Search PubMed⌕ Search

Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 325 records · Page 18Linked to original sources

Importance of loops of mitochondrial ADP/ATP carrier for its transport activity deduced from reactivities of its cysteine residues with the sulfhydryl reagent eosin-5-maleimide.

The effects of various compounds such as the transport substrate ADP and the transport inhibitors carboxyatractyloside (CATR) and bongkrekic acid (BKA) on the labeling of cysteine residues in the ADP/ATP carrier of bovine heart submitochondrial particles by the SH reagent eosin-5-maleimide (EMA) were studied. Of the four cysteine residues in the carrier, the labeling of Cys159 by EMA progressed predominantly and rapidly, and those of Cys56 and Cys256 moderately, but Cys128 was not labeled, as we reported previously [Majima, E., et al. (1993) J. Biol. Chem. 268, 22181-22187]. ADP inhibited the labelings of Cys56, Cys159, and Cys256 by EMA. BKA markedly inhibited the labeling of Cys159 by EMA, and also the labeling of Cys256, but did not affect the labeling of Cys56, suggesting that it binds from the matrix side to a region close to Cys159 in the second loop facing the matrix space. CATR completely inhibited the labeling by EMA when added on the cytosolic side, but had no effect when added on the matrix side. From these results, the conformational changes of the carrier induced by CATR, BKA, and ADP are discussed. Furthermore, a mechanism of adenine nucleotide transport through the ADP/ATP carrier in association with change in its conformation is proposed.

Adenine Nucleotides↗

A common region of homozygous deletion in malignant human gliomas lies between the IFN alpha/omega gene cluster and the D9S171 locus.

Deletions of the 9p-localized type-I interferon (IFN) genes and adjacent loci often occur during the development of malignant glioma. We have applied restriction fragment length polymorphism and microsatellite analysis to 12 loci covering this region of 9p and 3 loci on 9q in 74 human glial tumor tissues to define and further localize the smallest region of hemizygous or homozygous deletion common to the tumors. Three regions of homozygous deletion were evident among the panel of tumors; only one of these, however, residing between D9S171 and the IFN alpha/omega gene cluster, was involved in multiple cases (13 glioblastomas). Hemizygous deletion of this same region was observed in an additional 27 tumors. In total these data indicate the frequent inactivation of a novel tumor suppressor gene residing adjacent to and centromeric of the type-I IFN genes in malignant gliomas.

Alleles↗

Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis.

8-Hydroxydeoxyguanosine (oh8dG) is a promutagenic DNA lesion produced by oxygen radicals. We examined alterations in the oh8dG level in human livers which have chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The oh8dG content in livers with chronic hepatitis was significantly higher than the oh8dG content in normal livers (P < 0.05). There was also a significant correlation between the oh8dG content in noncancerous liver tissues with individual serum alanine aminotransferase concentration (r = 0.515; P < 0.001). Thus, chronic inflammation in the liver produces oxidative DNA damage, which may increase the risk for genomic alterations causing hepatocarcinogenesis.

Alanine Transaminase↗

Platelet release reaction during EDTA-induced platelet agglutinations and inhibition of EDTA-induced platelet agglutination by anti-glycoprotein II b/III a complex monoclonal antibody.

To characterize the nature of EDTA-induced platelet agglutination, the spontaneous release of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) was examined during EDTA-induced platelet agglutinations. A slight release of beta-TG and PF4 was observed when EDTA-anticoagulated whole blood from cases with EDTA-induced platelet agglutination was kept for 60 minutes, whereas a high spontaneous release of these proteins was found from normal blood anticoagulated with EDTA. These findings imply that EDTA-dependent platelet agglutinin may stabilize the platelet membrane surfaces. Secondly, we found that pretreatment of fresh blood with anti-glycoprotein (GP) II b/III a complex monoclonal antibody dramatically reduced EDTA-induced platelet agglutinations. This study indicated that the binding sites of EDTA-dependent antibody might be GP II b/III a complex. The use of an anti-GP II b/III a complex monoclonal antibody may be useful in avoiding analytical errors in some cases with EDTA-induced pseudothrombocytopenia.

