Biomedical subjects

H Hamaguchi

Publications and source records attributed to H Hamaguchi.

At least 145 records · Page 8Linked to original sources

PubMed1994

Dose-dependent association of apolipoprotein E allele epsilon 4 with late-onset, sporadic Alzheimer's disease.

We examined the apolipoprotein E (apo E) genotypes in 47 patients with late-onset sporadic Alzheimer's disease (mean age at onset +/- standard deviation, 72.2 +/- 6.4 years), 8 with late-onset familial Alzheimer's disease (75.5 +/- 5.1 years), 18 with early-onset sporadic Alzheimer's disease (52.8 +/- 4.7 years), and 10 with early-onset familial Alzheimer's disease (52.0 +/- 6.8 years) in Japan and compared them with genotypes in control subjects. In late-onset sporadic Alzheimer's disease, apo E-epsilon 4 frequency increased significantly (epsilon 4 frequency: 0.34 vs 0.095 in controls, p < 0.0001), and the odds ratio, which represents the strength of association between Alzheimer's disease and apo E-epsilon 4, markedly increased with increasing dose of apo E-epsilon 4 gene (3 [95% confidence interval, 2-6] in one dose; 43 [95% confidence interval, 12-154] in two doses). This study also suggested that apo E-epsilon 4 is associated with both late-onset (epsilon 4: 0.31) and early-onset familial Alzheimer's disease (epsilon 4: 0.35). In contrast, we found no association between apo E-epsilon 4 and early-onset sporadic Alzheimer's disease (epsilon 4: 0.08). These results indicate that the risk of developing late-onset sporadic Alzheimer's disease is markedly dependent on the dose of apo E-epsilon 4, while apo E-epsilon 4 does not appear to be a major risk factor for early-onset sporadic Alzheimer's disease.

Aged↗

PubMed1994

A novel complex mutation in the LDL receptor gene probably caused by the simultaneous occurrence of deletion and insertion in the same region.

A novel complex mutation with the presence of both deletion and insertion in very close proximity in the same region was detected in exon 8 of the LDL receptor gene from two apparently unrelated Japanese families with familial hypercholesterolemia (FH). In this mutant LDL receptor gene, the nine bases from nucleotide (nt) 1115 to nt 1123 (AGGGTGGCT) were replaced by six different bases (CACTGA), and consequently the four amino acids from codon 351 to 354, Glu-Gly-Gly-Tyr, were replaced by three amino acids, Ala-Leu-Asn, in the conserved amino acid region of the growth factor repeat B of the LDL receptor. The nature of the amino acid substitution and data on the families suggest that this mutation is very likely to affect the LDL receptor function and cause FH. The generation of this complex mutation can be explained by the simultaneous occurrence of deletion and insertion through the formation of a hairpin-loop structure mediated by inverted repeat sequences. This this mutation supports the hypothesis that inverted repeat sequences influence the stability of a given gene and promote human gene mutations.

Amino Acid Sequence↗

PubMed1994

Apolipoprotein E5 and E7 in apparently healthy Japanese males: frequencies and relation to plasma lipid levels.

In order to determine the frequencies of apolipoproteins (apo) E5 and E7 and their relation to plasma lipid levels, apo E phenotypes were determined in 608 healthy Japanese male adults by two-dimensional gel electrophoresis. Apo E5 and E7 were observed in 2.8% of the subjects, in addition to the three common apo E isoforms, E2, E3, and E4. Apo E5 was divided into two subtypes based on the migration rate on SDS/PAGE, E5f is the type with faster migration and E5s slower migration. The gene frequencies were: the epsilon 3 allele, 0.841; the epsilon 4 allele, 0.095; the epsilon 2 allele, 0.049; the epsilon 7 allele, 0.009; the epsilon 5 allele encoding apo E5f (the epsilon 5f allele), 0.004; and the epsilon 5 allele encoding apo E5s (the epsilon 5s allele), 0.001. The five individuals with apo E5f and the eleven with apo E7 were heterozygotes and normocholesterolemic. Also plasma apo B and apo E levels were not increased in any subjects with apo E5f or apo E7. The data suggests that apo E5f and E7 are not rare in the Japanese population but that neither apo E5f nor E7 are associated with hypercholesterolemia in most of the heterozygotes.

Adult↗

PubMed1994

Elevated plasma soluble interleukin 2 receptor level correlates with defective natural killer and CD8+ T-cells in myelodysplastic syndromes.

