Biomedical subjects

H Hamaguchi

Publications and source records attributed to H Hamaguchi.

At least 163 records · Page 9Linked to original sources

PubMed1993

Four new nucleotide sequence polymorphisms in the LDL receptor gene detected by SSCP analysis.

Seven nucleotide sequence polymorphisms were detected within exons of the low-density lipoprotein (LDL) receptor gene using single-strand conformation polymorphism (SSCP) analysis followed by direct sequence analysis on amplified DNA. Four nucleotide changes at nucleotide positions 1617, 1725, 2232, and 2635 were new nucleotide sequence polymorphisms not previously described. The remaining three nucleotide changes were identical with restriction fragment length polymorphisms and a previously reported nucleotide sequence polymorphism. These nucleotide sequence polymorphisms, detectable by SSCP analysis, are useful genetic markers for linkage analysis of the LDL receptor gene and familial hypercholesterolemia.

DNA, Single-Stranded↗

PubMed1993

Data on the CGG repeat at the fragile X site in the non-retarded Japanese population and family suggest the presence of a subgroup of normal alleles predisposing to mutate.

The fragile X mutation is the result of amplification in the repeat number of p(CGG)n in FMR-1; alleles with more than 52 repeats have been shown to be so unstable as to mutate in the repeat number in almost every transmission. To improve our understanding of mutations in normal alleles of FMR-1, the following studies were carried out in the Japanese population: a study on length variation in the repeat to determine the allele distribution of the repeat length in a non-retarded population, family studies to observe new mutations in normal allele, and haplotype analyses with microsatellite markers flanking the repeat to confirm estimated mutation rates and founder chromosomes in the fragile X syndrome. Analysis of the p(CGG)n in 370 unrelated males detected 24 distinct alleles with repeats of 18-44. A comparison with previously reported data suggests the presence of racial/ethnic differences in the allele distribution. No premutation allele was found in 824 unrelated X chromosomes examined by the polymerase chain reaction and Southern blot analysis. Family studies detected one new mutation in a total of 303 meioses. However, the mutation rate was not in accordance with the expected or observed heterozygosities in the population or with linkage disequilibrium observed between the repeat numbers and the haplotypes of the markers flanking the CGG. The haplotype in the chromosome in which the new mutation was found was the same as that frequently found in the Japanese fragile X chromosomes, and the variance in the CGG repeat number was wider in chromosomes with the haplotypes frequently found in the fragile X chromosome than in those with the other haplotypes. These observations suggest that a subgroup is present in normal alleles and that this subgroup is more liable to mutate than others.

Alleles↗

PubMed1993

Fetal nucleated cells in maternal peripheral blood: frequency and relationship to gestational age.

To determine the frequency of fetal nucleated cells in maternal peripheral blood during different stages of pregnancy, 50 primigravidas were investigated by determining the frequency of cells with the Y chromosome using fluorescence in situ hybridization (FISH) of Y-specific repetitive sequences of the DYZ1 family. Polymerase chain reaction (PCR) amplifying the same part of the DYZ1 used as the probe in FISH and a single-copy Y-specific fragment was also carried out for genomic DNA from the same samples. Cells with the hybridization signal were detected by FISH at and after 15 weeks of pregnancy in all pregnant women who gave birth to boys. The ratio of cells with the signal to those without the signal ranged from 1 in 144,000 to 1 in 4,000 with a tendency to increase as the pregnancy advanced. The frequency of fetal cells estimated by the PCR experiments was significantly and positively correlated with that found by FISH. The present study suggests that fetal nucleated cells increase in maternal peripheral blood with advancing gestation, from less than 1 in 100,000 nucleated cells in the first trimester to around 1 in 10,000 at term. These frequencies were much lower than those reported by cytological methods.

Blood Cell Count↗

PubMed1993

Topographic pattern of the rearrangement of the dystrophin gene in Japanese Duchenne muscular dystrophy.

