Search PubMed⌕ Search

Biomedical subjects

K Tsuji

Publications and source records attributed to K Tsuji.

At least 379 records · Page 21Linked to original sources
PubMed1993

Reproductive risk in mating between two translocation carriers: case report and review of the literature.

We conducted a study to determine the reproductive risk in a couple who were translocation carriers. This couple, who carried balanced reciprocal translocations, experienced habitual abortions. The wife had a karyotype of 46,XX,t(7;13)(p15.3;q12.3) and the husband of 46,XY,t(1;7)(p11.1;p11.1). Chromosome study of their fourth abortus demonstrated a chimera consisting of two cell lines with a 46,XY and a 46,XX,t(1;7)(p11.1;p11.1)pat, -13, + der(7)t(7;13)(p15.3;q12.3)mat, karyotype. A review of the literature indicates that the risk of having unbalanced live offspring or of spontaneous abortion/stillborns is similar in couples in whom both were translocation carriers and in couples in whom one individual was a translocation carrier. The apparent lack of increased reproductive failure may result from the selective disadvantage of aneusomic gametes at fertilization or very early spontaneous abortions of unbalanced conceptuses.

Abortion, Habitual↗
PubMed1993

Selective impairment of the cytoplasmic Ca2+ response to glucose in pancreatic beta cells of streptozocin-induced non-insulin-dependent diabetic rats.

Pancreatic islets from the streptozocin-induced non-insulin-dependent diabetes mellitus (NIDDM) rat model showed a diminished insulin response to 16.7 mmol/L glucose, but the insulin response to arginine remained intact. To evaluate the importance of intracellular calcium concentration ([Ca2+]i) in the diminished insulin response to glucose, the [Ca2+]i of pancreatic beta cells was investigated using fura-2. Glucose produced heterogeneous responses of [Ca2+]i, which were in beta-cell clusters of both the control and NIDDM groups. Many cells showed initial slight decreases of [Ca2+]i, which were followed by gradual and large increments of [Ca2+]i after glucose stimulation of beta cells in the control group. On the other hand, the increase of [Ca2+]i in response to glucose was markedly diminished in beta cells of the NIDDM group compared with controls. The average lag time to [Ca2+]i elevation of beta cells in the NIDDM group was significantly longer than that of the control group. Arginine produced marked increases of [Ca2+]i, in contrast to the effect of glucose stimulation in the NIDDM group. These results suggest that the diminished and delayed [Ca2+]i increases in beta cells of NIDDM rats in response to glucose stimulation are responsible for the selectively impaired insulin response to glucose in the rat model of NIDDM.

Animals↗
PubMed1993

Analysis of genes within the HLA region affecting susceptibility to ulcerative colitis.

To clarify the molecular relationship between HLA loci and ulcerative colitis (UC) in Japanese patients, we performed HLA-DP genotyping by the PCR-RFLP method and studied tumor necrosis factor beta-chain genetic polymorphism by Southern hybridization, in addition to conventional serologic typing. Significant increase was observed in Bw52, DPw9 (DPB1*0901), and DR2 (DRB1*1502) in Japanese patients with UC. Linkage analysis indicated that A24-Bw52-DR2-DPw9 alleles constitute a common haplotype in Japanese UC patients. Among the patients not carrying Bw52, B13 was significantly increased and B44 was relatively increased. These Bw52, B13, and B44 alleles share the unique amino acids, serine and aspartic acid at positions 67 and 77, respectively. These positions are in the second hypervariable region of the alpha 1-domain of the HLA-B13, B44, Bw52, and B49 antigens (B49 is quite rare in the Japanese population). The inflammatory region in UC patients was found to vary depending on their HLA-B alleles. These results suggest that the HLA-B locus itself plays an important role in the susceptibility to Japanese UC.

Adult↗
PubMed1993

Steroid hormones protect spinal cord neurons from glutamate toxicity.

