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Biomedical subjects

S Tsuchiya

Publications and source records attributed to S Tsuchiya.

At least 55 records · Page 3Linked to original sources

Induction of apoptosis in WEHI 231 cells by cationic liposomes.

PURPOSE: Liposomes are of considerable interest as drug carriers and immunoadjuvants. However, few investigators have studied the changes exerted by liposomes in the cells with which they interact. The purpose of this study was to investigate whether liposomes induce apoptosis in B cells. METHODS: The mouse immature B cell line WEHI 231 cells and mouse splenic B cells were treated with liposomes, and the induction of apoptosis was evaluated by monitoring changes in DNA content, DNA fragmentation and chromatin condensation by flow cytometry, agarose gel electrophoresis and by morphological investigation. RESULTS: Cationic liposomes induced apoptosis in WEHI 231 cells, but neutral and anionic liposomes did not. A contact time of 30 min between WEHI 231 cells and cationic liposomes was sufficient to induce apoptosis, and 80% of the cells showed hypodiploid DNA content. Apoptosis induced by cationic liposomes composed of stearylamine was inhibited by addition of the oxidant scavenger, N-acetyl-cysteine. CONCLUSIONS: Cationic liposomes induced apoptosis in WEHI 231 cells, and the production of reactive oxygen species is important in the regulation of apoptosis induced by cationic liposomes. It is well known that cationic liposomes show cytotoxicity, and apoptosis may be one of the causes of this toxicity.

Animals↗

Association of Trp64Arg polymorphism of the beta3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity.

OBJECTIVE: To investigate whether Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) gene and Gln223Arg polymorphism of the leptin receptor (Ob-R) gene are associated with obesity in Japanese schoolchildren. DESIGN: Population study of participants from a rural town located within 50 km northeast of Tokyo based on school medical examinations. SUBJECTS: 553 Japanese schoolchildren (291 boys and 262 girls) who were 9-15 y old with a mean age of 11.9 +/- 1.8 y. MEASUREMENTS: DNA was extracted from whole blood and genotyped by PCR-RFLP. Height, weight and blood pressure were measured in school medical examinations. Total cholesterol, triglyceride and HDL-cholesterol concentrations were measured by an autoanalyzer. Obesity index, body mass index (BMI) and LDL-cholesterol concentration were calculated by the respective formulae. RESULTS: In Trp64Arg polymorphism of the beta3-AR gene, the number of obese subjects with Trp/Arg or Arg/Arg genotypes was significantly higher than that of the non-obese subjects (chi2=5.79, P=0.02). The obesity index of subjects with the Arg/Arg or Arg/Trp genotype was significantly higher than that of those with the Trp/Trp genotype (8.2 +/- 18.7% vs 4.5 +/- 15.8%, P=0.04). Moreover, after adjustments for age and gender, BMI of subjects with the Trp/Arg or Arg/Arg genotype was significantly higher than that of those with the Trp/Trp genotype (19.4 +/- 3.6 kg/m2 vs 18.9 +/- 3.2 kg/m2, P= 0.02). However, no significant differences were observed in the clinical characteristics among the genotype groups of the Ob-R gene. CONCLUSIONS: Trp64Arg polymorphism of the beta3-AR gene appears to be a genetic risk factor for obesity in Japanese children, but Gln223Arg polymorphism of the Ob-R gene does not appear to be associated with obesity.

Adolescent↗

Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion.

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya's criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P = 0.001). There was no correlation between the ACD-present group and the ACD-absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c-erbB2; Ki-67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin-embedded tissue of a ACD case at 3 microm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using alpha-smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD-present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P = 0.001). All 44 ACD lesions had no staining of c-erbB2, regardless of staining in malignant lesions. The mean Ki-67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.

Adult↗

Cerebral blood volume and oxygenation among poststroke hemiplegic patients: effects of 13 rehabilitation tasks measured by near-infrared spectroscopy.

