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Biomedical subjects

T Tsukamoto

Publications and source records attributed to T Tsukamoto.

At least 19 recordsLinked to original sources
PubMed2007

Loss of MUC2 expression correlates with progression along the adenoma-carcinoma sequence pathway as well as de novo carcinogenesis in the colon.

AIMS: We have previously demonstrated links between clinicopathological findings and phenotypes using several gastric and intestinal phenotypic markers in stomach and pancreatic cancers. However, the clinicopathological significance of the phenotype and Cdx2 expression has hitherto remained unclear in colorectal carcinogenesis. METHODS AND RESULTS: We examined the correlation between gastric and intestinal phenotypic expression in 91 primary early carcinomas of the colon. MUC2 expression demonstrated a significant decrease from tubular/tubulovillous adenomas with moderate atypia, through intramucosal carcinomas, to cancers with submucosal invasion (P<0.0001). Intramucosal de novo carcinomas (flat type carcinomas without adenomatous components) exhibited a greater decrease of MUC2 than intramucosal lesions with adenomatous components. Expression of MUC5AC also decreased significantly with progression according to the tubular/tubulovillous adenoma-carcinoma sequence, carcinomas with villous adenomatous components having a higher level compared with their tubular adenomatous counterparts, suggesting differences in the pathway of malignant transformation. Cdx2 nuclear expression was maintained in all of the adenomas and early carcinomas examined. CONCLUSIONS: Our data suggest that the reduction of MUC2 expression may be associated with the occurrence and progression of colorectal carcinomas in both adenoma-carcinoma sequence pathway and de novo carcinogenesis. Tumor-suppressive effects of Cdx2 may be preserved during early stages of colorectal carcinogenesis.

Adenocarcinoma↗
PubMed2007

Gastric and intestinal phenotypic correlation between exocrine and endocrine components in human stomach tumors.

We have previously suggested that an origin of a stomach cancer is from a progenitor cell specializing toward exocrine cell (Exo-cell) lineages. To clarify whether our hypothesis is correct or not, we analyzed the expression of Exo-cell and endocrine cell (End-cell) markers in a series of lesions for comparison. We evaluated chromogranin A (CgA) expression in 37 early and 73 advanced stomach cancers, in 30 stomach adenomas, in 8 carcinoid tumors, and in 4 endocrine cell carcinomas (ECCs) with assessment of gastric and/or intestinal (G/I) phenotypes in both Exo-cell and End-cell by immunohistochemistry. CgA expression was observed in 10.8% of the early and 16.4% of the advanced stomach cancers, respectively. The End-cell G/I phenotypes were in line with the Exo-cell counterparts in the CgA-positive stomach cancerous areas, and there was strong association between Cdx2 expression and the intestinal End-cell markers. All of the adenoma cases had the intestinal Exo-cell phenotypic expression, with the positive link between Exo-cell and End-cell G/I phenotypes. All stomach carcinoids had CgA expression but no expression of Exo-cell markers. In conclusion, most stomach cancers might develop from a progenitor cell specializing towards Exo-cell lineages, but some cases possessed both Exo-cell and End-cell markers with maturely differentiated phenotypes. In such cases, Exo-cell and End-cell phenotypes were found to correlate strongly, suggesting the possibility of histogenesis from "cancer stem cells".

Adenocarcinoma↗
PubMed2006

Chromosomal instability by beta-catenin/TCF transcription in APC or beta-catenin mutant cells.

Adenomatous polyposis coli (APC/Apc) gene encodes a key tumor suppressor whose mutations activate beta-catenin/T-cell factor (TCF)-mediated transcription (canonical Wnt signaling). Here, we show that Wnt signaling can cause chromosomal instability (CIN). As an indicator of CIN, we scored anaphase bridge index (ABI) in mouse polyps and ES cells where Wnt signaling was activated by Apc or beta-catenin mutations. We found three to nine times higher ABI than in wild-type controls. Furthermore, karyotype analysis confirmed that the Wnt signal-activated ES cells produced new chromosomal aberrations at higher rates; hence CIN. Consistently, expression of dominant-negative TCFs in these cells reduced their ABI. We also found that Wnt signal activation increased phosphorylation of Cdc2 (Cdk1) that inhibited its activity, and suppressed apoptosis upon exposure of the cells to nocodazole or colcemid. The data suggest that Wnt signaling stimulates the cells to escape from mitotic arrest and apoptosis, resulting in CIN. In human gastric cancer tissues with nuclear beta-catenin, ABI was significantly higher than in those without. These results collectively indicate that beta-catenin/TCF-mediated transcription itself increases CIN through dysregulation of G2/M progression.

