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T Uchida

Publications and source records attributed to T Uchida.

At least 199 records · Page 11Linked to original sources

Increased choline kinase activity in 1,2-dimethylhydrazine-induced rat colon cancer.

Cancer cells acquire particular characteristics that benefit their proliferation. We previously reported that human colon cancers examined had increased choline kinase activity and phosphocholine levels. The elevated phosphocholine levels were in part due to both activation of choline kinase and increased choline kinase alpha protein levels. In this report, we analyzed choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in rat 1,2-dimethylhydrazine (DMH)-induced colon cancer. This study is the first to demonstrate increased choline kinase alpha enzymatic activity, protein levels, and mRNA levels in DMH-induced colon cancer as well as human colon cancer, although phosphocholine was not increased in DMH-induced rat cancer. The increase in the mRNA level was partly due to an increase in the transcription of the choline kinase alpha gene. The increased choline kinase activity may be a specific characteristic acquired by cancer cells that benefits their proliferation.

1,2-Dimethylhydrazine↗

Increased choline kinase activity and elevated phosphocholine levels in human colon cancer.

Nuclear magnetic resonance spectroscopy has detected elevated phosphocholine levels in human tumor tissues and cells, and in cells that were transformed with the activated Ha-ras gene and stimulated in vitro with growth-promoting factors such as platelet-derived growth factor, epidermal growth factor, and phorbol ester. However, the mechanism of the elevation and the function of the increased phosphocholine levels have not been clearly demonstrated. We studied phosphocholine levels enzymatically and analyzed the activity of choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in human colon cancer and adenoma. Both choline kinase activity and phosphocholine levels were increased in colon cancer and adenoma tissue. The activation of choline kinase and the increased levels of choline kinase alpha were partly responsible for the elevated phosphocholine levels. This study suggests that choline kinase might play a role in growth promotion or signal transduction in carcinogenesis.

Adult↗

Biosynthesis of glycosaminoglycans and aggrecan by tumor cells in salivary pleomorphic adenoma: ultrastructural evidence.

The present study attempted to discover the sites of synthesis of various glycosaminoglycans (GAGs) and aggrecan in salivary pleomorphic adenoma (PA) with the use of a highly sensitive and specific post-embedding immunogold-silver staining technique at the ultrastructural level. Silver particles representing various GAGs and aggrecan were found to accumulate frequently in the intercellular spaces of non-luminal cells in the epithelial clusters and were dispersed in the myxoid matrix of the mesenchyme-like areas. Furthermore, the non-luminal epithelial cells were demonstrated to contain immunopositive intracytoplasmic vesicles and vacuoles, some of which were of Golgi complex origin. In contrast, intracellular silver particles for hyaluronic acid were mostly attached to the inner surface of the cell membrane. These observations agree well with the current theories of the biosynthesis of GAGs and proteoglycans and provide direct evidence for the production of various GAGs and aggrecan by tumor epithelial cells of PA. Such findings support the ideas that in PA a loss of epithelium occurs by stromalization following epithelial secretion of extracellular matrix substances and transformation of epithelium to mesenchyme represents the basic principle of the tissue heterogeneity in this tumor.

Adenoma, Pleomorphic↗

Antigen-specific, IgE-selective unresponsiveness induced by antigen-liposome conjugates. Comparison of four different conjugation methods for the coupling of antigen to liposome.

BACKGROUND: We have previously reported that ovalbumin (OVA) coupled with liposome via glutaraldehyde (GA) induced OVA-specific- and IgE-selective unresponsiveness in mice. METHODS: In this study, OVA-liposome conjugates were made using four different coupling protocols: via GA, N-(6-maleimidocaproyloxy) succinimide (EMCS), disuccinimidyl suberate (DSS) and N-succimidyl-3(2-pyridyldithio)propionate (SPDP) and the induction of antigen-specific IgG and IgE antibody production was investigated for each. In addition, antigen-specific cytokine production by spleen cells of mice immunized either with OVA-liposome or with OVA adsorbed with aluminum hydroxide was investigated. RESULTS: OVA-liposome conjugates coupled via GA or DSS did not induce anti-OVA IgE antibody production but induced substantial anti-OVA IgG antibody production. On the other hand, the induction of anti-OVA IgE unresponsiveness by OVA-liposome conjugates coupled via EMCS or SPDP was incomplete. The amount of interleukin 4 (IL-4) produced by spleen cells stimulated in vitro with OVA correlated well with anti-OVA IgE antibody production in donor mice. However, the production of no other cytokine, i.e., IL-2, IL-5, IL-10 or interferon-gamma, was correlated with in vivo IgE antibody production. CONCLUSION: OVA-liposome coupled via GA or DSS induced complete suppression of anti-OVA IgE production. The results in this study further suggest that the regulation of IgE antibody production does not necessarily correlate with so-called Th1 cytokine production.

