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T Arai

Publications and source records attributed to T Arai.

At least 19 recordsLinked to original sources
PubMed1995

IL-10 is involved in the protective effect of dibutyryl cyclic adenosine monophosphate on endotoxin-induced inflammatory liver injury.

The effects of exogenous cAMP, dibutyryl cAMP (DBcAMP) on LPS-induced liver injury were examined in mice made hypersensitive to LPS by treatment with i.v. injection of Propionibacterium acnes. In vivo administration of DBcAMP significantly protected P. acnes-treated mice from LPS-induced liver injury, including apoptosis of hepatocytes. DBcAMP significantly increased circulating IL-10 level in correlation with suppression of the TNF-alpha level after LPS challenge in P. acnes-treated mice. Treatment with anti-IL-10 mAb abrogated the protective effect of DBcAMP on LPS-induced liver injury. Similar to in vivo findings, addition to DBcAMP to in vitro culture of liver adherent cells from P. acnes-treated mice enhanced IL-10 synthesis after LPS stimulation. These results suggest that the increment in IL-10 production by liver adherent cells is involved in the protective effect of DBcAMP on LPS-induced inflammatory liver injury.

Animals↗
PubMed1995

Lethal shock is inducible by lipopolysaccharide but not by superantigen in mice with retrovirus-induced immunodeficiency syndrome.

The retrovirus-induced murine AIDS (MAIDS) shares many features with human AIDS. Here, we examined the susceptibility of mice with MAIDS to staphylococcal enterotoxin-triggered shock. Following sensitization with D-galactosamine (D-Gal), mice with MAIDS were resistant to the otherwise lethal effect of superantigen staphylococcal enterotoxin A (SEA). Peak IL-2 levels in these mice after D-Gal/SEA challenge were 10-fold higher than those in uninfected controls, and concurrently, IL-10 levels rose markedly with reduction of circulating IL-1 and IFN-gamma. Treatment with neutralizing anti-IL-10 mAb before D-Gal/SEA challenge led to increased IFN-gamma levels in mice with MAIDS, and resulted in a dose-dependent mortality. In contrast, mice with MAIDS were more susceptible to the toxicity of bacterial endotoxin LPS than were uninfected controls. Administration of 100 micrograms LPS alone induced 50% lethality in mice infected with MAIDS virus 8 wk previously but not in uninfected controls. Administration of 10 micrograms LPS caused acute shock in D-Gal-sensitized mice with MAIDS. Peak TNF-alpha levels in these mice after LPS challenge were increased more than 10-fold, whereas IL-10 levels were one-third of those after SEA challenge. Moreover, serum IFN-gamma was undetectable in uninfected controls and rose to 1063 +/- 483 pg/ml in mice with MAIDS 4 h after LPS challenge. These results suggest that aberrant profiles of cytokine production are crucial in determining fatal outcome in these two types of septic shock in MAIDS.

Animals↗
PubMed1995

Endogenous interleukin 10 prevents apoptosis in macrophages during Salmonella infection.

To elucidate the biological roles of endogenous interleukin 10 (IL-10) in macrophage responses during bacterial infection, we examined in vitro effects of neutralizing IL-10 by anti-IL-10 monoclonal antibodies (mAb) on apoptosis of the peritoneal macrophages following Salmonella choleraesuis infection. Marked increments of TNF-alpha production were observed in the culture supernatant later than 6 h after in vitro culture with anti-IL-10 mAb. These macrophages succumbed to apoptosis at this stage accompanied by marked increment of IL-1 release, despite the expression of higher amount of endogenous heat shock protein 70, an inhibitor of TNF-alpha-mediated apoptosis. These results suggest that endogenous IL-10 plays an essential role in protection of Salmonella-infected macrophages from autocrine suicide caused by excessive production of TNF-alpha after killing of Salmonella.

Animals↗
PubMed1995

Radiation therapy alone for adenocarcinoma of the uterine cervix.

