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Biomedical subjects

I Kato

Publications and source records attributed to I Kato.

At least 235 records · Page 13Linked to original sources
PubMed1996

Chemoprevention trial on precancerous lesions of the stomach in Venezuela: summary of study design and baseline data.

A double-blind, placebo-controlled trial is being conducted in a population at high risk for gastric cancer in Venezuela. The main aim of the trial is to assess the effect of antioxidant vitamins (beta-carotene, vitamin C and vitamin E) in blocking the progression of precancerous lesions of the stomach. Within the framework of a screening programme for stomach cancer, 2200 subjects of 35-69 years of age have been recruited. At study entry, a dietary questionnaire was completed, and gastroscopy with the collection of seven gastric biopsies was performed. After baseline examinations, the study participants were randomized to receive antioxidant treatment or placebo for three years. The treatment phase will be completed in mid-1998. At the end of the treatment phase, the investigations performed at study entry will be repeated. Before the initiation of the trial, various pilot studies were carried out that showed an extremely high prevalence of Helicobacter pylori infection (over 90%). Two eradication trials using anti-H. pylori treatments that give good results in Europe and North America gave very poor results in our study population. The low eradication rates achieved (5-20%) suggest a high prevalence of antibiotic-resistant H. pylori strains or high reinfection rates. These disappointing results led to deletion of an anti-H. pylori treatment phase of the main trial.

Adult↗
PubMed1996

[Vascular ring].

Explore the source record for details and available documents.

Aorta, Thoracic↗
PubMed1995

Pretectofugal fibers from the nucleus of the optic tract in monkeys.

The nucleus of the optic tract (NOT) is the visuo-motor relay between the retina and preoculomotor structures in the pathway mediating optokinetic nystagmus (OKN). NOT lesions in monkeys produce no OKN toward the lesioned side. Then, efferent fibers from the NOT course through the brainstem and may reach the vestibular nucleus, which is proposed to be the final nucleus to the motor nucleus. In the present study, the tracer was injected through a micropipette in the NOT in four monkeys. Labeled terminals were observed ipsilaterally in the parabigeminal nucleus, superficial layers of the superior colliculus, dorsal and lateral terminal nuclei of the accessory optic system and pretectal nuclei and contralaterally in the NOT and superficial layers of the superior colliculus. Descending fibers from the NOT consisted of two major pathways: (1) fibers descended medially from the injection site through the reticularis pontis oralis to reach the lateral part of the ipsilateral nucleus reticularis tegmenti pontis; (2) fibers projecting into the dorsal cap of inferior olive, by far the greatest number of labeled fibers, descended ventrally along the lateral border of the reticularis pontis oralis and reached the medial lemniscus where they descended further and branched into the dorsolateral pontine nucleus, the lateral part of the nucleus reticularis tegmenti pontis, the peduncular pontine nucleus, the lateral pontine nucleus, the nucleus prepositus hypoglossi, the medial vestibular nucleus and finally the dorsal cap of the inferior olive. Consistent with the physiological data, the direct terminals to the medial vestibular nucleus could serve to drive the storage mechanisms and to produce OKN in the monkey.

Animals↗
PubMed1995

Requirement of calmodulin-dependent protein kinase II in cyclic ADP-ribose-mediated intracellular Ca2+ mobilization.

Cyclic ADP-ribose (cADPR) is generated in pancreatic islets by glucose stimulation, serving as a second messenger for Ca2+ mobilization from the endoplasmic reticulum for insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In the present study, we observed that the addition of calmodulin (CaM) to rat islet microsomes sensitized and activated the cADPR-mediated Ca2+ release. Inhibitors for CaM-dependent protein kinase II (CaM kinase II) completely abolished the glucose-induced insulin secretion as well as the cADPR-mediated and CaM-activated Ca2+ mobilization. Western blot analysis revealed that the microsomes contain the alpha isoform of CaM kinase II but do not contain CaM. When the active 30-kDa chymotryptic fragment of CaM kinase II was added to the microsomes, fully activated cADPR-mediated Ca2+ release was observed in the absence of CaM. These results along with available evidence strongly suggest that CaM kinase II is required to phosphorylate and activate the ryanodine-like receptor, a Ca2+ channel for cADPR as an endogenous activator, for the cADPR-mediated Ca2+ release.

