Search PubMed⌕ Search

Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 217 records · Page 12Linked to original sources
PubMed1995

Characterization of insulin-dependent diabetes mellitus induced by a new variant (DK-27) of encephalomyocarditis virus in DBA/2 mice.

A murine diabetes mellitus induced with a new diabetogenic variant (DK-27) which we isolated from the M variant of the encephalomyocarditis (EMC) virus was characterized. Male DBA/2 mice (9.5 weeks old) were infected with various infectious doses of DK-27 intraperitoneally. Blood glucose and insulin levels were examined in association with the viral replication. Pancreatic pathology and hormone contents and stable hemoglobin A1c (St-A1c) levels were also examined on the final day of observation (35 days of post-infection). In infected mice, blood glucose levels rapidly elevated at 72 hr, slightly decreased between 7 and 10 days and finally became sustained hyperglycemia. On the other hand, blood insulin levels elevated at 48 hr, promptly decreased, and subsequently became sustained hypoinsulinemia. Viral replication in pancreases reached the highest titers at 48 hr and rapidly disappeared with all infectious doses used. Pancreatic insulin contents in infected mice were not detectable, and glucagon contents were not affected. In pathological examination, atrophy of islets and marked diminution of B-cells were observed, and A-cells occupied the major part of an infected islet. St-A1c levels reflected lasting hyperglycemia. These findings show that DK-27 causes insulin-dependent diabetes mellitus by the specific and direct destruction of pancreatic B-cells in susceptible mice. Such a diabetic model mouse will be useful for therapeutic studies.

Animals↗
PubMed1995

Age- and sex-related alterations of microsomal drug- and testosterone-oxidizing cytochrome P450 in Sprague-Dawley strain-derived dwarf rats.

Effect of growth hormone (GH) on the age-related changes in hepatic cytochrome P450 (P450) was studied using GH-deficient dwarf and parental Sprague-Dawley rats. Microsomal testosterone (T) T2 alpha- and T2 beta-hydroxylations were lower in livers of mature male dwarf rats than the normals, whereas T16 beta-hydroxylation was rather higher in male dwarf rats. Although T2 alpha-, T2 beta-, T6 beta-, T16 alpha- and T16 beta-hydroxylations were barely detectable in senescence normal rats (24 months old), considerable levels of T6 beta-, T16 alpha- and T16 beta-hydroxylations were maintained in senescence dwarf rats (after 22 months old). These results are caused by the alteration of specific P450 forms including CYP2B1, CYP2B2, CYP2C11 and CYP3A2 in dwarf rats. Appearance of male-specific CYP2C11 and CYP3A2 and high levels of CYP2B1 and CYP2B2 in female dwarf rats indicate the role of pituitary GH on liver of normal rats. However, the additional role of a factor other than GH was suggested on the sex-related differences and age-associated alterations of specific P450 contents in dwarf rats. CYP2C11 appears in dwarf female rats with the same developmental profile as observed in normal male rats. This form appears apparently with the development of GH receptor in livers, suggesting the possibility that a factor independent from androgen and GH governs the ontogeny of this P450 in the liver. A female-specific protein, CYP2C12, in normal rat livers, also appeared in both sexes of senescence dwarf rats, suggesting the role of non-GH factor on the expression of this P450 in liver.

Age Factors↗
PubMed1995

[Pulmonary alveolar proteinosis associated with myelodysplastic syndrome].

A 57-year-old man with myelodysplastic syndrome developed dyspnea on exertion in September 1993. Chest X-ray film showed diffuse infiltrative shadows in the middle and lower lung fields on both sides. The infiltrates were prominent in the perihilar regions but less so in the periphery, consistent with a "bat wing pattern." Milky fluid was obtained by bronchoalveolar lavage. The specimens obtained from transbronchial lung biopsy were compatible with the pathological findings of pulmonary alveolar proteinosis with amorphous periodic acid-Sciff-positive materials in the alveolar spaces. Impaired function of alveolar macrophages was demonstrated from their abnormally low phagocytosis of FITC-labeled latex beads. Whole lung lavage under general anesthesia was done twice, but the patient died because of progression of respiratory failure.

Fatal Outcome↗
PubMed1995

Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat.

