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Biomedical subjects

M Terashima

Publications and source records attributed to M Terashima.

At least 55 records · Page 3Linked to original sources

Spontaneous coughing up of a polyp.

We report the case of an 18-year old female with right lower lobe atelectasis, who was admitted to our hospital because of a nonproductive cough. She underwent fiberoptic bronchoscopy that revealed a peduncular polyp in the right truncus intermedius or middle bronchus. Before admission for laser polypectomy, she spontaneously coughed up the tissue mass, and the right lower lobe atelectasis disappeared. We report a rare case of 'autopolypectomy' of a bronchial adenoma.

Adenoma↗

Toremifene-induced fatty liver and NASH in breast cancer patients with breast-conservation treatment.

We have described fatty liver, diagnosed by computed tomography scanning (CT) in more than 30% of patients with breast cancer who received tamoxifen. Therefore, it is urgent to elucidate the frequency and the degree of fatty liver induced by toremifene, an analogue of tamoxifen, which is also used in breast cancer. We enrolled 52 breast cancer patients who were treated with breast-conservation treatment and administered oral toremifene for 3-5 years as adjuvant endocrine therapy. We evaluated the degree of fatty liver by abdominal CT performed annually. CT demonstrated toremifene-induced fatty liver in four (7.7%) of 52 breast cancer patients. Toremifene-induced fatty liver did not correlate with abnormal levels of AST, ALT, GGT or total cholesterol. One patient who demonstrated moderate fatty liver by CT was histologically diagnosed as non-alcoholic steatohepatitis (NASH) by liver biopsy. The incidence of toremifene-induced fatty liver was significantly lower than that induced by tamoxifen. Accordingly, in terms of fatty liver and NASH, toremifene is considered to be more appropriate agent than tamoxifen. Though toremifene is less likely to induce fatty liver, the possibility remains that toremifene-induced steatohepatitis occurs. Because the diagnosis of fatty liver or NASH can be easily missed if only a blood test is performed, it is necessary to screen fatty liver by annual CT examination for patients who receive an antiestrogen agent.

Alanine Transaminase↗

Ionizing radiation-induced apoptosis in human lymphoma cell lines differing in p53 status.

Most of malignant lymphomas have been shown to be relatively radiosensitive clinically, but some, especially recurrent ones, are frequently highly radioresistant. To clarify the origin of the difference, we examined ionizing radiation (IR)-induced apoptosis in three closely related human lymphoma cell lines (DL-40, DL-95, and DL-110) that differ in p53 status. DL-95 and DL-110 cells have a wild-type p53, whereas DL-40 cells carry a T to G transition in exon 5 of the p53 gene, resulting in a change of Cys to Phe at codon 176. Irradiation of DL-40 cells (mutant-type p53) with 5 Gy gamma-rays resulted in delayed apoptosis with membrane changes (annexin-V expression) 13 h after IR, and caspase-3 activation 23 h after IR, whereas apoptotic response was not identified in DL-95 cells until 48 h after IR in spite of their normal p53 status. Concerning DL-110 cells, delayed and reduced apoptotic response was revealed both microscopically and by DNA fragmentation assay. These results suggested that IR-induced apoptosis in DL-40 cells is mediated by a mechanism involving the caspase-3 cascade of the p53-independent pathway, and that some unknown mechanism inhibited IR-induced apoptosis in existence of wild-type p53, especially for DL-95 cells.

Annexin A5↗

[Conceptual changes in cancer chemotherapy--biochemical modulation of 5-FU].