The plasma soluble interleukin 2 receptor (sIL-2R) level and its relationships with haematologic and immunologic data were examined in 40 patients with myelodysplastic syndromes (MDS). The plasma sIL-2R level was significantly higher in the high-risk MDS group (refractory anaemia with excess blasts (RAEB), RAEB in transformation and chronic myelomonocytic leukaemia) than in the low-risk MDS group (refractory anaemia (RA) and RA with ringed sideroblasts) or in normal subjects, although there was considerable variation in the plasma sIL-2R level within each MDS group. The plasma sIL-2R level correlated positively with the bone marrow cellularity and bone marrow blast mass, but not with the absolute number of CD25+ lymphocytes. This may support the idea that plasma sIL-2R is derived from malignant MDS cells in the bone marrow. The plasma sIL-2R level correlated negatively with the absolute numbers of the CD8+, CD3-CD16+, and CD3-CD56+ cell populations in freshly isolated lymphocytes, the percentage of CD3-CD56+ cells in lymphokine (interleukin 2)-activated killer (LAK) cells, and the cytotoxicity of LAK cells. We conclude that MDS patients having a high plasma sIL-2R level often have a defect in natural killer and CD8+ T-cells.

Adult↗

PubMed1994

Hepatic biliary transport after hepatocyte transplantation in Eizai hyperbilirubinemic rats.

The Eizai hyperbilirubinemic rat (EHBR) is a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia. Eizai hyperbilirubinemic rats have impaired canalicular excretory transport of organic anions, bile acid glucuronide and sulfate. Eizai hyperbilirubinemic rats, with and without a 68% partial hepatectomy, were treated by an intraportal injection of 1 x 10(7) wild-type Sprague-Dawley mutant rat hepatocytes. Serum bilirubin concentrations decreased significantly after hepatectomy and intraportal injection. Biliary excretion was demonstrated by biliary transport of indocyanine and sulfobromophthalein into the bile. These results indicate that hepatic transport of bile acid conjugates in Eizai hyperbilirubinemic rats can be restored by hepatocyte transplantation in conjunction with the recipient's excretory biliary system.

Animals↗

PubMed1994

Fetal nucleated cells in maternal peripheral blood after delivery.

OBJECTIVE: The purpose of this study was to determine the frequency of fetal nucleated cells and their serial changes in maternal peripheral blood after delivery. STUDY DESIGN: A total of 135 blood samples were investigated by means of fluorescence in situ hybridization by observing cells with Y chromosomes. Polymerase chain reaction amplifying two different Y-specific fragments were also carried out for genomic deoxyribonucleic acid from the same samples. RESULTS: The mean frequency of the Y-positive cells detected by fluorescence in situ hybridization in mothers who gave birth to male children was about 1 in 17,500 1 day after delivery. The frequency of these cells decreased with time, dropping below detectable levels 3 months after delivery. The frequency estimated by polymerase chain reaction experiments was significant and positively correlated with those found by fluorescence in situ hybridization. CONCLUSION: Fetal nucleated cells in maternal peripheral blood decrease in frequency with time after delivery. These cells disappear from maternal circulation 3 months after delivery in most, if not all, mothers.

Adult↗

PubMed1994

Assessment of therapeutic potential of interleukin 2 for myelodysplastic syndromes.

The therapeutic potential of interleukin 2 (IL-2) for myelodsplastic syndromes (MDS) was evaluated in vitro. IL-2-induced lymphokine-activated killer (LAK) cells were prepared from 38 MDS patients and 20 normal subjects. The cytotoxicity of LAK cells against K562 and Raji cell lines and MDS blasts was significantly reduced in high-risk MDS (refractory anaemia with excess blasts (RAEB), RAEB in transformation, and leukaemic transformation of MDS), but was relatively well-preserved in low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts). Examination of the immunophenotypes of freshly-isolated lymphocytes showed that the percentage of CD4+ cells in low-risk MDS and the percentage of CD3+, CD4+ and CD8+ cell populations in high-risk MDS was significantly reduced compared with these populations in normal subjects. After cultivation with IL-2, these three cell populations were still reduced in the corresponding MDS groups and the percentage of CD3-CD56+ cells were significantly reduced in high-risk MDS. There was a positive correlation between the percentage of K562 cells lysed by MDS LAK cells and the percentage of CD3-CD56+ lymphocytes in MDS LAK cells. These aberrant lymphocyte subpopulations appeared to explain, at least in part, the reduced LAK cell cytotoxicity in MDS. These results present a possibility that IL-2 and LAK therapies are ineffective for most high-risk MDS patients, whereas they have potential value for low-risk MDS patients whose lymphocyte cytotoxicity is usually preserved.

Adult↗

PubMed1994

Defective natural killer (NK) cell-mediated cytotoxicity does not imply clonal involvement of NK cells in myelodysplastic syndromes.