We investigated whether interleukin-1 (IL-1) activity in the rat hypothalamus was increased by immobilization stress (IS), and whether pretreatment with an interleukin-1 receptor antagonist (IL-1Ra) is capable of inhibiting IS-induced elevations of hypothalamic norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and the levels of their metabolites as well as of plasma adrenocorticotropic hormone (ACTH). IL-1 activity was estimated with a bioassay using mouse thymocyte proliferation in the presence of concanavalin A. IL-1Ra was administered directly into the anterior hypothalamus, and monoamines were determined using a microdialysis technique and an HPLC system. First, we found that levels of IL-1 activity in the rat hypothalamus reached a maximum at 60 min after starting IS. Second, IL-1Ra (2 micrograms) significantly inhibited IS-induced increases in hypothalamic NE, DA, and 5-HT levels as well as the levels of their metabolites. In addition, IL-1Ra (2 micrograms) also inhibited the IS-induced elevation of plasma ACTH levels. Third, timing effects of IL-1Ra administration on the IS-induced monoamines or ACTH responses were examined. IL-1Ra (2 micrograms) administered at 5 or 60 min before the start of IS, but not at 5 or 60 min after IS had been started, exerted inhibitory effects on these responses, indicating that the effects of IL-1 occurred within 5 min after the initiation of IS. In summary, these results suggest that IS enhances biologically active IL-1 in the hypothalamus, and that hypothalamic IL-1 plays a role in the regulation of IS-induced responses including elevated monoamine release in the hypothalamus and activation of the hypothalamo-pituitary-adrenal axis. Moreover, since 5 min is too short a time for IS to induce production of IL-1, IS may augment the effects of preexisting IL-1 in the hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1995

[Clinical usefulness of helical-scanning CT for the evaluation of arteriosclerotic carotid lesions].

We examined arteriosclerotic carotid lesions in 76 patients using helical scanning CT (HES-CT), and evaluated the clinical usefulness of this method. A high speed slip-ring X-ray CT system was used. Scanning of the neck was performed for a 30 second period following intravenous bolus injection of non-ionic contrast medium, while couch top movement was 2.0 mm/sec. Multiplannar reconstruction images (MPR-image) and 3-dimensional surface images (3D-image) were reconstructed from the continuous raw data. MPR-images offered axial, coronal and sagittal images in which the lesion could be seen from any direction, and 3D-images that could be freely rotated were obtained by using a track ball and monitor. Eighteen cases were also evaluated by conventional angiography. Excellent HES-CT images were obtained in 73 cases, showing occlusion in 13, stenosis in 34, plaques without calcification in 15 and plaques with calcification in 74 vessels. A good correlation was obtained between HES-CT and angiogram in most cases, and in 6 cases, HES-CT was superior in the detection of stenosis, because it enabled us to observe the lesion from various directions. These results suggested that HES-CT was a minimally invasive, useful diagnostic method for the evaluation of arteriosclerotic carotid disease.

Arteriosclerosis↗
PubMed1995

Intra-amniotic maternal hemorrhage in preterm labor: a case report.

A primigravid women was transferred to hospital because of preterm labor at 32 weeks' gestation with no vaginal bleeding. Hematologic studies showed severe anemia. Ultrasound examination revealed polyhydramnios and a clot around the umbilical cord without retroplacental hematoma. Diagnostic amniocentesis revealed heavily blood stained fluid, but HbF was not detected. With a clinical diagnosis of intra-amniotic maternal hemorrhage, immediate cesarean section was performed. The mechanism of intra-amniotic maternal hemorrhage is discussed.

Adult↗
PubMed1995

Activation and detoxication of carcinogenic arylamines by sulfation.

Hepatic sulfation of heterocyclic and non-heterocyclic arylamines was studied to assess enzymes responsible for their metabolisms. Both 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)- and non-IQ-type (beta-carboline) heterocyclic amines were N-sulfated to form their sulfamates in cytosols of rat livers in the presence of 3'-phosphoadenosine-5'-phosphosulfate (PAPS). An arylsulfo-transferase, ST1A1, whose cDNA was isolated from a rat cDNA library, was expressed in COS-1 cells. The expressed enzyme catalyzed N-sulfation of IQ, but not appreciably those of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-I), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). N-Sulfation of heterocyclic amines except IQ was higher in hepatic cytosols of female rats than of male rats. These results suggest the involvement of at least plural forms of sulfotransferase on the N-sulfation. In addition, N-sulfation of IQ was also observed in cytosol of a human liver, suggesting that N-sulfation is one of the metabolic pathways of heterocyclic amines in humans as well as rats. Hepatic sulfotransferase also catalyzes metabolic activation of N-hydroxy derivatives of carcinogenic arylamines. Using anti-HAST (hydroxylarylamine sulfotransferase) antibodies and ST1A1 cDNA as screening probes, several cDNA clones were isolated from the cDNA library. A new member of arylsulfotransferase, ST1C1, whose cDNA shows considerable sequence similarity to ST1A1 cDNA, was found to catalyze O-sulfation of N-hydroxy-2-acetylaminofluorence by the cDNA expression in COS-1 cells. From the close similarity of ontogenic profile and sex-specific expression of ST1C1 and HAST, ST1C1 cDNA was shown to encode a major sulfotransferase (HAST) mediating the metabolic activation of N-hydroxyarylamines in rat livers. In addition, properties of PAPS-dependent N-hydroxyarylamine activation and sulfotransferase in human livers are also discussed.