To compare the frequency and distribution of rearrangements in the dystrophin gene in Duchenne muscular dystrophy (DMD) between Japanese DMD patients and those in North America and Europe, Southern blot analyses of the dystrophin gene were carried out in 88 probands classified as DMD. Gene rearrangements were found in 61 (69%) subjects, and they were composed of partial gene deletions in 53 (60%) probands and partial duplications in 7 (8%) probands. A total deletion of the gene was found in 1 (1%) patient. Among 53 patients with deletions, 34 (64%) had breakpoints between introns 44 and 52 and 7 (13%) had breakpoints between introns 2 and 11. Both the frequency and the distribution of gene rearrangements found in this study were similar to those reported in North America and Europe. These data suggest that there are no ethnic or racial differences in the frequency and distribution of rearrangements thought to be caused by similar mechanisms in the dystrophin gene in all human racial groupings.

Adolescent↗

PubMed1993

High degree of genetic polymorphism in apolipoprotein(a) associated with plasma lipoprotein(a) levels in Japanese and Chinese populations.

We have developed a sensitive, high-resolutin method for the analysis of the apolipoprotein(a) [apo(a)] isoforms using sodium dodecyl sulfate (SDS)-agarose/gradient polyacrylamide gel electrophoresis. In an analysis of the genetic polymorphism of apo(a) isoforms and their relationship with plasma lipoprotein(a) [Lp(a)] levels in Japanese and Chinese, this method identified 25 different apo(a) isoforms and detected one or two apo(a) isoforms in more than 99.5% of the individuals tested. The apparent molecular weights of the apo(a) isoforms ranged from 370 kDa to 950 kDa, and 22 of the 25 different apo(a) isoforms had a higher molecular weight than of apo B-100. Studies on Japanese families confirmed the autosomal codominant segregation of apo(a) isoforms and the existence of a null allele at the apo(a) locus. The observed frequency distribution of apo(a) isoform phenotypes fit the expectations of the Hardy-Weinberg equilibrium in both the Japanese and Chinese populations. Our data indicate the existence of at least 26 alleles, including a null allele, at the apo(a) locus. The frequency distribution patterns of the apo(a) isoform alleles in Japanese and Chinese were similar to each other and also similar to that of apo(a) gene sizes reported in Caucasian American individuals. The average heterozygosity at the apo(a) locus was 92% in Japanese and 93% in Chinese. A highly significant inverse correlation was observed between plasma Lp(a) levels and the size of apo(a) isoforms in both the Japanese (r = 0.677, P = 0.0001) and the Chinese (r = -0.703, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

PubMed1993

Frequent occurrence of familial aggregations of high lipoprotein(a) levels associated with small apolipoprotein(a) isoforms.

School-age children with high lipoprotein(a) [Lp(a)] levels were screened and family studies were conducted to examine the relationship between high Lp(a) levels and apolipoprotein(a) [apo(a)] isoforms in families. All the probands from 17 families had one of the A2 to A12 apo(a) isoforms, which are the smaller apo(a) isoforms of the 25 different isoforms thus far detected. The ratio of subjects with high plasma Lp(a) levels was 0.47 among the first-degree relatives. All 15 relatives with high plasma Lp(a) levels shared one of the small apo(a) isoforms with the proband in each family, while 16 of 17 relatives with normal Lp(a) levels did not. These data indicate the frequent occurrence of familial aggregations of high Lp(a) levels associated with one of the small apo(a) isoforms.

Alleles↗

PubMed1993

Two novel frameshift mutations associated with the presence of direct repeats of the LDL receptor gene in familial hypercholesterolemia.

Two novel frameshift mutations were detected in the mutant LDL receptor genes responsible for familial hypercholesterolemia. One was a 5-bp insertion at codon 395 in exon 9, and the other was a one nucleotide deletion at codon 531 in exon 11. Both mutations alter the reading frame and consequently produce a premature stop codon in the region of the mature LDL receptor homologous to the epidermal growth factor (EGF) precursor. With regard to the mechanism responsible for the generation of these frameshift mutations, strand slipped mispairing mediated by short direct repeats is considered to be the most likely. The findings seem to support the hypothesis that a short direct repeat in DNA sequence can have a profound influence on the stability of a given gene and promote human gene mutations.

