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Biomedical subjects

T Tsukamoto

Publications and source records attributed to T Tsukamoto.

At least 91 records · Page 5Linked to original sources
PubMed2000

Nuclear receptor binding factor-2 (NRBF-2), a possible gene activator protein interacting with nuclear hormone receptors.

A protein named nuclear receptor binding factor-2 (NRBF-2) was identified by yeast two-hybrid screening, as an interaction partner of peroxisome proliferator-activated receptor alpha as well as several other nuclear receptors. NRBF-2 exhibited a gene activation function, when tethered to a heterologous DNA binding domain, in both mammalian cells and yeast.

Amino Acid Sequence↗
PubMed2000

Summation of initiation activities of low doses of the non-hepatocarcinogen 1,2-dimethylhydrazine in the liver after carbon tetrachloride administration.

Summation of initiation by low doses of the indirect-acting non-hepatocarcinogen, 1,2-dimethylhydrazine (DMH) after proliferative stimulation with a necrogenic dose of carbon tetrachloride (CCl4) was investigated in terms of the induction of glutathione S-transferase placental form (GST-P) positive liver cell foci. Cell kinetics of liver after CCl4 i.g. treatment were examined with bromodeoxyuridine (BrdU) labeling (experiment I). To assess the correlation between cell proliferation and induction of liver cell foci, DMH (10 mg/kg i.g.) was administrated to 7-week-old male F344 rats at 12, 24, 36, 48, 60, 96 h after CCl4 i.g. and initiated populations expanded using the resistant hepatocyte model (experiment IIA). Subsequently, effects of repeated administration (10 mg/kg, four times, i.g.) of DMH were compared with the results of a single administration (40 mg/ kg, i.g.) with the same total dose (experiment IIB). In experiments I and IIA, the numbers and areas of GST-P-positive foci increased with the BrdU labeling index at the time of DMH treatment (maximum after 60 h). In experiment HB, repeated exposure of DMH at 10 mg/kg, four times resulted in significant (P<0.05) increase in number and area of GST-P-positive foci compared with the single administration (40 mg/kg). Thus, multiple low dose treatments during cell proliferation might be most effective for detection of weak initiation activity.

1,2-Dimethylhydrazine↗
PubMed2000

Treatment of erectile dysfunction: what should we do next?

Because sildenafil (Viagra) is scheduled to be clinically available in the near future, urologists in Japan must prepare for changes in the treatment of erectile dysfunction. The drug will surely influence our current clinical style of diagnosis and treatment of the dysfunction. We herein discuss this issue, referring to favorable and unfavorable effects that will be brought about by the drug. We also propose several future studies that we should do, including those on testosterone replacement therapy. We present results of our experiment using testosterone replacement therapy in aged rats and speculate about the mechanism by which the hormone replacement works in the sex center of the brain.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Risk factors for recurrence after resection of hepatitis C virus-related hepatocellular carcinoma.

Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (> 65 years old), HCV viremia, elevated AST (> 40 IU/L) and ALT (> 45 IU/L), large tumors (> 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of malignancy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence.

Aged↗
PubMed2000

Detection of antimicrobial-treated Chlamydia trachomatis with Amplicor PCR test kit.

A polymerase chain reaction (PCR) method for the detection of Chlamydia trachomatis has been developed and is now available in the clinical setting. However, one of the major problems with this method is possible false-positive detection posttreatment. Nonviable C. trachomatis was established by in-vitro exposure to an antimicrobial agent, and we tried to detect the nonviable cells (NVCs) of C. trachomatis by PCR with variant primer sets. C. trachomatis strains (D/UW-3/Cx) were cultured in a medium containing the antimicrobial agent, at 8 x MIC (minimal inhibitory concentration) 15 to 20 h postinfection. Amplicor and two sets of PCR primers were used to detect the DNA of NVCs. Serial passages of NVCs were done five times. All samples were positive on Amplicor, and all except the fourth passage were positive for the two sets of primers. Although the PCR test appears to be valuable, NVCs may possibly be detected by this method, and this may be clinically responsible for the false detection of C. trachomatis after appropriate antimicrobial chemotherapy.

