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Biomedical subjects

S Kaneko

Publications and source records attributed to S Kaneko.

At least 19 recordsLinked to original sources
PubMed1995

Adenovirus-mediated gene therapy of hepatocellular carcinoma using cancer-specific gene expression.

Most patients with hepatocellular carcinoma have an elevated alpha-feto-protein (AFP) level. This high level of AFP expression is transcriptionally controlled by the 5'-flanking sequence of the AFP gene. Using the 5'-flanking sequence as a promoter for the herpes simplex virus thymidine kinase (HSV-TK) gene in an adenoviral vector (Av1AFPTK1), the therapeutic efficacy of adenovirus-mediated HSV-TK gene transduction, followed by ganciclovir (GCV) administration, was studied in tumors in athymic nude mice. Av1AFPTK1 transduction of two cell lines demonstrated HSV-TK enzyme activity only in the AFP-producing cells (HuH7) and not in the AFP nonproducing cells (SK-Hep-1). As expected, only transduced HuH7 cells were killed by GCV treatment. Transduction by an adenoviral vector harboring a Rous sarcoma virus promoter and HSV-TK gene (Av1TK1) showed enzymatic activity and GCV killing in both cell lines. All HuH7 tumors that were transduced with either Av1AFPTK1 or Av1TK1 completely regressed after GCV treatment. On the other hand, there was complete regression of SK-Hep-1 tumors only when treated with Av1TK1 and GCV and not when treated with Av1AFPTK1 and GCV. Thus, cell-specific killing was achieved by adenoviral vector containing AFP promoter for the HSV-TK gene and GCV treatment.

Adenoviridae↗
PubMed1995

Analysis by in vitro mutagenesis of PP2A alpha okadaic acid responsive sequences.

It has been shown that the protein serine/threonine phosphatase type 2A alpha catalytic subunit (PP2A alpha) has a mutation consisting of a glycine substitution for cysteine at 269 in the okadaic acid resistant variant of CHO cells, and that the mutant protein is resistant to okadaic acid (Shima, H. et al. Proc. Natl. Acad. Sci. USA 91, 9267-9271, 1994). In this study we analyzed okadaic acid responsive sequences in PP2A alpha by introducing a mutation at around codon 269 of the cDNA strand. The recombinant mutant PP2A alpha proteins Y265F, C266G, Y267G and C269Y were resistant to okadaic acid, with IC50s of 10, 24, 20 and 10 nM, respectively, as opposed to the recombinant wild PP2A alpha protein which had an IC50 of 0.24 nM. This observation suggests that not only cysteine at 269, but also other YCY amino acids, between 265-267, are necessary for the high sensitivity of PP2A to okadaic acid.

Amino Acid Sequence↗
PubMed1995

Structural change in dopamine D2 receptor gene in a patient with neuroleptic malignant syndrome.

Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D2 receptor (DRD2) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequences differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG-->TCG) of exon 7 of the DRD2 gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS.

Adult↗
PubMed1995

Synthesis of regioisomeric methyl alpha-L-arabinofuranobiosides.

The three regioisomers of methyl alpha-L-arabinofuranobioside, namely methyl O-alpha-L-arabinofuranosyl-(1-->2)-alpha-L-arabinofuranoside, methyl O-alpha-L-arabinofuranosyl-(1-->3)-alpha-L-arabinofuranoside, and methyl O-alpha-L-arabinofuranosyl-(1-->5)-alpha-L-arabinofuranoside, were synthesized for use as substrates in studies of the specificity of alpha-L-arabinofuranosidase. The regiospecifically protected precursors, namely methyl 3,5-di-O-benzoyl-alpha-L-arabinofuranoside, methyl 2,5-di-O-benzyl-alpha-L-arabinofuranoside, and methyl 2,3-di-O-benzoyl-alpha-L-arabinofuranoside, were prepared from 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl chloride (4) and methyl 5-O-trityl-alpha-L-arabinofuranoside, respectively, and glycosylated with 4 in the presence of silver trifluoromethanesulfonate and s-collidine. 1H and 13C NMR data for all compounds are presented.

Arabinose↗
PubMed1995

Interferon therapy in chronic hepatitis C virus: evidence of different outcome with respect to different viral strains.