The effects of steroid hormones on glutamate neurotoxicity were examined in cultured spinal cord neurons. The extent of neuronal damage, produced by glutamate exposure for 15 min, was estimated based on the activity of lactate dehydrogenase released from degenerated neurons to the media during 24 h of post-exposure incubation. This damage was dependent on the glutamate concentrations used. The addition of dexamethasone, a synthetic steroid, in post-exposure media remarkably reduced the extent of damage in a dose-dependent manner. The half effective concentration for the steroid was approximately 0.7 microM, which was in the range of pharmacological concentration. Dexamethasone was effective even when it was added 2 h after glutamate exposure. Some endogenous steroid hormones--aldosterone, progesterone and testosterone--also showed similar neuroprotective effects. However, cholesterol, a precursor of these steroid hormones, had no effect on glutamate neurotoxicity. This direct protective effect on neurons against glutamate neurotoxicity may explain, at least partly, the mechanisms of beneficial effects of steroid hormones on in vivo spinal cord injury.

Aldosterone↗
PubMed1993

Intraductal papillary neoplasms of the pancreas: diagnosis by endoscopic pancreatic biopsy.

Intraductal papillary neoplasms of the pancreas (IPN) are rare tumors, distinct from other pancreatic duct cell carcinomas both in terms of papillary polyp formation in the main pancreatic duct and their favorable prognosis. In the present study, endoscopic pancreatic biopsy (EPB) under fluoroscopic control was employed in three cases of IPN to obtain a tissue diagnosis prior to surgery. There were no complications and all biopsy specimens were adequate for histopathological evaluation. In our experience, EPB is a simple, safe and effective method, yielding sufficient material for preoperative tissue diagnosis of pancreatic tumors, especially in the case of IPN.

Adenocarcinoma, Papillary↗
PubMed1993

Modulation of aflatoxin B1-induced glutathione S-transferase placental form positive hepatic foci by pretreatment of rats with phenobarbital and buthionine sulfoximine.

Induction of glutathione S-transferase placental form (GST-P) positive hepatic foci has been examined by immunohistochemical analysis in young male Fischer rats 3 weeks after a single i.p. injection of aflatoxin B1 (AFB1). Pretreatment of rats with L-buthionine sulfoximine (BSO), a GSH depleter, at a dose of 4 mmol/kg body wt 4 and 2 h before 1.0 mg AFB1 treatment enhanced both the number of AFB1-induced hepatic foci and the area occupied by these foci by approximately 400 and 575% above their respective controls without affecting the mean diameter of these foci. Pretreatment of rats with 0.1% phenobarbital (PB) in their drinking water for 1 week before AFB1 (1 mg) treatment, inhibited AFB1-induced foci almost completely. However, the number of AFB1-induced foci in PB-pretreated rats was not significantly increased by BSO pretreatment.

Aflatoxin B1↗
PubMed1993

Transient depletion of T cells with bright CD11a/CD18 expression from peripheral circulation during acute Kawasaki disease.

To clarify the activation of peripheral blood T cells in Kawasaki disease (KD) patients, we investigated whether expression of lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) and/or intercellular adhesion molecule-1 (ICAM-1, CD54) on peripheral blood T cells increases during the acute stage. Expression of cellular adhesion molecules was measured using flow cytometry. There was a decrease in the percentage of CD3+ T cells in the bright LFA-1 alpha and LFA-1 beta population and a concomitant increase in the dim population of LFA-1 alpha and LFA-1 beta during the acute stage, in comparison with those of the convalescent stage. In addition, we observed no significant differences in ICAM-1 expression during the acute stage compared with that of the convalescent stage. In our view the present data, in conjunction with previous reports on T-cell function during acute KD, suggest that activated T cells are temporarily withdrawn from peripheral circulation during acute KD.

Acute Disease↗
PubMed1993

Comparison of hepatic drug-oxidizing activity after simultaneous administration of two probe drugs, caffeine and trimethadione, to human subjects.