OBJECTIVE: To measure with near-infrared spectroscopy (NIRS) the changes in cerebral hemodynamics and oxygenation in the prefrontal cortex of poststroke patients with hemiplegia performing several rehabilitation tasks and to analyze the different effects of the tasks. DESIGN: Case series pilot study. SETTING: Hospitals and facilities near Tsukuba, Japan. PARTICIPANTS: Twenty-four healthy volunteers and 44 patients with hemiplegia. INTERVENTIONS: For healthy volunteers, conventional rehabilitation tasks of head-up tilt (HUT), calculation, and ergometer. For patients with hemiplegia, these 3 tasks plus reading aloud, listening to music, reciprocal extension, nonparalyzed extension, passive range of motion, pulley, bridge, facilitation, stand-up, and gait. MAIN OUTCOME MEASURES: Changes in cerebral blood volume (CBV) and cerebral oxygen volume (COV) in the prefrontal region sensed by a noninvasive NIRS device placed midforehead in healthy volunteers or on the impaired side in patients with hemiplegia. Computer analysis of the quality and quantity of the CBV and COV change patterns. RESULTS: In healthy subjects, the change patterns of the 3 tasks were clearly different: decrease in COV with HUT, limited increase in CBV and COV with calculation tasks, and gradual increase in CBV and COV with ergometer tasks. In patients with hemiplegia, significant (positive) CBV changes were observed in ergometer, facilitation, stand-up, and gait and significant (negative) changes with Romover. Significant (positive) COV changes were observed in ergometer and facilitation and (negative) in HUT. CONCLUSIONS: NIRS is useful for monitoring the change in regional hemodynamics and oxygenation in rehabilitation; some tasks commonly used in rehabilitation, such as ergometer and facilitation, increase both CBV and COV in the affected prefrontal cortex of patients with hemiplegia.

Adult↗

Peroral pancreatoscopy in the diagnosis of mucin-producing tumors of the pancreas.

BACKGROUND: Mucin-producing tumor of the pancreas is an increasingly recognized clinical entity. However, the differentiation of benign from malignant mucin-producing tumors of the pancreas is challenging. Peroral pancreatoscopy as recently developed may have potential for the diagnosis of mucin-producing tumors of the pancreas. METHODS: The subjects were 41 patients with clinically diagnosed mucin-producing tumors of the pancreas, 40 of whom underwent surgical resection. Autopsy findings were available in another patient with unresectable disease. Histologically, hyperplasia was identified in 3 patients, mildly atypical adenoma in 11, severely atypical adenoma in 16, and adenocarcinoma in 11. Peroral pancreatoscopy was performed before surgery or pathologic examination. The findings were retrospectively evaluated and compared with the histopathologic diagnosis. RESULTS: Pancreatoscopic observation was successful in 30 patients (73.2%). Elevated lesions were identified in 22 (73.3%). Villous or vegetative elevations and red color markings were frequently found in severely atypical adenoma or adenocarcinoma. Tumor location (main or branch duct type) did not correlate with survival after resection. Partial resection was performed in 7 of 30 patients with nonmalignant tumors and resulted in favorable outcomes. CONCLUSION: Peroral pancreatoscopy can be used to differentiate benign mucin-producing tumors of the pancreas (hyperplasia and mildly atypical adenoma) from the more dysplastic lesions (severely atypical adenoma and adenocarcinoma) and may provide useful information for determining the type of surgery to be performed.

Adenocarcinoma↗

A phase II study of combined chemoradiotherapy for limited disease-small-cell lung cancer.

A study to evaluate the efficacy of cisplatin, doxorubicin, and etoposide chemotherapy with combined radiotherapy was undertaken in 26 patients with limited disease-small-cell lung cancer. Patients were treated with cisplatin (80 mg/m2) intravenously (i.v.) on day 1, doxorubicin (30 mg/m2) i.v. on day 1, and etoposide (80 mg/m2) i.v. on days 1, 3, and 5, every 4 weeks for four cycles. Thoracic irradiation of 40 Gy in 20 fractions was delivered during 4 weeks to the primary site starting on day 8 of the second cycle of chemotherapy. The objective response rate was 100%. A complete response was observed in 10 patients (38%). The median survival time was 23 months, and the 3-year survival rate was 42%. Seven patients (27%) continued to survive at least 8 years and remain free from disease. Grade III/IV leukopenia was observed in 25 patients (96%). Grade III/IV thrombocytopenia developed in 19 patients (73%). Grade III/IV esophagitis was not seen. Interstitial pneumonitis occurred in two patients. This regimen is effective and has acceptable toxicity for use in the treatment of limited disease-small-cell lung cancer.