Adenosine Diphosphate↗

Comparison of benzodiazepine receptor and regional cerebral blood flow imaging of epileptiform foci in hippocampal kindled rabbits: a study with in vivo double tracer autoradiography using 125I-iomazenil and 99mTc-HMPAO.

To clarify experimentally whether benzodiazepine (Bz) receptor or regional cerebral blood flow (rCBF) imaging is more sensitive in the detection of epileptic foci, we simultaneously examined the Bz receptor and rCBF distribution changes in hippocampal kindled rabbits with in vivo double tracer autoradiography using 125I-labeled Ro 16-0154 (125I-Iomazenil) and 99mTc-labeled hexamethylpropylene amine oxime (99mTc-HMPAO). In visual and quantitative analyses, 125I-Iomazenil accumulation in brain slices extracted after the completion of the kindling was markedly and extensively decreased in the kindled right CA1 region, and further in the right temporal lobe, dentate gyrus, CA2, CA4, and bilateral CA3 regions, regarded as the propagated sites of seizure discharges. 99mTc-HMPAO accumulation was much more slightly and less extensively decreased in the right CA1, frontal, temporal and dentate gyri. Further, this decrease in 125I-Iomazenil accumulation was not due to neuropathological abnormalities, which consisted only of tissue damage corresponding to electrode track in the CA1. Both the kindled and propagated sites are known to have a possibility of acquiring epileptogenesis as experimental epileptic foci. These results suggest that Bz receptor imaging is much more sensitive in the detection of epileptic foci than rCBF imaging, and therefore that Bz receptor imaging is useful in clinical epilepsy.

Animals↗

Carbamazepine-induced blockade of induction of long-term potentiation in the perforant path-dentate gyrus pathway in chronically prepared rabbits.

We investigated the effects of a representative anti-epileptic or anti-psychotic drug, carbamazepine (CBZ), on the induction of long-term potentiation (LTP) in the perforant path-dentate gyrus pathway in 15 chronically prepared rabbits. Pharmacokinetically injected low-dose CBZ, which produced steady serum levels of 2.2-3.3 micrograms/ml (mean +/- S.D. 2.85 +/- 0.40), variably affected the induction of LTP, blocking it or showing almost no effect. The high-dose CBZ, which produced steady serum levels of 6.5-8.6 micrograms/ml (8.01 +/- 0.87), always blocked the induction of LTP. These results indicate that CBZ dose-dependently blocks the induction of LTP. The possible mechanisms underlying this blockade are discussed, especially in association with the possible inhibitory action of CBZ on N-methyl-D-aspartate (NMDA) receptors.

Animals↗

A novel cytokine exhibiting megakaryocyte potentiating activity from a human pancreatic tumor cell line HPC-Y5.

Sixty-four kinds of cell lines were examined for their ability to produce megakaryocyte potentiating activity by means of conditioned media obtained from a protein-free culture system. Six human tumor cell lines were shown to produce this activity, and the cell line HPC-Y5, established from human pancreatic cancer, was shown to have the highest level of activity. The megakaryocyte potentiating factor (MPF) was purified from an HPC-Y5 conditioned medium by a combination of ion-exchange chromatography, gel filtration and reverse-phase HPLC. The purified MPF showed a megakaryocyte potentiating activity almost equal to human interleukin-6 in the presence of murine interleukin-3 in a colony formation assay with mouse bone marrow cells. The apparent molecular weight of MPF is 32,000 when determined by SDS-polyacrylamide gel electrophoresis. Glycopeptidase F digestion, and amino sugar analysis of the factor demonstrated that MPF is a glycoprotein carrying at least one N-linked sugar chain. The N-terminal amino acid sequence of MPF was determined to be Leu-Ala-Gly-Glu-Thr-Gly-Gln-Glu-Ala-Ala-Pro-Leu- Asp-Gly-Val-Leu-Ala-Asn. The same or homologous amino acid sequence has not been found in known proteins, demonstrating that MPF is a novel cytokine that has megakaryocyte potentiating activity in the murine assay system.

Amino Acid Sequence↗

CD21 antigen in T-lineage neoplastic lymphoid cells: characteristic expression at thymic stage.

