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Biomedical subjects

Y Fujiwara

Publications and source records attributed to Y Fujiwara.

At least 199 records · Page 11Linked to original sources
PubMed1999

Endoscopic resection of two granular cell tumours of the oesophagus.

Granular cell tumour of the oesophagus is rare and usually single. It is diagnosed by endoscopic appearance, results of endosonography, and histological examination of biopsy specimens. Although histological examination is required for diagnosis, it is difficult occasionally to obtain tumour samples by forceps because granular cell tumour is usually located in the submucosal layer. We report the case of a Japanese man with two granular cell tumours of the oesophagus. One lesion was diagnosed as a granular cell tumour by histological examination of a biopsy specimen, but the other was not. Endoscopic resection was performed to obtain the diagnosis and treat the lesions since some granular cell tumours are potentially malignant. Both tumours were completely resected endoscopically, and the diagnosis of granular cell tumour could be established by histological examination of resected tissue. Endoscopic resection is thus useful in the diagnosis and treatment of granular cell tumour of the oesophagus.

Adenocarcinoma↗
PubMed1999

Enhancement of the anti-tumor effect of 5'-deoxy-5-fluorouridine by transfection of thymidine phosphorylase gene into human colon cancer cells.

Thymidine phosphorylase (dThdPase) is an enzyme that converts 5'-deoxy-5-fluorouridine (5'DFUR) to the toxic substance 5-fluorouracil (5-FU); it is also known to be a platelet-derived endothelial cell growth factor. In order to investigate the feasibility of suicide gene therapy against colorectal cancer by means of the combination of 5'DFUR and the converting enzyme dThdPase, we transfected the dThdPase gene into the human colon cancer cell line SW480 and analyzed the growth pattern as well as the sensitivity to 5-FU or 5'DFUR of the dThdPase-transfected cells. The 50% inhibition (IC50) values of 5-FU against the SW480 parental cells, control vector-transfected cells SW480/V1, and dThdPase-transfected cells SW480/dThdPase were approximately 4.9, 6.3, and 2.9 microM, respectively. The IC50 of SW480/dThdPase was lower than that of SW480 or SW480/V1, although the differences were not statistically significant. The IC50 values of 5'DFUR for SW480, SW480/V1, and SW480/dThdPase were approximately 300, 330, and 3.2 microM, respectively. The sensitivity to 5'DFUR of SW480/dThdPase was increased by about 100-fold compared with that of SW480 or SW480/V1. With only 10% transfection efficacy, a high enough sensitivity to 5'DFUR was obtained to suppress the cell growth, indicating that a strong bystander effect was induced by this system. The in vivo growth of the s.c. transplanted SW480/dThdPase tumor in nude mice was significantly suppressed by i.p. injection of 5'DFUR compared with that in control mice that received phosphate-buffered saline (PBS) treatment. These results suggest that gene therapy using the combination of 5'DFUR and the dThdPase gene may be a useful approach for treatment of colon cancer.

Animals↗
PubMed1999

Complete regression of recurrent esophageal carcinoma with reduced expression of glutathione S-transferase-pi by treatment with continuous infusion of 5-fluorouracil and low-dose cisplatin infusion.

The mortality rate of recurrent esophageal carcinoma remains high because of its resistance to chemotherapy and radiation therapy. We present a patient with recurrent esophageal carcinoma, which dramatically disappeared after treatment with the combination of continuous infusion of 5-fluorouracil and low-dose cis-Diamminedichloroplatinum-II (cisplatin) infusion (FP therapy). Furthermore, we immunohistologically found that glutathione S-transferases (GST)-pi, a marker of resistance to cisplatin, was faintly expressed both in the endoscopical biopsy specimens of recurrent tumor and in the resected specimens of esophageal carcinoma and metastatic lymph nodes. FP therapy was suggested to be effective for recurrent esophageal carcinoma. Immunostaining for GST-pi might be a prospective marker for the sensitivity of esophageal carcinoma to FP therapy, particularly cisplatin.

