Search PubMed⌕ Search

Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 397 records · Page 22Linked to original sources

Clinical trial of continuous infusion of 5-fluorouracil using an ambulatory pump for metastatic colorectal cancer.

A clinical trial was conducted in order to evaluate the anti-tumor effect and toxicity of a continuous infusion of 5-fluorouracil (5-FU) for metastatic colorectal cancer. Two-hundred and fifty mg/m2/day 5-FU was administered as a continuous infusion through an indwelling central venous catheter with ambulatory pump. Twenty patients with metastatic colorectal cancer which could be measured or evaluated were enrolled in the trial. The objective response rate was 35% (95% confidence interval, 14-56%). The response rates by site were 33% in liver, 17% in lung, 60% in lymph nodes, 50% in adrenal gland and 50% in primary lesion. The major toxicity was stomatitis (50%; grades 2 and 3 on Eastern Cooperative Oncology Group (ECOG) criteria) and hand-foot syndrome (40%; grades 2 and 3 on ECOG criteria). The sequence of toxicity was stomatitis first, followed by hand-foot syndrome. The median cumulative dose of 5-FU from the initiation of therapy to the onset of toxicity was 7125 mg in stomatitis and 17,875 mg in hand-foot syndrome. These toxicities were mild and reversible after a short interruption to the 5-FU infusion. Neither hematological toxicity nor serious catheter-related complications were observed. We concluded that continuous infusion of 5-FU was a feasible treatment for the patient with metastatic colorectal cancer, and manageable on an out-patient basis.

Adult↗

[Anatomical analysis of small bronchial arteries in front of the trachea by 3D-CT and digital subtraction angiography: implications for esophageal cancer surgery].

To preserve blood supply to the trachea and bronchus in the surgical procedure for esophageal cancer, anatomical characteristics of small bronchial arteries which course in front of the trachea were analysed by three-dimensional computed tomography (3D-CT) and digital subtraction angiography (DSA). In the 3D-CT study using five mediastina, three dimensional images of the bronchial arteries were reconstructed after the injection of contrast medium into the intercostobronchial arteries. Thus the detailed vascular network of the course of the small bronchial arteries in front of the trachea could be delineated. In the DSA study using seven mediastina, through this network of bronchial arteries, the branches originating from the aorta and the arteries supplying the cranial portion of the trachea could be viewed. These results indicate that the bronchial arteries are connected by a vascular network in front of the trachea. Based on these detailed findings, it is considered critical to avoid damage to the intercostobronchial artery and also the network of bronchial arteries in order to preserve blood supply to the trachea and bronchus.

Angiography, Digital Subtraction↗

Twenty-four hour monitoring of pH in the gastric tube replacing the resected esophagus.

BACKGROUND: Peptic ulcers in the gastric tube replacing the resected esophagus develop silently and cause serious problems. In this study, the acidity of the gastric tube was examined by 24-hour pH monitoring to determine if the acidity of the gastric tube was sufficient to cause peptic ulcers. STUDY DESIGN: The acidity of a gastric tube was evaluated by 24-hour pH monitoring of both the fundus and the antrum in 55 patients treated for carcinoma of the esophagus. The correlation between the fasting serum gastrin concentration and the intraluminal acidity of the completely vagotomized gastric tube was examined. RESULTS: In the patients with high postoperative acidity in the fundus or the antrum (46 percent of the 41 patients examined), the intraluminal pH remained consistently low, even long after operative treatment. Significant correlations existed between the percentage of time that the pH remained below 3 preoperatively and postoperatively in both the fundus and the antrum (r = 0.4777, p = 0.0386, and r = 0.7597, p = 0.0002, respectively). The percentage did not decrease significantly postoperatively. A significantly negative correlation (r = -0.783401, p < 0.0001) was found between the fasting serum gastrin level and the proportion of time that the nocturnal pH in the antrum remained below 3. CONCLUSIONS: Even long after esophagectomy, the pH of the gastric tube is low enough to cause peptic ulcers, especially in patients with high preoperative acidity. In these patients, the intraluminal pH in the antrum of the gastric tube correlates inversely with the fasting serum gastrin level.

