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Biomedical subjects

H Hamaguchi

Publications and source records attributed to H Hamaguchi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families.

Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, we conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed significant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MLS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups.

Adolescent↗
PubMed2000

Significant evidence for linkage of febrile seizures to chromosome 5q14-q15.

Febrile seizures (FSs) represent the most common form of childhood seizure. In the Japanese population, the incidence rate is as high as 7%. It has been recognized that there is a significant genetic component for susceptibility to this type of seizure. Two putative FS loci, FEB1 (chromosome 8q13-q21) and FEB2 (chromosome 19p), have been mapped. Furthermore, a mutation in the voltage-gated sodium (Na(+))-channel beta1 subunit gene ( SCN1B ) at chromosome 19q13.1 was identified in a family with a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS(+)). These loci are linked to some large families. In this study, we conducted a genome-wide linkage search for FS in one large family with subsequent linkage confirmation in 39 nuclear families. Significant linkage was found at D5S644 by multipoint non-parametric analysis using GENEHUNTER ( P = 5.4 x 10(-6)). Estimated lambda(s)at D5S644 was 2.5 according to maximum likelihood analysis. Significant linkage disequilibria with FS were observed at the markers D5S644, D5S652 and D5S2079 in 47 families by transmission disequilibrium tests. These findings indicate that there is a gene on chromosome 5q14-q15 that confers susceptibility to FSs and we call this gene FEB4.

Child, Preschool↗
PubMed2000

The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia.

Preeclampsia is associated with thrombosis of the intervillous or spiral artery. A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 (PAI-1) gene is suggested to be involved in regulating the synthesis of the inhibitor, 4G allele, being associated with the enhanced gene expression and plasma PAI-1 levels. We assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI-1 gene in 115 preeclamptic patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of the homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women (P = 0.04) or in the healthy volunteers (P = 0.02). The 4G allele frequency was also significantly higher in the patients than in the control group of pregnant women (P = 0.03) and in the healthy volunteers (P = 0.02). These results suggest that the presence of the 4G/4G genotype of the PAI-1 gene is one of the risk factors for preeclampsia.

Alleles↗
PubMed2000

A novel translocation t(3;22)(q21;q11) involving 3q21 in myelodysplastic syndrome-derived overt leukemia with thrombocytosis.

We report here a novel translocation t(3;22)(q21;q11) in myelodysplastic syndrome (MDS)-derived overt leukemia with thrombocytosis. A 44-year-old female was initially diagnosed as MDS with a low platelet count and normal karyotype. After 4 months, blood leukemic cells and platelets rapidly increased concomitantly and a diagnosis of acute myeloblastic leukemia (AML M1) was made. Chromosome analysis showed 46, XX, t(3;22)(q21;q11) in 14 of 20 metaphases. Fluorescence in situ hybridization analysis confirmed both the der(3)t(3;22) and the der(22)t(3;22). Our results suggest that unidentified gene(s) at 3q21 breakpoint may be implicated in the pathogenesis of abnormal thrombopoiesis as observed in the 3q21q26 syndrome.

Adult↗
PubMed2000

Interstitial deletion of the short arm of chromosome 12 during clonal evolution in myelodysplastic syndrome with t(5;12)(q13;p13) involving the ETV6 gene.

We report here a 65-year-old man with a myelodysplastic syndrome (MDS), refractory anemia with excess of blasts. He had received chemotherapy with tegafur for renal carcinoma. Chromosome analysis of bone marrow cells revealed complex karyotypes; del(5)(q13) was observed in all 20 metaphase spreads, and two related aberrations, add(12)(p11) and add(12)(p13), were detected in 13 and 7 cells, respectively. Fluorescence in situ hybridization (FISH) analysis with chromosome-specific DNAs revealed that these alterations originated from a reciprocal translocation (5;12)(q13;p13). Therefore, del(5)(q13), add(12)(p11), and add(12)(p13) were revised as der(5)t(5;12)(q13;p13), der(12)del(12)(p11p13)t(5;12)(q13;p13), and der(12)t(5;12)(q13;p13), respectively. Fluorescence in situ hybridization with a series of cosmid probes spanning the ETV6 gene showed that the 12p13 breakpoint on the der(12)t(5;12)(q13;p13) was located in intron 1, but the exon 1 signal was deleted. Our results suggest that a fusion gene was generated between the 5'-end of an unidentified partner at 5q13 and the 3'-end of ETV6 by t(5;12)(q13;p13), and that the interstitial deletion (12)(p11p13) occurred following t(5;12) during clonal evolution. del(12)(p11p13), including the rearranged ETV6 gene, may be implicated in the progression of MDS.