Aged↗

Three new regions on chromosome 17p13.3 distal to p53 with possible tumor suppressor gene involvement in lung cancer.

We investigated loss of heterozygosity (LOH) at the distal portion of the p53 gene on the short arm of chromosome 17 in lung cancers in order to search for new tumor suppressor genes. The roles of the putative genes were also studied in terms of pathological features. One hundred and forty-five resected non-small cell lung cancers were examined for LOH using 11 markers mapped on, and distal to the p53 locus, and deletion maps were constructed. Four commonly deleted regions were found: one from TP53 to ENO3, where the p53 gene resides, and three others from ENO3 to D17S1566, D17S379 to D17S1574 and distal to ABR, with LOH frequencies almost the same as, or higher than, at the TP53 locus. Examination of the relationship between LOH of the latter three regions and histopathological parameters of adenocarcinomas (genetically negative for p53 mutation) revealed allelic losses on D17S379 to be associated with advanced lesions, while D17S513 was more frequently deleted in poorly differentiated tumors. These results indicate that new tumor suppressor gene(s) may reside on these three distinctly deleted regions on chromosome 17p13.3 distal to the p53 gene in lung cancer, with possible roles in progression and differentiation of adenocarcinomas.

Adenocarcinoma↗

Early biosynthetic pathway to abscisic acid in Cercospora cruenta.

A new biosynthetic intermediate of ABA, (2Z,4E)-gamma-ionylideneacetaldehyde, was isolated from young mycelia of Cercospora cruenta. Under an (18)O2 atmosphere, an oxygen atom of this endogenous aldehyde was exclusively labeled. Similarly, three (18)O atoms were incorporated into the ABA molecule recovered after prolonged incubation; selectively labeled were one of the carboxyl oxygen atoms and the two on the ring portion of ABA. A feeding experiment with [1-(13)C]glucose proved the exclusive operation of the mevalonate pathway for the formation of both ABA and beta-carotene. These results suggest that (2Z,4E)-gamma-ionylideneacetaldehyde can be a key ABA biosynthetic intermediate formed by the oxidative cleavage of a carotenoid precursor.

Abscisic Acid↗

Metabolism of chiral ionylideneacetic acids on the abscisic acid biosynthetic pathway in Cercospora.

A Chiralcel OJ column was used to determine the absolute configuration of naturally occurring alpha-ionylideneacetic acid from Cercospora rosicola and gamma-ionylideneacetic acid from C. cruenta as (R) enantiomers in accordance with their biosynthetic product, (S)-ABA. Both enantiomers of [1, 2-(13)C2]-alpha and gamma-ionylideneacetic acids were prepared and fed to C. rosicola and C. cruenta. Six combinations of feeding experiments comparatively and unequivocally demonstrated stereoselectivity in the biosynthetic conversions, including stepwise hydroxylation at C-1' and 4'. Enzymatic isomerization from the gamma to alpha-intermediate was suggested not to be involved in ABA biosynthesis in C. rosicola.

Abscisic Acid↗

Chromogranin A expression in hepatocellular carcinoma in a patient with germline MEN1 gene mutation.

Hepatocellular carcinoma (HCC) was found in a patient with multiple endocrine neoplasia type 1 (MEN 1). The intriguing finding was that the HCC in the patient was positively stained for chromogranin A (CgA), a cellular marker for endocrine and neuroendocrine tumors. The patient had a pancreas endocrine tumor and type C hepatitis, that made pathological diagnosis of the origin of the tumor complicated.