Recently, the demand for more useful therapies for cancer patients has increased. We describe in this paper a therapeutic modality based on a self-rescuing concept (SRC), and which features dual activity, i.e., an effect-enhancing activity and an adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: the oral fluoropyrimidine agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil, which is used in UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. S-1 is a combination drug with a molar ratio of 1:0.4:1 in FT, CDHP, and Oxo, respectively. A clinical pharmacology study was conducted to examine blood concentrations of 5-FU after twice-a-day administration of S-1 at a dose of 40 mg/m2. Blood concentrations of 5-FU were found to be 60 to 200 ng/ml in all twelve patients examined. The overall response rate was 44.6% (45/101). In addition, the incidence of adverse reactions judged to be grade 3 or higher was 10% or less. We have also reported a combination therapy with 5-FU (civ) (5-FU: 250 to 350 mg/body, 24-hour cvi, consecutive days) and low-dose cisplatin (CDDP: 3 to 5 mg/body, i.v., 5 days/week), in which CDDP was used as a modulator of 5-FU. Low-dose FP therapy provided response rates as high as 40 to 60% in 163 patients with various gastrointestinal cancers other than pancreas cancer. The incidence of the adverse reactions of nausea and vomiting which were judged to be grade 3 or higher was 2.5% (4/163). The incidences of other adverse reactions were 1% or less. In line with the theory and practice of combination therapy with 5-FU (cvi) 24 hr cvi; 5-FU: 750 to 1,000 mg/body/day on Monday, Wednesday, and Friday (withdrawal on Tuesday, Thursday, Saturday and Sunday) intermittent administration and low-dose CDDP (3 to 5 mg/body/day day 1-5/w) consecutive administration was utilized in which there was a difference in cell cycle between gastrointestinal mucosal cell and tumor cell, or between bone marrow cell and tumor cell. Few adverse reactions, e.g., diarrhea and stomatitis, were observed despite the overall response rate being as high as 52.4% (22/42). The incidence of adverse reaction judged to be grade 3 or higher was as low as 9.3% (5/54), with an incidence of 9.3% (5/54) in Grade 3 or higher myelotoxicity. We intend in the future to combine the abovementioned therapeutic modalities, which provoke fewer adverse reactions and are easy on patients with cancer in an effort to further increase their life expectancy.

Administration, Oral↗

[A novel fibrin clot with a sustained release of cis-platinum (CDDP)].

The authors devised a novel fibrin clot (FC) using an ultra-violet (UV)-crosslinking method. CDDP was impregnated into FCs, and the release profiles of the CDDP were examined in vitro. The microstructures of the FCs were studied with scanning electron microscopy (SEM). The release of CDDP from the FC-UV-CDDP was maintained for 10 days, while that from the FC-CDDP showed initial bursting with a following plateau of CDDP concentrations. SEM of UV-crosslinked FCs revealed highly organized, close and homogeneous micropore structures. Native FCs and non-crosslinked FCs showed rough fibrin networks with entangling fibrin fibers. These microstructural differences may play important roles in the release profiles of CDDP. Our newly devised UV-crosslinked material is promising as a drug carrier for sustained release.

Cisplatin↗

Systemic endothelial function is preserved in men with both active and inactive variant angina pectoris.

To test the hypothesis that coronary spasm could be a coronary manifestation of systemic endothelial dysfunction and that the activity of coronary spasm could influence systemic endothelial function, we examined brachial flow-mediated, endothelium-dependent vasodilation and nitroglycerin-induced endothelium-independent vasodilation with high-resolution ultrasound in 11 men with variant angina pectoris (6 active and 5 inactive) without established coronary atherosclerosis. Endothelium-dependent vasodilation in peripheral circulation was preserved in men with active and inactive variant angina pectoris, suggesting that systemic endothelial dysfunction is not involved in either the pathogenesis or the activity of coronary spasm.

Aged↗

Mutational analysis of the cardiac actin gene in familial and sporadic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) results in part from genetic disorders. Recently, missense mutations of the cardiac actin gene have been reported to cause DCM. We studied 136 Japanese DCM cases to elucidate how frequently the gene mutations are involved in its pathogenesis. Genomic DNA samples were obtained from 136 DCM cases (107 males, 29 females), containing 30 familial DCM (5 confirmed and 25 suspected). All six exons of the cardiac actin gene were analyzed by polymerase chain reaction, single-strand conformation polymorphism, and sequencing. We detected no mutations of the disease causation previously reported (G867A or A1014G) but two silent mutations (G979C and C1018T) in exon 6 and one point mutation (T1080A) in the 3'-untranslated region. As a result of screening 128 healthy subjects, these novel silent mutations were found to be mere genetic polymorphisms, not responsible for the disease. Although some genetic polymorphisms exist in the cardiac actin gene, mutations of the gene are rarely responsible for DCM, at least in the Japanese patients.

3' Untranslated Regions↗

Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction.