Amines↗
PubMed1994

Transcriptional activation of a ras-like gene (kir) by oncogenic tyrosine kinases.

We report the characterization of a member of the ras gene family that is overexpressed in cells transformed by abl tyrosine kinase oncogenes. The gene, named kir (for kinase-inducible ras-like), is induced at the transcriptional level. kir mRNA has a rapid turnover and encodes a protein of 33 kDa with guanine nucleotide-binding activity but undetectable intrinsic GTPase activity. kir was cloned by differential screening of genes present in fully malignant versus growth factor-independent cell lines expressing wild-type or mutant forms of BCR/ABL. BCR/ABL and v-Abl induce transcription of the kir gene via specific signaling pathway(s), but kir overexpression alone is not sufficient to mediate transformation.

3T3 Cells↗
PubMed1994

Structure of a gene and cDNA of a major constitutive form of testosterone 6 beta-hydroxylase (P450/6 beta A) encoding CYP3A2: comparison of the cDNA with P450PCN2.

P450/6 beta A gene was isolated from a rat genomic library and its encoding protein was characterized by the expression of the corresponding cDNA in COS-1 cells. Between exon regions of P450/6 beta A gene and P450PCN2 cDNA (F. J. Gonzalez, B.-J. Song, and J. P. Hardwick (1986) Mol. Cell. Biol. 6, 2969-2976), 12 nucleotide differences were observed, involving two amino acid changes, His-->Asp [429] and Asp-->Gly [445], respectively. A cDNA (6 beta-A cDNA), whose nucleotide sequence was completely identical with the corresponding exon of P450/6 beta A gene, was isolated from a rat cDNA library. Northern blotting using specific oligonucleotide probes showed that 6 beta-A mRNA, but not P450PCN2 mRNA, was a major form in livers of the male rats. 6 beta-A protein expressed in COS-1 cells (at about 0.1 to 0.3% of total microsomal protein) catalyzed testosterone 6 beta-hydroxylation. The reaction was enhanced by the addition of NADPH-P450 reductase (2.5-fold) and by the simultaneous addition of cytochrome b5 and NADPH-P450 reductase (13.7-fold). Catalytic properties of 6 beta-A for typical CYP3A substrates were consistent with those of purified rat P450(6 beta-1) and P450(6 beta-3), corresponding, respectively, to CYP3A2 or the variant form (K. Nagata, F. J. Gonzalez, Y. Yamazoe, and R. Kato (1990) J. Biochem. 107, 718-725). Apparent Michaelis constants (Km) of 6 beta-A for testosterone 6 beta-hydroxylation and a O-dealkylation ratio of propoxycoumarin to pentoxycoumarin, however, showed higher degrees of similarity to those of purified P450(6 beta-3) than those of P450(6 beta-1).

Amino Acid Sequence↗
PubMed1994

Inhibition of anthralin-caused skin tumor promotion and interleukin-1 alpha production by potent immunosuppressant FK506.

The effect of FK506, a potent immunosuppressive agent, on 7,12-dimethylbenz[alpha]anthracene-initiated and anthralin-promoted skin tumor formation was examined in CD-1 mice. A topical application of 0.1 mumol FK506 to mouse skin 15 min prior to each anthralin treatment markedly inhibited skin tumor formation. Anthralin stimulated IL-1 alpha production in primary cultured mouse epidermal cells, and the peak IL-1 alpha level was observed at 6 h after the stimulation. Anthralin also stimulated IL-1 alpha release into culture medium. Both production and release of Il-1 alpha were markedly inhibited by FK506 (0.1 or 1 microM). FK506 (1 microM) alone neither affected IL-1 alpha production nor its release. It may be possible that the inhibition of IL-1 alpha production by FK506 is related to its anti-tumor-promoting action.

Administration, Topical↗
PubMed1994

An essential gene, ESR1, is required for mitotic cell growth, DNA repair and meiotic recombination in Saccharomyces cerevisiae.

A new mutant, which was sensitive to both methyl-methanesulfonate (MMS) and ultra-violet light (UV) and defective in meiotic recombination, was isolated from Saccharomyces cerevisiae. The gene, ESR1, was cloned by complementation of the MMS sensitivity of the mutant and found to be essential for cell growth, as the deleted haploid strain was lethal. The ESR1 gene was adjacent to the CKS1 gene on chromosome II and encoded a putative 2368-amino acid protein with a molecular weight of 273 k. The ESR1 transcript was 8.0 kb long and was induced during meiosis. The predicted Esr1 protein had a mosaic structure composed of homologous regions and showed amino acid sequence similarities to Schizosaccharomyces pombe rad3+ protein, which monitors completion of DNA repair synthesis, and cut1+ protein, which is required for spindle pole body (SPB) duplication. The Esr1 protein was also similar to phosphatidylinositol (PI) 3-kinases, including Saccharomyces cerevisiae TOR2 (and DRR1), which are involved in G1 progression. These results suggest that ESR1 is multi-functional throughout mitosis and meiosis.

