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Biomedical subjects

N Kato

Publications and source records attributed to N Kato.

At least 595 records · Page 33Linked to original sources

[Alcohol dependence and affective disorders].

The complex relationship between alcohol dependence and affective disorder has long been noted. Alcohol is capable of producing sadness in both alcoholics and nonalcoholics, but this sadness is time-limited and should not be confused with an affective disorder. Secondary alcohol dependence can occur in the midst of almost any psychiatric disorder. However, primary alcohol dependence with secondary affective disorder is not seen so often in inpatient alcoholics. There have been a large number of genetic-marker studies in the attempt to detect association and linkage with alcohol dependence, but there is no consistent evidence of genetic overlap between alcohol dependence and affective disorders. The administration of lithium may be useful in the treatment of alcohol dependence, but further research is required to determine whether lithium is useful in the treatment of depressive state of alcohol dependence.

Alcoholism↗

Proteolytic processing and membrane association of putative nonstructural proteins of hepatitis C virus.

By using a plasmid-based transient protein expression system in cultured cells and an in vitro transcription/translation system, we analyzed the proteolytic processing of the putative nonstructural protein region of the precursor polyprotein from a Japanese type of hepatitis C virus. In addition to the previously reported viral proteins, p21 and p70, we identified products of 4 kDa (p4), 27 kDa (p27), 56 kDa (p56), 58 kDa (p58), and 66 kDa (p66). These products were produced in a viral serine proteinase (proteinase 2)-dependent manner from the region downstream of p70 in the precursor polyprotein and were arranged as NH2-p70-p4-p27-p58(p56)-p66-COOH as determined with region-specific antibodies. We showed that p56 was an N-terminally truncated form of p58, which suggested that a small polypeptide of 2 kDa (p2) was produced from the N-terminal part of p58. Cleavage between p4 and p27 was inefficient in vitro and we saw the 31-kDa precursor polypeptide (p31) accumulate. Furthermore, efficient cleavage at this site in vivo required the presence of p58/p56. Immunoprecipitation analysis in vitro also suggested the mutual interaction of those nonstructural protein products. An especially close association of p4 with p70 may contribute to association of p70 with microsomal membranes.

Animals↗

Epidermal growth factor elevates the activity levels of glycolipid sulfotransferases in renal-cell-carcinoma cells.

Accumulation of sulfoglycolipids associated with markedly elevated levels of glycolipid-sulfotransferase activity was previously demonstrated in human renal-cell-carcinoma cells. To elucidate the regulatory mechanisms of sulfoglycolipid metabolism in renal-cell carcinoma, effects of various growth factors on the sulfotransferase-activity levels were investigated using a human renal-cell-carcinoma cell line, SMKT-R3. Exogenous epidermal growth factor (EGF) significantly increased the activity levels of the sulfotransferases in a dose-dependent manner, but did not change that of arylsulfatase A, which hydrolyzes sulfoglycolipids. Furthermore, metabolic labeling with 35S-sulfate revealed that the addition of EGF to the culture medium of the cells resulted in an increment of sulfoglycolipid synthesis. The expression of the EGF receptor on SMKT-R3 cells was demonstrated by affinity cross-linking with 125I-EGF. These observations suggest that EGF can regulate sulfotransferase-activity levels in renal-cell-carcinoma cells, and function as one of the regulatory factors of sulfoglycolipid synthesis in these carcinoma cells.

Carcinoma, Renal Cell↗

Regulation of xanthine dehydrogenase in rat liver in response to peroxisome proliferators.

Previously we found a depression in the activity of hepatic xanthine dehydrogenase in rats fed clofibrate or di(2-ethylhexyl)phthalate. The present study further demonstrated that dietary addition of other peroxisome proliferators, including bezafibrate, dehydroepiandrosterone and perfluoro-n-octanoic acid also depressed activity of hepatic xanthine dehydrogenase in rats. Western and Northern blot analyses indicated the depression in hepatic xanthine dehydrogenase protein and mRNA by feeding bezafibrate. These results suggest that administration of a wide variety of peroxisome proliferators depresses the activity of hepatic xanthine dehydrogenase in rats and that the depression in activity of this enzyme by the proliferator might be mediated by decreased mRNA of the enzyme. Further, nuclear run-on analysis revealed no influence of feeding bezafibrate on the transcriptional activity of hepatic xanthine dehydrogenase gene, suggesting increased degradation of the enzyme mRNA by the chemical.

Animals↗

Reduced Mg2+ block of N-methyl-D-aspartate receptor-mediated synaptic potentials in developing visual cortex.