Pharmacokinetic interactions between caffeine 2 mg/kg and trimethadione 4 mg/kg were evaluated in 10 healthy volunteers. Whether administered alone or together, the total body clearance (CL), the apparent volume of distribution (Vd) and half-life (t1/2) of caffeine and trimethadione were the same, however, there was a weak correlation between the CL of caffeine and trimethadione [alone: r = 0.51 (P < 0.05); coadministered: r = 0.56 (P < 0.05)]. There were also weak correlations between the CL of trimethadione and the area under the serum concentration-time curves (AUC) of theobromine (r = -0.61, P < 0.05), paraxanthine (r = -0.69, P < 0.05) and theophylline (r = -0.60, P < 0.05), when the two drugs were administered alone. After combined administration, the correlation between the CL of trimethadione and the AUCs of the metabolites of caffeine were as follows: theobromine r = -0.63 (P < 0.05); paraxanthine r = -0.68 (P < 0.05); theophylline r = -0.65 (P < 0.05). These findings suggest that caffeine and trimethadione metabolism in healthy subjects is mediated by only in part by a form(s) of P450 enzymes involved.

Adult↗
PubMed1993

Kainic acid injection into medullary raphe produces gastric lesions through the vagal system in rats.

There is little evidence of a role of nuclei in the brain stem, other than the dorsal motor nucleus of the vagus nerve in the medulla oblongata, in terms of central mechanisms for gastric ulcer formation. Recent reports suggest that the medullary raphe nuclei may be involved in the central regulation of gastric functions such as gastric acid secretion and motility. In the present study, we examined whether neurons in the nucleus raphe obscurus (NRO) played a significant role in the formation of gastric ulcers with the use of Sprague-Dawley rats. First, we determined whether excitation of the medullary raphe resulted in the development of gastric lesions. Chemical stimulation of neurons in the NRO by kainic acid produced gastric erosions within 4 h in 24-h fasted rats. Saline tested under the same conditions did not modify the integrity of the gastric mucosa. It was also demonstrated that kainic acid injection outside the raphe obscurus boundaries failed to develop gastric lesions. Next, we examined the effects of the vagal system on the gastric lesion formation induced by stimulation of the raphe nucleus. Bilateral gastric branch vagotomies completely prevented the development of the raphe nucleus-provoked gastric mucosal damage. All these results suggest, for the first time, that excitation of neurons in the medullary raphe obscurus induces gastric ulceration through vagal stimulation.

Animals↗
PubMed1993

The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma).

HLA class II alleles were determined using the PCR-RFLP method in Japanese systemic sclerosis (scleroderma) patients with (n = 28) or without (n = 34) anti-topoisomerase I antibodies (anti-topo I). Either the DQB1*0601 or *0301 allele was recognized in all anti-topo I positive patients, compared with 44% of anti-topo I negative patients (P < 0.00001, relative risk [RR] > 41) or 58% of Japanese healthy control subjects (P < 0.00001, RR > 24). Tyrosine at position 26 in the second hypervariable region in the beta 1 domain of the DQB1 gene is common to these two alleles and is not present in any other known DQB1 alleles. We also examined immunoreactivities of anti-topo I positive sera to four different autoantigenic B cell epitopes of topo I molecule that were expressed as recombinant fusion proteins. One major B cell epitope, located within the region corresponding to amino acid residues 74-248, was perfectly associated with the amino acid sequence FLEDR at positions 67-71 in the beta 1 domain of the DRB gene. Two other epitopes, corresponding to 316-441 or 658-700, were associated with the serologically defined HLA-DR52 antigen. Patients with both FLEDR and DR52 demonstrated higher anti-topo I antibody titers. These results suggest that the HLA-DR and DQ genes together control the autoimmune response to topo I in systemic sclerosis.

Amino Acid Sequence↗
PubMed1993

Apparent genetic difference between hypothyroid patients with blocking-type thyrotropin receptor antibody and those without, as shown by restriction fragment length polymorphism analyses of HLA-DP loci.