PURPOSE: Radiation therapy alone for adenocarcinoma of the cervix is currently evaluated by the accumulation of long-term results because of the low incidence of this disease. MATERIALS AND METHODS: Fifty-eight patients with adenocarcinoma of the cervix treated with radiation therapy alone between 1961 and 1988 were studied. The radiation therapy consisted of a combination of intracavitary and external pelvis irradiation. Intracavitary treatment was performed with low dose rate and/or high dose rate sources. RESULTS: The 5-year survival rates for Stages I, II, III, and IV were 85.7%, 66.7%, 32.3%, and 9.1%, respectively, and the 10-year survival rates were 85.7%, 60.0%, 27.6%, and 9.1%, respectively. The local control rate with high dose rate treatment was 45.5%, significantly lower than 85.7% and 72.7% with low and mixed dose rate treatments, respectively. Five-year survival and local control rates by tumor volume were 68.6% and 80.0% for small tumors, 63.6% and 66.0% for medium tumors, and 14.4% and 18.2% for large tumors, respectively. The survival rate and local control rate for large tumors were significantly lower than those for small and medium tumors. Multiple regression analysis indicated that stage and tumor volume were independent variables for survival and local control, respectively. Isoeffective dose expressed by time dose fractionation (TDF) was not associated with local control. Radiation complications developed in 10 patients (17.2%), most of which were of moderate degree. CONCLUSION: Radiation therapy alone for adenocarcinoma of the cervix was regarded to be an effective treatment, comparable to combination therapy of surgery and radiation therapy.

Adenocarcinoma↗
PubMed1995

Numerous glial fibrillary tangles in oligodendroglia in cases of subacute sclerosing panencephalitis with neurofibrillary tangles.

Both neurons and oligodendroglia are preferentially infected in subacute sclerosing panencephalitis (SSPE). Massive argyrophilic and tau-positive glial fibrillary tangles (GFT) were found in oligodendroglia in two autopsy cases of SSPE with neurofibrillary tangles (NFT). GFT shared common phosphorylated tau-epitopes with NFT, but were negative for ubiquitin. Electron microscopically, GFT consisted of compact bundles of irregularly woven tubules. Thus, GFT in SSPE differed from NFT showing regular constriction of tubules and from GFT in some other cytoskeletal disorders in which GFT reportedly consisted of straight tubules.

Adolescent↗
PubMed1995

Frequency of exon 15 missense mutation (442D:G) in cholesteryl ester transfer protein gene in hyperalphalipoproteinemic Japanese subjects.

Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from high density lipoprotein (HDL) to apo B-containing lipoproteins. The hyperalphalipoproteinemia caused by CETP deficiency is fairly common in Japan and one of the most common mutations in the CETP gene is the splicing defect of the intron 14, the allelic frequency of which has been shown to be 0.0049 in the Japanese general population. Recently, we have reported a missense mutation in exon 15 of the CETP gene (442D:G), showing a dominant effect on the CETP activity and HDL-cholesterol level. In the current study, we determined the frequency of this new mutation in Japanese hyperalphalipoproteinemic (HDL-cholesterol > or = 100 mg/dl) subjects. A rapid and easy screening method for this new mutation was developed using a polymerase chain reaction (PCR)-mediated site-directed mutagenesis. Among 117 Japanese hyperalphalipoproteinemic subjects (HDL-cholesterol; 116.7 +/- 16.5 mg/dl, mean +/- S.D.) without the intron 14 splice defect, three homozygotes (2.5%) and 34 heterozygotes (29.1%) were found to have the 442D:G mutation. The relative allelic frequency of this mutation was calculated to be 0.17. One of the homozygotes for the 442D:G mutation was the patient previously described by us as having hyperalphalipoproteinemia with corneal opacity and coronary heart disease. This was the first reported subject homozygous for the CETP deficiency who also demonstrated atherosclerotic symptoms. In homozygous subjects, CETP activity ranged from 37% to 62% of the normal value, which was consistent with the results obtained from the transient expression experiment previously reported; however, the specific activity of CETP was not as low as expected.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗
PubMed1995

Mouse uterus peptidylarginine deiminase is expressed in decidual cells during pregnancy.