Adenoma↗
PubMed2006

Pattern of dietary fiber intake among the Japanese general population.

OBJECTIVES: To evaluate the dietary fiber (DF) intake pattern among the Japanese general population. DESIGN: We performed a dietary survey among the general population in northern Japan to evaluate the intake patterns. DF intake was calculated by substituting the DF content of each food in the Dietary Fiber Table for the intake of each food from this dietary survey. SUBJECTS: Five hundred and seventy-seven subjects participated in the study, 198 men and 379 women. RESULTS: In subjects with higher DF intakes the origins of the DF that were from all food groups, but with the notable exception of rice. The contribution of the seaweed group was of particular interest. From multiple regression analysis, as for food group, seaweeds showed the highest positive correlation with DF intake in both genders, followed by vegetables, pulses, fruits. On the other hand, rice showed the negative correlation with DF intake in both genders. As for life factor, body mass index showed the negative correlation with DF intake in women. CONCLUSION: Seaweed, a typical Japanese food, was most related to the increase in DF intake for the Japanese general population, whereas rice, the Japanese staple, had a small influence on decreased DF intake.

Adult↗
PubMed2006

Cytosolic overexpression of p62 sequestosome 1 in neoplastic prostate tissue.

AIMS: To investigate the expression of p62 in various prostatic tissues, and to demonstrate different immunohistochemical patterns of p62 expression in distinct pathological entities of the prostate. The p62 sequestosome 1 (SQSTM1) gene product is a multifunctional protein with ubiquitous expression in normal adult tissue. METHODS AND RESULTS: Overexpression of p62 was detected in prostate cancer cell lines and tissues by reverse transcriptase-polymerase chain reaction. Immunohistochemical staining for p62 was performed on 73 cases of paraffin-embedded prostatic tissue. p62 was negative or weakly positive only in the nucleus (pattern N) of prostatic gland epithelium in nine normal and hyperplastic prostate specimens, whilst most cancerous tissue showed intense, uniform staining for p62 in the cytoplasm (pattern C). Of the prostate cancer specimens, 91% showed positive pattern C immunoreactivity. Of the cases with high-grade prostatic intraepithelial neoplasia (PIN) around cancer, 77% showed pattern C. However, in specimens from the patients without prostate cancer PIN displayed pattern C in only 32% of cases. Western blot analysis showed that all cancer cell lines expressed p62 in the cytoplasm but there was little nuclear expression. CONCLUSION: Cytosolic overexpression of p62 is a novel immunohistochemical characteristic in prostatic adenocarcinoma and high-grade PIN, suggesting that p62 might be a novel marker for prostatic malignancy.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Mutations and nuclear accumulation of beta-catenin correlate with intestinal phenotypic expression in human gastric cancer.

AIMS: Abnormal localization of beta-catenin is frequently observed in human gastric cancers. The aim of the present study was to evaluate relationships among gastrointestinal differentiation phenotypes, beta-catenin localization and mutations of Wnt signalling genes. METHODS AND RESULTS: Seventy-seven regions in 39 gastric adenocarcinomas were classified according to beta-catenin localization and gastric and intestinal phenotypes. Cases with membranous beta-catenin localization showed a gradual decrease from gastric (G) (55% = 6/11) and gastric-and-intestinal-mixed (GI) (17% = 5/29) to intestinal (I) (0% = 0/21) phenotypes, while those with nuclear localization showed a concomitant increase: 18% (2/11), 41% (12/29), 95% (20/21) and 63% (10/16) for G, GI, I and null type (N), respectively (P < 0.001, membranous versus nuclear localization in G, GI through I). Mutations in exon 3 of the beta-catenin gene were found in G (50% = 1/2), GI (67% = 8/12), I (45% = 9/20) and N (0% = 0/10) regions with nuclear beta-catenin localization (GI versus N, P < 0.01; I versus N, P < 0.05). Adenomatous polyposis coli (APC) gene mutations were demonstrated only in GI, I and N types, irrespective of beta-catenin localization. Molecular analysis of these genes revealed 10 tumours to be heterogeneous out of 16 informative cases (62.5%). CONCLUSION: Intestinal phenotypic expression is accompanied by a shift from membranous to cytoplasmic/nuclear accumulation of beta-catenin. In contrast, N-type regions may progress along a different pathway.

Adenocarcinoma↗
PubMed2005

Recurrence rate and transplantability after liver resection in patients with hepatocellular carcinoma who initially met transplantation criteria.