Adolescent↗

PubMed1993

Effect of cyclosporine on liver regeneration after orthotopic reduced-size hepatic transplantation in the rat.

These experiments were undertaken to study the effects of cyclosporine A (CsA) on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation (RSHT) in rats. Male Wistar rats were treated with or without a daily injection of CsA beginning 24 hr before surgery and were subjected to a 68% partial hepatectomy. A isogeneic orthotopic reduced-size hepatic transplantation was performed in recipient rats pretreated with or without CsA. A daily injection of CsA was continued until the recipient rats were sacrificed. Animals were sacrificed at various time points (12, 24, 36, 48, and 72 hr) postoperatively. The incorporation of bromodeoxyuridine (BrdU) into the DNA of the remnant hepatocytes was evaluated by immunohistochemical staining with a monoclonal antibody against BrdU. CsA (10 mg/kg/day) significantly augmented BrdU incorporation into hepatocytes after hepatectomy. The maximum labeling index (LI) was observed at 24 hr after hepatectomy. In contrast, the maximum LI in the recipient rats not receiving CsA was seen at 36 hr after RSHT, and 10 mg/kg/day of CsA decreased the LI at 36 hr after RSHT. A lower dose of CsA (3 mg/kg/day), however, significantly increased the LI in the recipient rats (P < 0.01), and it reached a peak at 24 hr after RSHT when compared to the transplant recipients not receiving CsA. The time course of the increase in the LI in the transplant recipient rats receiving 3 mg/kg/day of CsA was similar to that observed in the rats after hepatectomy. This dosage improved the delay in the reduced-size hepatic transplant LI reaching its peak.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of cyclosporine on distribution of macrophage subpopulations in rat hepatic allograft.

Macrophage subpopulations infiltrating the grafts of ACI(RT1a) to LEW(RT1(1)) orthotopic rat liver transplants treated with or without immunosuppressive therapy were studied using immunohistochemical staining. LEW recipients of ACI liver transplants experienced severe acute graft rejection, with a mean survival of only 10.2 +/- 0.7 days. An indirect immunoperoxidase technique on cryostat sections of the liver grafts was used to determine the localization of macrophage subpopulations infiltrating the grafts, as defined by specific anti-rat macrophage monoclonal antibodies, designated TRPM-1 (pan-macrophage), TRPM-3 (activated macrophage) and Ki-M2R (tissue macrophage). TRPM-1+ or TRPM-3+ cells gradually increased on days 5 and 7 in the untreated hepatic allografts, whereas no significant changes in the number of these cells were observed in the isografts. Treatment with cyclosporine (CsA) greatly decreased the number of these two different types of cells infiltrating the hepatic allografts, compared to the untreated hepatic allografts or the isografts. The time course of the accumulation of these cells in the allografts treated with CsA showed a similar pattern; the cells increased gradually by day 5 and thereafter decreased. This pattern is different from that observed in the untreated allografts or in the isografts. There was no significant difference in the number of Ki-M2R+ cells between the untreated hepatic allografts and the isografts. However, the number of the Ki-M2R+ cells in the hepatic allografts treated with CsA was much less than that of either the untreated allografts or the isografts. These findings suggest that a progressive relative increase in host TRPM-3+ macrophage is a characteristic feature of ongoing first-set rejection in the rat hepatic allograft.2+ allograft, even when compared with the isografts.

Animals↗

PubMed1993

Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus.

