Search PubMed⌕ Search

Biomedical subjects

R Fukuda

Publications and source records attributed to R Fukuda.

At least 109 records · Page 6Linked to original sources
PubMed1994

No allelic association between Parkinson's disease and dopamine D2, D3, and D4 receptor gene polymorphisms.

Parkinson's disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson's disease. Genetic association studies between Parkinson's disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson's disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson's disease is associated with the dopamine receptor polymorphisms examined.

Adult↗
PubMed1994

No evidence of linkage or allelic association of schizophrenia with DNA markers at pericentric region of chromosome 9.

Based on our previous study suggesting the pericentric region of chromosome 9 as of potential importance in schizophrenia, we have carried out a linkage study between the schizophrenia phenotype and the dinucleotide repeat polymorphisms D9S55, D9S15, and D9S202 in three pedigrees multiply affected with schizophrenia. In addition, we have conducted allelic association studies using 60 patients with schizophrenia and 60 controls with polymorphisms at D9S55 and D9S15 markers. No evidence for linkage or association was found. The results indicate that susceptibility genes for schizophrenia are less likely to be located at the pericentric region of chromosome 9, assuming genetic homogeneity of the pedigrees.

Alleles↗
PubMed1994

Further evidence of no linkage between schizophrenia and the dopamine D3 receptor gene locus.

The dopamine hypothesis of schizophrenia proposed that dopaminergic pathways are involved in the etiology of the disease. In particular, interest among psychiatrists has focused on the D2 receptor because of its affinity to antipsychotic drugs. Recently a new dopamine receptor gene has been cloned, and named the dopamine D3 receptor. The D3 receptor is a potential site for antipsychotic drug action and may be involved in the pathophysiology of schizophrenia. We have carried out a linkage study between the susceptibility gene for schizophrenia and polymorphism of the dopamine D3 receptor gene in two Japanese pedigrees. The LOD scores were negative for all genetic models and for all affective status at a recombination fraction theta = 0. Linkage of DRD3 has been excluded for the model 1 (dominant model) and the model 3 (recessive model). The LOD score was -3.43 at theta = 0 for model 1 (dominant model) and broad definition of affected status. These results were consistent with previous studies.

DNA↗
PubMed1994

Mismatch PCR RFLP detection of DRD2 Ser311Cys polymorphism and schizophrenia.

We tested 100 schizophrenics and 100 controls to find association at the Serine311 Cysteine polymorphism of dopamine D2 receptor in Japanese population. There were no significant differences between the two groups. One homozygote for Cys311 was confirmed in the controls by mismatch-polymerase chain reaction and restriction fragment length of polymorphism (PCR-RFLP) analysis. None with Cys was detected among 61 individuals of nine multiply affected families with schizophrenia. Our data thus provide strong evidence against an etiological association between schizophrenia and the Ser311Cys variant. The polymerase chain reaction amplification of specific alleles (PASA) analysis was compared with the mismatch PCR-RFLP typing, revealing that the latter is more reliable than the former.

Alleles↗
PubMed1994

Association of apolipoprotein E4 with sporadic Alzheimer's disease is more pronounced in early onset type.

Apolipoprotein E genotypes in 88 unrelated Japanese patients with NINCDS-ADRDA sporadic Alzheimer's disease (AD) were examined and compared with those of 93 healthy controls. Frequency of epsilon 4 allele was increased in patients with AD (31%) compared with controls (10%), as was reported previously. Individuals homozygous or heterozygous for the allele epsilon 4 had a 5.9-fold increased risk of AD. This tendency was more pronounced in early onset sporadic (= non-familial) type than late onset type. The relative risk was also greater for early onset type (RR = 11.7; 95% CI, 4.9-28.3) than late onset type (RR = 4.3; 95% CI, 2.1-8.8). Moreover, patients with homozygote for the allele epsilon 4 had a 14.7-fold increased risk of early onset sporadic AD (P < 0.005, chi 2 = 9.0, df = 1, 95% CI, 2.5-85.1). Our findings indicated that association of apolipoprotein epsilon 4 with sporadic Alzheimer's disease is more pronounced in early onset type than in late onset type.