The aim of the study was to assess the role of different viral strains of hepatitis C virus (HCV) in determining the outcome of the alpha-interferon (IFN) therapy. Fifty-seven patients (34 from Italy and 23 from Japan) with HCV-positive liver disease were enrolled in the study. The NS4 region of HCV was amplified in sera by "nested" polymerase chain reaction (PCR) using a primer pair synthesized according to the sequence of JK-1. The NS4 region was positive in 14 (41%) Italian and in 13 (56%) Japanese patients. In positive patients the sequence of the NS4 region was also obtained. Subsequently, HCV genotype was determined in all patients by PCR amplification of the core region. All patients received recombinant alpha 2a-interferon (IFN), 6 million units 3 times a week for 1 month followed by 3 million units 3 times a week for 5 months. The patients were followed for 1 year after the end of treatment. At the end of the follow-up, 17 (30%) had sustained normal levels of serum alanine aminotransferase (ALT). The outcome of treatment was not correlated with race, age, sex, histology, and pretreatment ALT level, but was significantly (P < 0.00001) associated with the presence of both the NS4-JK-1 region and HCV type II. Among the 27 NS4-positive patients, only 1 patient (3.7%) achieved a complete response, whereas the remaining 26 patients (95.3%) either were non-responders or relapsed after IFN was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Patch sensor detection of glutamate release evoked by a single electrical shock.

We tried to detect minimal stimulation-induced glutamate overflow from the surface of a hippocampal slice using an outside-out patch electrode excised from pyramidal cell membranes. The amplitude of the stimulation-induced patch current was dependent on the distance between the slice surface and the tip of patch sensor. The current-voltage relations of the stimulation-induced patch current were similar to those of the current evoked puff by application of L-glutamate to the patch. This indicates that the stimulation-induced patch current was produced by glutamate released from presynaptic terminals, and thus this technique may be useful in the study of transmitter release evoked by minimal electrical stimulation in brain slices.

Action Potentials↗
PubMed1995

The close relationship between growth factors and the nucleolar organizer regions in adenocarcinoma of the lung.

We examined immunohistochemically 111 cases of primary adenocarcinoma of the lung, for transforming growth factor alpha (TGF alpha) or epidermal growth factor (EGF), and argyrophilic nucleolar organizer regions (AgNORs). The presence of more than 75% positive cells for both growth factors was designated as a high-GF, while all others were considered to be a low-GF. If AgNORs counts were more than 5.00, it was considered to be a high-AgNORs group, while less than 5.00 was designated as a low-AgNORs group. In our 111 examined specimens, there were 51 (46%) cases of high-GF, and 64 (58%) with high AgNORs. The 5-year survival rates of the patients with a high-GF and low-GF were 34% and 57% (P < 0.05) respectively, while those with high-AgNORs and low-AgNORs were 21% and 81% (P < 0.001), respectively. In the cases of high-AgNORs, the 5-year survival rates of the patients with high-GF and low-GF were 0% and 36% (P < 0.05), respectively. However, in the cases of low-AgNORs, the 5-year survival rates of the patients with high-GF and low-GF were 83% and 79%, respectively. These data suggest that growth factors might be related to the biological malignancy of tumours with a high cell proliferation.

Adenocarcinoma↗
PubMed1995

Trazodone treatment increases plasma prolactin concentrations in depressed patients.

m-Chlorophenylpiperazine (m-CPP), which is a metabolite of trazodone, is a serotonin agonist. To examine for the possibility that m-CPP is involved in biochemical effects during treatment with the parent compound, prolactin response to trazodone treatment (150 mg at bedtime for 3 weeks) was studied in 12 depressed patients. The means +/- S.D. of plasma prolactin concentrations before treatment, 12 h, and 1, 2 and 3 weeks after initiation of treatment were 9.1 +/- 5.6, 14.7 +/- 9.1, 15.3 +/- 8.5, 13.2 +/- 7.0 and 13.0 +/- 7.0 ng/ml, respectively. The mean prolactin concentrations at 12 h (p < 0.01), 1 week (p < 0.001) and 2 weeks (p < 0.05) were significantly higher than that before treatment. The present study thus shows that trazodone treatment increases prolactin concentrations, suggesting that m-CPP is involved in biochemical effects during treatment with the parent compound.

Adult↗
PubMed1995

Inhibition of trazodone metabolism by thioridazine in humans.

To clarify the involvement of cytochrome P4502D6 (CYP2D6) in the metabolism of trazodone, the effects of coadministration of thioridazine, which is an inhibitor of this isozyme, on plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were studied. The subjects were 11 depressed patients receiving trazodone at bedtime for 1-18 weeks. The dose was 150 mg in 10 patients and 300 mg in one. Thioridazine 40 mg/day was coadministered for 1 week, and blood samplings were performed before and after the coadministration. Thioridazine significantly (p < 0.001) increased plasma concentrations of both trazodone (713 +/- 252 vs. 969 +/- 370 ng/ml) and m-CPP (61 +/- 22 vs. 94 +/- 34 ng/ml). The present study thus suggests that CYP2D6 is involved in the metabolism of trazodone.