Peptidylarginine deiminase is localized in the cytosol of the luminal and glandular epithelia of the nonpregnant murine uterus and its expression is regulated by sex hormones [Takahara et al., [1989]: J Biol Chem 264, 13361-13368; Takahara et al. [1992]: J Biol Chem 267,520-525]. Here, we demonstrate that changes occur in the enzyme level in the mouse uterus during pregnancy and parturition. After a rapid decrease in enzymatic activity from day 1 to day 5 of pregnancy, the activity sharply increased during the middle stage of pregnancy (day 8 to day 10) and then gradually decreased during late pregnancy. Expression of the enzyme occurred only in the decidual cells that had differentiated from endometrial stroma cells surrounding the implantation site. The immunochemical properties of the enzyme expressed in the decidualized cells was indistinguishable from those in the uterine epithelia. These results suggest that peptidylarginine deiminase has important roles in decidual cells and not just in the epithelia of the nonpregnant uterus. Moreover, the level of enzyme activity increased slightly just before parturition (day 17), and then decreased during the 12 h period after parturition. The tissue localization of the enzyme expressed around the time of parturition changed from decidua to the luminal and glandular epithelia. Semiquantitative analyses of the enzyme mRNA content in the pregnant uteri showed a remarkable increase from day 7 leading to the onset of the enzyme synthesis in the decidual cells. After reaching the maximal level at day 12, small peaks in the mRNA level were observed at two times during late pregnancy. Since these serial changes in the mRNA level did not correlate with changes in sex hormones, the expression of decidual peptidylarginine deiminase seemed to be controlled by factors other than sex hormones.

Animals↗
PubMed1995

Role of apoptosis in modulation of the growth of human colorectal tubular and villous adenomas.

To estimate the effect of cell proliferation and deletion on the growth of the human colorectal adenoma, 27 tubular adenomas and eight villous adenomas were examined. Tubular adenomas were categorized into three grades of cellular atypia: mild, moderate, and severe. Villous adenomas were given a single grade. Morphological characteristics of apoptosis (nuclear condensation and budding) were used to quantify an apoptotic index, AI (percentage of apoptotic cells in viable adenomatous cells). The apoptotic cells were found mainly among the basal site of the adenomatous tubules. The AIs of tubular adenomas with mild, moderate, and severe grades of atypia were 3.5, 5.7 and 8.8 per cent, respectively. The AI of villous adenomas was 1.8 per cent, which was significantly lower than that of tubular adenomas. The mitotic indices, MIs (percentage of mitotic cells in viable adenomatous cells) of tubular adenomas were 0.41 per cent (mild), 0.58 per cent (moderate), and 0.83 per cent (severe), and for villous adenomas the MI was 0.38 per cent. There was a close positive relationship between the AI and MI of tubular adenomas, which paralleled the grade of atypia. These results indicate that both cell proliferation and death were more frequent in adenomas with severe atypia than in adenomas with mild atypia. Moreover, the significantly lower AI of villous adenomas, known to develop into large tumours when compared with tubular adenomas, suggests that reduced apoptoses may lead to a shift in tissue kinetics towards expansive growth.

Adenoma↗
PubMed1995

Formation of 6 beta-OH-deoxycorticosterone from deoxycorticosterone by A6 cells.

We have investigated the metabolism of deoxycorticosterone in A6 cells, a continuous cell line derived from the kidney of Xenopus laevis. A6 cells at confluence were incubated with serum-free culture media containing 2.5 microM [3H] deoxycorticosterone. When radioactive compounds in incubation media were separated by reverse-phase high-pressure liquid chromatography, the formation of polar metabolites was observed. One component of polar metabolites cochromatographed with 6 beta-hydroxydeoxycorticosterone. In order to identify this component more rigorously, large scale cultures were performed and this compound was separated and purified by reverse-phase high-pressure liquid chromatography. The purified material was analyzed by gas chromatography-mass spectrometry, secondary ion mass spectrometry, and nuclear magnetic resonance spectroscopy. These procedures revealed that this material was 6 beta-hydroxydeoxycorticosterone.

Animals↗
PubMed1995

The effect of a naphthalene derivative, TEI-6472, on histamine release and tyrosine phosphorylation in rat basophilic leukemia cells.

It is well known that rat basophilic leukemia cells (RBL-2H3) express high-affinity IgE receptors (Fc epsilon RI) and that the aggregation of these receptors causes the release of chemical mediators. When RBL-2H3 cells are sensitized with IgE antibody and subsequently stimulated by an antigen, significant histamine release and the tyrosine phosphorylation of several proteins are observed. In this study, we examined the effects of a synthetic naphthalene derivative, (7E)-N-(2-carboxyphenyl)-8-(2-naphthyl)-5,6-trans-5,6-methano-7-++ +octenamide (TEI-6472), on the Fc epsilon RI-mediated histamine release from RBL-2H3 cells. Preincubation for 10 min with 100 microM TEI-6472 caused significant inhibition of Fc epsilon RI-mediated histamine release from RBL-2H3 cells. Furthermore, Western blotting analysis using anti-phosphotyrosine antibody showed that Fc epsilon RI-mediated tyrosine phosphorylation of 78 and 92 kDa proteins in RBL-2H3 cells was also significantly inhibited. Tyrosine phosphorylation of these 78 and 92 kDa proteins was not induced by direct activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) and the calcium ionophore A23187. However, the inhibition of histamine release from TEI-6472-treated RBL-2H3 cells was restored by direct activation of PKC. Taken together, these results suggest that tyrosine phosphorylation of the 78 and 92 kDa proteins in RBL-2H3 cells is involved in a signal transduction system for histamine secretion, and that these tyrosine phosphorylations may occur upstream of PKC activation.