Adenosine Diphosphate Ribose↗
PubMed1995

Regulatory role of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in insulin secretion by glucose in pancreatic beta cells. Enhanced insulin secretion in CD38-expressing transgenic mice.

Cyclic ADP-ribose (cADPR) serves as a second messenger for Ca2+ mobilization in insulin secretion, and CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activities (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here, we produced transgenic mice overexpressing human CD38 in pancreatic beta cells. The enzymatic activity of CD38 in transgenic islets was greatly increased, and ATP efficiently inhibited the cADPR hydrolase activity. The Ca2+ mobilizing activity of cell extracts from transgenic islets incubated in high glucose was 3-fold higher than that of the control, suggesting that ATP produced by glucose metabolism increased cADPR accumulation in transgenic islets. Glucose- and ketoisocaproate-induced but not tolbutamide- nor KCl-induced insulin secretions from transgenic islets were 1.7-2.3-fold higher than that of control. In glucose-tolerance tests, the transgenic serum insulin level was higher than that of control. The present study provides the first evidence that CD38 has a regulatory role in insulin secretion by glucose in beta cells, suggesting that the Ca2+ release from intracellular cADPR-sensitive Ca2+ stores as well as the Ca2+ influx from extracellular sources play important roles in insulin secretion.

ADP-ribosyl Cyclase↗
PubMed1995

Nicotinamide inhibits IRF-1 mRNA induction and prevents IL-1 beta-induced nitric oxide synthase expression in pancreatic beta cells.

Nitric oxide produced by inducible nitric oxide synthase in islets exerts inhibitory and cytotoxic effects on pancreatic beta cells and is therefore thought to be a potent mediator in the pathogenesis of Type I diabetes mellitus. Here, using isolated rat pancreatic islets, we show that high-concentration nicotinamide (20 mM), but not low-concentration nicotinamide (5 mM), attenuates the interleukin-1 beta-evoked inhibition of glucose-induced insulin secretion by preventing the induction of interferon regulatory factor-1, a transcriptional factor which plays an essential role in inducible nitric oxide synthase gene expression, and the interleukin-1 beta-induced nitric oxide formation. High-concentration nicotinamide also restored an interleukin-1 beta-induced decrease in ATP content in pancreatic beta cells, suggesting that interleukin-1 beta-induced nitric oxide inhibits the mitochondrial function. The present results show the molecular basis of the preventive effect of high-dose nicotinamide on Type I diabetes mellitus.

Adenosine Triphosphate↗
PubMed1995

Determinants of plasma pepsinogen levels in a population at high risk for stomach cancer in Venezuela.

Determinants of plasma pepsinogens (PG) levels were studied in 1365 participants in a chemoprevention trial for gastric pre-cancerous lesions being conducted in Venezuela. Gastric biopsies, plasma samples and information on smoking and dietary habits were obtained at baseline examination. Both PG-I and PG-II levels increased progressively with the level of Helicobacter pylori infection in gastric biopsies, resulting in no clear trend in the I/II ratio. Instead, there was a progressive decrease in the I/II ratio with increasing degrees of infiltration of polynuclear cells and monocytes, atrophy, intestinal metaplasia and the stage of pre-cancerous lesions. The mean I/II ratios for atrophic gastritis or more advanced lesions were less than 4.0. When subjects with the I/II ratio 4 or higher were used as controls, severe reduction in the I/II ratio (< 2.0) was inversely associated with tobacco consumption. This may be due to a pharmacological effect of nicotine. The severe reduction of I/II ratio was also inversely associated with fresh fruit consumption. In addition, a decreased I/II ratio was positively associated with rice/pasta and arepas (tortilla made from corn) consumption and inversely associated with plantain consumption. Possible effects of vitamins and starchy food on the development of atrophic gastritis need to be studied further.

Adult↗
PubMed1995

Enhanced transglycosylation activity of Arthrobacter protophormiae endo-beta-N-acetylglucosaminidase in media containing organic solvents.