Carcinoma, Hepatocellular↗

Direct infusion of ascites into the blood circuit during hemodiafiltration in uremic patients with cirrhosis.

Two chronic dialysis patients with massive ascites caused by cirrhosis were treated by infusion of their ascites directly into the blood circuit. This stabilized their hemodynamics during dialysis, facilitating the control of weight gain and ascites, and thus markedly improving their general condition. Long-term use of this therapy was able to prevent the accumulation of ascitic fluid. Interestingly, fever occurred when this therapy was performed with hemodialysis, but not with hemofiltration or hemodiafiltration, suggesting that a pyrogen in the ascites was removed by filtration.

Aged↗

Necessity of correcting cancer antigen 125 appearance rates by body surface area.

Attention has been focused on cancer antigen 125 (CA125) levels in dialysate as an index for evaluating the severity of peritoneal mesothelial cell impairment. However, the method of evaluating CA125 levels in the dialysate has not been standardized. We determined that CA125 levels in the dialysate should be corrected by body surface area (BSA). Using 51 patients who had been undergoing peritoneal dialysis (PD), CA125 levels in the dialysate were measured to evaluate the appearance rate of CA125 (CA125AR). Because only 18 of the 51 patients (35%) had a BSA greater than 1.73 m2, CA125 levels in the dialysate might be underestimated in other patients when absolute values of CA125 are not corrected by BSA. When correlations between corrected CA125AR and various parameters were evaluated, corrected CA125AR positively correlated with age, but negatively correlated with serum creatinine and albumin levels. Moreover, no positive correlation was seen between corrected CA125AR and the duration of PD or the peritoneal permeability test. However, in 5 patients with ultrafiltration loss after prolonged PD, the values of CA125AR persistently or rapidly decreased before transfer to hemodialysis. Although CA125 can be used as an index of peritoneal deterioration, the absolute value of CA125 should be corrected by BSA. However, it is most important to evaluate changes in CA125 in individual patients.

Adult↗

Surgical treatment for sclerosing encapsulating peritonitis.

Sclerosing encapsulating peritonitis (SEP) is recognized as a serious complication of continuous ambulatory peritoneal dialysis (CAPD). To date, in our hospital, 12 cases of SEP have been successfully treated by active intervention. The development of SEP was observed in these patients after removal of a peritoneal catheter. SEP was relieved by steroid administration in 3 of these patients, and by total parenteral nutrition (TPN) performed after exploratory laparotomy in 1 patient. In the remaining 8 patients, SEP was relieved by total intestinal enterolysis. In patients who underwent total intestinal enterolysis, the severity of encapsulation and adhesion varied. White, rigid encapsulation was observed in 4 patients who had been treated by peritoneal dialysis (PD) for less than 10 years. Seemingly normal serosae were observed under the capsules, and total intestinal enterolysis was easily performed in these patients. In the patient who underwent renal transplantation, more severe intestinal adhesion was observed, although the duration of PD was limited to 70 months and the intestinal serosae were seemingly normal. These findings were considered specific to SEP developing after immunosuppressant administration. In 3 patients who had undergone PD for more than 10 years, degeneration of the visceral peritoneum was observed, together with an ill-defined boundary between the capsules and the serosae. Therefore, total enterolysis was performed in these patients, including a wide area of the muscular layer. Furthermore, calcification was observed in several regions, where the capsules were severely adherent to the parietal peritoneum. The post-operative course for all 8 patients was satisfactory, and these patients finally returned to their previous social activities. We conclude that when SEP symptoms are not improved by steroid administration or TPN, active total intestinal enterolysis should be performed. However, it is absolutely important to avoid inducing anastomosis or impairing the intestine.

Adult↗

Induction of apoptosis in macrophages by cationic liposomes.

The effects of liposomes on apoptosis in macrophages were evaluated from DNA content and DNA fragmentation. Cationic liposomes composed of different kinds of cationic lipids induced apoptosis in mouse splenic macrophages and the macrophage-like cell line, RAW264.7 cells. Generation of reactive oxygen radicals from macrophages treated with cationic liposomes was detected using flow cytometry, and further apoptosis was inhibited by the addition of oxidant scavenger, N-acetylcysteine. From these findings, the production of reactive oxygen species may be important in the regulation of apoptosis induced by cationic liposomes.