Aged↗
PubMed2000

Human herpesvirus 8-associated solid lymphomas that occur in AIDS patients take anaplastic large cell morphology.

Human herpesvirus type 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is a recently isolated human herpesvirus frequently identified in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Here we report three cases of HHV-8-bearing solid lymphomas that occurred in AIDS patients (Cases 1-3). All three patients were homosexual men presenting extranodal masses in the lungs (Case 1) or skin (Cases 2 and 3), together with the presence of Kaposi's sarcoma (Case 1), primary effusion lymphoma (Case 2), or multicentric Castleman's disease (Case 3). These solid lymphomas exhibited anaplastic large cell morphology and expressed CD30, corresponding to the recent diagnostic criteria of anaplastic large cell lymphoma (ALCL). The chromosomal translocation t(2;5)-associated chimeric protein p80NPM/ALK was not observed in any of these cases. HHV-8 was detected in all of these cases by polymerase chain reaction, immunohistochemistry of HHV-8-encoded ORF73 protein, and in situ hybridization of T1.1. Epstein-Barr virus was detected only in Cases 2 and 3 by in situ hybridization. It is interesting that inoculation of a cell line obtained from a primary effusion lymphoma cell in Case 2 to severe combined immunodeficiency mice produced HHV-8-positive and Epstein-Barr virus-negative tumors in inoculated sites. These tumor cells exhibited phenotypes of ALCL that were identical to the subcutaneous tumor cells of this particular patient. These findings clearly show that HHV-8 can associate with solid lymphomas and that it can take anaplastic large cell morphology. Those lymphomas should be distinguished from the classical ALCL as were defined by the revised European-American classification of lymphoid neoplasms even though morphology and a part of immunophenotype mimic that of classical ALCL.

Adult↗
PubMed2000

Association of Trp64Arg polymorphism of the beta3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity.

OBJECTIVE: To investigate whether Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) gene and Gln223Arg polymorphism of the leptin receptor (Ob-R) gene are associated with obesity in Japanese schoolchildren. DESIGN: Population study of participants from a rural town located within 50 km northeast of Tokyo based on school medical examinations. SUBJECTS: 553 Japanese schoolchildren (291 boys and 262 girls) who were 9-15 y old with a mean age of 11.9 +/- 1.8 y. MEASUREMENTS: DNA was extracted from whole blood and genotyped by PCR-RFLP. Height, weight and blood pressure were measured in school medical examinations. Total cholesterol, triglyceride and HDL-cholesterol concentrations were measured by an autoanalyzer. Obesity index, body mass index (BMI) and LDL-cholesterol concentration were calculated by the respective formulae. RESULTS: In Trp64Arg polymorphism of the beta3-AR gene, the number of obese subjects with Trp/Arg or Arg/Arg genotypes was significantly higher than that of the non-obese subjects (chi2=5.79, P=0.02). The obesity index of subjects with the Arg/Arg or Arg/Trp genotype was significantly higher than that of those with the Trp/Trp genotype (8.2 +/- 18.7% vs 4.5 +/- 15.8%, P=0.04). Moreover, after adjustments for age and gender, BMI of subjects with the Trp/Arg or Arg/Arg genotype was significantly higher than that of those with the Trp/Trp genotype (19.4 +/- 3.6 kg/m2 vs 18.9 +/- 3.2 kg/m2, P= 0.02). However, no significant differences were observed in the clinical characteristics among the genotype groups of the Ob-R gene. CONCLUSIONS: Trp64Arg polymorphism of the beta3-AR gene appears to be a genetic risk factor for obesity in Japanese children, but Gln223Arg polymorphism of the Ob-R gene does not appear to be associated with obesity.

Adolescent↗
PubMed2000

p53 alterations in human leukemia-lymphoma cell lines: in vitroartifact or prerequisite for cell immortalization?