Antimetabolites, Antineoplastic↗
PubMed1999

Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene.

The lineage-restricted transcription factor GATA-1 is required for differentiation of erythroid and megakaryocytic cells. We have localized a 317 base pair cis-acting regulatory element, HS I, associated with a hematopoietic-specific DNase I hypersensitive site, which lies approx. 3.7 kilobases upstream of the murine hematopoietic-specific GATA-1 IE promoter. HS I directs high-level expression of reporter GATA-1/lacZ genes to primitive and definitive erythroid cells and megakaryocytes in transgenic mice. Comparative sequence analysis of HS I between human and mouse shows approx. 63% nucleotide identity with a more conserved core of 169 base pairs (86% identity). This core contains a GATA site separated by 10 base pairs from an E-box motif. The composite motif binds a multi-protein hematopoietic-specific transcription factor complex which includes GATA-1, SCL/tal-1, E2A, Lmo2 and Ldb-1. Point mutations of the GATA site abolishes HS I function, whereas mutation of the E-box motif still allows reporter gene expression in both lineages. Strict dependence of HS I activity on a GATA site implies that assembly of a protein complex containing a GATA-factor, presumably GATA-1 or GATA-2, is critical to activating or maintaining its function. Further dissection of the 317 base pair region demonstrates that, whereas all 317 base pairs are required for expression in megakaryocytes, only the 5' 62 base pairs are needed for erythroid-specific reporter expression. These findings demonstrate differential lineage requirements for expression within the HS I element.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Specification of hematopoietic and vascular development by the bHLH transcription factor SCL without direct DNA binding.

Transcription factors, such as those of the basic-helix-loop-helix (bHLH) and homeodomain classes, are primary regulators of cell fate decisions and differentiation. It is considered axiomatic that they control their respective developmental programs via direct binding to cognate DNA sequences in critical targets genes. Here we test this widely held paradigm by in vivo functional assay of the leukemia oncoprotein SCL, a bHLH factor that resembles myogenic and neurogenic proteins and is essential for both hematopoietic and vascular development in vertebrates. Contrary to all expectation, we find that SCL variants unable to bind DNA rescue hematopoiesis from gene-targeted SCL(-)(/)(-) embryonic stem cells and complement hematopoietic and vascular deficits in the zebrafish mutant cloche. Our findings establish DNA-binding-independent functions of SCL critical for transcriptional specification, and should encourage reassessment of presumed requirements for direct DNA binding by other transcription factors during initiation of developmental programs.

Animals↗
PubMed1999

The position and size of radiological nephrogram in Japanese preschool children.

The early detection of retroperitoneal masses in children, such as neuroblastoma, Wilm's tumor, hydronephrosis and cystic renal diseases, has a great clinical importance for the improvement of their prognosis. The kidney is often affected in its size or position by these lesions, and occasionally allows clinicians to find a clue to reach the correct diagnosis before the patient become symptomatic. Since we had no clinically available nomogram on the position and the size of the kidney in Japanese children, we measured the size and position of the kidneys on plain abdominal x-rays in 347 Japanese children in preschool years with a special attention to their relationship with the spine. As a result, the nomogram showed age dependent growth of the kidneys keeping almost the same ratio with the spine, while the distance between the upper pole of the kidney and the spine remained less than 10 mm in all age groups. Our nomogram may be useful not only for picking up the malposition of the kidneys but also for the follow up of the patients with chronic renal diseases affecting the growth of the kidneys.

Aging↗
PubMed1999

[A case of right ventricular rupture due to blunt trauma].