Animals↗

NC/Nga mice: a mouse model for atopic dermatitis.

Atopic dermatitis (AD) is a common pruritic disease that occurs primarily in infancy and childhood. AD is characterized by itching and the patient having an individual or family history of atopic diseases. Although AD is also frequently associated with elevated serum IgE levels and with common environmental factors contributing to its pathogenesis, the etiology of AD is still unknown. We examined NC/Nga mice (NC mice) that showed AD-like skin lesions with aging as a possible mouse model for AD. NC mice were maintained under conventional (Conv) or specific pathogen-free (SPF) conditions. Clinical symptoms, serum IgE levels and histopathology of the skin were compared between these 2 groups, and we explored their application as a model of human AD. It was found that the skin lesions of inbred NC mice were clinically and histologically very similar to human AD when the mice were raised under Conv conditions, but not under SPF conditions, and we assumed that some kinds of environmental factors might trigger AD-like signs and symptoms in NC mice. To further investigate the pathophysiology and treatment of AD, a suitable animal model is absolutely required, and NC mice are very useful for this purpose.

Aging↗

Synthesis of polystyrene nanospheres having lactose-conjugated hydrophilic polymers on their surfaces and carbohydrate recognition by proteins.

We prepared a poly(vinylamine)-grafted polystyrene nanosphere by the free radical polymerization of poly(N-vinylacetamide) macromonomer and styrene with AIBN in ethanol and subsequent acid hydrolysis. We conjugated lactose on the nanosphere by an amide linkage and found that the lactose was recognized by a galactose-specific lectin RCA120, which was analyzed by enzyme-linked lectin assay (ELLA). The binding ability of the lectin to lactose on the nanosphere was at least 10(2) times larger than that to a monomeric lactose. Binding ability was clearly affected by the lactose density on the nanosphere and showed a maximum value at the suitable surface density of lactose. We found that the carbohydrate-conjugated nanosphere would be a useful biomaterial for a site specific drug carrier.

Carbohydrate Metabolism↗

Scanning electron microscopic observation of apical sites of open-type paraneurons in the stomach, intestine and urethra.

The apical region of open-type paraneurons in tubular organs functions as a receptor site for chemical information in the lumen. Electron microscopic studies have demonstrated a tuft of microvilli on the luminal surface of cells, but failed to visualize it three-dimensionally. The present scanning electron microscope (SEM) observation succeeded in viewing, from the luminal side, open-type paraneurons distributed in epithelia of the stomach, intestine, and urethra. The pyloric antrum of avian species and the duodenum of human fetuses, the latter forming an endocrine cell colony at every villus tip, were chosen for SEM observation in order to eliminate visual obstruction by adjacent epithelial cells with developed microvilli. The luminal surface of gut endocrine cells was consistently covered with a tuft of 80-200 microvilli. Pyloric paraneurons possessed thick and stiff microvilli as compared with those of exocrine cells. The microvilli on intestinal paraneurons were more irregular in length and more loosely grouped than those composing the striated border of enterocytes. Urethral paraneurons containing serotonin were surrounded by three or four polygonal epithelial cells. Their narrow apical surface was provided with 30-100 microvilli which varied in length from cell to cell, and which were conspicuously projected above the luminal surface of the urethra. The microvillous crown of the gut and urethral paraneurons was so prominent and constant a structure on the apical surface as to allow easy identification of open-type paraneurons under the SEM.

Animals↗

Relationship between levels of aspartate aminotransferase in gingival crevicular fluid and conventional measures of periodontal status assessed using PocketWatch: a cross-sectional study.

