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Biomedical subjects

H Hirai

Publications and source records attributed to H Hirai.

At least 19 recordsLinked to original sources
PubMed1992

Reversal by phosphatidylglycerol and cardiolipin of inhibition of transcription and replication by histones in vitro.

We examined the effects of phospholipids on transcription and replication in vitro in the presence of histones. Phosphatidylglycerol and cardiolipin were shown to reverse the inhibitory effects of histones in both random RNA synthesis with purified RNA polymerase II and accurate transcription initiated from the adenovirus 2 major late promoter in a nuclear extract. Phosphatidylserine, phosphatidic acid, and phosphatidylcholine did not activate RNA synthesis although they bound as strongly as phosphatidylglycerol and cardiolipin to histones. Phosphatidylglycerol and cardiolipin also reversed the in vitro inhibition of SV40 DNA replication by histones. Unsaturation of the fatty acid residues was shown to be necessary for the restoration of transcription and replication by phosphatidylglycerol.

Adenoviruses, Human↗
PubMed1992

Molecular cloning of bovine actin-like protein, actin2.

Actins are major cytoskeletal components and highly conserved in evolution. In mammals, there are six actin isoforms, a pair of which shows at least 93% identity in the amino acid sequence. We have cloned cDNA for a bovine protein that is distantly related to members of the mammalian actin isotypes. The predicted amino acid sequence (418 residues long, calculated molecular mass 47369) shows that this protein, which we have named actin2, exhibits 36% identity to mammalian actins and 60% identity to the yeast actin-like protein, act2. We have concluded that actin2 defines a new class of mammalian actin-like proteins. It was also revealed that actin2 messenger RNA is expressed in a broad range of tissues.

Actins↗
PubMed1992

Lectin affinity electrophoresis of alpha-fetoprotein. Increased specificity and sensitivity as a marker of hepatocellular carcinoma.

alpha-Fetoprotein (AFP) is widely used as a marker of hepatocellular carcinoma (HCC) for assisting diagnosis and also for screening purposes, even though its sensitivity has been decreased slightly as a result of the earlier detection of HCC by ultrasonography. Using lectin-dependent fractionation of AFP, the diagnostic sensitivity as well as the specificity of AFP can be increased compared with measurement of total AFP. Furthermore, lectin-reactive forms of AFP, AFP-L3 and AFP-P4, have been shown to serve as preclinical markers of HCC. Accordingly, AFP is still the most reliable marker of HCC in screening and monitoring high-risk patients.

Biomarkers, Tumor↗
PubMed1992

Frequent mutations in the p53 gene in human myeloid leukemia cell lines.

The p53 gene is currently considered to function as a tumor-suppressor gene in various human malignancies. In hematologic malignancies, alterations in the p53 gene have been shown in some human leukemias and lymphomas. Although mutations in the p53 gene are infrequent in acute myelogenous leukemia (AML) patients, we show in this report that alterations in the p53 gene are frequent in myeloid leukemia cell lines. We studied alterations of the p53 gene in nine human myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR), single-strand conformation polymorphism (SSCP) analysis, and direct sequencing. Expression of the p53 gene was not detected at all by RT-PCR in two of the nine cell lines. In these two cell lines, Southern blot analysis showed gross rearrangements and deletions in both of the p53 alleles. Six of the nine cell lines were found to express only mutant p53 mRNA by RT-PCR/SSCP analysis and direct sequencing, and wild-type p53 mRNA was not detected. Two of the mutant p53 mRNAs were shown to be products of abnormal splicing events induced by intronic point mutations. Taken together, eight of nine human myeloid leukemia cell lines expressed no or an undetectable amount of wild-type p53 mRNA. Three of the eight cell lines were growth factor-dependent. Our results suggest that inactivation of the p53 gene may be a common feature in myeloid leukemia cell lines and may play an important role in the establishment of these cell lines.

Base Sequence↗
PubMed1992

Identification of a soluble GM-CSF binding protein in the supernatant of a human choriocarcinoma cell line.

We identified two forms of the receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) made by the human choriocarcinoma cell line JEG-3 using an affinity-labeling technique. The protein was identified in the detergent-extract was 78 kDa, very similar to that of the membrane-bound GM-CSF receptor alpha chain expressed in a wide variety of hematopoietic and nonhematopoietic cells, including JEG-3. In contrast, a 62-kDa GM-CSF binding protein, or the soluble GM-CSF receptor, was identified in the supernatant of JEG-3 cells. Utilizing the same affinity labeling technique, we did not detect the soluble GM-CSF binding protein in the supernatant of several hematopoietic cell lines, such as U-937 and KG-1, which express membrane bound alpha chain as well as beta chain. The 62-kDa soluble GM-CSF receptor is produced in abundant amounts by JEG-3, but in very small amounts, if any, by hematopoietic cell lines.