A 33-year-old male was involved in a single motor vehicle accident and was referred to our hospital 135 minutes after injury. He had a sign of cardiac tamponade and immediately pericardial window was performed at the emergency department, but hypotension went worse. We transferred him to the operating room, and a median sternotomy could be done after cardiopulmonary resuscitation. There was a 4 cm tear in the right ventricular outlet and that was repaired primarily. Cardiac rupture due to blunt trauma is highly lethal, and prompt diagnosis is necessary for a favorable outcome. A high index of suspicion, avoidance of unnecessary diagnostic studies, and immediate surgical intervention are critical for successful management.

Accidents, Traffic↗
PubMed1999

Overexpression of cyclooxygenase-2 in carcinoma of the pancreas.

The level of cyclooxygenase (COX)-2 has been investigated recently in various human carcinomas. In the present study, we examined the distribution and extent of COX-2 protein in human pancreatic tumors using immunohistochemistry. A strong expression of COX-2 protein was present in 23 of 52 (44%) pancreatic carcinomas, a moderate expression was present in 24 of 52 (46%) pancreatic carcinomas, and a weak expression was present in 5 of 52 (10%) pancreatic carcinomas. In contrast, benign tumors showed weak expression or no expression of COX-2, and only islet cells displayed COX-2 expression in normal pancreatic tissues. Overexpression of COX-2 in carcinoma tissues was also confirmed by Western blot analysis. Furthermore, consistent with the results at protein levels, reverse transcription-PCR analyses indicated that COX-2 mRNA was overexpressed in 7 of 13 (54%) carcinomas, but in none of 3 benign tumors. Our findings suggest that COX-2 inhibitors might be potentially effective against pancreatic carcinomas and that COX-2 may be involved in certain biological processes in pancreatic islets.

Adenocarcinoma↗
PubMed1999

Questionnaire survey on the prescribing practice of Japanese psychiatrists for mood disorders.

The answers to a questionnaire on the practical prescription in mood disorders from 298 Japanese psychiatrists was obtained. As the first-line treatment, a majority of respondents chose newer tricyclic agents (TCA) or non-TCA for moderate depression and older TCA for severe depression both with and without psychotic features. Combination therapy with antidepressants and anxiolytics was fairly popular in moderate depression, while antidepressant/neuroleptic combination was more common in severe psychotic depression. Sulpiride was the most favored drug for dysthymia. Although lithium was the most popular for bipolar mania, respondents were divided on the treatment of bipolar depression.

Anti-Anxiety Agents↗
PubMed1999

Gastroprotection by Liu-Jun-Zi-Tang (TJ-43): possible mediation of nitric oxide but not prostaglandins or sulfhydryls.

Liu-Jun-Zi-Tang (TJ-43), a herbal medicine exerting gastroprotective action, was examined for its mechanism of action in rats. TJ-43 significantly inhibited gastric mucosal damage caused by absolute ethanol at doses over 500 mg/kg in a dose-dependent way. Pretreatment with indomethacin or with N-ethylmaleimide did not affect the gastroprotective effect of TJ-43. However, pretreatment with NG-nitro-L-arginine partially but significantly reversed the protective effect of this drug. These findings suggest that the gastroprotective effect of TJ-43 occurs partly through nitric oxide but not through prostaglandins or sulfhydryls.

Animals↗
PubMed1999

Effect of culture conditions on morphological changes of Helicobacter pylori.