Anti-Bacterial Agents↗
PubMed2000

Limitations of urinary telomerase activity measurement in urothelial cancer.

The reported frequency of detectable telomerase activity in spontaneously voided urine samples from patients with urothelial cancer varied from 0 to 85%. We examined stasis in the bladder and specimen storage as interfering conditions in this assay. Telomerase activity in exfoliated cells was measured by a polymerase-chain-reaction-based assay in spontaneously voided urine from urothelial cancer patients. Effects of retention in the bladder and specimen storage from voiding to measurement of telomerase activity were modeled by suspending 10(6) cells from the cancer-derived T24 line in normal urine (pH 6.5) at 37 degrees C and 25 degrees C, respectively. Hematuria was modeled by adding hemoglobin. In T24 cells suspended in urine at 37 degrees C, telomerase activity had decreased to approximately 20% of preincubation activity after 1 h, and had disappeared after 3 h. In urine at 25 degrees C, telomerase activity in T24 cells had decreased to approximately 40% of preincubation activity at 1 h and to <10% at 6 h. When we examined telomerase activity in exfoliated cells in spontaneously voided urine from urothelial cancer patients (excluding first-voided morning specimens), telomerase activity was detected in only 21% of samples (four of 19) despite measurement with 1 h of voiding and steps to avoid hemoglobin interference. Measurement of telomerase activity in spontaneously voided urine is insufficiently sensitive and reliable for the diagnosis of urothelial cancer.

Carcinoma, Transitional Cell↗
PubMed2000

Subclinical Cushing syndrome due to adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia: changes in plasma cortisol levels during long-term follow-up.

A 63-year-old man with bilateral adrenal tumors was treated for hypertension and diabetes mellitus. Endocrinologic examination during follow-up revealed the production of cortisol to be independent of the regulation of the hypothalamo-pituitary-adrenal axis. Therefore, he was diagnosed as having subclinical Cushing syndrome, and these tumors were removed. Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia (AIMAH) was endocrinologically and histopathologically diagnosed. This is the first report demonstrating that endocrinologic changes of AIMAH can be observed during long-term follow-up.

Adrenal Gland Neoplasms↗
PubMed2000

Risk factors for the development of bladder cancer after upper tract urothelial cancer.

OBJECTIVES: To determine the clinical and pathologic risk factors for initial intravesical recurrence in patients with primary renal pelvic and/or ureteral cancer and to examine the progression in the bladder in patients having high risk factors for intravesical recurrence. METHODS: This study included 69 patients with renal pelvic and/or ureteral cancer. We excluded patients with distant metastases, those with a short period of follow-up, and those having a previous history or concomitance of bladder cancer. The exclusion criteria were chosen to avoid contamination by patients with a poor prognosis who might die of the primary cancer before bladder cancer development. Multivariate analysis by Cox's proportional hazards model was used to determine what clinical and pathologic variables significantly affected the initial intravesical recurrence of cancer. We also studied the stage progression of cancer that recurred in the bladder. RESULTS: Initial intravesical recurrence of the cancer was found in 22 patients during a median follow-up period of 53 months (range 12 to 225). The intravesical disease-free rate after upper tract urothelial cancer was 65% (rate of disease recurrence in bladder 35%) at 5 years by the Kaplan-Meier method. The extent (multifocality) of the upper urinary cancer (P = 0.0038) and pathologic stage (P = 0.0409) independently influenced intravesical recurrence. Age, sex, adjuvant chemotherapy, configuration of the primary tumor, primary cancer size, and pathologic grade did not affect recurrence. The rate of stage progression also was not influenced by the extent of the disease in the upper urinary tract. CONCLUSIONS: The extent and pathologic stage of cancer in the upper urinary tract were significant and independent factors for initial intravesical recurrence of cancer. However, no difference was found in clinical outcome in terms of stage progression between patients having high risk factors for intravesical recurrence and those without them.

Adolescent↗
PubMed2000

Restoration of biochemical function of the peroxisome in the temperature-sensitive mild forms of peroxisome biogenesis disorder in humans.