The clonality of purified cells was examined in 10 myelodysplastic syndromes (MDS) patients by analysing the restriction fragment length polymorphism and methylation pattern of the phosphoglycerate-kinase gene. Natural killer (NK) cell-mediated cytotoxicity was also examined. The granulocytes and monocytes were monoclonal or oligoclonal in all cases, except for the monocytes in one case. Conversely, the NK and T cells had a polyclonal pattern in most cases, including all cases who had defective NK cell-mediated cytotoxicity. The hypothesis that reduced NK cell-mediated cytotoxicity in MDS is caused by a clonal involvement of NK cells was not supported by the present study.

Adult↗

PubMed1994

Plasminogen with type-I mutation in the Chinese Han population.

A functionally inactive plasminogen (PLG) variant, PLG M5, is polymorphic in the Japanese population and has a codon 601 mis-sense mutation (GCT for Ala to ACT for Thr), designated type-I mutation. The present study aimed to reveal whether the plasminogen with type-I mutation is present in the Chinese Han population. Among 104 healthy Chinese students, phenotype PLG AM5 was found in three subjects (2.9%), while 100 subjects were phenotype A and one was phenotype AA3. In the three subjects with PLG AM5, plasma concentrations of immunoreactive PLG were normal but PLG activities were decreased. Analysis using PCR and dot-blot hybridization with allele-specific oligonucleotide probes revealed the presence of the type-I mutation in the PLG gene of all three subjects with PLG AM5. The data indicate that PLG with type-I mutation is present in the Chinese Han population, possibly at a polymorphic frequency.

Asian People↗

PubMed1994

Therapeutic efficacy of lanoconazole, a new imidazole antimycotic agent, for experimental cutaneous candidiasis in guinea pigs.

The therapeutic efficacy of 1% cream and 1% solution of lanoconazole, a new imidazole antimycotic agent, in the model of cutaneous candidiasis in prednisolone-treated guinea pigs was evaluated in comparison with that of comparable formulations of bifonazole. Each preparation was topically applied once a day for 3 consecutive days, starting on the fifth day postinfection, and quantitative culture study wsa conducted on the ninth day postinfection. Both formulations of lanoconazole were much more highly effective in terms of eradication of fungi than the bifonazole formulations.

Administration, Topical↗

PubMed1994

[Apolipoproteins A].

Apolipoproteins A include apoA-I, apoA-II and apoA-IV. These apolipoproteins are involved in the metabolism of HDL and reverse cholesterol transport. The genes encoding apoA-I, apoA-II and apoA-IV have arisen from a common ancestor. This review describes the structures of the genes encoding apoA-I, apoA-II and apoA-IV, and the structures and functions of the gene products with special reference to the metabolism of HDL and reverse cholesterol transport. Further studies are required to elucidate the full role of apolipoproteins A, especially apoA-II and apoA-IV in HDL metabolism. Analysis of human genetic deficiency and transgenic animal model will be useful for the elucidation of the functions of apolipoproteins A.

Amino Acid Sequence↗

PubMed1994

[Pick's disease in senescence].

We report two patients with Pick's disease in senescence. Patient 1 is a 78-year-old woman. She developed abnormal behavior at the age of 76 years. Neurological examination at age 76 revealed poor rapport, easy angriness, "Denkfaulheit", oral tendency, and slight dementia [WAIS (Wechsler Adult intelligence Scale) total IQ 62]. Cranial CT scan and MRI showed bilateral atrophy of the frontal and temporal lobe, especially of the temporal lobe. Patient 2 is a 73-year-old man. He developped sexual abnormal behavior and "triebhafte Hemmungslossigkeit" at the age of 71 years. Neurological examination at age 72 revealed poor rapport, lack of spontaneity, easy angriness, "Denkfaulheit", and slight dementia [WAIS total IQ 91]. Transient "stehende Redensarten" was noticed. Cranial CT scan and MRI showed bilateral atrophy of the frontal and temporal lobe, especially of the frontal lobe. To our knowledge, Pick's disease with an onset in the senescence is very rare. Pick's disease should be included in the differential diagnosis of abnormal behavior in the senescence.

Aged↗

PubMed1994

[Therapeutic efficacy of lanoconazole ointment in guinea pig model of tinea pedis, in comparison with that of cream preparations].

The therapeutic efficacy of ointment and cream preparations of lanoconazole in a guinea pig model of tinea pedis was compared. When infected animals were treated once daily with 0.25% and 0.5% lanoconazole ointments, 7 of 10 and 8 of 10 infected feet became culture-negative, respectively. In animals treated with 1% lanoconazole ointment, fungus was not recovered from any infected foot. Comparing these results with those of culture study in animals which were treated with comparable concentrations of lanoconazole cream, no significant differences were found. These studies, therefore, suggested that ointment and cream preparations of lanoconazole on topical application in the tinea pedis model would show basically equivalent therapeutic efficacy.

Administration, Topical↗

PubMed1994

Liver regeneration after orthotopic reduced-size hepatic transplantation in the rat.