Aged↗

[Recent advances in chemotherapy for advanced gastric cancer: from the standpoint of survival advantages].

Recently, there have been many reports indicating higher response rates in combination chemotherapies for advanced gastric cancer. Since 1990, several randomized controlled trials (RCT) have been reported, which showed evidences of survival impacts in such cases. Patients treated with chemotherapy obtained significant survival advantages over those with best supportive care in three RCTs. The RCT from EORTC also resulted in more significant survival prolongation in FAMTX than in FAM, and FAMTX should be a reference arm for new regimens. Some RCTs are now under way to establish a standard therapy for advanced gastric cancer. From the analysis of long-term results of Japanese studies, 3% of entry cases survived longer than 5 years with no evidence of disease by chemotherapy. Chemotherapy for gastric cancer should be evaluated with survival advantages or rate of long-term survivors in future studies.

Antineoplastic Combined Chemotherapy Protocols↗

p53 mutation, murine double minute 2 amplification, and human papillomavirus infection are frequently involved but not associated with each other in esophageal squamous cell carcinoma.

We examined the relationship between p53 mutation, murine double minute 2 (MDM2) gene amplification, and human papillomavirus (HPV) infection in 72 esophageal squamous cell carcinomas. We identified p53 mutations in 29 tumors (40.3%) by PCR-single-strand conformation polymorphism analysis and direct sequencing. Amplification of the MDM2 gene was detected by Southern blot hybridization in 13 (18.1%) of 72 tumor tissues and in 4 (33.3%) of 12 cultured esophageal squamous cell lines. All four cell lines with MDM2 amplifications showed overexpression of the MDM2 mRNA in Northern blotting. We observed HPV infection in 15 (20.8%) of 72 tumor tissues by specific PCR amplification and Southern blot hybridization. In most tumors, amplification of the MDM2 gene or infection of HPV was not associated with p53 mutations, except in four cases with p53 mutation and MDM2 amplification, and three cases with p53 mutation and HPV infection. Since p53 mutations, MDM2 overexpression, and HPV infection are all considered to abrogate the normal function of p53 protein, each of these genetic changes may be equally important in tumorigenesis. In addition, we found that patients with MDM2 amplification exhibited a significantly shorter survival period (P = 0.0053).

Amino Acid Substitution↗

Molecular cloning and chromosomal localization of the human thrombopoietin gene.

The complete gene for human thrombopoietin (TPO) has been cloned by screening a human genomic library using human TPO cDNA as a probe. This gene is 6.2 kb in length and contains six exons and five introns. It is shown that the human genome contains a single copy of the human TPO gene according to Southern blotting analysis. The transcription initiation site was determined by S1 nuclease mapping. The human TPO gene expressed TPO activity when transfected into COS-1 cells. The human TPO gene has been mapped to chromosome 3q27 by in situ hybridization using a biotin-labeled probe.

Amino Acid Sequence↗

Analysis of gene amplification and overexpression in human esophageal-carcinoma cell lines.

Gene amplification/overexpression was analyzed in 23 cell lines derived from human esophageal squamous-cell-carcinoma tissues by Southern and Northern hybridizations to c-myc, c-erbB, hst-1 and cyclin-D1 probes. Amplification of the c-myc gene was observed in 5 cell lines derived from well-differentiated carcinomas and all of them were accompanied by co-amplification of other examined oncogenes. The c-erbB gene was amplified in 3 cell lines. Co-amplification of hst-1 and cyclin D1, both of which are located in chromosome 11q13, was found in 9 cell lines. Without exception their amplification was simultaneous and the magnitudes were similar. Their amplification, but not their overexpression, was significantly correlated with poor prognosis in patients from whom the cell lines were established. While hst-1-gene expression was not detected, at least 1 of the genes analyzed was overexpressed in 20 cell lines vs. its expression in normal esophageal mucosal tissues. However, gene amplification was not necessarily accompanied by overexpression of the corresponding genes. Expression of the cyclin D1 gene, which has been assumed to be a target gene for 11q13 amplification, was not detected in one particular cell line with amplification of 11q13. These results suggest that the amplification/overexpression of more than I oncogene is involved in the carcinogenic process of esophageal carcinoma and that c-myc-gene amplification is associated with a well-differentiated subtype. There remains a possibility that key oncogenes other than cyclin D1 are involved in 11q13 amplification.