We have found that peroxisome assembly is temperature-sensitive (ts) in mild forms of peroxisome biogenesis disorders (PBDs), that is all infantile Refsum disease (IRD) patients and a few neonatal adrenoleukodystrophy patients of several complementation groups. The number of peroxisomes increased daily in incubation at 30 degrees C in the ts cells. Oxidation of very long-chain fatty acids, processing of acyl-CoA oxidase and dihydroxyacetonephosphate acyltransferase activity also improved after 8 days incubation at 30 degrees C in the IRD fibroblasts. These biochemical functions of the peroxisome did not change at 30 degrees C in Zellweger fibroblasts. Number of peroxisomes gradually decreased after 4 days when the temperature shifted from 30 to 37 degrees C in the ts cells. These results indicate that the biochemical functions of peroxisome are also restored by incubation at 30 degrees C in the mild and ts phenotype of PBDs, and the results will aid to predict the severity and the prognosis of affected children.

Animals↗
PubMed2000

The development of (99m)Tc-analog of Cu-DTS as an agent for imaging hypoxia.

Works on dithiosemicarbazone (DTS) derivatives radiolabeled with divalent Cu (Cu-62, Cu-64) indicate its potentiality as an ischemic tissue detecting agent. Development of analogous derivatives labeled with the more accessible technetium-99m (Tc) is most desirable. Various synthesized DTS derivatives are radiolabeled with a novel approach, using a macromolecular Sn(II)-complex under an anaerobic condition at pH 3.4-4.5 and stabilization by ascorbate solution at pH 6.7-7.0. Characterization of Tc-DTS derivatives done by various analytical methods (TLC, HPLC, EP, PC) and by in vivo studies in normal mice and in rats myocardial LAD (left anterior descent coronary artery) occlusion model. Among tested DTS, only Tc-ATSE, Tc-ATSM and Tc-ATSM(2) showed distinctive characteristics, with the latter presenting high myocardium uptake in regions of ischemia in LAD rat myocardium model. Potentiality of the Cu-DTS mimetic agent, Tc-ATSM(2) as an ischemia-damaged myocardium agent is discussed.

Animals↗
PubMed2000

Detection and characterization of Shiga toxin-producing Escherichia coli from seagulls.

Shiga toxin (Stx)-producing Escherichia coli (STEC) strains isolated from a seagull in Japan were examined. A total of 50 faecal samples was collected on a harbour bank in Hokkaido, Japan, in July 1998. Two different STEC strains, whose serotypes were O136:H16 and O153:H-, were isolated from the same individual by PCR screening; both of them were confirmed by ELISA and Vero cell cytotoxicity assay to be producing active Stx2 and Stx1, respectively. They harboured large plasmids, but did not carry the haemolysin or eaeA genes of STEC O157:H7. Based on their plasmid profiles, antibiotic resistance patterns, pulsed-field gel electrophoresis analysis (PFGE), and the stx genes sequences, the isolates were different. Phylogenic analysis of the deduced Stx amino acid sequences demonstrated that the Stx toxins of seagull-origin STEC were closely associated with those of the human-origin, but not those of other animal-origin STEC. In addition, Stx2phi-K7 phage purified from O136 STEC resembled Stx2phi-II from human-origin O157:H7, and was able to convert non-toxigenic E. coli to STEC. These results suggest that birds may be one of the important carriers in terms of the distribution of STEC.

Animals↗
PubMed2000

Visualization of gene activity in living cells.

Chromatin structure is thought to play a critical role in gene expression. Using the lac operator/repressor system and two colour variants of green fluorescent protein (GFP), we developed a system to visualize a gene and its protein product directly in living cells, allowing us to examine the spatial organization and timing of gene expression in vivo. Dynamic morphological changes in chromatin structure, from a condensed to an open structure, were observed upon gene activation, and targeting of the gene product, cyan fluorescent protein (CFP) reporter to peroxisomes was visualized directly in living cells. We found that the integrated gene locus was surrounded by a promyelocytic leukaemia (PML) nuclear body. The association was transcription independent but was dependent upon the direct in vivo binding of specific proteins (EYFP/lac repressor, tetracycline receptor/VP16 transactivator) to the locus. The ability to visualize gene expression directly in living cells provides a powerful system with which to study the dynamics of nuclear events such as transcription, RNA processing and DNA repair.