The transglycosylation activity of endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (endo-A) was enhanced by inclusion of organic solvents in the reaction mixture. In aqueous solution, the transglycosylation yield relative to starting substrate was 32% using Man9GlcNAc2Asn as donor and 0.5 M GlcNAc as acceptor. However, in the media containing 30% (v/v) acetone, dioxane, N,N-dimethylformamide, or dimethyl sulfoxide with 0.5 M GlcNAc as acceptor, the transglycosylation attained yields of 89, 13, 28, and 75%, respectively, as analyzed by high performance anion exchange chromatography. The enzyme was stable in media containing up to 30% acetone, 30% dimethyl sulfoxide, or 20% N,N-dimethylformamide at 37 degrees C for at least 30 min. The acceptor (GlcNAc) concentration must be greater than 0.2 M for efficient transglycosylation. Electrospray mass spectrometry analysis of the transglycosylation product obtained in 30% acetone with Man5GlcNAc2Asn as donor and methyl alpha-2-acetamido-2-deoxy-D-glucopyranoside as acceptor showed a mass ion of m/z 1249.4, consistent with the expected molecular weight. Analysis by 1H NMR of the product revealed that transglycosylation occurred at the C-4 of GlcNAc and the linkage was of the beta-configuration. In the acetone-containing medium, Glc, Man, 2-deoxy-Glc, and methyl alpha-D-GlcNAc can serve as a good acceptor as GlcNAc. Less favorable acceptors are xylose, fructose, 6-deoxy-Glc, and 3-O-methyl-D-glucose. On the other hand, GalNAc, Gal, allose, and 3-deoxy-Glc could not serve as acceptors of the enzyme transglycosylation.

Acetylglucosamine↗
PubMed1995

Synthesis of neoglycoconjugates by transglycosylation with Arthrobacter protophormiae endo-beta-N-acetylglucosaminidase. Demonstration of a macro-cluster effect for mannose-binding proteins.

The transglycosylation activity of endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (endo-A) can be enhanced dramatically by inclusion of organic solvent in the reaction mixture (see accompanying article; Fan, J.-Q., Takegawa, K., Iwahara, S., Kondo, A., Kato, I., Abeygunawardana, C., and Lee, Y. C. (1995) J. Biol. Chem. 270, 17723-17729). This finding was extended to synthesis of important intermediates for preparation of neoglycoconjugates. When 0.2 M GlcNAc-O-(CH2)6NH2, GlcNAc-O-CH2CH = CH2, GlcNAc-O-(CH2)3-CH = CH2, GlcNAc-O-(CH2)3NHCOCH = CH2, GlcNAc-S-CH2CN, GlcNAc-S-(CH2)3CH3, or GlcNAc-S-CH2-CONHCH2CH(OMe)2 were used as acceptors in 30% acetone-containing media, the transglycosylation was accomplished with about 80% yield. The transglycosylation yields to benzyl beta-GlcNAc (67%), 4-methyl-umbelliferyl beta-GlcNAc (66%), p-nitrophenyl beta-GlcNAc (33%), and (GlcNAc-beta-S-CH2CH2CH2)2 (43%) were lower, because their poor solubilities allowed only 0.05 M or lower concentrations in the reaction mixture. A micromole-scale synthesis of Man9GlcNAc2-O-(CH2)3-NHCOCH = CH2 (Man9GlcNAc2-NAP) was accomplished with 90% yield, and the structure of the transglycosylation product was confirmed by 1H NMR. Man9GlcNAc2-NAP was co-polymerized with acrylamide. The ratio of sugar side chain to acrylamide in this glycopolymer was 1:44 and the molecular weight of glycopolymer was estimated to be between 1,500,000 and 2,000,000 by high performance gel filtration chromatography. The glycopolymer was shown to be a much more efficient inhibitor of binding by recombinant rat mannose binding protein-carbohydrate recognition domains (MBP-CRD) from serum (I50 = 3.5 microM Man9GlcNAc2-sugar chain) and liver (I50 = 74.5 nM) than soybean agglutinin.

Acetylglucosaminidase↗
PubMed1995

Sse8387I, a useful eight base cutter for mammalian genome analysis (influence of methylation on the activity of Sse8387I).