The morphological conversion of Helicobacter pylori from the spiral form to the coccoid form may be the expression of a transitory adaptation to an unsuitable environment. The mechanism(s) of this conversion are not clear. In this study, we examined whether the morphological conversion of H. pylori is affected by various culture conditions, such as oxygen concentration, pH, temperature, or the presence of beta-cyclodextrin. H. pylori (NTCC11916) was cultured on Brucella agar, followed by culture in Brucella broth containing 1% agar under several conditions. Morphological conversion of individual H. pylori on the agar plate was investigated with time after incubation under phase contrast microscopy. When H. pylori was inoculated in Brucella broth containing beta-cyclodextrin, the spiral form of the organism was observed even after 6 days of incubation under standard culture conditions: 37 degrees C, pH 7, and microaerobic atmosphere (5% O2/10% CO2/85% N2) (control). The morphological conversion of H. pylori was completed on day 3 in an aerobic atmosphere (20% O2 supply) and on day 2 in an undermicroaerobic atmosphere (<0.1% O2). Its complete morphological conversion was observed at pH 8 on day 5 and at pH 4 on day 6. All of the H. pylori (100%) incubated at 20 degrees or 42 degrees C had converted from the bacillary to the coccoid form on day 4. Conditioned medium without beta-cyclodextrin caused complete conversion on day 5. These results suggest that oxygen concentration, pH, temperature, and beta-cyclodextrin may be related to the H. pylori morphological conversion from the bacillary to the coccoid form.

Culture Media↗
PubMed1999

[PMC (pharmacokinetic modulating chemotherapy) for advanced gastric cancer].

We performed pharmacokinetic modulating chemotherapy (PMC) postoperatively in patients with advanced gastric cancer and examined its antitumor and the side effects. Nineteen patients with advanced gastric cancer (all were above Stage II) were treated: 10 had undergone total gastrectomy and 9 distal gastrectomy. UFT (400 mg/day) was orally administered daily and a continuous infusion of 5-FU (600 mg/m2/24 hr) was given once a week. The average observation period was 14.26 months (4-30 months). All patients with Stage II or III disease have survived, but two patients with Stage IV disease died. One patient received insufficient PMC and the other had a liver metastasis. Two patients experienced Grade 3 inappetence, but all other side effects were Grade 2 or lower and the incidence was less than 25%. In conclusion. PMC has tolerable side effects and may be effective in postoperative chemotherapy for advanced gastric cancer.

Administration, Oral↗
PubMed1999

[Review process of new oncology drug application in Japan--role of MD reviewer].

On the basis of discussion by the Committee for Drug Safety Ensuring Measures, the Japanese Ministry of Health and Welfare (MHW) has amended the Pharmaceutical Affairs Law and related laws, and is reforming its review system for approving new drugs. One of the most important changes in the review system is the establishment of Pharmaceuticals and Medical Devices Evaluation Center (PMDEC) in July, 1997 under the National Institute of Health Sciences, a research institute under MHW. PMDEC, the Evaluation and Licensing Division at MHW and the Organization for Drug ADR Relief, R&D Promotion and Product Review (the Drug Organization) are in charge of drug approval, and reexamination and reevaluation applications. Before the reform new drug application reviews had been conducted mainly by the Central Pharmaceutical Affairs Council (CPAC). After the reform PMDEC, employing technical officials who have expertise in pharmacology, toxicology, biostatistics, clinical medicine, or other scientific fields, jointly review the applications with CPAC. The Evaluation and Licensing Division takes charge of administrative matters, such as final decisions on approvals, developing guidelines concerning the review process, international affairs, and regulatory instructions. During the early part of review the Drug Organization conducts a compliance review on the documents, which a sponsor submits with the approval application, and GCP inspection.

Antineoplastic Agents↗
PubMed1998

A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis.

XRCC4 was identified via a complementation cloning method that employed an ionizing radiation (IR)-sensitive hamster cell line. By gene-targeted mutation, we show that XRCC4 deficiency in primary murine cells causes growth defects, premature senescence, IR sensitivity, and inability to support V(D)J recombination. In mice, XRCC4 deficiency causes late embryonic lethality accompanied by defective lymphogenesis and defective neurogenesis manifested by extensive apoptotic death of newly generated postmitotic neuronal cells. We find similar neuronal developmental defects in embryos that lack DNA ligase IV, an XRCC4-associated protein. Our findings demonstrate that differentiating lymphocytes and neurons strictly require the XRCC4 and DNA ligase IV end-joining proteins and point to the general stage of neuronal development in which these proteins are necessary.

Animals↗