Animals↗

[Huge leiomyosarcoma of the mesentery: a case report].

A patient, a 63 year-old-man, was admitted suffering from discomfort in the left abdominal area; this proved to be a case of leiomyosarcoma of the mesentery. An upper gastrointestinal series revealed stenosis in the 3rd portion of the duodenum, and shift of the entire intestine to the right side. Computed tomography showed a giant mass lesion with a central necrosis. Selective arterial angiography showed a heterogeneous tumor stain with several feeders and drainage veins. A partial resection of the intestine around the Treitz's ligament and left hemicolectomy was required due to the tumor's invasion of the intestinal wall and transverse colon. The operation was successfully performed supported by the angiographic findings. The resected tumor was 23 cm in diameter, 2330 g in weight, and was filled with blood. The histological diagnosis was leiomyosarcoma of the mesentery. The patient has been doing well during the 6 months postoperative period.

Humans↗

Allelotype analysis of esophageal squamous cell carcinoma.

In previous studies, we have shown that allelic loss on chromosome 17p, on which the p53 gene is located, is very frequent, and loss-of-function mutations of the p53 gene are closely associated with the tumorigenesis of esophageal cancer. In this study, we performed allelotype analysis to investigate whether other tumor suppressor genes are also involved in esophageal cancer. Using 55 polymorphic DNA markers covering every autosomal arm except 13p, 21p, and 22p, restriction fragment length polymorphism analysis was performed on 36 esophageal squamous cell carcinomas (ESCs) and their adjacent normal tissue samples. Frequent loss of heterozygosity (LOH) of > 30% of the informative cases was observed on chromosomes 3p (41.1%), 5q (52.6%), 6p (30.4%), 8p (33.3%), 9p (35.7%), 9q (30.8%), 11p (32.4%), 13q (52.7%), 17p (55.2%), 17q (33.3%), 18q (45.7%), and 19q (30.4%). Among these, LOH on 5q, 13q, 17p, and 18q was previously reported in ESC and is considered to involve the APC, RB, p53, and DCC genes, respectively. However, our deletion analysis of chromosome 18q revealed that the region commonly lost did not include the DCC locus, suggesting that a possible tumor suppressor gene on 18q other than the DCC gene is involved in ESC. We screened 60 primary ESC tumors and 20 cultured ESC cell lines for the mutation of the APC gene within a mutation cluster region in exon 15, where the "hot spot" of somatic mutation for colorectal and pancreatic cancers is thought to be. We could not find any mutation despite the high frequency of LOH on chromosome 5q. We also analyzed the relationship between the clinicopathological data and the allelic loss and found that LOH on chromosomes 6p and 13q was associated with poor prognosis.

Alleles↗

Endonuclease V from bacteriophage T4 interacts with its substrate in the minor groove.

The binding of bacteriophage T4 endonuclease V to its substrate has been studied using synthetic oligodeoxyribonucleotide duplexes containing a cis-syn thymine dimer. Substrate analogues containing a methylphosphonate linkage with a defined configuration at the thymine dimer site were prepared, and the binding of the enzyme to each diastereomer was analyzed by the filter-binding method. The duplex containing a methylphosphonate with the SP configuration formed a complex with the enzyme, although the dissociation constant for this substrate analogue was about 8 times larger than that for the 12-mer substrate containing a phosphodiester linkage at this site. In contrast, no binding was observed when a duplex containing the RP-methylphosphonate linkage was used. The glycosyl bond of the thymine dimer in the SP isomer was cleaved by the enzyme, while no incision was detected in the case of the RP isomer, even after alkali treatment. Another substrate analogue containing a sulfur atom in place of the 3'-oxygen of the 5'-component at the thymine dimer site showed a reduced affinity for the enzyme. These results suggest that T4 endonuclease V interacts with its substrate in the minor groove. This mode of binding was confirmed by methylation protection experiments.