Animals↗
PubMed2000

A case of neuroleptic malignant syndrome in a patient with hemodialysis.

A 63-year-old man with chronic renal failure who had received hemodialysis three times per week for 4 years developed neuroleptic malignant syndrome 10 days after taking amoxapine. His condition was characterized by muscle rigidity, elevation of body temperature and altered consciousness. Although he was treated with dantrolen and supportive care as well as discontinuation of amoxapine, his condition rapidly deteriorated, resulting in death. Because the pharmacokinetics of drugs, especially those such as antidepressants, in patients with chronic renal failure has not been fully clarified, one should be careful about giving such patients these drugs.

Amoxapine↗
PubMed2000

Hypercalcemia in a patient with renal cell carcinoma producing parathyroid hormone-related protein and interleukin-6.

A patient with renal cell carcinoma who developed humoral hypercalcemia of malignancy is reported. A 52-year-old male patient was diagnosed with renal cell carcinoma and multiple lung metastases. A cell line isolated from the surgical specimen exhibited continuous production of parathyroid hormone-related protein (PTHrP) in vitro. The production of PTHrP from the cancer cells was confirmed by RT-PCR and immunoradiometric assay. The serum calcium level was not enhanced, whereas the lung lesion was developing and producing interleukin-6, a possible modulator of osteoclastic resorption. Hypercalcemia was induced when the PTHrP concentration increased up to 3.3 pmol/L.

Carcinoma, Renal Cell↗
PubMed2000

Anatomical segmentectomy of the head of the pancreas along the embryological fusion plane: a feasible procedure?

BACKGROUND: Less extensive resection of the head of the pancreas has been the procedure of choice recently for low-grade malignant neoplasms. The anatomical detail of the head of the pancreas is currently insufficient for segmental resection along the embryological fusion plane. METHODS: The anatomy of the head of the pancreas was analyzed in 31 consecutive autopsy specimens. An anterior (n = 10) or posterior (n = 10) segmentectomy of the head of each pancreas was performed along the macroscopically found fusion plane. The pancreatic arteries, the portal vein, the bile duct, and the pancreatic duct were visualized by injecting 3 silicon dyes of different colors. Another 11 specimens were examined by pancreatography before and after anterior (n = 5) or posterior (n = 6) segmentectomy. Eight of these 11 specimens were stained immunohistochemically to reveal the distribution of pancreatic polypeptide cells after segmentectomy. RESULTS: The cleavage between the anterior and posterior segments was discovered at the anterior inferior edge or at the posterior superior edge of the head of the pancreas. Anterior segmentectomy was accomplished while preserving the anterior and posterior pancreaticoduodenal arcades and the lower bile duct in the posterior segment. Posterior segmentectomy involved the removal of the lower bile duct and the posterior pancreaticoduodenal arcades. Pancreatography after segmentectomy showed the division of the ducts of Wirsung and Santorini with the peripheral branches. The immunohistochemical boundary of pancreatic polypeptide cells coincided with the surgical plane. These results showed the anterior and posterior segments were originated from the embryologically dorsal and ventral primordia, respectively. CONCLUSIONS: The current anterior or posterior segmentectomy of the head of the pancreas corresponded to the resection of the embryologically dorsal or ventral primordium, respectively. Anterior segmentectomy of the head of the pancreas might be a clinically applicable procedure; however, posterior segmentectomy involving the resection of the lower bile duct may be impractical.

Adult↗
PubMed2000

p53 knockout mice (-/-) are more susceptible than (+/-) or (+/+) mice to N-methyl-N-nitrosourea stomach carcinogenesis.