The aim of this cross-sectional study was to determine, using PocketWatch, the relationship between the level of aspartate aminotransferase (AST) in gingival crevicular fluid (GCF) and conventional measures of periodontal status, such as probing depth, attachment level, bleeding on probing and gingival index, in patients with untreated chronic periodontitis. A total of 15 patients with chronic periodontitis were enrolled. Their periodontal status and AST levels in their GCF were measured (n = 93) and statistically analyzed. There was a statistically significant difference in AST levels between diseased periodontal sites and healthy sites (p < 0.0001). The coefficients of correlation between AST levels and probing depth, attachment level and gingival index at all sites were 0.436, 0.266 and 0.468 (Spearman rank correlation). The correlation coefficients were too small to show a definite relationship between AST levels and individual measures of clinical periodontal status. However, AST levels may help to confirm clinical observations in patients with chronic periodontitis before therapy, since AST levels differentiate active and inactive periodontal diseased sites.

Adult↗

[Histological characteristics and clinical significance of Japanese prostate cancer with low levels of prostate specific antigen of 4.0 ng/ml or lower].

PURPOSE: They set a normal limit of prostate specific antigen (PSA) to 4.0 ng/ml in Tandem R assay at most institutions. We investigated clinical and histological characteristics of prostate cancer based on whole mount step-section histology of radical prostatectomy specimens, and taking notice of Japanese prostate cancer whose levels of PSA are less than 4.0 ng/ml in normal levels. MATERIALS AND METHODS: One hundred and twenty-two patients underwent radical prostatectomy for clinically resectable prostate cancer at University Hospital from February 1992 to April 1997. Clinicopathological findings were stratified according to the preoperative PSA levels in 111 patients without preoperative endocrine therapy. Immunohistochemical study for PSA was conducted in 7 randomly selected patients. RESULTS: Of the patients 22 (19.8%) had normal (4.0 ng/ml or lower) preoperative serum PSA. Mean tumor volume in this PSA range was 1.5 cm3 with one pT 0 case included. Pathologically organ confined, potentially curable disease (< pT 3) was found in 17 (77.3%) patients and extracapsular extension and seminal vesicle invasion in 5 (23.8%), respectively. No patients had positive pelvic lymph nodes. Well differentiated tumors of Gleason scores 2-4 were found in 9 (40.9%) of the patients, moderately differentiated tumors (Gleason scores 5, 6) in 5 (22.7%) and poorly differentiated histology (Gleason scores 7-10) in 7 (31.8%). Sixteen (72.7%) patients had clinically significant tumors (> 0.5 cm3, Gleason score > or = 7). All 7 patients had positive staining for PSA, but its intensity did not correlate with serum PSA levels. CONCLUSIONS: Many prostate cancers found in surgical specimens were clinically significant despite the low levels of PSA and potentially curable by definitive treatment. Age, co-morbidity and other clinicopathological variables as well as PSA levels should all be taken into account when treatment options are discussed.

Aged↗

[p53 tumor suppressor gene mutation and prognosis in 105 cases of bladder cancer--the relationship between mutation of the p53 gene with clinicopathological features and smoking].

PURPOSE: Alterations of the p53 tumor suppressor gene are the most common genetic change detected in human cancers. The incidence of p53 gene mutation in bladder tumor patients were studied and were compared with clinicopathological findings, smoking history and prognosis. MATERIALS AND METHODS: Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) was used for analysis from exon 4 to 9 of p53 gene in 105 cases of primary bladder tumors. RESULT: p53 matations were detected in 38 or 105 patients (36.2%). Kaplan-Meier Survival curves fo groups wit or without p53 gene mutation show a statistically significant difference (p = 0.0098). The mutation of p53 gene in stages pT 1 pT 1. pT 2, pT 3, pT 4 was found in 2 of 12 (16.7%), 8 of 32 (25.0%), 10 of 25 (40.0%), 12 of 20 (60.0%), 6 of 16 (37.5%) and in grades I, II, III, was noted in 1 of 17 (5.9%), 16 of 49 (32.7%), 21 of 39 (53.8%) cases, respectively. Significant differences were found for groups with grade I and grade II-III (p = 0.0045) cancers and in cases of superficial (stage pTa-1) and muscle-invasive (pT 2-4) tumors (p = 0.0148). However, mutation of p53 was not related to either age or sex in 105 patients. Recurrence rates in stage pTa-1 superficial tumor group with or without p53 mutation showed a statistically significant difference (p = 0.0419). No statistically significant difference was noted between p53 mutation and habitual smoking as well as durations of smoking. CONCLUSIONS: p53 mutations occur more commonly in higher grades and later stages of bladder tumors. Our results suggest that the prognostic factor is linked to not only histological findings but also to the presence of p53 mutation. The mutations of the p53 gene may be involved in the late events of tumorigenesis and might be used as good molecular markers for prognosis in bladder tumor.