To understand the recurrence rate and transplantability after liver resection (LR), which are essential factors to predict the prognosis of initial resection and salvage transplantation for hepatocellular carcinoma (HCC), we reviewed the clinical records of 279 consecutive HCC patients who met the Milan criteria and underwent LR between 1990 and 2000. Recurrence-free survival rates after 1, 2, 3, 5, and 10 years following LR were 84%, 62%, 49%, 29%, and 17%, respectively. Multivariate analysis using clinical factors such as age, sex, histological differentiation, serum levels of alpha-fetoprotein and 7S domain of type IV collagen (7S collagen), platelet counts, indocyanin green retention test after 15 minutes, and type of LR (resection of one or more segments, or less than one segment) revealed 7S collagen to be a independent factor that significantly affects recurrence-free survival. Yearly recurrence rates up to 5 years after resection ranged from 14% to 27%, averaging 20%. Concerning 169 patients who underwent tests for 7S collagen, the average yearly recurrence rate (27%) in patients with 7S collagen levels 8.0 ng/mL or higher was remarkably greater than that in the patients with levels less than 8.0 ng/mL (16%). The transplantability rate at the time of recurrence meeting the Milan criteria was roughly 60%. There were no pre-LR factors that significantly predicted transplantability. This result indicates that patients with lower 7S collagen levels are more eligible for initial LR and then salvage LT rather than primary LT.

Adult↗
PubMed2005

Sox2 expression in human stomach adenocarcinomas with gastric and gastric-and-intestinal-mixed phenotypes.

AIMS: Other than ectopic expression of intestinal transcription factors, Cdx1 and Cdx2, the molecular mechanisms underlying gastric and intestinal phenotypes of human stomach adenocarcinomas have yet to be clarified in detail. We have reported that Sox2, an HMG-box gastric transcription factor, is expressed in normal gastric mucosa and down-regulated in intestinal metaplasia. METHODS AND RESULTS: We analysed mRNA levels of Sox2 and other differentiation markers in 50 surgically resected stomach adenocarcinomas, immunohistochemically classified into gastric (G), gastric-and-intestinal (GI)-mixed, solely intestinal (I), and null (N) types. Sox2 was found to be transcribed in G and GI-mixed type adenocarcinomas in accordance with MUC5AC and MUC6 expression, while Cdx1 and Cdx2 were up-regulated in GI-mixed and I types along with the expression of MUC2 and villin. In the N type, both gastric and intestinal transcription factors were suppressed. Immunohistochemistry confirmed expression of Sox2 in MUC5AC+ lesions and Cdx2 localization together with MUC2. A stomach adenocarcinoma cell line, KATOIII, demonstrated both MUC5AC and Sox2, although MUC5AC mRNA was not detected in the Sox2+ AGS cell line. CONCLUSIONS: Sox2 may play an important role in maintaining a gastric phenotype in stomach cancers as well as in normal tissue, in cooperation with other cofactor(s).

Adenocarcinoma↗
PubMed2004

Existence of a threshold for induction of aberrant crypt foci in the rat colon with low doses of 2-amino-1-methyl-6-phenolimidazo[4,5-b]pyridine.

Until recently it has been generally considered that genotoxic carcinogens have no threshold in exerting their potential for cancer induction. However, the nonthreshold theory can be challenged with regard to assessment of cancer risk to humans. In the present study we show that a food derived, genotoxic hepatocarcinogen, 2-amino-1-methyl-6-phenolimidazo[4,5-b]pyridine (PhIP), does not induce aberrant crypt foci (ACF) as preneoplastic lesions at low dose (below 50 ppm) or 8-hydroxy-2'-deoxyguanosine (below 400 ppm) in the rat colon. Moreover PhIP-DNA adducts were not formed at the lowest dose (below 0.01 ppm). Thus, the dose required to initiate ACF is approximately 5000 times higher than that needed for adduct formation. The results imply a no-observed effect level (existence of a threshold) for colon carcinogenesis by a genotoxic carcinogen.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Inactivation of Escherichia coli by ultrasonic irradiation.

Ultrasonic inactivation of Escherichia coli XL1-Blue has been investigated by high-intensity ultrasonic waves from horn type sonicator (27.5 kHz) utilizing the "squeeze-film effect". The amplitude of the vibration face contacting the sample solution was used as an indication of the ultrasonic power intensity. The inactivation of the E. coli cells by ultrasonic irradiation shows pseudo first-order behavior. The inactivation rate constant gradually increased with increasing amplitude of the vibration face and showed rapid increase above 3 microm (p-p). In contrast, the H2O2 formation was not observed below 3 microm (p-p), indicating that the ultrasonic shock wave might be more important than indirect effect of OH radicals formed by ultrasonic cavitation in this system. The optimal thickness of the squeeze film was determined as 2 mm for the E. coli inactivation. More than 99% of E. coli cells was inactivated within 180-s sonication at the amplitude of 3 microm (p-p) and 2 mm of the thickness of the squeeze film.