Animals↗
PubMed1995

Oligomeric structures required for complement activation of serum mannan-binding proteins.

Serum mannan-binding protein (S-MBP) comprises a series of homooligomers, and activates complement when it binds to appropriate carbohydrate ligands. In this study, the structural requirements necessary for complement activation were examined for rat, rabbit, and human S-MBPs. On SDS-PAGE under non-reducing conditions, the S-MBPs gave three major bands: large, middle, and small oligomers. Since three subunits (23-25 kDa) form a triple helix (the base structural unit) at the collagen-like domain within the S-MBP molecule, it was estimated that human and rabbit S-MBPs comprise a mixture of pentamers, tetramers, and trimers of the respective structural units. In contrast, rat S-MBP is composed of tetramers, trimers, and dimers. The large and middle oligomers were almost equal in their ability to activate complement, whereas the small oligomers had very low or no activity. Upon digestion with bacterial collagenase, the large and small oligomers were degraded almost completely. In contrast, the middle oligomers remained largely intact, and the surviving middle oligomers retained complete ability to activate complement. The degraded product, trimers of the carbohydrate recognition domain (CRD), did not show any complement activating activity. These data indicate that not only the structural integrity of the S-MBP collagen-like domain and CRD, but also a unique conformational structure present in the middle oligomers are critically important for carbohydrate-mediated complement activation.

Animals↗
PubMed1995

Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency.

We have reported that the disorder of lipoprotein metabolism in hyperalphalipoproteinaemic patients with a deficiency of cholesteryl ester transfer protein (CETP) is characterized by the polydisperse low density lipoprotein (LDL) particles and the accumulation of cholesteryl ester (CE) in high density lipoprotein (HDL) particles, forming cholesterol-induced HDL (HDLc)-like particles. In the present study we have investigated the interaction of these abnormal LDL with LDL receptors of normal human fibroblasts. Since the ultracentrifugally separated LDL fraction (1.019 < d < 1.063 g mL-1) from the CETP-deficient patients contained HDLc-like particles, these particles were removed by anti-apolipoprotein (apo) A-I immunoaffinity column chromatography. The lipoproteins eluted in the unbound fraction of this column did not contain apo A-I, so this fraction was considered to be authentic LDL. The authentic LDL of the patients were deficient in CE and rich in triglycerides and apo B. The authentic LDL itself showed polydispersity, ranging in size from 23 nm to 30 nm. The affinity of these abnormal LDL particles for LDL receptors was analysed by a competitive assay in which cold LDL from the patients or control compete with 125I-labelled LDL for fibroblast LDL receptors. The concentration of LDL particles at which 50% of 125I-labelled normal LDL was replaced was two to three times higher for the patients than for the normal control. Therefore, the affinity of patient LDL was thought to be reduced compared to that of control LDL. These results demonstrate that CETP may play an important role in making LDL particles homogeneous and rich in CE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Primary osteosarcoma arising from cirrhotic liver.

An autopsy case of a 67 year old man with primary osteosarcoma arising in cirrhotic liver is reported. His son had von Recklinghausen disease and he had had a history of hepatitis C virus infection for 10 years. A large tumor, about 10 cm in diameter, was found in the right liver lobe. This tumor showed marked central necrosis and hemorrhage, and histologically diffuse sarcomatous cell proliferation associated with extensive osteoid formation and calcification of the periphery. Examination of the whole tumor and the cirrhotic liver (155 tissue blocks) showed that the tumor consisted of sarcoma cells mixed with osteoid with no region resembling hepatocellular carcinoma or hepatoblastoma. Minute hepatocellular carcinomas were found in the cirrhotic liver distant from the sarcomatous area. On immunohistochemical examination, the main tumor gave a distinct positive reaction for vimentin, but not for keratin or other epithelial markers. These findings indicate that the tumor was a true primary osteosarcoma, not an osteoid metaplasia of hepatocellular carcinoma.

