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T Arai

Publications and source records attributed to T Arai.

At least 415 records · Page 23Linked to original sources
PubMed1997

[Mechanism of regression of metastatic liver tumors in rats treated with angiogenesis inhibitor with special reference to apoptosis].

We examined the mechanism of the reduction of metastatic liver tumors in rats treated with angiogenesis inhibitor TNP-470 on the histological basis of patterns of tumor cell death. Metastatic tumors were developed by intravenous injection of AH-130 cell line, followed by a dose of TNP-470. Alteration in the size and number of metastatic liver tumors and its cell death pattern were analyzed. The number and size of the metastatic tumors at 2 weeks in untreated rats were larger than those in treated rats. The number of tumors in untreated rats decreased, whereas their size increased. All rats treated were alive and free from tumors after 4 weeks, although all untreated rats died of metastatic tumors. Necrosis was predominant in the tumors of untreated rats, while most tumors in treated rats showed apoptosis. Consequently, the metastatic tumor in untreated rats might grow faster than its angiogenesis, suggesting the occurrence of central necrosis due to apparent ischemia. On the other hand, the tumor in treated rats might be reduce a by weak ischemic stimulus, which triggers apoptosis.

Animals↗
PubMed1997

[A case of transient cortical blindness due to reversible ischemic neurological deficit (RIND) after caesarean section under lumbar anesthesia].

We report a case of 31-year-old woman with pregnant toxicosis, who developed transient blindness after caesarean section under lumbar anesthesia. The patient was hypoxic due to atelectasis when she developed blindness, but she had no ophthalmologic abnormalities. MRI depicted abnormal high intensity areas (HIA) with T 2-weighted images (T 2 WI) in the occipital lobes and the basal ganglia. CT could not detect any of these MRI findings. The patient regained her vision four days after the onset. The HIA disappeared in a follow up MRI (T 2 WI) two weeks after the onset. The patient was diagnosed as cortical blindness due to RIND. Although most of the transient cortical blindness are accompanied with pregnant toxicosis with hypertension, there are some cases without pregnant toxicosis. We stress the importance of maintaining the blood pressure within the normal range in patients with hypertension who undergo surgery under spinal anesthesia.

Adult↗
PubMed1997

Stage-dependent evaluation of microsatellite instability in gastric carcinoma with familial clustering.

Familial clustering of gastric cancer is probably caused by multifactorial processes, both environmental and genetic. In this report, the incidence of microsatellite instability (MSI) in 31 cases of gastric cancer in Japanese (33 lesions) with familial clustering (two or more gastric cancers within second-degree relatives) was compared to MSI in Japanese cases without a family of any cancer in age ( +/- 10 years)-, stage-, and histological subtype-matched case-control study. Although the difference noted was not significant, we noted a strong trend for MSI at any of up to seven loci of CA repeats to occur more frequently in the patients with a family history of gastric than in the control patients in early cancer (intramucosal and submucosal), whereas the prevalence of MSI was similar in both groups in more advanced cases, in which the tumor invaded beyond the proper muscle layer of the gastric wall. Because the contribution of a family history of gastric cancer to MSI apparently differs in early and advanced gastric cancer, interpretation of MSI in familial gastric cancer cases published previously require reevaluation in terms of stage and proper controls. An acquisition of CA repeat alterations in the early stage rather than in the late stage of gastric carcinogenesis may have in common etiological factors, at least in some cases, with the familial clustering of gastric cancer.

Adult↗
PubMed1997

[An elderly patient with progressive supranuclear palsy without neurological signs].

We report an elderly patient with progressive supranuclear palsy (PSP) who showed no neurological signs clinically. A 70-year-old man presented with irritation and poor hygiene, thereafter he showed excitement and violence. A cranial CT scan revealed bilateral moderate atrophy of the temporal lobes and slight enlargement of the lateral ventricle. The brain stem was slightly atrophic. Although he died at the age of 80 years, he had no neurological signs throughout the clinical course. Neuropathological study showed typical findings of PSP, neuronal loss with gliosis and neurofibrillary tangles in the basal ganglia, amygdala, midbrain, pons, dentate nucleus and inferior olivary nucleus. Staining by Gallyas-Braak methods revealed argyrophilic and tau-positive glial fibrillary tangles in the cerebral cortex. Neurofibrillary tangles showed greater frequency than usual for the physiological level in that age group in the hippocampus regions as well as in the amygdala. The possibility that the psychotic symptoms, mainly personality change, are connected with the degeneration of limbic system is indicated. Since there have not been any previous reports of PSP without neurological signs, this case represents an important in terms of clinico-pathological variation of PSP. We suggest that there is discrepancy between symptomatic and neuropathological aspects in elderly patients with PSP.