Escherichia coli↗
PubMed2004

Beliefs of chronically ill Japanese patients that lead to intentional non-adherence to medication.

OBJECTIVE: To identify factors, associated with personal beliefs, involved in intentional non-adherence to prescribed medication of Japanese patients with chronic diseases. METHODS: A cross-sectional study of Japanese subjects with chronic, primarily liver, gastrointestinal, or nervous system diseases who had been prescribed oral medicines for regular use, was performed. The subjects were admitted to a university hospital and were interviewed face-to-face on admission. Intentional non-adherence was defined as experience of deliberate adjustment of self-managed prescription medicines during the few months prior to hospital admission. Patients' beliefs about taking medicines were assessed from the perspective of what the patient valued in order to take medicines without anxiety; whether the patient valued information about the medication such as its function and side-effects and/or mutual reliance on doctors. Using logistic multivariate regression analyses, factors associated with intentional non-adherence were identified. RESULTS: Among 154 subjects, 51 showed intentional non-adherence. Intentional non-adherence was associated with the following three factors: (a) the patients' beliefs with respect to taking medicines without anxiety, especially putting no value on mutual reliance on the patient-doctor relationship (P < 0.001) and putting great value on knowing the drug's side-effects (P < 0.001), (b) poor comprehension of general aspects of medication (P for trend < 0.001), and (c) being in the prime of life (40-59 years) (P = 0.011). Comprehension of the function of each medicine, experience of side-effects, anxiety about taking medicines, and the number of types of medicines taken, were not associated with non-adherence. CONCLUSIONS: Beliefs on which individual Japanese patients with chronic diseases attach value in order to take medicines without anxiety were potential factors for intentional non-adherence. This emphasizes the necessity of a patient-oriented approach to take account of patients' personal beliefs about medicines to increase adherence rate in Japan.

Administration, Oral↗
PubMed2004

Multifocal angiomyolipoma affecting the liver and lung without tuberous sclerosis.

The occurrence of angiomyolipoma (AML) in tissue other than the kidney is uncommon, as is multiple AML developing exclusively in organs other than the kidney. This report describes a case in which AML occurred multifocally in the liver and lung, but spared the kidney, and which might have been associated with tuberous sclerosis complex (TSC). A Japanese woman underwent a partial hepatectomy for a suspected malignant liver tumour at the age of 57. The tumour consisted predominantly of a trabecular arrangement of myoid cells with a sinusoidal pattern and inflammatory cell infiltration, and was diagnosed as a primary liver AML by HMB-45 immunoreactivity. Five years later, multiple nodules were found in both lungs, for which video assisted thoracic surgery was performed. The tumour showed a mixture of epithelioid cells containing HMB-45 positive material and mature lipocytes, and was subsequently diagnosed as AML. Molecular analysis of both lesions showed no allelic loss of the TSC1 and TSC2 regions. Molecular analysis of the tumours ruled out an association with TSC, and both liver and lung lesions displayed benign histological features, so that these were probably multifocal lesions of AML without TSC.

Angiomyolipoma↗
PubMed2004

A novel splice site mutation of the thiazide-sensitive NaCl cotransporter gene in a Japanese patient with Gitelman syndrome.

Gitelman syndrome (GS, MIM 263800) is an inherited disorder characterized by metabolic alkalosis with hypokalemia, hypomagnesemia, and hypocalciuria. The genetic abnormalities causing GS are known to lie in the thiazide-sensitive NaCl cotransporter (TSC), which is expressed in the distal tubule of the kidney. The TSC gene, located at chromosome 16, consists of 26 exons and encodes the protein containing 12 putative transmembrane domains with long intracellular amino and carboxy termini. Most of the abnormalities identified in GS were missense mutations, distributed throughout the TSC gene without a hot spot. A 42-year-old Japanese man was introduced for close examination of hypokalemia. In renal clearance studies using furosemide or thiazide, chloride clearance was increased after furosemide but not after thiazide administration. Furthermore, the distal fractional chloride reabsorption was dramatically decreased by furosemide but not thiazide administration, suggesting a defect in the distal tubule. We then analyzed the TSC gene to confirm the diagnosis of GS, and identified a novel G to T mutation at the acceptor splice site preceding exon 14, resulting in disruption of a conventional 3'AG consensus splice site. Abnormal splicing by this mutation is predicted to cause the formation of truncated TSC with a partial deletion of the transmembrane domain, which will loose the function of transporter. In conclusion, we have identified a unique novel splice site mutation of the TSC gene in GS. The predicted structure of this mutant TSC can conceivably cause an impairment of the transporter activity and thereby be responsible for the development of GS in our patient.