Age of Onset↗
PubMed1994

The prosequence of Rhizopus niveus aspartic proteinase-I supports correct folding and secretion of its mature part in Saccharomyces cerevisiae.

Extracellular Rhizopus niveus aspartic proteinase-I (RNAP-I) was secreted effectively by Saccharomyces cerevisiae when RNAP-I with its preprosequence was synthesized in this organism (Horiuchi, H., Ashikari, T., Amachi, T., Yoshizumi, H., Takagi, M., and Yano, K. (1990) Agric. Biol. Chem. 54, 1771-1779). Certain deletions (delta pro, delta 1, delta 2), and amino acid substitutions (M1) in the prosequence blocked secretion of RNAP-I, although the protease protection assay revealed that even delta pro could be translocated across the membrane of the endoplasmic reticulum. When delta pro or M1 was synthesized simultaneously with the wild-type preprosequence in S. cerevisiae, secretion of RNAP-I was recovered. Therefore, the physical linkage of the prosequence to the mature region is not a prerequisite for secretion of active RNAP-I. Purified RNAP-I with the prosequence once denatured in 6 M guanidine HCl could be renatured and activated to have its enzymatic activity by removing guanidine HCl in vitro, but RNAP-I without the prosequence could not. Furthermore, the wild-type prosequence helped the recovery of the activity of the denatured RNAP-I in trans, but the prosequences of M1 with which secretion of RNAP-I was not observed in vivo, did not. From these results we concluded that the prosequence of RNAP-I supports correct folding of RNAP-I in the endoplasmic reticulum lumen and its subsequent secretion in S. cerevisiae. The functional role of the prosequence of an aspartic proteinase was elucidated.

Amino Acid Sequence↗
PubMed1994

Changes of immunological functions after acute exacerbation in schizophrenia.

We investigated the changes of immunological functions in 14 schizophrenic patients (DSM-III-R; six men and eight women) who were hospitalized due to acute exacerbation of schizophrenia. The following immunological functions were studied on admission, 4 and 8 weeks after admission: serum immunoglobulins (Ig)G, A, and M; serum complement CH50; lymphocyte responses to mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen); lymphocyte subpopulations (CD3%, 4%, 8%, 16%, 20%, 25%, and 56%); and natural killer cell (NK) activity. Psychological status of the patients, which was assessed by using Brief Psychiatric Rating Scale, improved gradually after admission. Changes in immune functions were analyzed using one-way analysis of variance and a randomized block analysis of variance with multiple comparison. NK activity on admission was significantly lower than those at 4 and 8 weeks after admission (p < .03). Serum IgG levels on admission and at 4 weeks after admission were significantly decreased as compared with those at 8 weeks after admission (p < .05); they were also lower than those in controls (p < .05). CD56% on admission and CD25% 4 weeks after admission were significantly increased as compared with controls (p < .05). These results indicate that several immunological functions might change related to time course after acute exacerbation. It is suggested that clinical conditions be carefully taken into consideration to evaluate immunological studies in schizophrenia.

Acute Disease↗
PubMed1994

Hepatitis may precede the occurrence of precore region mutation in hepatitis B virus genome during infection in young carriers.

To understand when the mutation with a stop codon of precore region in hepatitis B virus genome occurs, the prevalence of the mutation of viral DNA clones propagated from sera of school-age carriers was investigated with respect to hepatitis B e antigen (HBeAg)/anti-HBe and sequential changes of mutants along HBeAg seroconversion were analyzed. Of 32 carriers aged 8-18 years, 14 HBeAg(+) patients had 2.2% mutant clones, whereas 8 patients with low titer anti-HBe had a higher rate of 18.1% (P < 0.01) and the highest rate of 61.3% was found in 10 patients with high anti-HBe titer (P < 0.001). By contrast, the amount of viral DNA decreased significantly in patients with anti-HBe. Sequential analysis in six cases revealed three types of seroconversion with time difference of the emergence and increase of mutant clones. It is concluded that mutation occurs at a relatively young age and increases along time and/or HBeAg seroconversion. Hepatitis might precede or accelerate the emergence and increase of mutant population which might be predictive of sustained resolution of the disease.