The expression of CD21 antigen, a receptor for the C3d fragment of complement and Epstein-Barr virus (EBV), was investigated in a total of 85 cases of neoplastic lymphoid cells including 39 cases of T-lineage acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL), although CD21 antigen is usually regarded as a pan-B antigen. The CD21 antigen was expressed by one of the eight cases of neoplastic lymphoid cells expressing the CD7 antigen as a sole pan-T antigen, by three of the 20 cases of pro- or early thymic stage (CD7+ CD5+ CD2-, CD7+ CD5- CD2+, or CD7+ CD5+ CD2+, and ten of 11 cases of thymic stage (CD3+/- CD4+ CD8+), but not by one case of late thymic stage (CD3+ CD4+ CD8-) T-ALL/LBL cells. The CD21 antigen was not expressed by any of the 11 cases of adult T-cell leukemia (ATL) or two cases of chronic T-lineage leukemia. At most 4% of the normal thymocytes obtained from seven infants or children expressed the CD21 antigen. While only a very limited population of normal thymocytes expresses CD21 antigen, T-ALL/LBL cells at the thymic stage characteristically express CD21 antigen in contrast to pro- or early thymic ALL/LBL or peripheral-stage neoplastic T cells. The estimation of the expression of CD21 antigen is useful for delineating stages of differentiation in T-ALL/LBL. Furthermore, these observation are notable, considering the possibility that the reported EBV-carrying T-cell lymphomas result from the penetration of EBV into EBV-negative neoplastic T cells.

Adolescent↗

Lineage determination of CD7+ CD5- CD2- and CD7+ CD5+ CD2- lymphoblasts: studies on phenotype, genotype, and gene expression of myeloperoxidase, CD3 epsilon, and CD3 delta.

The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+ CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T-lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO-negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T-lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+ CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5- CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases with entire germ-line genes and without mRNA of the three molecules (MPO, CD3 epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior to their commitment to either T- or myeloid-lineage. The co-expression of the genes of MPO and CD3 epsilon in a CD7+ CD5- CD2- case MPO, CD3 epsilon, and CD3 delta in a CD7+ CD5+ CD2- case suggested the presence of some overlapping phase for T- and myeloid-lineage commitment during immature stages of differentiation. This helps understand the conversion of some T-ALL/LBL cases to acute myeloblastic leukemia (AML).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Quantitative EEG analysis at rest and during photic stimulation in drug-naive patients with first-episode paranoid schizophrenia.

In the present study, quantitative EEG analysis was performed at rest and during 10 Hz photic stimulation in 14 drug-naive patients with first-episode paranoid schizophrenia and 20 sex- and age-matched control subjects. Compared with the normal controls, the patients had significantly lower alpha-2 band amplitude in the resting EEG over all recording regions. No significant group differences were found in other frequency bands. In addition, EEG analysis during photic stimulation demonstrated that the patients had a rather uniform topographic profile in EEG amplitude for the alpha band, with significant group differences being confined to the posterior regions in the left hemisphere. There were no significant group differences in the amplitude for the frequency bands harmonically related to the stimulus frequency. These findings provide further evidence that schizophrenic patients have abnormal EEG activity in both non-stimulus and stimulus conditions, and suggest a dysfunction in the mechanisms underlying EEG alpha generation in schizophrenia.

Adult↗

In vivo dopamine-D2 and serotonin-5-HT2 receptor binding study of risperidone and haloperidol.

An in vivo receptor binding technique was applied to evaluate the affinities of risperidone and haloperidol for dopamine-D2 receptors (D2) and serotonin-5-HT2 receptors (5-HT2) in rat brain with [3H]YM-09151-2 and [3H]ketanserin as selective ligands. Radioactivities were obtained in the striatum frontal cortex, and cerebellum of the rats treated with the ligands. Time course study of receptor occupancy at 25 to 250 min after single doses of the drugs (1 mg/kg, IP) showed higher 5-HT2 occupancy in the frontal cortex and lower D2 occupancy in the striatum by risperidone than by haloperidol. Dose-response analysis of receptor occupancy revealed risperidone demonstrated higher binding affinity for 5-HT2 than for D2, while the reverse was observed with haloperidol. It appeared that risperidone (1 mg/kg, IP), but not haloperidol (1 mg/kg, IP), demonstrated regional selectivity in D2 occupancy favouring frontal cortex more than the striatum. That risperidone displayed a higher ratio of 5-HT2 to D2 in occupancy than haloperidol is in agreement with the previous findings obtained in vitro.