Choriocarcinoma↗
PubMed1992

Correlation of L-myc RFLP with metastasis, prognosis and multiple cancer in lung-cancer patients.

For further study of the correlation of L-myc restriction-fragment-length polymorphism (RFLP) and metastasis of lung cancer to lymph nodes or other organs at the time of surgery, L-myc RFLP was analyzed in 252 Japanese lung-cancer patients. A close correlation between L-myc RFLP and metastasis was confirmed in this large number of patients (p = 0.01). The correlation was particularly pronounced in cases of adenocarcinoma and squamous-cell carcinoma. Poor prognosis (additional metastases after surgery) was observed in lung-cancer patients with L-S (identified as long and short bands produced with EcoRI) and S-S type L-myc RFLP. In addition, the death rate of lung-cancer patients with the L-S and S-S types was greater than that of those with the L-L type. Lung-cancer patients of the L-S and S-S types had almost 4 times higher incidence of multiple cancer in the lung, pharynx and other organs than those with the L-L type. Our results indicate that, in patients with lung cancer, genetic disposition with respect to the L-myc gene influences the extent of metastasis, the incidence of multiple cancers and prognosis.

Combined Modality Therapy↗
PubMed1992

Anti-tumor effects of interleukin-4 and interleukin-5 against mouse B cell lymphoma and possible mechanisms of their action.

We investigated the anti-tumor effects of recombinant mouse interleukin (IL)-4 and IL-5 by using a transplantable B cell lymphoma 38C13 cell line as a model. Daily local administration of either IL-4 or IL-5 produced moderate but significant inhibition of the rate of local tumor growth and prolongation of mean survival time (MST) in syngeneic C3H/HeJ mice; these anti-tumor effects appeared to plateau at low doses. Histopathologic and immuno-histochemical examination revealed necrotic changes in the cytokine-treated tumors, associated with infiltration of inflammatory cells such as eosinophils, macrophages, and lymphocytes. The infiltrating lymphocytes were found to be Thy-1.2+ T cells. To elucidate the importance of T cells, the rate of tumor growth and the MSTs were compared between athymic T cell-deficient BALB/c nude mice and immunocompetent C3H/HeJ mice. In the nude mice the transplanted tumor grew more rapidly and the MST was shorter than in the normal mice, suggesting a significant contribution of infiltrating T cells in the anti-tumor effects of the interleukins. Lastly, in vitro, growth inhibition of the 38C13 cells was observed in a dose-dependent manner at relatively high concentrations of either cytokine. Therefore, we conclude that both IL-4 and IL-5 have moderate anti-tumor effects against 38C13 B cell lymphoma both in vivo and in vitro, and that the observed in vivo anti-tumor effects are probably mediated both by tumoristatic action of infiltrating cells, such as eosinophils, macrophages and T lymphocytes, and by direct anti-proliferative action of the recombinant cytokines.

Animals↗
PubMed1992

Two myelodysplastic syndrome cases with the inv(11)(p15q23) as a sole chromosomal abnormality.

Two myelodysplastic syndrome cases (one with acute nonlymphocytic leukaemia (M2) transformed from myelodysplastic syndrome (MDS), and the other with chronic myelomonocytic leukaemia following refractory anaemia with excess of blasts in transformation) showed the inv(11)(p15q23) as a sole chromosomal abnormality. Gene probes for c-Ha-ras-1 and c-ets-1 were hybridized to metaphase cells from bone marrow of these patients. c-ets-1 gene, which is mapped to 11q23, was demonstrated to have translocated to the short arm in the rearranged chromosome 11 in both cases. On the other hand, c-Ha-ras-1 gene, which is located at 11p15, was translocated to the long arm in the rearranged chromosome 11 in patient 1, and deleted in patient 2. Our findings suggest that there may be heterogeneity in molecular events involved in the chromosomal rearrangement among the inv(11)-carrying MDS.

Adolescent↗
PubMed1992

Preventive effect of exercise training on recurrent stenosis after percutaneous transluminal coronary angioplasty (PTCA).