Aged↗
PubMed1997

[Combination hepatic intra-arterial 5-fluorouracil and CDDP administration with oral regimen in patients with colorectal cancer metastasis to the liver].

We investigated therapeutic effectiveness and side effects of a combination weekly high-dose 5-FU plus one shot CDDP HAI (WHF + CDDP method) with oral regimen in patients with colorectal cancer metastasis to the liver. All 24 patients enrolled in this study showed 54% efficacy whereas patients combined HAI with oral regimen over one week obtained 83% efficacy for multiple liver metastasis. They showed good quality of the life during combination chemotherapy without any symptoms of metastatic lesions. The WHF + CDDP method combined with oral regimen is a promising treatment for colorectal cancer metastasis to the liver as well as extrahepatic distant organs, and this protocol may be satisfactorily accepted by most colorectal cancer laden patients because of negligible side effects.

Administration, Oral↗
PubMed1997

[Obesity and disturbance of sexual function].

Insulin-resistance is a central character of the simple obesity, resulting from decrease of the insulin receptor and dysfunctions of the post receptor systems. It induces hyper-insulinemia. Excess insulin gives rise to the synthesis of androgens by binding to the receptor of the ovary, and suppresses the SHBG and IGFBG in the liver. As a result, in obese women, the sexual function is disturbed by hyperandrogenic milieu. The conversion of androgens to estrone in the lipocytes evokes overproduction of estrone, which stimulates LH release and induces overproduction of androgens. Hyperandrogenemia is a cause of disturbance of the sexual function in obese women.

Amenorrhea↗
PubMed1997

[Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall].

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.

Brachytherapy↗
PubMed1996

Evidence for membrane remodeling in ipsilateral thalamus and amygdala following left amygdala-kindled seizures in awake rats.

We examined regional cerebral metabolic rates for glucose (rCMRglc) and brain incorporation coefficients (k*) of each of three intravenously infused fatty acid radiotracers, [9,10-(3H)]palmitate ([3H]PAM), [1-(14C)]arachidonate ([14C]AA) and [1-(14C)]docosahe-xaenoate ([14C]DHA), in awake rats fully kindled by once-daily electrical stimulation of the left amygdala. Compared with sham-stimulated animals, rCMRglc was increased bilaterally during a seizure, particularly in midbrain-brain stem regions, thalamus and basolateral nucleus of the amygdala. At 24 h and 2 weeks after a seizure, there was no significant change in k* for either [14C]AA or [14C]DHA in any brain region, whereas k* for [3H]PAM at 24 h was increased significantly (by 32-53%) ipsilateral to stimulation in regions of the amygdala and thalamus. Contralateral regions showed no significant change. Two weeks after a seizure, k* for [3H]PAM was increased in the ipsilateral lateral dorsal nucleus of the thalamus. These results argue for membrane remodeling involving phosphatidylcholine in the ipsilateral amygdala and thalamus at the completed phase of amygdala kindling. Remodeling may continue for up to 2 weeks after a seizure during the completed phase.

Amygdala↗
PubMed1996

Degradation of topoisomerase IIalpha during adenovirus E1A-induced apoptosis is mediated by the activation of the ubiquitin proteolysis system.

The human epithermoid carcinoma-derived cell line MA1, established by introduction of the adenovirus E1A 12 S cDNA linked to the mouse mammary tumor virus long terminal repeat, elicits apoptosis after induction of E1A12S in response to dexamethasone. The level of topoisomerase IIalpha begins to decrease steeply within 36 h preceding the onset of DNA fragmentation, whereas its mRNA level is unchanged (Nakajima, T., Ohi, N., Arai, T., Nozaki, N., Kikuchi, A., and Oda, K. (1995) Oncogene 10, 651-662). Topoisomerase IIalpha prepared by immunoprecipitation or extraction of the nuclear matrix was degraded much more efficiently in the S10 extract prepared from MA1 cells treated with dexamethasone for 42 h (the 42-h extract) than in the extract from untreated MA1 cells (the 0-h extract) in an ATP- and ubiquitin-dependent manner. The proteolytic activity for degradation of topoisomerase IIalpha was suppressed specifically by inhibitors for the proteasome and was much reduced in the 42-h extract prepared from MA1-derivative cell lines expressing E1B19k or Bcl-2. The proteolytic activity was lost after fractionation of the 42-h S10 extract into the S70 and P70 fractions by centrifugation at 70,000 x g for 6 h but partially recovered when these fractions were combined. Polyubiquitinated forms of topoisomerase IIalpha could be detected by incubating it in the S70 or S100 extract, which lacks most of the proteasome activity. The ubiquitination activity in S70 prepared from the 42-h extract was 4- to 5-fold higher than that prepared from the 0-h extract. These results suggest that a component(s) in the ubiquitin proteolysis pathway, responsible for ubiquitination and degradation of topoisomerase IIalpha, is activated or induced during the latent phase of E1A-induced apoptosis.