HLA types in Japanese patients with primary hypothyroidism were analyzed to see whether those with blocking-type TSH receptor antibody (TSH-R BAb M) differed genetically from those with idiopathic myxedema (IM). HLA typings of -A, -B, -C, -DR, and -DQ (73 antigens) were performed serologically, and those of -D and -DP (29 antigens) were analyzed by the restriction fragment length polymorphism method. Thirty patients were studied with TSH-R BAb M, and 28 with IM. The data were analyzed and compared with our previous results from 88 Graves' patients, 46 Hashimoto patients, and 186 control subjects. Overall, 192 patients with 4 autoimmune thyroid disorders showed a decrease in -Aw19 and an increase in -DQw4 (corrected P < 0.05) and significant associations of -Aw33, -Bw46, -Cw3, -DRw8, -DR9, and -DQw3. In TSH-R BAb M patients, increases in -B35, -Bw60, and -Dw8 and decreases in -DR4 and -DPw2 were seen, whereas IM patients showed increased -DPw2, -Bw61, and -Dw23. In comparisons between TSH-R BAb M and IM, the difference in -DPw2 was highly significant. HLA-B35 differed significantly in these 2 types of hypothyroidism. In conclusion, TSH-R BAb M patients have decreased frequency of -DPw2 and are genetically similar to Graves' disease, whereas IM patients are characterized by high frequency of -DPw2 and are genetically similar to Hashimoto's thyroiditis.

Adult↗
PubMed1993

HLA-DPB1 allele associates with early-onset myasthenia gravis in Japan.

We investigated the HLA-DPB1 allele in 43 unrelated Japanese patients with myasthenia gravis (MG) using digestion of polymerase chain reaction (PCR)-amplified DNA with allele-specific restriction endonucleases (PCR-RFLP method). We found a higher frequency of the DPB1*0201 allele in female patients whose ages at onset were less than 30 years (83.3%) than in controls (35.6%). The study also included serologic typing of HLA-A, -B, -C, and -DR antigens in 72 patients with MG, and confirmed previous results demonstrating a strong association of HLA-DR53 with early onset of MG in females. These results indicate that both the DPB1*0201 allele and DR53 play key roles in the disease process of MG in early-onset females, and that the genetic background of Japanese females with early-onset MG is different from that of other patients with MG.

Adolescent↗
PubMed1993

Studies on antiinflammatory agents. III. Synthesis and pharmacological properties of metabolites of 4'-acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide (FK3311).

We synthesized putative metabolites of 4'-acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide (FK3311, 1), a novel antiinflammatory agent, in order to confirm their structures and also to investigate their pharmacological properties. The structures of the metabolites 2-5 were confirmed by direct comparison with the synthesized authentic compounds. We employed the following tests to assess pharmacological activities: zymosan-induced prostaglandin E2 production for in vitro activity, adjuvant-induced arthritis for antiinflammatory activity, and acetic acid-induced writhing for analgesic activity. Metabolite 2 is nearly equipotent to 1 in the in vivo tests and metabolite 3 is an active metabolite with in vitro activity comparable to that of 1.

Analgesics↗
PubMed1993

Modification of the amino group of guanosine by methylglyoxal and other alpha-ketoaldehydes in the presence of hydrogen peroxide.

Methylglyoxal is directly mutagenic to Salmonella typhimurium TA100 and its mutagenicity is markedly enhanced in the presence of hydrogen peroxide. We found that methylglyoxal in phosphate buffer was decomposed easily by hydrogen peroxide at room temperature to yield acetic acid and formic acid as major products and diacetyl as a minor product; acetyl radical was detected in the solution by ESR spectroscopy by the use of a spin-trapping reagent, 5,5-dimethyl-1-pyrroline N-oxide. Furthermore, guanosine was converted into N2-acetylguanosine by a combination of methylglyoxal and hydrogen peroxide in 0.1 M phosphate buffers (pH 6.1 to 7.4). This acetylation may be related to the enhancement of methylglyoxal mutagenicity by hydrogen peroxide. Other alpha-ketoaldehydes such as glyoxal and phenylglyoxal also yielded the corresponding acids and alpha-dicarbonyls upon reaction with hydrogen peroxide under the same conditions as above. These acids would have been produced through Baeyer-Villiger reaction or coupling of acyl radical with hydroxy radical, and dicarbonyls by dimerization of acyl radicals. In addition, when phenylglyoxal was used, the generation of benzoyl radical and the conversion of guanosine to N2-benzoylguanosine were observed. However, it remains to be established whether the generation of acyl radicals is directly involved in the N-2 acylation of guanosine.

Aldehydes↗