Molecular cloning has demonstrated a diversity of artificially expressed N-methyl-D-aspartate (NMDA) receptors, implying a similar diversity of naturally occurring NMDA receptors in situ. Particularly significant was the success in expression of NMDA receptor classes exhibiting various sensitivities to Mg2+ block, a voltage-dependent channel blockade by Mg2+ that is essential to NMDA receptor functioning. Release from Mg2+ block often allows or facilitates the occurrence of long-term potentiation, a form of synaptic plasticity. Here we show that in the immature visual cortex, which is more susceptible to long-term potentiation than adult visual cortex, synaptically activated NMDA receptors, unlike those in the adult, have varying but clearly reduced sensitivities to Mg2+ block. We propose that the initially expressed, later-eliminated NMDA receptors exhibiting a reduced Mg2+ block may underlie the greater susceptibility to plasticity in the immature neocortex.

Age Factors↗

Facilitatory effects of substance P on the susceptibility to long-term potentiation in the visual cortex of adult rats.

We studied whether substance P (SP) facilitates induction of long-term potentiation (LTP) in adult rat visual cortex slices, using intracellular recordings of postsynaptic potentials (PSPs) elicited by white matter stimulation. Tetanic stimulation in normal medium induces no change of the PSP amplitude. In SP-containing medium, by contrast, tetanization potentiated the PSP amplitude in 5 over 7 cells examined. Although the other 2 cells underwent no change, the overall effect of SP was an increase in the probability of LTP induction. This effect of SP was canceled out by bath-application of the non-peptide antagonist CP96,345 (n = 7) or intracellular application of guanosine 5'-beta-thio-diphosphate (GDP beta S; n = 7). These results suggest that SP increased LTP susceptibility of neurons in the adult rat visual cortex through SP receptor-mediated mechanisms.

2-Amino-5-phosphonovalerate↗

Scratching behavior induced by bombesin-related peptides. Comparison of bombesin, gastrin-releasing peptide and phyllolitorins.

Bombesin and 10 bombesin-related peptides were administered intracerebroventricularly to conscious and freely moving rats. All peptides tested were found to elicit excessive grooming, especially scratching behavior. Bombesin itself had the most potent and long-lasting activity in eliciting scratching behavior. Naturally occurring peptides such as neuromedin B and gastrin-releasing peptide (GRP)-(18-27) were short-acting compared with exogenous peptides such as bombesin and synthesized analogs. Two phyllolitorins, a new bombesin subfamily, were also examined in this study. [Leu8]phyllolitorin induced more scratching than [Phe8]phyllolitorin and proved to be virtually equipotent to bombesin. Corticotropin-releasing factor (CRF) and substance P induced considerable excessive grooming, but both peptides were strikingly weak in inducing scratching behavior. It is suggested that (1) scratching represents a specific behavior commonly induced by bombesin-related peptides and (2) the relative potency to induce scratching behavior reflects the metabolic stability of the peptide, e.g. endogenous versus exogenous, shorter versus longer sequences, or chemical protection of N-terminus.

Amino Acid Sequence↗

Detection of hepatitis C virus RNA in acute non-A, non-B hepatitis as an early diagnostic tool.

The presence of hepatitis C virus RNA was examined in the sera of 32 patients with acute non-A, non-B hepatitis. Hepatitis C virus RNA was extracted from serum, reverse transcribed to cDNA and amplified by two rounds of polymerase chain reaction. Hepatitis C virus RNA was detected in all patients who developed anti-C100-3 as well as 79% who did not. These data suggest that hepatitis C virus accounts for most cases of acute non-A, non-B hepatitis whether anti-C100-3-positive or not. In addition, hepatitis C virus RNA was detected in the earliest serum samples, 9 +/- 11 weeks before anti-C100-3, and thus may be valuable as a diagnostic marker for acute hepatitis C.

Base Sequence↗

Effects of neonatal ablation of area 18 on corticocortical projections from area 17 to extrastriate visual areas in cats.

Using retrogradely transported fluorescent dyes, we investigated the distributions of corticocortical neurones in area 17 projecting to area 19 and to the lateral suprasylvian visual area in a normal cat and two cats in which area 18 had been ablated at 4 days old. Cells projecting to area 19 were distributed in a much more continuous manner in the lesioned cats than in the normal one, whereas those projecting to the lateral suprasylvian cortex were located in discrete patches in all three cats. Neonatal ablation of area 18 can thus prevent the normally occurring developmental removal of neurones or their axons projecting from area 17 to area 19, but not the removal occurring in the projection from area 17 to the lateral suprasylvian cortex.

Animals↗

Dependence of long-term depression on postsynaptic metabotropic glutamate receptors in visual cortex.

Long-term depression (LTD) is held relevant to memory and learning. Its induction is known to require postsynaptic calcium increases. However, the source of these calcium increases remains unclear. In visual cortex slices, LTD was induced by tetanization after blockade of N-methyl-D-aspartate (NMDA) and non-NMDA ionotropic glutamate receptors. LTD induced under this condition was prevented by an intracellular injection of each of the following drugs into the postsynaptic neuron: (i) guanosine 5'-[beta-thio]diphosphate, which competitively inhibits the binding of GTP to GTP-binding regulatory proteins; (ii) heparin, which antagonizes 1,4,5-inositol triphosphate binding; and (iii) calcium chelators. Moreover, LTD was induced without tetanization by applying quisqualate (10 microM), a metabotropic glutamate receptor agonist, but not another agonist, trans-aminocyclopentane-1,3-dicarboxylic acid (10 microM). Together, these results suggest that activation of 1,4,5-inositol trisphosphate-linked subtypes of metabotropic glutamate receptor is responsible for the increase in postsynaptic calcium concentration, which results in homosynaptic LTD.