Adult↗
PubMed1995

Immunohistochemical analysis of giant cell glioblastoma.

Giant cell glioblastoma (GCG) is one of a group of rare tumors in which the cell population is abnormally large and includes multinucleated cells of gigantic sizes. Immunohistochemical studies were performed on four GCG cases and found that all giant cells and/or tumor cells were positive for glial fibrillary acidic protein (GFAP), S-100 protein, and vimentin, thus verifying the tumor's glial origin. The nuclei of multinucleated giant cells of three adult cases were frequently immunostained for proteins expressed during the cell cycle (proliferating cell nuclear antigen (PCNA) and Ki-67), thereby demonstrating the proliferative capacity of these cells. By contrast, those of a 12 year old girl expressed these cell cycle markers rather infrequently. Alpha I-antitrypsin was detected with relatively high frequency in the giant cells, and its presence may explain their bizarre sizes and pericellular reticulin fiber formation. A literature review of 32 cases revealed that the GCG that occurs preferentially in young girls is a type of pleomorphic xanthoastrocytoma. By contrast, GCG in adult males has the same age incidence as ordinary glioblastomas and, as these, expresses high levels of cell cycle-related proteins. Thus, GCG, which is subclassified morphologically as ordinary glioblastoma, has distinct biological and clinical characteristics, with that in children requiring re-evaluation because of its similarities to pleomorphic xanthoastrocytoma.

Age Factors↗
PubMed1995

Prevention of endotoxin-induced acute lethality in Propionibacterium acnes-primed rabbits by an antibody to leukocyte integrin beta 2 with concomitant reduction of cytokine production.

Acute lethality was induced in rabbits by the sequential injection of Propionibacterium acnes and lipopolysaccharide (LPS). P. acnes induced the infiltration of inflammatory cells into the liver lobules during the early phase, and LPS in the late phase caused death in association with pathological changes mimicking hepatocellular necrosis or degeneration around infiltrated mononuclear cells and fibrin deposition in the liver, lung, and kidney, suggestive of a systemic Schwartzman-like reaction. These pathological changes were accompanied by the elevation of plasma tumor necrosis factor (TNF) and interleukin-8 (IL-8) levels. A neutralizing antibody to a leukocyte adhesion molecule, integrin beta 2 (CD18), administered at the time of LPS challenge, prevented reduced the elevation of plasma TNF and IL-8 levels. An anti-TNF alpha antibody but not an anti-IL-8 mediator in this model. These results indicate that CD18 is critically involved in vivo in activating leukocytes to produce cytokines in response to LPS.

Animals↗
PubMed1995

[Prognostic factors for metastatic renal cell cancer].

We examined various prognostic factors of metastatic renal cell carcinoma. Patients who had metastasis at nephrectomy (A group, 38 cases) and those who had metastasis as recurrent tumors after nephrectomy (B group, 38 cases) entered in this study. Five-year survival rate of total cases after confirmation of metastatic foci was 15% and there was no statistical significant difference between A and B groups. Several pathological factors were related to poorer prognosis and included large diameters of original tumors, positive lymph nodes, higher grade tumors and non-clear cell type tumors. Patients who have a solitary lung metastasis showed better prognosis compared to those with multiple lung metastases or metastases of other organs. Two factors related to treatment were shown to contribute to better prognosis. These were the response to interferon alfa (IFN alpha) and the possibility of total resection of visible metastatic tumors. Patients who belong to A group were shown to achieve markedly better therapeutic benefit from IFN alpha or IFN alpha plus anticancer drugs. Five-year survival rate for the responders was 40%, as compared to less than 5% for the non-responders. Ten-year survival rate for patients with metastasis who had undergone complete resection of visible tumor was 50%, and the for patients belonging to B group Showed 80%. We concluded that these prognostic factors should be considered to decide how to select patients with metastatic renal cell cancer.

Adult↗
PubMed1995

[Results of mutation analyses of von Hippel-Lindau disease gene in Japanese patients: comparison with results in United States and United Kingdom].

Recently the gene responsible for the von Hippel-Lindau (VHL) disease was identified as a tumor suppressor gene. Our ongoing studies on the mutation of the VHL gene in Japanese 28 VHL families with single strand conformational analyses of DNA and Southern blot analyses revealed 6 cases of insertion or deletion, 1 cases of splice site mutation and 9 cases of missense mutation, and 3 possible intragenic deletions. Our analytical findings are essentially similar to those observed in the western countries. The VHL families associated with pheochromocytoma had the same mutational hot spot as those in the western countries. Molecular analyses of the VHL gene in the Japanese VHL disease substantially improved the understanding of this disease and its inheritance character.

Blotting, Southern↗