Alteration of the p53 gene is one of the most frequent events in human tumorigenesis. The inactivation of p53 tumor suppressor function can be caused by chromosome deletion, gene deletion, or mainly by point mutations. p53 mutations occur moderately often in hematopoietic malignancies. A significantly higher frequency of p53 alterations in cell lines vs primary samples has been observed for all types of malignant hematopoietic cell lines. It has been postulated that p53 gene abnormalities arise in cell lines during in vitro establishment of the culture or prolonged culture; but it is also conceivable that those cases that carry p53 mutations may be more suitable for in vitro establishment as permanent cell lines. We analyzed data on the p53 gene status in a panel of matched primary hematopoietic tumor cells and the respective cell lines derived from this original material. In 85% (53/62) of the pairs of matched primary cells and cell lines, the in vivo and in vitro data were identical (both with p53 wild-type or both with the same p53 mutation). In some instances, serial clinical samples (eg at presentation and relapse) and serial sister cell lines were available. These cases showed that a clinical sample at presentation often had a p53 wild-type configuration whereas the derived cell line and a relapse specimen carried an identical p53 point mutation. These findings suggest that a minor clone, at first undetectable by standard analysis, represents a reservoir for the outgrowth of resistant cells in vivo and also a pool of cells with a growth advantage in vitro, providing a significantly higher chance of immortalization in culture. This was further supported by studies employing mutant allele-specific gene amplifications, a technique which is significantly more sensitive (100- to 1000-fold) than the commonly applied SSCP assay with a sensitivity threshold of about 10% mutated cells within a pool of wild-type cells. Taken together, this analysis confirms the usefulness of human hematopoietic cell lines as in vitro model systems for the study of the biology of hematopoietic malignancies. It further underlines the notion that p53 gene alterations confer a survival advantage to, at least some, malignant cells in vitro and presumably also in vivo; however, it is highly unlikely that a p53 mutation alone would suffice for the immortalization of a cell line in vitro or tumor development in vivo. Leukemia (2000) 14, 198-206.

Adolescent↗
PubMed2000

Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma.

BACKGROUND: IL-4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL-4 gene cluster and asthma and/or asthma-related traits. Interferon regulatory factor 1 (IRF-1) is located approximately 300 kb telomeric to IL-4 and recent study reveals that IRF-1 deficiency results in an elevated production of Th2-related cytokines and a compensatory decrease in the expression of native cell- and Th1-related cytokines. OBJECTIVE: To determine if there are any mutations associated with the development of atopy and asthma present in the coding exons and 5' flanking region of the IRF-1 gene. METHODS AND RESULTS: We have screened the promoter and coding regions of the IRF-1 gene in atopic asthmatics and controls by SSCP method. We found three novel nuclear variants (the -300G/T and 4396 A/G polymorphisms and the 6355G > A rare variant) in the IRF-1 gene. No variants causing amino acid alterations of IRF-1 were detected. The -300G/T polymorphism was in nearly complete linkage disequilibrium with the 4396 A/G polymorphism. An association between the 4396 A > G polymorphism and atopy/asthma was examined by transmission disequilibrium test in 81 asthmatic families. Either of 4396 A or 4396G alleles was not significantly preferentially transmitted to atopy- or asthma-affected children. CONCLUSION: The IRF-1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population.

Adolescent↗
PubMed2000

Cardiovascular effects of medetomidine, detomidine and xylazine in horses.

The cardiovascular effects of medetomidine, detomidine, and xylazine in horses were studied. Fifteen horses, whose right carotid arteries had previously been surgically raised to a subcutaneous position during general anesthesia were used. Five horses each were given the following 8 treatments: an intravenous injection of 4 doses of medetomidine (3, 5, 7.5, and 10 microg/kg), 3 doses of detomidine (10, 20, and 40 microg/kg), and one dose of xylazine (1 mg/kg). Heart rate decreased, but not statistically significant. Atrio-ventricular block was observed following all treatments and prolonged with detomidine. Cardiac index (CI) and stroke volume (SV) were decreased with all treatments. The CI decreased to about 50% of baseline values for 5 min after 7.5 and 10 microg/kg medetomidine and 1 mg/kg xylazine, for 20 min after 20 microg/kg detomidine, and for 50 min after 40 microg/kg detomidine. All treatments produced an initial hypertension within 2 min of drug administration followed by a significant decrease in arterial blood pressure (ABP) in horses administered 3 to 7.5 microg/kg medetomidine and 1 mg/kg xylazine. Hypertension was significantly prolonged in 20 and 40 microg/kg detomidine. The hypotensive phase was not observed in 10 microg/kg medetomidine or detomidine. The changes in ABP were associated with an increase in peripheral vascular resistance. Respiratory rate was decreased for 40 to 120 min in 5, 7.5, and 10 microg/kg medetomidine and detomidine. The partial pressure of arterial oxygen decreased significantly in 10 microg/kg medetomidine and detomidine, while the partial pressure of arterial carbon dioxide did not change significantly. Medetomidine induced dose-dependent cardiovascular depression similar to detomidine. The cardiovascular effects of medetomidine and xylazine were not as prolonged as that of detomidine.