Animals↗

Time course of dopamine1,2 and serotonin2 receptor binding of antipsychotics in vivo.

An in vivo receptor binding technique was applied to evaluate the affinities of clozapine (20 mg/kg), RMI-81582 (20 mg/kg), and haloperidol (1 mg/kg) for dopamine D1, D2 and serotonin 5-HT2 receptors in rat brain with [3H]-SCH23390, [3H]-YM-09151-2, and [3H]-ketanserin as selective ligands. The time course study of receptor occupancy at 25 to 250 min after intraperitoneal administration of the drugs showed higher 5-HT2 and lower D2 receptor occupancies of clozapine and RMI-81582 than those of haloperidol both in the striatum and frontal cortex. The 5-HT2/D2 ratios of receptor occupancy for clozapine and RMI-81582 were about 6 to 8 times higher than that for haloperidol. Stable occupancies of D1 receptors were observed only with RMI-81582 and clozapine, the former demonstrating the higher occupancy. These findings are in agreement with the previous findings obtained under in vitro conditions and may account for some part of the properties of atypical antipsychotic drugs.

Animals↗

Comparison of benzodiazepine receptor and regional cerebral blood flow imaging of epileptiform foci in hippocampal kindled rabbits: a preliminary report.

To clarify experimentally which of benzodiazepine (BZ) receptor or regional cerebral blood flow (rCBF) imaging is more sensitive in the detection of epileptic foci, we simultaneously examined the BZ receptor and rCBF distribution changes in hippocampal kindled rabbits with in vivo double tracer autoradiography using 125I-labeled Ro 16-0154 (125I-Iomazenil) and 99mTc-labeled hexamethyl-propyleneamine oxime (99mTc-HMPAO). In visual analysis of brain slices extracted after the intravenous injection of the double tracer following the kindling completion, 125I-Iomazenil accumulation was more markedly and extensively decreased in the kindled right CA1 region mimicking a primary epileptic focus than 99mTc-HMPAO accumulation. Further, this decrease in 125I-Iomazenil accumulation was not due to neuropathological abnormalities which consisted only of tissue damage corresponding to electrode track in the right CA1. These results suggest that BZ receptor imaging is more sensitive in the detection of epileptic foci than rCBF imaging and, therefore, that BZ receptor imaging is useful in clinical epilepsy.

Animals↗

Epilepsy and SPECT.

SPECT studies for rCBF imaging in clinical epilepsy are reviewed divided into interictal, ictal and postictal SPECT studies in partial and generalized epilepsies, as compared with the corresponding PET studies, and at times referring to SPECT studies in experimental models of epilepsy. All of the interictal, ictal and postictal SPECT scans in partial epilepsy are useful for the regional determination of epileptic foci, in view of the high appearance rates of focal abnormalities on these SPECT scans and good correlation with epileptic EEG foci. Mechanisms underlying the focal abnormality on interictal SPECT scans (i.e., focal hypoperfusion) image are complicative, and therefore, studies concerning the underlying mechanisms are reviewed with regard to correlations of the SPECT abnormality with the following various clinical factors: focal organic lesions on X-ray CT or MRI scans, frequencies of clinical seizures or interictal seizure discharges on EEGs, background EEG activity, propagation of epileptic activity, antiepileptic drugs, and cognitive functions. Further, new neurochemical SPECT studies using 123I-Iomazenil for benzodiazepine receptor imaging in clinical epilepsy are reviewed and compared with earlier SPECT studies for rCBF imaging with regard to their utility in regional determination of epileptic foci. In addition, the few SPECT or PET studies available on epileptic psychosis are reviewed.

Animals↗