BACKGROUND: Rupture of the fibrous cap of an atherosclerotic plaque is a key event that predisposes to acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) may contribute to weakening of the cap, which favors rupture. Stromelysin, a member of MMP family, is identified extensively in human coronary atherosclerotic lesions. It can degrade most of the constituents of extracellular matrix as well as activating other MMPs, which suggests that it may play an important role in plaque rupture. Recently, a common variant (5A/6A) in the promoter of the stromelysin gene has been identified. The 5A/6A polymorphism could regulate the transcription of the stromelysin gene in an allele-specific manner. METHODS AND RESULTS: To investigate the relation between the 5A/6A polymorphism in the promoter of the stromelysin gene and AMI, we conducted a case-control study of 330 AMI patients and 330 control subjects. The prevalence of the 5A/6A+5A/5A genotype was significantly more frequent in the patients with AMI than in control subjects (48.8% vs 32.7%, P<0.0001). In logistic regression models, the odds ratio of the 5A/6A+5A/5A was 2.25 (95% CI, 1.51 to 3.35). The association of 5A/6A polymorphism with AMI was statistically significant and independent of other risk factors. CONCLUSIONS: The 5A/6A polymorphism in the promoter of the stromelysin gene is a novel pathogenetic risk factor for AMI.

Alleles↗

Synergistic effect of ubiquitin on lipopolysaccharide-induced TNF-alpha production in murine macrophage cell line RAW 264.7 cells.

Ubiquitin synergistically augmented the production of tumor necrosis factor alpha (TNF-alpha) in the presence of lipopolysaccharide (LPS) in murine macrophage cell line RAW 264.7. To investigate the mechanism of this augmentation, we analyzed the effect of ubiquitin during TNF-alpha mRNA synthesis and degradation, and TNF-alpha degradation on RAW 264.7 cells stimulated by LPS. It is found that ubiquitin augmented TNF-alpha mRNA synthesis. Ubiquitin did not affect the degradation of TNF-alpha mRNA and TNF-alpha. In the presence of LPS, extracellular accumulation of TNF-alpha by ubiquitin was twice than those by LPS, but intracellular accumulation of TNF-alpha produced by ubiquitin with LPS or by LPS had no difference. These data indicate that ubiquitin might induce TNF-alpha accumulation mainly by up-regulation of the TNF-alpha gene transcription. Although extracellular functions of ubiquitin remain largely unknown, we postulate that ubiquitin might be involved in the modulatory mechanisms of immune response.

Animals↗

Lipid A directly inhibits IL-4 production by murine Th2 cells but does not inhibit IFN-gamma production by Th1 cells.

Lipopolysaccharide (LPS) is known to be an immunopotentiator but its effect on cytokine production by Th1 and Th2 cells is unknown. We found that high amounts of LPS, its lipid A moiety, and a lipid A analog all induced a decrease in IL-4 production and an increase in IFN-gamma production when given to keyhole limpet hemocyanin (KLH)-restimulated lymph node cells prepared from KLH-primed mice. Lipid A was similarly found to inhibit IL-4 production by purified CD4+ T cells and Th2 clones activated with immobilized anti-CD3epsilon and anti-CD28 antibodies, suggesting that the inhibition is not indirectly mediated through effects on antigen-presenting cells. No inhibitory effect of lipid A was observed on IFN-gamma production by a Th1 clone. Production of both IL-4 by the Th2 clones and IFN-gamma by the Th1 clone were inhibited by the immunosuppressive agent cyclosporin A. These findings indicate that lipid A can directly inhibit IL-4 production by CD4+ T cells without inhibiting the production of IFN-gamma. Lipid A may therefore become a useful tool to study the intracellular events that differentiate Th1 and Th2 cells.

Animals↗

Results of surgery for primary lung cancer based on the new international staging system.

OBJECTIVES: This study clarified the results of surgery for primary lung cancer based on the new international staging system. BACKGROUND: On December 1997, the Japan Lung Cancer Society adopted a new TNM staging system which had already received international recognition. SUBJECTS AND METHODS: The subjects of this study were 1062 consecutive previously untreated patients who underwent pulmonary resection for primary non-small cell lung cancer between January 1975 and December 1992. RESULTS: The postoperative 5-year survival rate for all patients was 58.5%. Pathological staging demonstrated a survival rate which was 73.2% in stage I, 46.8% in stage II, 26.7% in stage III, and 20.0% in stage IV. In the staging subgroups, the survival rate was 79.6% in stage IA, 62.4% in stage IB, 62.2% in stage IIA, 42.0% in stage IIB, 26.9% in stage IIIA, and 26.3% in stage IIIB. Concerning the pm patients, the survival rate was 20.2% in pm1 and 20.0% in pm2, while the survival rate of the patients with N0 was 45.7% in pm1 and 40.0% in pm2. CONCLUSIONS: A significant difference in the 5-year survival rate was recognized between the new stages IA and IB, and between the new stages IIA and IIB. When pm patients are diagnosed without lymph node metastasis, the opportunity for resection should not be lost.