To develop restriction enzymes that are useful for genome analysis, we previously performed screening and isolated Sse8387I from Streptomyces sp. strain 8387. Sse8387I is a restriction enzyme that recognizes 5'-CCTGCA/GG-3' and cleaves DNA at the site shown by the diagonal (Nucleic Acid Res., 18, 5637-5640). The present study evaluated the effects of methylation that is important when Sse8387I is used for genome analysis. Sse8387I lost cleavage activity after methylation of adenine or methylation of cytosine at any site in the recognition sequence. However, the recognition sequence of Sse8387I contains no CG sequence, which is the mammalian methylation sequence. In addition, we evaluated the effects of methylation of CG at sites other than the recognition sequence. The cleavage activity of Sse8387I was maintained even when CG sequences were present immediately before or after, or near the recognition sequence, and cytosine was methylated. These results suggest that CG methylation does not affect the cleavage activity of Sse8387I. Therefore, Sse8387I seems to be very useful for mammalian genome analysis.

5-Methylcytosine↗
PubMed1995

HNK-1-reactive novel oligosaccharide, sulfate-O-3GlcA beta 1-4Xyl beta 1-(4-methylumbelliferone), synthesized by cultured human skin fibroblasts.

4-Methylumbelliferyl-beta-D-xyloside (Xyl-MU) was added to the medium of cultured human skin fibroblasts. After incubation, the culture medium was pooled, and the Xyl-MU-induced oligosaccharides in the medium were purified by gel filtration chromatography. A novel Xyl-MU derivative was obtained, in addition to the previously reported Xyl-MU derivatives such as Gal-Gal-Xyl-MU, Gal-Xyl-MU, Sia-Gal-Xyl-MU, GlcA-Xyl-MU, and Xyl-Xyl-MU. The novel Xyl-MU derivative was purified using gel-filtration chromatography and high performance liquid chromatography and then subjected to carbohydrate composition analysis, enzymic digestion, Smith degradation, and ion spray mass spectrometric analysis. The results indicated that it was sulfate-O-3GlcA beta 1-4Xyl beta 1-MU. The structure of the nonreducing terminal of this Xyl-MU-induced oligosaccharide was the same as that of the oligosaccharide chain of a human peripheral nerve-derived glycolipid, reactive with the mouse monoclonal antibody HNK-1, and this Xyl-MU-induced oligosaccharide also reacted with HNK-1. These results suggest that the oligosaccharide, which is structurally identical to that of human peripheral nerve-derived glycolipid synthesized by nervous tissue and related to cell adhesion, is synthesized also by mesenchymal cells.

Antigens, CD↗
PubMed1995

A novel Streptomyces restriction endonuclease, Sse1825I, cleaving at 5'-GG/GWCCC-3'.

We isolated and characterized from a Streptomyces species a new class-II restriction endonuclease, which recognizes the palindromic heptanucleotide sequence [sequence: see text] (where W = A or T) and cleaves double-stranded DNA after the second G in this sequence. This Sse1825I enzyme cleaves phage lambda DNA at one site, adenovirus type 2 DNA at eight sites, but does not cleave pBR322, SV40, ColE1, pUC18 and pUC19, and replicative forms of M13mp18 and M13mp19, and phiX174 DNAs.

Base Sequence↗
PubMed1995

Sse8647I, a new type II restriction endonuclease from a Streptomyces species cutting at 5'-AG/GWCCT-3'.

We isolated and characterized a new type II restriction endonuclease which recognizes the palindromic heptanucleotide sequence 5'-AGGWCCT-3' and cleaves double-stranded DNA after the first G in the sequence from a microorganism belonging to Streptomyces species. This enzyme cleaves adenovirus 2 DNA at eight sites, but does not cleave lambda phage, pBR322, pUC18 and 19, M13mp18 and 19, SV40, ColE1 and phi X174 DNAs.

Base Sequence↗
PubMed1995

Synthesis of neoglycoproteins using oligosaccharide-transfer activity with endo-beta-N-acetylglucosaminidase.