Adolescent↗
PubMed1994

Precore region mutation in hepatitis B virus genome in early stage of infection: a study in hepatitis B e antigen-positive young carriers.

To determine when the precore mutation at the 83rd nucleotide occurs, leading to the formation of a stop codon in the hepatitis B virus genome in carriers, which would indicate the presence of antibody to hepatitis B e antigen (anti-HBe), we investigated this mutation by direct sequencing and subcloning in 22 young hepatitis B antigen (HBeAg) (+) carriers. These subjects were 7-17 years old and were found during a survey for hepatitis B surface antigen (HBsAg) in three elementary schools, a junior high, and a senior high school. None of these carriers had clinical manifestations, although one-third of them had elevated serum alanine aminotransferase levels. All were HBeAg-positive by radioimmunoassay (RIA), and 6 of them had preserved titers of anti-HBe at the same time. Precore mutations were found in 4 subjects (18.2%), with predominance of the wild type. Although 3 of these 4 had preserved titers of HBeAb, the other had no HBeAb titers. In an other 3 subjects with preserved titers of HBeAb, the precore mutation was not detected, even after the subcloning of viral DNA. The remaining 15 subjects with HBeAg showed no precore mutation. Subjects with ALT levels exceeding 100 IU/l were all HBeAg-positive without the mutation. It was clear that the precore mutation itself occurred in the subjects at an early age during the course of infection. However, the chronological relationship between the emergence of the precore mutation and the onset of hepatitis requires further study.

Adolescent↗
PubMed1994

Linkage studies between affective disorder and dopamine D2, D3, and D4 receptor gene loci in four Japanese pedigrees.

Dopamine antagonists are effective in the treatment of episodes of acute mania. Conversely, drugs which increase dopamine activity can induce a switch to mania. Therefore, disturbances in dopamine transmission and dopamine receptors might be implicated in the pathophysiology of bipolar affective disorder. We have carried out linkage studies between the susceptibility gene for effective disorder and polymorphisms of dopamine DRD2, DRD3, and DRD4 receptor genes in four Japanese pedigrees. Linkages of both DRD2 and DRD3 have been excluded, at least for dominant and intermediate models. The result for DRD2 was consistent with previous studies. For DRD3 this is the first exclusion of affective disorder from this locus in the 3q13.3 where DRD3 has been localized. On the other hand, our data could not exclude linkage of DRD4.

Adolescent↗
PubMed1994

Neurotrophin-3 gene polymorphism associated with schizophrenia.

The recent possible neurodevelopmental etiology of schizophrenia makes the neurotrophin-3 (NT-3) gene an interesting candidate locus. We studied the allelic distributions of dinucleotide repeat polymorphism at the NT-3 gene locus in 70 patients with schizophrenia and in 70 controls. A highly significant difference between the two groups was observed at the allele A3. Even Bonferroni's correction was used, the difference was still significant. Individuals with homozygous or heterozygous for the allele A3 had a 2.4-fold increased risk of schizophrenia. Determination of NT-3 genotype may help to identify those at greater risk of schizophrenia. Furthermore, this finding supports evidence implicating neurodevelopmental deficit in the pathogenesis of this disorder.

Adult↗
PubMed1994

[Clinical studies of a newly developed miconazole preparation for intravenous drip infusion (MJR-1761) in hematologic disease patients with deep-seated fungal infections].