Aged↗

[Clinical study of grade 3, superficial transitional cell carcinoma of the urinary bladder].

PURPOSE: To evaluate the treatment of grade 3 superficial (stage pTa and pT 1) transitional cell carcinoma (T.C.C.) of the urinary bladder, retrospective analysis was performed with special reference to tumor prognostic factors. MATERIALS AND METHODS: From July 1971 to september 1995, 51 cases with grade 3 superficial T.C.C. of the urinary bladder were treated. The survival rates and prognostic factors of these patient were analyzed. RESULTS: Five year survival rate of grade 3, superficial tumors was 92.3% and showed significantly better prognosis compared to patients with pT 2 and pT 3 tumors of grade 3 (p < 0.001). As a initial treatments, transurethral resection (TUR) was conducted in 45 patients (88%). Intravesical recurrence was observed in 20 of 45 patients (44%) and 12 of 20 patients (60%) were recurred within 1 year. Non-recurrent rates of the patients treated with TUR were 69.6% at 1 year, 58.8% at 3 year, 49.7% at 5 year, respectively. No significant differences were noted regarding factors of tumor size, figures and a number of tumor. Of the 51 patients, 10 (19.6%) progressed beyond stage T 2 and 6 died with the disease. Survival rates at 10 years follow up in patients with non-papillary and papillary tumor were 57.1% and 97.8%, respectively. CONCLUSION: These results suggested that TUR should be performed as a initial treatment for the patients with grade 3 superficial T.C.C. of the urinary bladder. However, non-papillary tumors should be considered of more intensive treatment like as radical cystectomy, adjuvant chemotherapy or irradiation.

Adult↗

[Cardiac events in vasospastic angina: site and morphology of coronary artery spasm is related to the long-term prognosis of vasospastic angina].

To determine whether the site and morphology of coronary artery spasm provoked with acetylcholine can predict the long-term prognosis of vasospastic angina, coronary artery spasm (more than 90% narrowing) provoked with acetylcholine was studied in 66 consecutive patients (56 males, 10 females, mean age 56 +/- 9 years) with vasospastic angina. All patients were followed for 6.7 +/- 0.9 years and the incidence of cardiac events such as sudden death, myocardial infarction or worsened unstable angina was compared with the site and morphology of provoked spasm. The site of spasm was regarded as proximal when spasm occurred in the proximal site of 3 major coronary arteries which was designated as segment 1, 6 or 11, according to the classification of the American Heart Association, and distal in other segments. The morphology of spasm was classified into 3 types, focal (12 cases, localized more than 90% narrowing with adjoining parts constricting less than 25%), diffuse (17 cases, diffuse more than 90% narrowing), and intermediate (37 cases, localized more than 90% narrowing with adjoining parts constricting 25-90%). The site of spasm was classified into 2 types, the proximal group (24 cases) and the distal group (42 cases). Cardiac events occurred in 7 patients during the follow-up period: sudden death in 2, myocardial infarction in 2, and worsened unstable angina in 3. As to the site of spasm, the incidence of cardiac events was 21% (5/24 patients) in the proximal group, significantly higher than 5% (2/42) in the distal group (p < 0.05). As to the site of spasm, the incidence of cardiac events was 41% (5/12) in the focal group, significantly higher than 3% (1/37) in the intermediate group and 6% (1/17) in the diffuse group (p < 0.001). The presence of proximal and focal coronary artery spasm was associated with a significantly higher incidence of cardiac events. The site and morphology of coronary artery spasm provoked with acetylcholine is related to the long-term prognosis of vasospastic angina.