The purpose of this study is to evaluate whether exercise training for 12 weeks prevents the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Symptom-limited treadmill exercise with thallium-201 myocardial single photon emission computed tomography (SPECT) was performed one and 13 weeks after PTCA in 18 patients with exercise training and in 20 patients without. For quantitative analysis, the average count of region of interest in the hypoperfused area on the polar map was calculated. A percentage T1 uptake was determined by dividing average count of the hypoperfused area by that of a normal reference area at an initial image (%IU) and a delayed image (%DU). A percentage redistribution (%RD) was obtained by subtracting %IU from %DU as the parameter of residual ischemia in the hypoperfused area. Total treadmill exercise duration and maximal pressure rate product 13 weeks after PTCA increased significantly (p less than 0.01) in the trained group, whereas there was no significant change in the untrained group. %DU increased significantly (p less than 0.01) in the trained group, whereas there was no significant change in the untrained group. %RD decreased significantly (p less than 0.01) in the trained group, whereas there was no significant changes in the untrained group. The restenosis rates at the third month after PTCA was 17% (3/18) in the trained group and 40% (8/20) in the untrained group. These findings suggest that in patients with coronary artery disease exercise training improves myocardial perfusion by preventing the progression of coronary artery stenosis after PTCA.

Aged↗
PubMed1992

The p53 gene expression and its developmental regulation in schistosomes.

We have studied the gene expression, especially of the oncoproteins, and its regulation in schistosomes. Schistosomes have a complex life cycle with a defined dimorphic lifestyle. The parasite are so far unique in biology in expressing oncogene products in their adult stage. In order to characterize the expression and developmental regulation, a lambda gt 11 cDNA library and lambda EMBL4 genomic DNA library of each growth stage of Schistosoma mansoni and S. japonicum was constructed, and was screened with various monoclonal antibodies against oncogene products. One positive plaque reacted to anti-p53 antibody (Ab-2, Oncogene Science, Inc.) was further analyzed. This fusion protein was about 120 KDa in molecular weights, and expressed as 1.4 Kb RNA in the adult stage. P53 gene is well-known as the negative regulator of the cell cycle, and the mutations in the gene are turning out to be the most common genetic alterations in human cancers. The comparison of the gene structure among species and stages were being conducted. Chromosome structures, C-band formation, and the results of in situ hybridization using the phage probe would be discussed.

Animals↗
PubMed1992

Cerebellar astrocytoma with repeated episodes of fourth ventricle isolation causing peritoneal shunt tube obstruction--case report.

A 9-year-old girl underwent total removal of a cerebellar astrocytoma complicated by hydrocephalus after postoperative meningitis, requiring a ventriculoperitoneal shunt. Five months later, headache, vomiting, and gait disturbance appeared and computed tomography detected enlarged fourth ventricle. A fourth ventriculoperitoneal shunt resulted in immediate relief of all symptoms. After 2 months, obstruction of the peritoneal tube required shunt reconstruction. This recurred three times in 8 months. At the last operation, tumor cells were detected in the cerebrospinal fluid and the substance clogging the tube. This suggested that the tumor had recurred and clogging by tumor cells had caused the repeated episodes of isolated fourth ventricle. Radiation therapy prevented further shunt obstruction and achieved remission of all signs and symptoms.

Astrocytoma↗
PubMed1992

Decreased level of transforming growth factor-beta in blood lymphocytes of patients with aplastic anemia.

Levels of transforming growth factor-beta (TGF-beta) activity in the conditioned medium of blood lymphocytes of twelve patients with aplastic anemia (AA), nine patients with myelodysplastic syndromes (MDS) and five normal volunteers were investigated. We were able to observe growth inhibitory activity on porcine endothelial cells only after acidification of the materials. The growth inhibitory activity is neutralized by anti-TGF-beta antibody. It indicates that TGF-beta exists as a latent form in the conditioned medium. On the basis of growth inhibition assay, the mean level of TGF-beta production of MDS patients was estimated to be 188 +/- 199 pg/1 x 10(7) cells and that of normal volunteers was 668 +/- 314 pg/1 x 10(7) cells. In contrast, the lymphocytes of almost all of the AA patients failed to produce detectable amounts of TGF-beta. No correlation between TGF-beta levels and peripheral blood parameters could be detected. Stimulation of lymphocytes by phytohemagglutinin is known to increase the production of TGF-beta. Induction of TGF-beta production was also observed in AA (45% of normal controls). Possible roles of the decreased production of TGF-beta in the pathogenesis of AA were discussed.

Adult↗
PubMed1992

[Effects of exercise training on restoration of residual myocardial ischemia after percutaneous transluminal coronary angioplasty].