The efficacy and safety of a newly developed miconazole preparation (MJR-1761) for intravenous drip infusion were evaluated in 22 patients with hematological diseases complicated by documented or suspected deep-seated fungal infections. They consisted of 15 patients with fungemia, 2 patients with pulmonary mycosis, and 5 patients with mycosis of the digestive tract. Of the 5 patients, 3 had a complication of fungemia and 1 a complication of urinary tract mycosis. Of the 22 patients, 21 were clinically evaluable. All the patients were included in safety evaluation. The effective rate was 86% (18/21) when moderately improved or better evaluations were included, and the usefulness rate was 81% (17/21) when moderately or more useful evaluations were taken into consideration. Side effects occurred in 4 patients, and abnormal laboratory values were obtained in 4 patients. All these changes, which were previously reported, improved after the discontinuation of the treatment. The results presented indicate that the miconazole intravenous drip infusion solution used in this study is as effective as conventional similar preparations. Since the infusion solution need not be diluted immediately before use, it is simple to use, and its safety may be highly rated. The purpose can be met with less volume of solution per use than before because the preparation contains as much as 200 mg of miconazole in 75 ml of solution. This preparation seems to lend itself better to clinical application than conventional similar infusion solutions.

Adult↗
PubMed1994

Upregulation of cell surface expression of T-lymphoid antigens and adhesion molecules on acute myeloid leukaemia cells after in vivo administration of granulocyte colony-stimulating factor.

We herein report a case of acute myeloid leukaemia (AML, FAB:M0) who showed upregulation of T-lymphoid antigens (CD2, CD7) and adhesion molecules (CD11a, CD11b, CD18) on leukaemic cells after in vivo administration of granulocyte colony-stimulating factor (G-CSF). To our knowledge, this is the first report which describes in vivo changes of cell surface antigen expression on AML cells after the administration of G-CSF.

Aclarubicin↗
PubMed1994

Circadian variations and prednisolone-induced alterations of circulating lymphocyte subsets in man.

We determined the circadian variations and prednisolone (PSL)-induced alterations of circulating lymphocyte subsets in 10 healthy adults by two-color flow cytometry using monoclonal antibodies to various lymphocyte subsets in order to collect fundamental data for monitoring of the subsets in clinical practice. This study first examined the changes of CD5+ B cells, gamma delta+ or gamma delta-T cells, activated (HLA-DR+) CD4+ or CD8+ cells, CD11b+ or CD11b-CD8+ cells, and natural killer (NK) cell subsets (CD16+CD57-, CD16+CD57+, CD16-CD57+), in addition to other subsets described before. Compared with the base line values obtained at 9:00 (AM) on day 1, lymphocytes, total B cells, CD5+ B cells, total T cells, gamma delta-T cells, CD4+ cells, activated CD4+ cells, CD45RA-CD4+ cells, and activated CD8+ cells were significantly increased at 20:00 (PM). However, the numbers of CD45RA+CD4+ cells, CD11b+ or CD11b-CD8+ cells and three NK cells subsets did not show significant circadian variations. After oral PSL (30 mg), which was given at 7:00 (AM) on day 2, lymphocytes and almost all lymphocyte subsets, except for CD16+CD57- cells, were significantly decreased; these changes recovered between 13 and 26 hours after PSL administration. The circadian variations and PSL-induced alterations of lymphocyte subsets were relatively comparable, but PSL administration cause a decrease in a wider range of lymphocyte subsets including relatively corticosteroid-resistant subsets such as CD45RA+CD4+ cells, CD8+ cell and NK cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Effects of cytarabine ocfosfate on colony-stimulating factor in myelodysplastic syndrome with monosomy 7].

A 42-year-old man was admitted to our hospital because of pancytopenia in April 1992. A diagnosis of refractory anemia was made. The karyotype was normal male type on the initial study. Subcutaneous administration of granulocyte colony-stimulating factor (G-CSF) initially increased the peripheral neutrophil count, bat in January 1993, although blast cells did not increase, neutrophils had decreased in spite of the continuation of G-CSF administration. Chromosome analysis showed 46XY, +Y, -7 at this point. By adding 50 mg of cytarabine ocfosfate (SPAC) daily, the peripheral neutrophil count again rose dramatically. However, anemia, thrombocytopenia and the chromosomal abnormality were unchanged. These results indicate that SPAC may upregulate the effect of G-CSF on granulopoiesis in patients with myelodysplastic syndrome.

Adult↗