Adrenergic alpha-Agonists↗
PubMed2000

[A randomized trial of conventional dose vs reduced dose in BHAC-DM therapy for acute myelogenous leukemia in elderly patients].

Twenty-nine patients aged 60-75 years with newly diagnosed acute myelogenous leukemia (AML) were randomized to receive BHAC-DM either at a reduced dose (S-1 group, n = 13; BHAC 150 mg/m2 1-7 day, DNR 30 mg/m2 1-3 day, 6MP 70 mg/m2 1-7 day) or the conventional dose (S-2 group, n = 16; BHAC 200 mg/m2 1-7 day, DNR 40 mg/m2 1-3 day, 6MP 70 mg/m2 1-7 day). On day 7, patients were given therapy for 2 more days if the ratio of blasts in their bone marrow was more than 15%. Granulocyte-colony stimulating factor was injected when the leukocyte count decreased below 1,000/microliter. The rates of complete remission were 46.2% in the S-1 group and 43.8% in the S-2 group. No significant differences in response distinguished the 2 groups. The mortality rate during myelosuppression was 1/13 in the S-1 group and 1/16 in the S-2 group. The rate of treatment-related death was 10.1% for all patients. Grade-4 adverse effects were not seen in any of the patients. We concluded that the conventional dose of BHAC-DM was as acceptable as the reduced dose in elderly patients with AML.

Aged↗
PubMed2000

[Coagulation/fibrinolysis disorders in the elderly].

To establish reference intervals for the interpretation of hemostatic tests in the elderly, 11 hemostatic tests were performed on 120 elderly individuals(26 males and 94 females) aged 78.6 years in average. The subjects lived in hostel for the elderly, walked without assistance, and were independent in activities in daily living. In 25.8% to 93.3% of the subjects, the results of the tests, except for prothrombin time and thrombin-antithrombin III complex, deviated from reference intervals obtained from young healthy subjects. This suggests the necessity of setting up reference intervals for the elderly. Fibrinolysis was more activated than coagulation, although coagulation had been considered to be more activated because thrombosis is common in the elderly. Wilcoxon test on the test values of the early elderly(65 to 74 years of age) and late elderly(75 to 92 years of age) as well as the correlation coefficient for age and test values revealed that separate reference intervals for antithrombin III, protein C, D-dimer, and thrombomodulin should be established for the early elderly(65 to 74 years) and late elderly(75 years or over). Our proposed reference intervals for the elderly are appropriate for the diagnosis of disseminated intravascular coagulation.

Aged↗
PubMed2000

[Successful treatment of refractory thrombotic thrombocytopenic purpura with cyclosporine A and splenectomy].

A 19-year-old girl was admitted to our hospital because of general fatigue, headache and purpura. A number of her laboratory findings suggested hemolytic anemia and thrombocytopenia. Direct/indirect Coombs tests gave negative results. Although the patient had no neurological or renal abnormalities, peripheral blood smears showed marked red cell fragmentation, and therefore she was diagnosed as having thrombotic thrombocytopenic purpura (TTP). Fresh frozen plasma (FFP) was transfused daily. The thrombocytopenia and hemolysis immediately improved, but worsened again after reduction of the FFP transfusion. Plasma exchange was instituted every other day, but the patient's condition worsened. Palsy and consciousness disturbance developed, and finally she lapsed into a coma. Daily plasma exchange and methylprednisolone pulse therapy were performed, together with weekly vincristine therapy, and this led to a gradual improvement in the patient's condition. However, several attempts at weaning from plasma exchange resulted in exacerbation of the TTP activity. Therefore oral cyclosporine A was started and splenectomy was performed. After these interventions, despite transient relapse, the patient was successfully weaned off the FFP transfusion, and she is now in remission. Because in this case splenectomy and cyclosporine A resulted in sustained remission of TTP that was refractory to intensive plasma therapy, an autoimmune mechanism may have been involved in the pathogenesis.