Amino Acid Sequence↗
PubMed1994

Purification of the N-type calcium channel associated with syntaxin and synaptotagmin. A complex implicated in synaptic vesicle exocytosis.

omega-Conotoxin-sensitive N-type calcium channels control neurotransmitter release at the nerve terminal and interact with proteins implicated in secretion. Solubilized omega-conotoxin receptors from rat brain synaptic membrane were immunoprecipitated by antibodies against calcium channel alpha 1 subunits, syntaxin, and a 105-kDa plasma membrane protein. A multimeric complex, composed of calcium channel subunits, and synaptic proteins that showed varying degrees of association, was purified by a procedure involving anti-syntaxin immunoaffinity chromatography. A 250-kDa N-type alpha 1 subunit, containing cAMP-dependent phosphorylation site(s), was identified by photoaffinity labeling with 125I-azidonitrobenzoyl omega-conotoxin and immunoblotting with sequence-directed antibodies. An immunologically related 210-kDa form of the alpha 1 subunit was detected that displayed different pharmacological and regulatory properties. Protein bands of 140, 70, 58, and 35 kDa comigrated with purified alpha 1 subunits upon sucrose gradient centrifugation, whereas the 105-kDa protein was removed. The 58- and 35-kDa bands contained, respectively, the synaptic vesicle protein synaptotagmin and syntaxin, a plasma membrane protein that binds synaptic vesicle proteins. Purified omega-contoxin receptors were quantitatively immunoprecipitated by anti-syntaxin antibodies. These proteins may constitute an isolated exocytotic complex in which the N-type calcium channel tightly interacts with a synaptic vesicle docking site.

Amino Acid Sequence↗
PubMed1994

Another family with tricho-rhino-phalangeal syndrome type III (Sugio-Kajii syndrome).

Tricho-rhino-phalangeal syndrome Type III (TRPS III) is a newly defined genetic entity. Only 9 patients in a family and one sporadic patient have been reported. We add another family in which 4 individuals in 3 generations are affected with this autosomal dominant trait. Although they manifested short stature, sparse hair, "pear-shaped" nose, and cone-shaped epiphyses, sharing these findings with TRPS Type I, the presence of a severe form of generalized shortness of all phalanges and metacarpals, and the absences of mental deficiency and exostoses in this family distinguish the disorder from the TRPS Types I and II. Their manifestations are quite similar to those of the patients reported as TRPS III (Sugio-Kajii syndrome).

Abnormalities, Multiple↗
PubMed1994

Platelet-activating factor (PAF) and the development of chronic subdural haematoma.

Platelet activating factor (PAF) content and PAF-acetylhydrolase (PAFAH) activity were measured in the plasma and haematoma of 34 chronic subdural haematoma (CSH) patients. The plasma PAF level in patients with CSH was higher than that in healthy controls. Although there was no correlation between the plasma PAF levels and the interval between the onset of symptoms and the day of sampling, namely, the interval after bleeding, the haematoma PAF level gradually decreased according to the interval after the onset of symptoms. There was no difference between plasma PAFAH activity in patients with CSH and that in healthy controls, and haematoma enzyme activity gradually increased correlated with the interval between the onset of symptoms and surgery. In addition, the localization of PAF in haematoma capsules was histochemically determined. PAF was solely localized to the peri-sinusoidal vessels in the outer membrane of haematoma capsules. Based on these biochemical and histochemical studies, we speculated that PAF may play a role in the development of chronic subdural haematomas.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1994

Structural similarity and diversity of sulfotransferases.

In the present study, four new forms of aryl sulfotransferase cDNAs have been isolated and their structures determined. A compilation of primary structures of 16 different sulfotransferases, including enzymes metabolizing endogenous chemicals and xenobiotics, showed a considerable extent of similarity among bacterial, plant and mammalian species, and indicates that these enzymes constitute a supergene family. Aryl sulfotransferase and estrogen sulfotransferase are shown to belong to a single gene family (ST1) which consists of at least four subfamilies, whereas, based on the sequence similarity, hydroxysteroid sulfotransferases constitute a distinct family (ST2). Little or no clear similarity was observed between the primary structures of enzymes N-sulfating aminosugars and those sulfating hydrophobic chemicals such as phenols, alcohols or amines, indicating that both types of enzymes diverged early in their evolutionary history. Two regions in the C-terminal parts are, however, conserved among all enzymes examined, which suggests a possibly essential role of these sites for the binding of a PAPS cofactor or for sulfate transfer.

Amino Acid Sequence↗