The effects of exercise training on the restoration of hibernating myocardium after percutaneous transluminal coronary angioplasty (PTCA) were evaluated. Symptom-limited treadmill exercise with thallium-201 myocardial single photon emission CT (SPECT) was performed at one and 13 weeks after PTCA in 15 patients with training and in 15 control patients without training who had no restenosis on repeat angiography. For quantitative analysis, counts for the regions of interest (ROI) were calculated in the hypoperfused area on the polar map. Percent T1 uptake was determined by dividing counts of the hypoperfused area by counts of a normal reference area on the initial image (%IU) and delayed image (%DU). The difference between %DU and %IU, defined as percent redistribution (%RD), was a parameter of residual ischemia in the hypoperfused area. %DU increased significantly in the trained group (65 +/- 11 to 73 +/- 9.3%, p < 0.01) and in the untrained group (66 +/- 14 to 70 +/- 15%, p < 0.05). %RD decreased significantly in the trained group (6.3 +/- 3.2 to 2.8 +/- 2.3%, p < 0.01); whereas, there was no significant change in the untrained group (6.1 +/- 2.8 to 5.2 +/- 3.8%). These findings suggest that, after successful PTCA, exercise training helps alleviate myocardial ischemia, probably by fostering the promoting effects which restore the hibernating myocardium.

Aged↗
PubMed1992

Treatment of acute nonlymphocytic leukemia by combination of recombinant human granulocyte colony-stimulating factor and cytotoxic agents: a report of six cases.

Six patients with recurrent and/or refractory acute nonlymphocytic leukemia (ANLL) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) and cytotoxic agents administered simultaneously. Neither of the two patients who received cytosine arabinoside (ara-C) in combination with G-CSF achieved complete remission. The other four patients, who received multi-drug combination therapy together with G-CSF, all achieved complete remission. No major side effects due to G-CSF were observed. These results demonstrated that the effects of G-CSF in enhancing the sensitivity of leukemic cells to cytotoxic agents and accelerating the recovery of leukocytes could lead to its possible use in the treatment of ANLL.

Adult↗
PubMed1992

[Quantitative analysis of sodium fast and slow component in in vivo human brain tissue using MR Na image].

In vivo sodium concentrations in the normal brain tissue and a tumorous tissue were analyzed using MR Na image. The nuclear magnetic resonance enabled us to divide the signal from sodium in the living tissue into 2 parts based on the differences of T2 value. Those are fast component having the T2 value of less than 5 msec and slow component of 15-40 msec. We investigated the effect of macromolecules on T2 value of sodium image using polyvinyl alcohol (PVA) powder. MR Na image was taken with the parameters of TR/TD, 110 ms/1.9 ms (FID image) and TR/TE, 110 ms/20 ms (SE image). Saline solution showed high intensity on both FID image and SE image. Saline solution added PVA (PVA phantom) also showed high intensity on FID image, whereas the signal intensity of PVA phantom in SE image extinguished. To know the relation between the signal intensity and sodium concentration, sodium concentration--signal intensity curve was obtained using phantoms with various sodium concentrations (0.05-1.0%). This curve showed a direct proportion between sodium concentration and signal intensity on Na image. We measured further the sodium concentrations of the human brain tissue. Sodium phantoms were arranged around the heads and the MR Na images of the normal brains from 3 volunteers and a patient with a brain tumor (meningioma) were taken. The sodium concentrations of occipital lobe, basal ganglia and the tumorous tissue were calculated using the sodium concentration--signal intensity curve obtained from the phantoms arranged around the heads.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1992

Transcriptional activator Tax of HTLV-1 binds to the NF-kappa B precursor p105.

Human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia and also a neurological disease, tropical spastic paraparesis. Tax protein (p40tax) of HTLV-1 activates in trans its own transcriptional enhancer in the long terminal repeat and also those in some cellular genes such as interleukin 2 receptor alpha, granulocyte-macrophage colony-stimulating factor, Fos, Jun and MHC class I. Thus, Tax has been proposed to play a critical role in the pathogenesis induced by HTLV-1 infection. Here, we report formation of a complex of Tax protein with the precursor protein p105 of the NF-kappa B p50 subunit. p105 was co-immunoprecipitated with Tax protein from cells infected with HTLV-1 from cells transfected with the Tax expression plasmid, but not from cells transfected with inactive mutants of Tax. Furthermore, a GST-p105 fusion protein produced in Escherichia coli bound to Tax protein. These results strongly suggest that the trans-activator Tax protein forms a complex with precursor NF-kappa B p105 and plays a role in trans-activation of transcriptional initiation.

Gene Products, tax↗