Acetylcholine↗

[Hepatic involvement in a case of lysosomal glycogen storage disease with normal acid maltase].

A 19-year-old man, who could run only slowly since childhood and who walked on his toes since 12 years of age, noted difficulty in climbing upstairs at 17 years of age. He was admitted to Kyushu University Hospital because of elevated AST, ALT and CK levels. On admission, the liver was palpable two fingerbreadths beneath the right costal margin. A neurological examination revealed a low IQ on WAIS-R, a decreased muscle tonus in his four limbs, moderate weakness of the neck flexor and bilateral tibialis anterior muscles, contracture of the ankle joints, and bilateral pes cavus. The serum CK was elevated to 1,124U/l. Hepatic enzymes, such as AST, ALT, LDH and gamma-GTP were also moderately increased in the sera. A needle EMG disclosed myogenic patterns in the limb muscles. Biopsied biceps brachii muscle showed a mild variation in the fiber size and multiple tiny vacuoles in 5-10% of the muscle fibers. PAS and acid phosphatase were strongly positive in some vacuoles. On electron microscopy, numerous autophagic vacuoles containing glycogen granules were observed. The acid maltase activities were, however, normal in the peripheral blood lymphocytes, the biopsied muscle, and the cultured skin fibroblasts. He was thus diagnosed to have lysosomal glycogen storage disease with normal acid maltase. A histological examination of the biopsied liver revealed the portal and central veins to be slightly sclerotic. In addition, mild fatty changes and frequent nuclear vacuolization were present in the hepatocytes. On electron microscopy, enlarged mitochondria with irregular cristae were also observed. Due to the fact that the cardiac function was well preserved, these hepatic lesions were thought to result from the metabolic abnormalities underlying in this disorder.

Adult↗

[Extragonadal seminoma with testicular microlithiasis: a case report].

A 43-year-old men presented with left supraclavicular growing mass. Ultrasonography revealed a 31 x 21 mm solid mass with a homogeneous echoic pattern. Lymph node metastasis of some malignant neoplasms was highly suspected. However, whole body evaluation with computed tomographic scan revealed no findings in the primary region. In addition, tumor markers including alpha fetoprotein, human chorionic gonadotropin and carcinoembryonic antigen were within normal limits. Then, extirpation of supraclavicular mass was performed and pathological diagnosis was made as pure seminoma. Evaluation of testicle by ultrasonography revealed a diffuse calcification. However, histological examination of biopsy specimen of testicle revealed no malignancy. The mass was finally diagnosed as extragonadal or "burned-out" pure seminoma. The patient received two courses of Peplomycin, vinblastine and cisplatin (PVP) therapy, and there has been no evidence of recurrence for 34 months.

Adult↗

[Monitoring of plasma concentration of low molecular weight heparin--comparative evaluation with chromogenic and clotting assays].

The efficacy of low molecular weight heparin (LMWH) in the treatment of thrombosis is increasing interest in its clinical potential. However, the measurement of in vitro anticoagulant activities of LMWH has been controversial for its appropriate clinical dose. The study has been carried out to compare two methods for measurement of anti-factor Xa activity of LMWH (fragmin). One is 'HEPTEST' recently developed as a new clotting assay method and the other is an authentic chromogenic assay using S-2222. The coefficients of variation in intra-assay were 1.87-2.75% in clotting assay, and 0.61-0.89% in chromogenic assay. The sensitivity to detect minimum concentration was 0.02 IU/ml in clotting assay, and 0.04 IU/ml in chromogenic assay. The correlation between two methods was good (r = 0.935), whereas clotting assay has been revealed as a very simple rapid method. LMWH (fragmin) with 75 IU/kg/day was administered to three patients with coagulopathy; two disseminated intravascular coagulopathy (DIC) and one veno-occlusive disease (VOD). Hemostatic abnormalities have been improved serially after treatment in all patients. During treatment, the plasma concentration of LMWH was measured, showing 0.05-0.23 IU/ml in DIC and 0.02-0.10 IU/ml in VOD. These results suggest that measurement of plasma concentration of LMWH using the easy and rapid clotting assay method as 'HEPTEST' is clinically useful for monitoring to detect clinical dose of LMWH for DIC and thrombosis.

Anticoagulants↗