Adenosine Triphosphate↗
PubMed1996

Investigation of enantioselective separation of quinolonecarboxylic acids by capillary zone electrophoresis using vancomycin as a chiral selector.

When a chiral selector that is a pharmaceutical compound is added to the separation buffer in capillary electrophoresis, the enantioselectivity and the mobility of analytes which interact with that chiral selector may be altered. The changes in enantioselectivity and mobility of the analyte are a function of the strength of the affinity interaction, which depends on the structure of each. The macrocyclic antibiotic vancomycin contains a variety of functionalities that are known to be useful for enantioselective interactions (e.g., hydrogen bonding groups, hydrophobic pockets, aromatic groups, amide linkages). Capillary electrophoresis with vancomycin as a buffer additive was used to separate the enantiomers of different compounds. In this study, the chiral separation of quinolonecarboxylic acids that exhibit marked antibacterial activity and of related compounds was achieved by capillary electrophoresis using vancomycin. The correlations between the separation parameters and analyte structures were investigated. The molecular interaction, which is based on the differences of structure, and the effect of experimental parameters on the enantioselective separation between the quinolonecarboxylic acids and vancomycin are discussed.

Anti-Infective Agents↗
PubMed1996

Substitution of specific amino acids in insulin-like growth factor (IGF) binding protein 5 alters heparin binding and its change in affinity for IGF-I response to heparin.

Heparin binding to insulin-like growth factor (IGF)-binding protein 5 (IGFBP-5) leads to a 17-fold decrease in its affinity for IGF-I, and a region that contains several basic amino acids (Arg201-Arg218) may be involved in this affinity shift. In the present study, mutagenesis was used to analyze the effect of substitutions for basic amino acids in the Arg201-Arg218 region of IGFBP-5 on heparin-binding and the heparin-induced affinity shift. Nine mutant forms were prepared. Their association constants (Ka) for IGF-I were similar to native IGFBP-5. When 10 microg/ml of heparin was added, the Ka of native IGFBP-5 decreased 17-fold, and the Ka of the K134A/R136A mutant decreased 16-fold. In contrast, substitutions for specific basic amino acids in the Arg2O1-Arg218 region decrease the affinity shift to 1.1-3.2-fold. Lys 211 was especially important. When a mutant containing that single substitution was tested, heparin caused only a 2.5-fold reduction in IGF-I affinity. Affinity cross-linking studies showed that heparin was equipotent in inhibiting the formation of 125I-IGF-I-K134A/Rl36A mutant complexes compared to native IGFBP-5. In contrast, heparin had minimal effects on the formation of complexes between 125I-IGF-I and the other mutants. The heparin-binding activity of each mutant was determined. Four mutants, R201A/K202N, K202A/K206A/R207A, R201A/K202N/K206N/K208N, and K211N/R214A/K217A/R218A, had reduced heparin binding compared to native IGFBP-5. The other five mutants, including the K21IN mutant, showed no change in heparin binding. The four mutants with reduced heparin binding could be dissociated from heparin-Sepharose with much lower NaCl concentrations, indicating that they had reduced affinity. These findings suggest that Arg201 Lys202, LysS206, and Arg214 are important for heparin binding. In contrast, LyS211 is not important for the binding of IGFBP-5 to heparin, but substitution for it reduced the heparin-induced affinity shift.

Affinity Labels↗
PubMed1996

Thrombopoietin modulates platelet activation in vitro through protein-tyrosine phosphorylation.

