS, which plays a role in reducing hepatic injury.

Acute Disease↗
PubMed1999

Increased levels of aldose reductase in peripheral mononuclear cells from type 2 diabetic patients with microangiopathy.

Aldose reductase (AR) protein was measured in peripheral mononuclear cells (PMCs) from 55 patients with type 2 diabetes by a two-site ELISA using anti-human AR monoclonal antibody. AR levels did not correlate with age, duration of diabetes, and HbAlc. Furthermore, no significant differences were found in AR levels between the patients and healthy subjects. Thirty seven patients had at least one of diabetic microangiopathy; retinopathy, neuropathy, or nephropathy. AR levels were significantly higher in the patients with microangiopathy than in those without it (52.3 +/- 15.7 vs. 43.0 +/- 15.2 ng/10(6) cells, P < 0.05). The patients with neuropathy had significantly higher AR levels than those without neuropathy (53.7 +/- 15.8 vs. 42.7 +/- 14.3 ng/l0(6) cells, P < 0.05). The same result applied to the patients with retinopathy (54.5 + 15.4 vs. 44.6 +/- 15.3 ng/10(6) cells, P < 0.05). The AR levels in the patients with nephropathy tended to give a higher value than those without it. However, there were no significant differences between the two (53.9 +/- 3.6 vs. 46.4 +/- 2.6 ng/10(6) cells, NS). These results indicate that AR levels in PMCs from type 2 diabetic patients are associated with the presence of microangiopathy. The measurement of AR proteins in PMCs with this ELISA system is a useful tool for the clinical study of diabetic complications, and would increase our understanding of the pathogenesis of the disease.

Adult↗
PubMed1999

Influence of TNF microsatellite polymorphisms (TNFa) on age-at-onset of insulin-dependent diabetes mellitus.

The TNF-alpha gene is located in the HLA region and has been implicated in the pathogenesis of Type I (insulin-dependent) diabetes mellitus (IDDM). We investigated the frequency of TNFa microsatellite alleles in 76 young-onset IDDM patients, 65 adult-onset IDDM patients, and 90 control subjects. We also examined the association of these TNFa alleles with HLA-DRB1 alleles, HLA-class I alleles, and TNF-alpha production. The frequency of the TNFa2 and TNFa9 alleles was increased in the young-onset IDDM patients compared to control subjects, but the increased frequency of TNFa2 was not significant after the correction for the number of comparisons was made. We did not find any association of TNFa2 or TNFa9 with any of the HLA-DRB1 alleles. In contrast, the frequency of the TNFa13 allele was decreased in both the young-onset and the adult-onset IDDM patients compared to the control subjects, but the difference lost significance after the correction was made in the adult-onset IDDM. The TNFa13 allele was strongly associated with DRB1*1502. Patients with TNFa2 or TNFa9 had greater TNF-alpha production, while those positive for TNFa13 had lower TNF-alpha production than patients with non-TNFa2, a9, and a13 alleles. These results suggest that TNFa polymorphisms are associated with age-at-onset of IDDM and influence the inflammatory process of pancreatic beta cell destruction in the development of IDDM.

Adolescent↗