We describe a novel method for the enzymatic synthesis of neoglycoproteins. Endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) had high levels of transglycosylation activity. The enzyme activity of Endo-A was markedly increased by adding 4-L-aspartyl-glycosylamine (GlcNAc-Asn) to the reaction mixture. Digesting (Man)6(GlcNAc)2 with the enzyme in the presence of GlcNAc-Asn gave a mixture of hydrolytic ((Man)6GlcNAc) and transglycosylic ((Man)6(GlcNAc)2-Asn) products. By means of transglycosylation, (Man)6GlcNAc was transferred en bloc to the partially deglycosylated ovalbumin glycopeptide (EEKYN(GlcNAc)LTSVL) concomitant with the hydrolysis of (Man)6-GlcNAc)2Asn. The structure of the transglycosylation product was designated as (Man)6(GlcNAc)2-peptide by amino acid composition and sequence analysis as well as ion mass spectrometry. The enzyme also transferred oligosaccharide to partially deglycosylated ribonuclease B (GlcNAc-protein) during the hydrolysis of (Man)6-(GlcNAc)2Asn. Native ribonuclease B had (Man)5-9 (GlcNAc)2 as its heterogeneous N-linked sugar chains. High performance liquid chromatography showed that all of the N-linked sugar chains of the synthetic neoribonuclease of the pyridylamino derivatives were modified to (Man)6(GlcNAc)2.

Amino Acid Sequence↗
PubMed1995

Cervical cancer and herpes simplex virus type 2: case-control studies in Spain and Colombia, with special reference to immunoglobulin-G sub-classes.

Two case-control studies, including 449 histologically confirmed cases of cervical intra-epithelial neoplasia (CIN) III and 425 controls, and 2 studies on invasive cervical cancer, involving 316 histologically confirmed cases and 330 population controls, were conducted in Colombia and Spain to assess the role of herpes simplex virus type 2 (HSV-2) in cervical neoplasia. Antibodies to this virus were also measured in the sera of 931 husbands of cases and controls. A serological assay using type-specific antigens, glycoprotein C for type I (gC-I) and glycoprotein G for type 2 (gG-2) was employed. Immunoglobulin-G (IgG) sub-classes, IgG1 and IgG3, were measured in women positive for HSV-2 antibodies. No increase in risk of CIN III or invasive cancer was found in women whose sera or whose husbands' sera were positive to HSV-2. However, compared with women negative to HSV-2, the risk of CIN III progressively increased with increasing levels of IgG1. The trend was statistically significant in Colombia. There was also a statistically significant increasing trend in risk of invasive cancer with levels of IgG1 in Spain. The levels of IgG3 and its ratio to IgG1, which may indicate recurrent infections, were not associated with the risk of either type of cancer. When the association with IgG1 was analyzed by human papillomavirus (HPV) DNA status, as determined by polymerase chain reaction, the trend was clearer in women whose HPV status was not determined or in those with negative HPV DNA. These results suggest that the role of HSV-2 is merely marginal and do not support the hypothesis that recurrent HSV-2 infections are of importance for cervical neoplasia.

Adult↗
PubMed1995

Role of the heparin-binding domain of chimeric peptides derived from fibronectin in cell spreading and motility.

Cellular responses to fibronectin (FN) are likely to have a complex molecular basis involving the interactions between multiple functional domains of FN and specific cell surface molecules. We have utilized several types of recombinant FN fragments and their chimeric fragments to examine the regulatory mechanisms of the spreading and chemotactic migration of HT1080 human fibrosarcoma cells on FN. The CH-271 fusion fragment, in which the cell-binding domain (C-274) of FN is adjacent to the heparin-binding domain (H-271), promoted cell spreading more efficiently than C-274, H-271, or their mixture (C-274 + H-271) over a 60-min incubation. The CH-271 variants containing various modules in the heparin-binding domain (CHV peptide) showed different promotion of cell migration, spreading, and vinculin accumulation at focal adhesion, respectively. The preincubation of the cells with heparitinase I resulted in significant inhibition of chemotactic migration to FN and its fragments containing the III13 and/or III14 modules of the heparin-binding domain. Additionally, migration to CH-271 was inhibited by the presence of the RGDS peptide in a concentration-dependent fashion. Thus, the spread and migration responses of HT1080 cells onto FN fusion peptides require the adjacent coexistence of cell- and heparin-binding domains and are mediated by the interactions between cell surface heparan sulfate and the heparin-binding domain, in concert with the interaction between cell surface integrin and the cell-binding domain. In conclusion, our present study demonstrated that fusion peptides of fibronectin can efficiently induce two signals from the cell-binding and heparin-binding domains required for the completion of cell spreading, the formation of focal contact, and motility at the early stage of the culture, suggesting that the III13 or III14 modules within the heparin-binding domain are responsible for the initiation of different cellular responses.

Amino Acid Sequence↗