We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotypes in 152 patients (123 males, 29 females) undergoing maintenance hemodialysis (HD) with or without diabetes mellitus (DM), in 101 patients with diabetes mellitus without hemodialysis (58 males, 43 females), and in 421 normal controls (333 males, 88 females). Serum Lp(a) levels were significantly (P < 0.01) higher in patients than in controls (26.2 +/- 18.3 mg/dl in HD with DM, 26.4 +/- 22.0 mg/dl in HD without DM, 27.1 +/- 27.3 mg/dl in DM without HD, and 14.9 +/- 13.7 mg/dl in controls, respectively). Apo(a) phenotyping was performed by a sensitive, high resolution technique using SDS-agarose/gradient (3 to 6%) PAGE. In normal controls, the molecular weights of apo(a) isoforms were inversely correlated with plasma Lp(a) levels, and the same tendency was found in patients who were undergoing hemodialysis and/or who had diabetes mellitus. We assumed the differences in apo(a) phenotypes detectable with our method reflected consecutive differences in molecular weights of apo(a). The results of an analysis of covariance and a least square means comparison indicated that the regression lines between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in patient groups were significantly (P < 0.01) elevated for every apo(a) phenotype, as compared to the regression line of the control group. Even after the low molecular weight apo(a) phenotypes (A1-A8) were omitted, the same tendency was observed. However, no differences were observed between the patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Moebius syndrome: continuous tachypnea verified by a polygraphic study.

Four polygraphic recordings were obtained in three cases of Moebius syndrome. The cases were a 4-month-old girl (Case 1), a 4-year-old boy (Case 2), and a 5-year-old girl (Case 3). The recordings revealed that in all three cases there was a lack of rapid eye movements to the lateral side, continuous low amplitude on chin EMG, and continuous tachypnea. In Case 3, polygrams were recorded at 2 and 5 years of age, both records showing the same pattern of tachypnea. Arterial blood gas analysis (AGA), PH, PaCO2 and PaO2 were found to be within normal limits. It has been assumed that this syndrome includes brainstem dysplasia, according to the chief symptoms, and autopsy and auditory brainstem response (ABR) findings. ABR examination showed low amplitude of waves, a prolonged wave I-V interval, and the absence of wave V. It is known that there is a close relationship between this syndrome and respiratory disorders. But there have only been a few reports on respiratory disorders in this syndrome. It is strongly believed that continuous tachypnea is an important symptom of Moebius syndrome.

Abducens Nerve↗

PubMed1993

A novel megakaryocyte potentiator produced by MC-1 human lung cancer cell line.

The hematopoietic stimulating activity of a human lung cancer cell line, MC-1, was investigated. The protein fraction (MC-1 protein) was prepared from the serum-free culture supernatant of MC-1 cells using hydroxyapatite and concanavalin A-agarose columns. In serum-containing cultures, MC-1 protein stimulated colony formation by megakaryocyte colony-forming units (CFU), erythroid burst-forming units and granulocyte/macrophage (GM) CFU. The stimulating effect was strongest for megakaryocyte CFU. The factor having megakaryocyte colony-stimulating activity was shown to be a protein whose molecular weight was determined to be 23,000 daltons by gel filtration. By various analyses, this protein was shown to be molecularly different from the heretofore-identified cytokines that may affect megakaryocytopoiesis, i.e., interleukin-1 (IL-1), IL-2, IL-3, IL-6, IL-7, IL-11, granulocyte colony-stimulating factor (CSF), macrophage CSF, GM-CSF, leukemia inhibitory factor, stem cell factor and tumor necrosis factor. Under serum-free conditions, MC-1 protein augmented murine megakaryocyte colony formation in the presence of murine IL-3 and increased the acetylcholinesterase activity of purified murine megakaryocytes. It was also shown that MC-1 protein stimulated human megakaryocyte colony formation. It was concluded that MC-1 cells produce a megakaryocyte potentiator which is molecularly different from any heretofore-identified cytokines.

Animals↗

PubMed1993

High serum lipoprotein(a) levels are an independent risk factor for cerebral infarction.