Mutations of the p53 tumor suppressor gene constitute one of the most frequent molecular changes in a wide variety of human cancers. Mice deficient in p53 have recently attracted attention for their potential to identify chemical genotoxins. In this study we have investigated the susceptibility of p53 nullizygote (-/-), heterozygote (+/-) and wild-type (+/+) mice to N:-methyl-N:-nitrosourea (MNU) gastric carcinogenesis. p53 knockout mice were treated with 30 p.p.m. MNU in the drinking water 1 week on and 1 week off and killed after 5 weeks. The numbers of pepsinogen-altered pyloric glands (PAPG), putative preneoplastic lesions, were 1.8, 1.7 and 22.6 in p53 (+/+), (+/-) and (-/-) mice, respectively. In a 15 week experiment, adenomas were found in 0 of 19 (+/+) (0%), 2 of 21 (+/-) (9.5%) and 6 of 10 (-/-) (60.0%) animals. Also, one well-differentiated adenocarcinoma was observed in a p53 (-/-) mouse. After 40 weeks treatment with 120 or 30 p.p.m. MNU there was no significant difference in the incidence of gastric tumors between p53 (+/+) and (+/-) mice. However, mortality from carcinogen-induced lymphomas, leukemias and sarcomas was very much greater in the latter group. Homozygous knockout animals could not be maintained long term. PCR-single strand conformation polymorphism analysis of exons 5-8 of the p53 gene of DNA extracts from 68 gastric tumors consisting of 16 and 20 30 p.p.m. MNU-treated p53 (+/+) and (+/-) mice and 14 and 18 120 p.p.m. MNU-treated p53 (+/+) and (+/-) mice demonstrated no mutations. These results suggest that p53 may not be a direct target of MNU but rather play an important role as a gatekeeper in mouse stomach carcinogenesis induced by this direct acting agent.

Animals↗
PubMed2000

Isolation of differentiated squamous and undifferentiated spindle carcinoma cell lines with differing metastatic potential from a 4-nitroquinoline N-Oxide-induced tongue carcinoma in a F344 rat.

One differentiated squamous cell carcinoma (SCC) cell line (RSC3-E2) and two undifferentiated tumor cell lines (RSC3-LM and RSC3-E2R) with different metastatic potential were established from a 4-nitroquinoline N-oxide (4NQO)-induced differentiated SCC in F344 rat tongue. The RSC3-E2 subline was isolated from a parental cell line (RSC3-P) by single cell cloning in vitro, whereas the RSC3-LM subline was isolated from a lung metastatic focus after subcutaneous (s.c.) injection of RSC3-P cells. The RSC3-E2R cell line was isolated from a lung metastatic focus following s.c. injection of RSC3-E2 cells after X-irradiation in vitro. The RSC3-E2 cell line is keratin-positive and grows as a keratinizing tumor in nude mice, whereas RSC3-LM and RSC3-E2R cells are keratin-negative, vimentin-positive and form undifferentiated tumors. When s.c. injected into nude mice, the RSC3-E2 cell line proved to be non-metastatic, while the RSC3-LM cell line was metastatic by both hematogenous and lymphogenous routes, and the RSC3-E2R cell line was metastatic only hematogenously. In vitro relative growth rates and in vitro invasion activity of these cell lines were in the order RSC3-LM > RSC3-E2R > RSC3-E2. Chromosome analysis revealed two peaks with modal chromosome numbers of 83 and 78 for RSC3-P cells and single peaks at 83, 78 and 56 for RSC3-LM, RSC3-E2 and RSC3-E2R cell lines, respectively. Common structural abnormalities on chromosome 11 were shared by all cell lines. Mutation analysis of the p53 gene using a yeast functional assay demonstrated RSC3-LM cell line to have a point mutation at codon 269, whereas RSC3-E2 and RSC3-E2R had double mutations at codons 106 and 170 on each allele. These results suggest that the two undifferentiated RSC3-LM and RSC3-E2R tumor cell lines with different metastatic potential were generated from differentiated SCC cells via different genetic pathways as a consequence of tumor progression in vivo and in vitro, respectively. These cell lines should provide a useful model for understanding mechanisms of hematogenous and lymphogenous metastasis, as well as tumor progression of oral SCCs.

4-Nitroquinoline-1-oxide↗