Carcinoma, Non-Small-Cell Lung↗

Production of functional human alpha 1-antitrypsin by plant cell culture.

Recombinant human alpha 1-antitrypsin (rAAT) was expressed and secreted from transgenic rice cell suspension cultures in its biologically active form. This was accomplished by transforming rice callus tissues with an expression vector, p3D-AAT, containing the cDNA for mature human AAT protein. Regulated expression and secretion of rAAT from this vector was achieved using the promoter, signal peptide, and terminator from a rice alpha-amylase gene Amy3D. The Amy3D gene of rice is tightly controlled by simple sugars such as sucrose. It was possible, therefore, to induce the expression of the rAAT by removing sucrose from the cultured media or by allowing the rice suspension cells to deplete sucrose catabolically. Although transgenic rice cell produced a heterogeneous population of the rAAT molecules, they had the same N-terminal amino acids as those found in serum-derived (native) AAT from humans. This result indicates that the rice signal peptidase recognizes and cleaves the novel sequence between the Amy3D signal peptide and the first amino acid of the mature human AAT. The highest molecular weight band seen on Western blots (AAT top band) was found to have the correct C-terminal amino acid sequence and normal elastase binding activity. Staining with biotin-concanavalin A and avidin horseradish peroxidase confirmed the glycosylation of the rAAT, albeit to a lesser extent than that observed with native AAT. The rAAT, purified by immunoaffinity chromatography, had the same association rate constant for porcine pancreatic elastase as the native AAT. Thermostability studies revealed that the rAAT and native AAT decayed at the same rate, suggesting that the rAAT is correctly folded. The productivity of rice suspension cells expressing rAAT was 4.6-5.7 mg/g dry cell. Taken together, these results support the use of rice cell culture as a promising new expression system for production of biologically active recombinant proteins.

Amino Acid Sequence↗

Pulmonary function after segmentectomy for small peripheral carcinoma of the lung.

OBJECTIVE: The aim of this study is to compare the pulmonary function after a segmentectomy with that after a lobectomy for small peripheral carcinoma of the lung. PATIENTS AND METHODS: Between 1993 and 1996, segmentectomy and lobectomy were performed on 48 and 133 good-risk patients, respectively. Lymph node metastases were detected after the operation in 6 and 24 patients of the segmentectomy and lobectomy groups, respectively. For bias reduction in comparison with a nonrandomized control group, we paired 40 segmentectomy patients with 40 lobectomy patients using nearest available matching method on the estimated propensity score. RESULTS: Twelve months after the operation, the segmentectomy and lobectomy groups had forced vital capacities of 2.67 +/- 0.73 L (mean +/- standard deviation) and 2.57 +/- 0.59 L, which were calculated to be 94.9% +/- 10.6% and 91.0% +/- 13.2% of the preoperative values (P =.14), respectively. The segmentectomy and lobectomy groups had postoperative 1-second forced expiratory volumes of 1.99 +/- 0.63 L and 1.95 +/- 0.49 L, which were calculated to be 93.3% +/- 10.3% and 87.3% +/- 14.0% of the preoperative values, respectively (P =.03). The multiple linear regression analysis showed that the alternative of segmentectomy or lobectomy was not a determinant for postoperative forced vital capacity but did affect postoperative 1-second forced expiratory volume. CONCLUSION: Pulmonary function after a segmentectomy for a good-risk patient is slightly better than that after a lobectomy. However, segmentectomy should be still the surgical procedure for only poor-risk patients because of the difficulty in excluding patients with metastatic lymph nodes from the candidates for the procedure.

Aged↗

The influence of lung cancer mass screening on surgical results.