Bacteriophage T4↗

Effects of neuropeptide Y on lung vascular permeability in the pulmonary circulation of rats.

The effects of neuropeptides on the capillary filtration coefficient in the vessels of the pulmonary circulation were examined, using isolated lung perfusion preparations from rats. Neuropeptide Y and neurokinin A elevated the filtration coefficient, and calcitonin gene related peptide diminished it. Neurotensin and substance P did not affect the value at concentrations less than 10(-7) M. The number of extravasated carbon particle deposits subsequent to tracheal application of neuropeptide Y during spontaneous respiration increased in a dose-dependent manner. From these results, we conclude that neuropeptide Y may increase vascular permeability in the pulmonary circulation.

Animals↗

Effects of pectenotoxin-1 on liver cells in vitro.

The effects of pectenotoxin-1 (PTX1), a nondiarrheagenic toxin from mussels, on liver cells were investigated by fluorescence microscopy. The in vitro application of PTX1 to these cells induced reduction in number and loss in radial arrangement of microtubules. It also induced disruption of stress fibers and accumulation of actin at the cellular peripheries. Further studies are worthwhile to explore the feasibility of using PTX1 as a tool for analyzing the properties of cytoskeletal proteins.

Animals↗

Does interleukin-1 mediate tumour necrosis factor alpha-induced fever in rabbits?

We investigated the humoral mechanisms involved in tumour necrosis factor alpha (TNF alpha)-induced fever in rabbits. No change in lymphocyte-activating factor activity was detected in serum drawn during TNF alpha-induced fever. The pyrogenic activity of recombinant rabbit interleukin-1 beta (IL-1 beta) was entirely abolished by pre-incubation with anti-IL-1 beta antiserum from the goat. Fever induced by intravenous (i.v.) injection of IL-1 beta was significantly diminished by i.v. infusion of the antiserum. However, i.v. infusion of the antiserum for 1 h did not affect fever induced by i.v. injection of TNF alpha, when the antiserum infusion began either simultaneously with, or 2 h after, the injection of TNF alpha. Furthermore, intracerebroventricular injection of the anti-serum did not affect TNF alpha-induced fever. The intracerebroventricular administration of naloxone (an opioid receptor antagonist) significantly diminished TNF alpha-induced fever. The results suggest that IL-1, both in the blood circulation and in the brain, may not be involved in TNF alpha-induced fever. Similar to the contribution of eicosanoids, the opioid system in the brain seems somehow to contribute to the mechanism of the development of fever induced by TNF alpha in rabbits.

Animals↗

Amyloid deposition in the digestive tract in casein-induced experimental amyloidosis in mice.

In mice with casein-induced experimental amyloidosis, the incidence of amyloidosis in various organs was examined in relation to time, and the extent of amyloid deposition in the digestive tract was investigated. Amyloid was deposited first in the spleen, a little later in the digestive tract, and then in the liver and kidney. In the digestive tract, amyloid appeared simultaneously in the small and large intestine, and later in the glandular stomach. Amyloid deposition was most severe in the ileum, while it was not induced in the esophagus or non-glandular stomach. Initially, amyloid deposition was observed along the small blood vessels and/or epithelial basement membranes in the lamina propria mucosa (LPM); it then extended to the stroma in the LPM. Amyloid deposition in each portion of the digestive tract had characteristic patterns in the LPM. Deposition of amyloid fibrils was confirmed by electron microscopy. The results suggest that the gastrointestinal biopsy used widely to diagnose human reactive amyloidosis is a sensitive early indicator of amyloidosis.

Amyloid↗