Adult↗
PubMed1999

A new translocation, t(2;4;12)(p21;q12;p13), in CD7-positive acute myeloid leukemia: a variant form of t(4;12).

We describe a 41-year-old man with CD7-positive acute myeloid leukemia (AML-M0) with trilineage-myelodysplasia. Chromosome analysis of the bone marrow cells showed 46.XY.t(2;4;12) (p21;q12;p13). Cytological and clinical features of our case were quite similar to those of AML with t(4;12)(q11-12;p13). The karyotypic interpretation was confirmed by fluorescence in situ hybridization (FISH) by using the whole-chromosome painting probes specific for chromosomes 2, 4, and 12. FISH analysis with the use of the YAC 936e2 probe, which covers the TEL gene, did not show the split signal, suggesting that a gene other than TEL was involved in the leukemogenesis of the present case. Our case with AML with t(2;4;12)(p21;q12;p13) appears to be the first case of a variant type of AML with t(4;12) (q11-12;p13).

Acute Disease↗
PubMed1999

Microsatellite instability in lymphoid leukemia and lymphoma cell lines but not in myeloid leukemia cell lines.

Microsatellite instability (MSI) represents a defect in the DNA mismatch repair system and has been shown to take part in the genesis and/or progression of several human malignancies. In hematological malignancies, the relevance of MSI has been a matter of controversy. Therefore, 29 microsatellite loci were examined for MSI in 57 leukemia and lymphoma cell lines by PCR analysis. Ladder formation of bands representing MSI was observed at multiple loci in 6 of 24 lymphoid leukemia/lymphoma cell lines and in 0 of 33 myeloid leukemia cell lines. Analysis for the BAT-26 and BAT-25 loci confirmed the presence of MSI in five of six lymphoid cell lines exhibiting ladder formation of bands. Thus, at least 5 out of 24 (21%) lymphoid leukemia/lymphoma cell lines were considered as being MSI-positive. These results indicate that MSI contributes to the development of lymphoid but not to myeloid malignancies.

Humans↗
PubMed1999

Plasma lipoprotein (a) levels in children with minimal lesion nephrotic syndrome.

We studied the plasma lipoprotein (a)[Lp(a)] levels in 31 children with minimal lesion nephrotic syndrome (MLNS) in both stages of acute NS and remission. The mean Lp(a) levels in acute NS were significantly higher than those of the controls. The Lp(a) levels in remission were significantly lower than the Lp(a) levels in acute NS. In addition, the Lp(a) levels in remission were not significantly different from those of the controls. However, there were 5 patients whose Lp(a) levels remained higher than 30 mg/dl (the generally accepted limit for cardiovascular risk) after remission. Two of these 5 patients had Lp(a) levels greater than 40 mg/dl. In these patients apoprotein (a) [apo(a)] phenotypes were of lower molecular weight than those of the other 23 patients whose apo(a) phenotypes were examined. Additional episodes of relapse may put the patient with sustained elevated Lp(a) levels at significant risk for the development of cardiovascular disease in the long term.

Adolescent↗
PubMed1999

No association between atopic asthma and a coding variant of Fc epsilon R1 beta in a Japanese population.

Susceptibility to atopic diseases is known to involve genetic factors. The Gly237 allele of a polymorphism (Glu237Gly) of the Fc epsilon R1 beta gene is reportedly associated with atopic asthma in Japanese. To confirm this association, we conducted transmission disequilibrium tests in 76 families identified through atopic asthmatics. A case-control study was also carried out in atopic asthmatic subjects and non-atopic controls. The Gly237 allele was not preferentially transmitted to atopic asthma-affected offspring. Neither the Gly237 allele nor the Gly237/Gly237 + Glu237/Gly237 genotypes were significantly more prevalent in the atopic asthmatics than in the controls. This study failed to confirm a substantial role of the Gly237Glu polymorphism of the Fc epsilon R1 beta gene in the genetic predisposition for atopic asthma in this Japanese population.

Amino Acid Substitution↗