BACKGROUND: After the introduction of the mass screening program for lung cancer, the number of patients detected by mass screening increased as well as the number of early staged patients. Therefore, we examined the influence of lung cancer mass screening on surgical results. METHODS: A total of 1177 primary lung cancer cases, who underwent surgery from 1963 to 1992, were retrospectively reviewed. They were grouped according to the changes in the mass screening system: the first period (1963-1977) before lung cancer screening started, the second period (1978-1986) when mass screening was conducted by the local government, and the third period (1987-1992) after the launching of the national screening program. RESULTS: The rate of cases detected by mass screening increased over time and the 5-year survival rate improved significantly, from 33.7% in the first period, to 51.8% in the second period and finally, to 58.4% in the third period. The improvement is attributable to a relative increase of rate of stage I cases and better stage I survival rate. Specifically, in stage I cases, improvement resulted from a relative increase of stage IA in peripheral type and roentgenographically occult lung cancer cases and from better survival rate of these two groups. CONCLUSION: As lung cancer screening has come into widespread use, detection of peripheral small-sized lung cancer and roentgenographically occult lung cancer have increased and consequently, surgical results have improved.

Adenocarcinoma↗

Production of organic acids and amino acids from fish meat by sub-critical water hydrolysis

Fish meat was easily liquefied by hydrolysis under subcritical conditions without oxidants, and aqueous phase and water-insoluble phase containing oil and fat-like solid were formed. Lactic acid found in the raw fish meat (about 0.03 g/g-dry meat) was stable up to the reaction temperature 513 K (3.35 MPa). Pyroglutamic acid was produced with a yield of 0.095 kg/kg of dry meat by 30 min reaction at 553 K (6.42 MPa). Amino acids such as cystine, alanine, glycine, and leucine were produced in the temperature range 513-623 K with a maximum peak at 543 K. Amounts of cystine, alanine, glycine, and leucine produced in 5 min at 543 K (5.51 MPa) were 0.024, 0.013, 0. 009, and 0.004 kg/kg of dry meat, respectively. The oil extracted with hexane contained useful fatty acids such as eicosapentanoic acid (EPA) and docosahexianoic acid (DHA). Thus, subcritical water hydrolysis would be an efficient process for recovering useful substances from organic waste such as fish waste discarded from fish market.

Journal Article↗

Respiratory distress due to tracheal compression by the dilated innominate artery.

The case reported is of an 88 yr old female with hypertension and respiratory distress. A chest radiograph revealed a widening of the upper mediastinum. Computed tomographic scanning revealed tracheal compression by the innominate artery, which was elongated and curved. After intubation, she was treated with antihypertensive drugs. This resulted in the remarkable recovery of the patient from respiratory distress. To the authors' knowledge, this is the first reported case of respiratory distress owing to tracheal compression by elongation and curvature of the innominate artery.

Aged↗

Introduction of NAD decreases fMLP-induced actin polymerization in chicken polymorphonuclear leukocytes--the role of intracellular ADP-ribosylation of actin for cytoskeletal organization.

We reported previously that the arginine-specific ADP-ribosyltransferase in chicken polymorphonuclear leukocytes specifically modified actin, thereby inhibiting actin polymerization in vitro. In the present study, we investigated the effect of ADP-ribosylation on actin polymerization in situ. In the leukocytes, the introduction of NAD inhibited the increase in filamentous actin contents induced by a chemotactic peptide formyl-methionyl-leucyl-phenylalanine, while introduction of NAD together with novobiocin, a specific inhibitor for ADP-ribosyltransferase, did not. These results suggest that ADP-ribosylation regulates the formation of filamentous actin by the covalent modification of the protein in vivo.

Actins↗

A case of systemic sclerosis associated with gastric cancer.

We report the case of a 47-year-old woman who began to experience stiffness and Raynaud's phenomenon of her fingers and toes as well as easy fatigability approximately one year before initial evaluation. Histopathologic examination revealed dense fibrosis and perivascular lymphoid cell infiltration in the dermis. The patient's diagnosis was systemic sclerosis (SSc). Esophageal sclerosis was not revealed, but an early type IIb carcinoma of the gastric antrum was noted by endoscopic examination. Other recent reports have discussed the association of SSc with various malignant carcinomas. We also reviewed the literature for associations between SSc and gastric cancer in Japanese patients.

Biopsy, Needle↗