2-Amino-5-phosphonovalerate↗

Synaptic N-methyl-D-aspartate receptors in the neonatal rat visual cortex are less sensitive to MK-801 than in adult.

The excitatory postsynaptic potential mediated by N-methyl-D-aspartate (NMDA) receptors (NMDA-EPSP) was intracellularly obtained in slices from the visual cortex of adult and 2-week-old rats. Bath application of 0.3 microM (+)-MK-801, an NMDA receptor open-channel blocker, completely blocked NMDA-EPSPs in slices from adult rats. By contrast, in slices from the younger rats, a 10 microM solution was needed for the complete blockade. This difference in sensitivity to an open-channel blocker implies a major developmental change in the conformation of NMDA receptors in situ.

Animals↗

Base transitions and base transversions seen in mutations among various types of the hepatitis C viral genome.

We counted base transitions (Ts) and transversions (Tv) in mutations among various types of hepatitis C virus (HCV) sequences. The Ts/Tv ratio was useful for distinguishing the (geno)type of the compared HCV sequences, since the ratio was 4.0 or more among sequences of the same type, while it was less than 2.0 among sequences of different types. This observation reflects the evolutionary pathway of HCV in which Tv accumulate among distant genomes by mechanisms including multiple base substitutions.

DNA, Viral↗

Molecular analysis of HLA-B39 subtypes.

Serological studies have suggested the presence of a new HLA-B39 subtype (B39.2) in the Japanese population. To identify the new HLA-B39 subtype and compare it with an other HLA-B39 subtype (B39.1), the genes encoding HLA-B39.1 (B*39013) and B39.2 (B*3902) have been cloned from Japanese. We have sequenced these genes and completed the sequence of HLA-B39.1 (B*39011) gene from a Caucasian that was partially sequenced. Comparison of the sequence data revealed that B*3902 and B*39013 differ by three nucleotide substitutions which result in a two amino acids change at residues 63 and 67, while one silent substitution at codon 312 is found between B*39011 and B*39013. These results suggest that B*3902 has evolved from B*39013 rather than B*39011.

Amino Acid Sequence↗

Two proteinase activities in HCV polypeptide expressed in insect cells using baculovirus vector.

Processing of HCV viral precursor protein requires at least two viral proteinases, Cpro-1 and Cpro-2, in addition to cellular proteinases. The HCV polypeptide that covers the region for the two viral proteinase domains was expressed in insect cells using a baculovirus expression system. The two proteinase activities were demonstrated in the infected cells. The Cpro-1-dependent cleavage site was estimated from the amino acid sequence of the N-terminus of the processed product. Analyses of the susceptibilities of various mutants altered at position P1 and P1' of the putative cleavage site suggested that amino acid residues at these positions is not essential for recognition and cleavage by Cpro-1-dependent activity.

Amino Acid Sequence↗

Tumoricidal effect of human macrophage-colony-stimulating factor against human-ovarian-carcinoma-bearing athymic mice and its therapeutic effect when combined with cisplatin.

The effect of human macrophage-colony-stimulating factor (hM-CSF) on tumoricidal activity was examined in athymic mice bearing the human ovarian cancer cell line, HRA, injected intraperitoneally (i.p.). The survival period and survival rate in the groups treated daily with hM-CSF were significantly longer (P < 0.01) than in the untreated group. The peritoneal cell smears showed that ascitic tumor cells were markedly decreased in the hM-CSF-treated groups, and macrophages phagocytosed tumor cells, indicating a contact-mediated direct cytolysis. The combined therapeutic effects of cisplatin and hM-CSF on HRA-bearing athymic mice were also studied. The mean survival period was 25.4, 47.2, 42.4 and 67.4 days, respectively, in the untreated group, and in the groups treated with cisplatin alone, with hM-CSF alone, and with combined cisplatin and hM-CSF. The survival period and rate were significantly longer (P < 0.01) in the group treated with combined cisplatin and hM-CSF than in those treated with cisplatin or hM-CSF alone, indicating the therapeutic effectiveness of the combined use. Moreover, hM-CSF is effective against granulocytopenia due to bone marrow suppression caused by cisplatin. Our data demonstrate that hM-CSF administered i.p. has a tumoricidal activity in athymic mice bearing human ovarian cancer i.p., which is mediated by activated macrophages, and that the combined administration of cisplatin and hM-CSF has a significant therapeutic effect.

Agranulocytosis↗