To determine the roles of thrombopoietin (TPO) in platelet function in vitro, we examined the effects of TPO on platelet aggregation. Although several proteins in platelets were tyrosine-phosphorylated by TPO treatment, TPO alone was unable to induce platelet aggregation. However, the secondary wave of platelet aggregation induced by adenosine diphosphate (ADP) was enhanced by TPO in a dose-dependent manner. TPO in conjunction with ADP augmented tyrosine phosphorylation of platelet proteins, including tyrosine-phosphorylated proteins induced by TPO alone. Genistein inhibited protein-tyrosine phosphorylation in platelets induced by TPO with ADP and suppressed TPO-enhanced platelet aggregation. Moreover, tyrosine phosphorylation of MAP-kinases induced by TPO alone and TPO with ADP was consistent with TPO-enhanced platelet aggregation. These findings in the present study suggest that signal transduction involved in TPO-enhanced platelet aggregation is mediated in part by tyrosine-phosphorylated proteins, including MAP-kinases, in platelets through TPO-stimulated c-Mpl, TPO receptor.

Adenosine Diphosphate↗
PubMed1996

A possible mechanism for host-specific pathogenesis of Salmonella serovars.

We have identified the complement receptors on human and murine macrophages involved in the recognition of Salmonella serovars, and investigated their relevance to the intracellular survival. S. typhi was capable of surviving within human monocyte-derived macrophages, whereas S. typhimurium was not. Conversely, S. typhimurium, but not S. typhi, resisted intracellular killing by murine macrophages, demonstrating that the intracellular survival of Salmonella serovars is host-dependent. In the presence of serum opsonin, human monocyte-derived macrophages recognized S. typhi and S. typhimurium via complement receptor type 1 (CR1) and type 3 (CR3), respectively. In contrast, murine macrophages recognized S. typhi and S. typhimurium via CR3 and CR1, respectively. These findings demonstrate that the intracellular fate of Salmonella serovars following phagocytosis may depend on the type of complement receptors involved in their recognition, in that CR1-mediated recognition is closely correlated to subsequent intracellular survival. The Tn5 insertion mutant of S. typhimurium which lacks the ability to interact with CR1 was sensitive to intracellular killing by murine macrophages in vitro, and was much less virulent to mice in vivo, confirming the relevance of CR1-mediated bacterial recognition to the pathogenicity of S. typhimurium for mice. These results suggest that selective recognition of Salmonella serovars through CR1 may lead to their subsequent intracellular survival, and is responsible for the host-specific pathogenesis of Salmonella serovars.

Animals↗
PubMed1996

Synchronous lymphoma and adenocarcinoma occurring as a collision tumor in the stomach: report of a case.

We report herein the rare case of a 71-year-old man who was initially operated on under the diagnosis of advanced gastric cancer, but was subsequently found to have synchronous lymphoma and early adenocarcinoma of the stomach, confirmed by postoperative pathological examination. The patient had a history of lymphoma of the left tonsil, and histologically the gastric lymphoma was observed to be of the non-Hodgkin's, diffuse, large-cell type. Conversely, the gastric cancer was early well-differentiated tubular adenocarcinoma of type 0-IIa, according to the Japan Gastroenterological Endoscopy Society classification. The two tumors had collided at the fornix. The relationship between these two tumors is analyzed and the most appropriate methods of diagnosis and treatment are discussed.

Adenocarcinoma↗
PubMed1996

Activation of neutrophil function by recombinant human granulocyte colony-stimulating factor improves the survival of rats with peritonitis.

We examined the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and cefmetazole sodium on survival, neutrophil count, and neutrophil function in rats with peritonitis produced by cecal ligation and puncture. Rats with peritonitis received either rhG-CSF (50 or 100 micrograms/kg) with or without cefmetazole (50 mg/kg) for 3 days, cefmetazole alone, or no treatment and were evaluated as controls. The mortality rate of all treated rats was significantly lower than that of the untreated rats. The survival rate was 57.1% for the rats given both rhG-CSF and cefmetazole, but there was no significant improvement of survival as compared with cefmetazole therapy alone. Treatment with rhG-CSF at 100 micrograms/kg caused the circulating neutrophil count to increase significantly. The phagocytic activity for latex beads and neutrophil H2O2 production showed a greater enhancement by phorbol myristate acetate (PMA) in the untreated rats, thus indicating that neutrophils from treated rats were more activated. These findings show that rhG-CSF can improve survival and neutrophil function in rats with peritonitis, while combined therapy with cefmetazole was also found to be beneficial.

Animals↗