Aged↗
PubMed1995

Abnormal cardiac histology in severe intrauterine growth retardation infants.

Four infants with severe intrauterine growth retardation (IUGR) weighing less than 1000 g at birth developed heart failure and died in our unit, where heart failure of IUGR infants is the main reason of death in extremely low birth-weight infants. The causes of their heart failure are one of the main themes in current neonatal medicine. The subjects of this study were four small for gestational age infants; all died due to heart failure 5 to 10 days after birth. Microscopic specimens of hearts from autopsies were evaluated with respect to the following characteristics: thickness of myocardial fibers, maturation of nuclei, presence of dysgenesis or necrosis in myocardium, and amount of glycogen in the heart. Neither dysgenesis nor infarction of the heart was found but hypoplasia in myocardial fibers and decreased glycogen levels were observed. Maturation delay in myocytes' nuclei did not appear to be severe. We conclude that these infants' hearts failed to adapt to postnatal hemodynamic changes because of inadequate myocardial function and inadequate glycogen reserves.

Fetal Growth Retardation↗
PubMed1995

Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase.

Hyperalphalipoproteinemia (HALP) has been regarded as a beneficial state accompanied by a longevity syndrome. However, we reported the cases of markedly hyperalphalipoproteinemic subjects with juvenile corneal opacification. The patients had reduced postheparin hepatic triglyceride lipase (HTGL) activities, and one of them has recently been identified to be homozygous for a missense mutation in exon 15 (D442: G) in the cholesteryl ester transfer protein (CETP) gene. In the current study, to elucidate the clinical significance of and atherogenicity in marked HALP, we determined the incidence of atherosclerotic cardiovascular disease (ACD) in patients with marked HALP and characterized the lipoprotein abnormalities in those who had ACD, focusing especially on CETP and HTGL. The subjects were 201 patients (111 males and 90 females) with marked HALP ( > or = 2.58 mmol/L [100 mg/dL]), 67% of whom were demonstrated to have the CETP gene mutations in the intron 14 splice donor site or in exon 15. Their mean age was 54 +/- 15 years. Plasma levels of total cholesterol, HDL cholesterol, and triglyceride in all subjects were 6.28 +/- 1.78, 3.15 +/- 0.90, and 1.08 +/- 0.53 mmol/L, respectively. Ten of the male patients (9.0%) and two of the female patients (2.2%) had apparent ACD such as myocardial infarction, angina pectoris, and peripheral vascular diseases. Ten patients with HALP who had ACD were identified to be heterozygotes for CETP deficiency. To further clarify the characteristics of marked HALP in patients with ACD, we compared the plasma lipids, lipoproteins, CETP, and HTGL activities between heterozygotes for CETP deficiency who were with and without ACD.

Adult↗
PubMed1995

Generation of 28 sequence-tagged sites (STSs) from yeast artificial chromosome (YAC) clones anchored at human chromosome 21q22.1 region.

Twenty-eight sequence-tagged sites (STSs) were newly generated from the DNA sequences of vector-insert junctions from yeast artificial chromosomes (YACs) anchored at chromosome 21q22.1 region. The insert DNAs adjacent to vector arms were specifically amplified through inverse PCR method to clone into pUC19 vector for sequencing. Sixty DNA junctions from 44 CEPH YAC clones were cloned and sequenced. Of these DNA sequences of junctions between vector-arms and DNA inserts, twenty-eight STSs were finally obtained to show the accurate amplification, which is specific for human chromosome 21. The sets of 28 STSs were useful to build fine YAC contigs by STS-mediated YAC walking at the 21q22.1 region.

Animals↗
PubMed1995

Staining etched epoxy resin sections for light microscopy.

Staining of etched sections for light microscopy is described. Azan staining was successful after treatment with potassium dichromate and the use of concentrated dye solutions. To remove osmium for hematoxylin-eosin staining, removal by reduction with ferrocene was used instead of oxidation. Highly selective differentiation after hematoxylin staining was achieved using p-toluenesulfonic acid-DMSO. To enhance eosin staining, a 2-bromoethylamine link between eosin and the tissue was used. Ferrocene also facilitated counterstaining of nuclei with hematoxylin after the PAS reaction. Periodic acid-methenamine silver staining was carried out without modification.

Epoxy Resins↗