BACKGROUND AND PURPOSE: This study was conducted to evaluate the role of high serum lipoprotein(a) levels in a group of patients with a relatively early onset of cerebral infarction as a whole and in a subgroup with the perforating artery occlusion subtype of cerebral infarction. METHODS: Fifty-four patients with cerebral infarction, the onset of which was before age 65 years (37 men, 17 women; mean age, 61.9 +/- 7.7 years) were examined in this study. When patients with atrial fibrillation were excluded to omit cardiac embolic strokes from analysis, the group consisted of 45 patients. The patients were classified into two subtype groups, the perforating artery occlusion group and the cortical artery occlusion group, by using magnetic resonance imaging. Lipoprotein(a) levels were measured by an enzyme-linked immunosorbent assay. Four biochemical variables (serum levels of lipoprotein(a), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) and other potential risk factors such as hypertension, diabetes mellitus, smoking habits, alcohol intake, and family history were analyzed by stepwise logistic regression to determine the independent and significant risk factors for cerebral infarction without atrial fibrillation. RESULTS: The incidence of subjects with serum lipoprotein(a) levels > or = 42.6 mg/dL, which is the 95th percentile level of the control subjects, was significantly increased in the total cerebral infarction group (P < .025) and the perforating artery occlusion group (P < .025) compared with the control group. In addition, by using stepwise logistic regression analysis in the total and perforating artery occlusion patient groups we identified three independent and significant risk factors: hypertension, a low high-density lipoprotein cholesterol level, and a high serum lipoprotein(a) level. In the cortical artery occlusion group, the sample size was not large enough for the statistical analysis. Diabetes mellitus is the only known factor that correlates with serum lipoprotein(a) levels, but there were no significant correlations between serum lipoprotein(a) levels and history of diabetes mellitus or fasting blood sugar. CONCLUSIONS: These findings indicate that high serum lipoprotein(a) levels are an independent risk factor in the development of cerebral infarction when subjects with atrial fibrillation were excluded from the total group and the perforating artery occlusion subtype group.

Adult↗

PubMed1993

Spa bathing activates fibrinolysis in patients with cerebral infarction.

The effects of spa bathing on blood coagulation and fibrinolysis were studied in 20 patients with chronic cerebral infarction. Blood was obtained before and after a 10-minute period of spa bathing at 41 degrees C. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII activity, von Willebrand factor activity, and antithrombin III activity did not show significant changes after bathing, but euglobulin lysis time was significantly reduced (p < 0.01) and fibrin lysis activity was increased (p < 0.05). These findings suggest that spa bathing activates fibrinolysis without markedly changing blood coagulation in patients with chronic cerebral infarction. It is thought that the activation of fibrinolysis without the activation of coagulation has a favorable effect on blood circulation. The results of fibrin-plate assays using C1 inactivator indicated that tissue-type plasminogen activator was the major contributor to the activation of fibrinolysis during spa bathing.

Aged↗

PubMed1993

Effects of stem cell factor (SCF) on the in vitro growth of leukemic blast progenitors in acute non-lymphocytic leukemia.

We studied the effects of recombinant human stem cell factor (SCF) on the growth of leukemic blast progenitors obtained from 27 acute non-lymphocytic leukemia (ANLL) patients and 1 chronic myelocytic leukemia patient in myeloid crisis; the effects varied among the patients. While SCF did not have stimulatory effects in the cells of 7 patients, it stimulated primary and secondary blast colony formation in methylcellulose culture and the recovery of clonogenic cells in suspension cultures from 21 patients. SCF stimulated leukemic blast progenitors in a manner almost comparable to or more prominently than that of other CSFs, namely, IL-3, GM-CSF, and G-CSF, in 9 patients. One patient responded to SCF but not to the other CSFs. In another 11 patients, SCF was less effective on leukemic blast progenitors than the other CSFs tested. To explain the variable effects of SCF, we investigated the relation between the phenotype of leukemic blasts and responsiveness to this agent; the response was significantly higher in patients with CD34-positive blasts than in those with CD34-negative blasts. These results imply that responsiveness to SCF differs among leukemic blast progenitors originating at different hematopoietic stages. In some ANLL patients, SCF showed synergy with other CSFs, suggesting that SCF may be involved in the cytokine network affecting leukemic hematopoiesis.