Acetylcysteine↗

p53 null mutations undetected by immunohistochemical staining predict a poor outcome with early-stage non-small cell lung carcinomas.

The importance of p53 mutations in the pathogenesis of human lung carcinoma is well established, but it is still controversial whether the presence of p53 mutations or overexpression of p53 protein adversely affects an individual patient's chances of survival. The controversy may be partially due to the methodological differences in examination for p53 alterations: gene analysis or immunohistochemical staining. Furthermore, recent studies have suggested that different types of mutations of the p53 tumor suppressor gene confer different biological properties. To clarify the relationship between immunohistochemical staining and prognosis, we investigated mutations using single-strand conformation polymorphism followed by sequencing for exons 4-8 and 10 in 144 surgically treated non-small cell lung carcinoma patients with intensive clinical follow-up. Of 144 cases, 107 adenocarcinomas were examined for immunohistochemical staining with RSP53 antibody. p53 gene mutations were observed in 65 tumors (45%), including 44 missense and 21 null mutations, the latter comprising 7 nonsense mutations, 8 deletions, 2 insertions, and 4 splicing junction mutations. Presence of p53 mutations was an independent prognostic factor with a statistical trend (P = 0.14) in stage I patients but not in all cases. When examined by mutational pattern, null mutation was a significant indicator of poor outcome by multivariate analysis (P = 0.03) in stage I patients, whereas cases with missense mutations and without mutations did not differ (P = 0.76). Forty (37%) tumors demonstrated overexpression of the p53 protein but without any survival difference. Most tumors (76%) with missense mutations were immunopositive, but those with null mutations with one exception (93%) were not, and the concordance between the mutations and immunohistochemical staining was rather low at 65%. These data suggest that the type of p53 mutation is important for prediction of outcome in early-stage non-small cell lung carcinoma patients, whereas immunohistochemical staining for abnormal p53 gene products is nonpredictive. Furthermore, null mutations causing loss of function of the gene product may play more important roles than missense mutations in tumor progression.

Adenocarcinoma↗

Cytologic and cytochemical features of adenoma malignum of the uterine cervix.

BACKGROUND: We previously reported that adenoma malignum (the mucinous type of minimal deviation adenocarcinoma [mucinous MDA]) of the uterine cervix expresses gastric phenotypes. The application of immunocytochemistry using HIK1083, a monoclonal antibody for gastric gland mucous cell mucin, enabled us to identify cellular clusters derived not only from typical lesions of mucinous MDA and less well differentiated lesions but also from gastric metaplasia. In this study, we tried to clarify the cellular features of such clusters in cervical and endometrial smears. METHODS: Twelve cases of mucinous MDA were studied. Papanicolaou stain and immunostaining with HIK1083 were performed on histologic and cytologic slides, including cervical and endometrial smears, decolorized smear slides, imprint slides of the tumors, and imprint slides of normal endocervical and gastric mucosa. RESULTS: Cellular clusters derived from metaplastic lesions, typical lesions, and less well differentiated lesions were found in 9, 4, and 2 cases, respectively. The cellular clusters derived from the metaplastic lesions lacked atypia but resembled those from gastric mucosa. Those derived from the typical lesions showed slight atypia. The cytoplasmic mucins of these cellular clusters, which were positive for HIK1083, were stained yellowish-orange by Papanicolaou stain, whereas those of normal endocervical cells were negative for HIK1083 and were stained pinkish by Papanicolaou stain. CONCLUSIONS: Yellowish-orange staining of cytoplasmic mucins by the Papanicolaou method is an important diagnostic clue aiding identification of mucinous MDA and related lesions by cytology. Moreover, immunostaining with HIK1083 is a useful tool in the diagnosis of these lesions by cytology as well as by histology. Cancer (Cancer Cytopathol)

Adenocarcinoma, Mucinous↗