Adult↗
PubMed2003

Hypoglycaemia in patients with liver diseases administered levothyroxine.

OBJECTIVE: Experience of a few hypoglycaemic patients with liver disease and receiving levothyroxine suggested to us that the prevalence of hypoglycaemia might be higher in such patients. The purpose of this study was to ascertain whether the prevalence of hypoglycaemia this was actually the case. METHODS: This study was a retrospective, cross-sectional analysis of a medical computerized database and/or written reports from our university hospital. Patients with primary liver disease who were admitted to our hospital between April 1998 and August 2000 were divided into two groups; the first group received levothyroxine and the second group did not. The patients in the second group were selected from three different time periods within the period shown. The prevalence of hypoglycaemia (blood glucose level <70 mg/dL) was compared between the two groups. RESULTS: The prevalence of hypoglycaemia was significantly higher in the group receiving levothyroxine compared with the group not receiving levothyroxine (four of eight patients (50.0%) vs. three of 59 (5.1%), P = 0.003, Fisher's exact test). CONCLUSIONS: The results suggest that levothyroxine may be a risk factor for hypoglycaemia in patients with liver disease. While a larger study, perhaps with an alternative study design is needed to confirm this, and to investigate possible mechanisms of effect, it would be prudent to monitor the blood glucose level of such patients closely.

Aged↗
PubMed2003

Effect of parathyroidectomy on bone mineral density in hemodialysis patients with secondary hyperparathyroidism: possible usefulness of preoperative determination of parathyroid hormone level for prediction of bone regain.

PURPOSE: To examine longitudinal changes of bone mineral density (BMD) after parathyroidectomy (PTx) in patients undergoing maintenance hemodialysis (HD) with severe secondary hyperparathyroidism (HPT) to determine which factor contributes most to bone changes. METHODS: Fifteen Japanese HD patients who had been refractory to medical therapy were subject to PTx with autotransplantation. We measured BMD by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L2 - 4 BMD) and the distal 1/3 region of the radius (1/3R BMD) at 1, 3, 6, 12, 24, and 36 months after PTx. RESULTS: Baseline Z-score of BMD was markedly low at 1/3R (- 3.07) and slightly low at L2 - 4 (-0.59) in this group. A significant increase in L2 - 4 BMD was observed as early as one month after PTx, which was sustained afterwards. Annual percent changes in L2 - 4 and 1/3R BMD were + 15.6 % and + 6.4 %, respectively. The annual percent changes in BMD at both sites were positively associated with preoperative intact PTH levels (L2 - 4; r = 0.642, p = 0.010, 1/3R; r = 0.884, p < 0.001) and total alkaline phosphatase (ALP) levels (L2 - 4; r = 0.663, p = 0.007, 1/3R; r = 0.858, p < 0.001). Stepwise multiple regression analysis revealed that serum levels of intact PTH and ALP were the best predictors of both percentage and net changes in radial BMD with high determination coefficients (r 2 > 0.8). CONCLUSION: Successful PTx following appropriate supplementation with vitamin D and calcium provides a marked increase in lumbar BMD and a modest increase in radial BMD in HD patients with secondary HPT. Preoperative levels of PTH and ALP are useful for predicting postoperative changes in bone mass.

Absorptiometry, Photon↗
PubMed2003

Limbic encephalitis presenting with topographical disorientation and amnesia.

A case of paraneoplastic limbic encephalitis presenting with topographical disorientation is reported. A 70 year old woman became unable to identify familiar buildings and landscapes and could not recall the way to destinations she had known very well for years. She also showed attentional disturbance and severe anterograde amnesia. Her retrograde amnesia extended for one year at most. No other neuropsychological deficits were noted. Thus her topographical disorientation was of the primary form. Specific tests related to topographical disorientation showed that her two main symptoms seem to fall into the categories of landscape agnosia and heading disorientation. T2 weighted magnetic resonance imaging revealed high intensity signals in the anteromedial temporal lobes bilaterally, in the right posterior parahippocampal gyrus, in the right retrosplenial region, and in the right inferior precuneus. Anti-Hu antibody was found in the serum. This case shows that topographical disorientation can be a primary symptom of limbic encephalitis.

Aged↗