Adolescent↗

PubMed1993

Philadelphia-chromosome-positive, monosomy 7 biphenotypic acute mixed lineage leukemia in adults: a pluripotent stem cell disorder.

Two adult patients with acute mixed lineage leukemia (AMLL) having combined Philadelphia chromosome (Ph1) positivity and monosomy 7 are presented. The phenotypes of leukemic blasts from both cases were almost same (early B-lymphoid lineage and myeloid lineage); CD10+, CD13+, CD19+. HLA-DR+, and dual-color analysis showed simultaneous expression of CD10 (CD19) and CD13 antigens in individual blasts (biphenotypic) in both cases. On molecular analysis, the leukemic blasts showed rearrangement in the first intron of the BCR gene with breakpoint just outside of 3' end of m-BCR-2 (bcr 3) in case 1, and in the M-BCR in case 2. Immunoglobulin heavy chain gene (IgH) rearrangement was noted in both cases, but rearrangement of the T-cell receptor beta-chain gene (TCR beta) was detected only in case 1. Clinically, both cases achieved complete remission by the combination chemotherapy consisting of L-asparaginase, doxorubicin, vincristine, and prednisolone (L-AdVP). In remission, all these molecular abnormalities disappeared in both patients. These results suggest that the Ph1-positive and monosomy 7 AMLL in adults is de novo acute leukemia with both early B-lymphoid and myeloid phenotypes and may arise from malignant transformation of pluripotent stem cell, and expresses a heterogenous rearrangement pattern of the BCR gene.

Acute Disease↗

PubMed1993

[Cardiovascular risk factors among Japanese school-age children: a screening system for children with high risk for atherosclerosis in Ibaraki, Japan].

Total cholesterol levels, obesity index and blood pressure were measured in 6,278 school-age children living in Ibaraki Prefecture in 1991, and children with high risk for atherosclerosis were identified. The frequencies of the school-age children with hypercholesterolemia (total cholesterol > or = 200 mg/dl), obesity (obesity index > or = 40%) or hypertension were 7%, 5%, 1%, respectively. In half of the area where the children lived, lipid measurements were also obtained in the parents of hypercholesterolemic children. Twenty-nine out of ninety fathers (32%) and 22 out of 140 mothers (16%) were hypercholesterolemia (total cholesterol > or = 240 mg/dl). Among them five families of familial hypercholesterolemia were diagnosed. Seventy children with hypercholesterolemia and 81 obese children, who were screened and received health counseling, were re-examined after one year. The levels of LDL-cholesterol, triglyceride and atherogenic index were significantly decreased and HDL cholesterol level was significantly increased in the children with hypercholesterolemia. Obesity index, triglyceride level and atherogenic index were significantly decreased and HDL cholesterol level was significantly increased in the children with obesity. In addition, the frequencies of the children with dyslipidemia or liver dysfunction were significantly decreased in the obese children after one year. These data suggested that the screening system and the plans after the examinations described here were effective in reducing risk factors for atherosclerosis in children.

Adolescent↗

PubMed1993

Solitary bone plasmacytoma terminally developed myeloma with multiple extramedullary lesions and myelomatous pleural effusion and ascites.

A rare case of IgG-kappa type multiple myeloma associated with multiple extramedullary tumor-forming lesions and myelomatous pleural effusion and ascites is reported. The patient suffered from sternal solitary plasmacytoma, which 5 years later developed disseminated tumor formation with myeloma cells mostly in the soft tissues. At autopsy, multiple extramedullary lesions particularly in the abdominal cavity and myelomatous pleural effusion and ascites were observed without diffuse infiltration of myeloma cells in the bone marrow. The disseminating change from solitary bone plasmacytoma to extramedullary tumor formation seen in this case seemed to be unusual but suggestive of a feature of an aggressive tendency of multiple myeloma.

Abdominal Neoplasms↗