These experiments were undertaken to study the effects of cyclosporine on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation in rats. The incorporation of bromodeoxyuridine into the DNA of the remnant hepatocytes was evaluated at various time points by immunohistochemical staining. Cyclosporine (10 mg/kg/day) significantly augmented BrdU incorporation into hepatocytes after hepatectomy. The maximum labeling index was observed at 24 hr after hepatectomy. In contrast, the maximum labeling index in the recipient rats not receiving cyclosporine was seen at 36 hr after reduced-size hepatic transplantation, and 10 mg/kg/day of cyclosporine decreased the labeling index at 36 hr after grafting. A lower dose of cyclosporine (3 mg/kg/day), however, significantly increased the labeling index in the recipient rats, which reached a peak at 24 hr after grafting as compared with the transplant recipients not receiving cyclosporine. This dosage shortened the time it took for the reduced-size hepatic transplant labeling index to peak. These findings suggest that after reduced-size hepatic transplantation, the liver graft is more sensitive to both hepatotrophic and hepatotoxic effects of cyclosporine.

Animals↗

PubMed1993

A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys).

No structural change of the dopamine D2 receptor (DRD2) has been reported so far, though the DRD2 gene has been suggested to be one of the candidate genes for mental disorders. Herein we report one missense nucleotide mutation from C to G resulting in a substitution of serine with cystein at the codon 311 located in the third intracellular loop of the DRD2 that was found in the analyses of the sequence of the DRD2 gene in 50 schizophrenics. The allele frequency, 0.04, of this Cys311 allele in 50 schizophrenics was slightly increased compared with that, 0.023, in 110 controls though the difference was not significant. The schizophrenics with Cys311 tended to have a lower age of onset and a positive family history of schizophrenia.

Alleles↗

PubMed1993

Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene.

Primary hypoalphalipoproteinemia is associated with atherosclerosis and exhibits significant familial aggregation. To reveal the presence of autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene, the apolipoprotein A-I gene was analyzed in a Japanese family with low levels of HDL cholesterol and apolipoprotein A-I. An insertion of a C in the region of the seven C run between codons 3 and 5 was detected in the apolipoprotein A-I gene. The heterozygous state for the mutation was associated with approximately 50% of the normal HDL cholesterol levels and of the normal apolipoprotein A-I levels. The data suggest that a part of familial hypoalphalipoproteinemia might be an autosomal dominant trait due to a completely defective apolipoprotein A-I gene.

Adult↗

PubMed1993

Time-resolved infrared spectral analysis of the KL-to-L conversion in the photocycle of bacteriorhodopsin.

Time-resolved infrared spectra of the hydrated film of light-adapted bacteriorhodopsin were recorded from earlier than 200 ns to 450 microseconds after light excitation in the 1800-900-cm-1 region on a newly designed dispersive-type infrared spectrometer [Iwata & Hamaguchi (1989) Appl. Spectrosc. 44, 1431-1437]. Both the KL-to-L and L-to-M conversions were detected in this time range. The spectral shape of KL is similar to K measured at 77 K except for the intense hydrogen out-of-plane vibrational band at 984 cm-1. The kinetics of this band are different from those of the other KL-specific bands at 1510, 1296, and 956 cm-1. Since the hydrogen out-of-plane vibrational bands are intensified by twists of the polyene chain, a change in the twist of the chromophore is suggested within the lifetime of KL. During the decaying process of L, the KL-specific vibrational bands are observed in parallel with L, indicating that KL and L are in equilibrium.

Bacteriorhodopsins↗

PubMed1993

Association between severity of alcoholism and the A1 allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese.

The allelic association of TaqI A restriction fragment length polymorphism (RFLP) of the dopamine D2 receptor gene with alcoholism was examined in 78 Japanese alcoholics and compared with Japanese controls. A significantly higher frequency of the A1 allele (0.42) was found in 100 Japanese unscreened controls compared with those reported in white populations. Among 70 alcoholics whose severities were determined, the A1 allele was present in 77% of 43 more severe alcoholics and in 59% of 27 less severe alcoholics. The A1 allele was present significantly less frequently in the alcoholics at the age of 60 or older (42%), compared with those under the age of 60 (74%). In the subjects under the age of 60, the A1 allele was present in 83% of the 35 more severe alcoholics, being significantly more frequent than in 60% of the 35 nonalcoholic controls. All of the 7 alcoholics homozygous for the A1 allele were classified as severe. The average severity of alcoholism increased in the order A2/A2, A1/A2, and A1/A1 genotypes. These data suggest that the A1 allele is associated with severe alcoholism in the Japanese population and that the effect is related to or has a linkage disequilibrium with a genetic factor that has a small but not negligible additive effect on alcoholism.

Age Factors↗