Biomedical subjects

M Terashima

Publications and source records attributed to M Terashima.

At least 91 records · Page 5Linked to original sources

PubMed1998

[Severe pulmonary hypertension due to mitral regurgitation without overt sign of congestive heart failure: a case report].

A 49-year-old man was found to have a heart murmur at a local hospital and was referred to our hospital for further examination. Although he had no signs of congestive heart failure, echocardiography and cardiac catheterization showed severe pulmonary hypertension caused by severe mitral regurgitation. Mitral valve replacement was performed, followed by reduction of pulmonary artery pressure. This patient had an unusual combination of no signs of lung congestion despite severe mitral regurgitation with pulmonary hypertension.

Echocardiography↗

PubMed1998

[Pharmacokinetic analysis of low-dose intra-peritoneal cis-platinum administration].

Pharmacokinetic parameters after intra-peritoneal administration of low-dose cis-platinum (CDDP) were analysed in order to evaluate the possibility of applying low-dose 5-FU/CDDP therapy (1-FP) for outpatients. Four patients with advanced gastric cancer were the subjects of this study. CDDP at a dose of 20 mg/body was administered intra-peritoneally, and peripheral venous blood was collected at 30 min, 4, 8, 24, 48, 72, 96 and 120 hr after drug administration. The plasma platinum (Pt) concentration was determined by atomic absorption spectrometry. Pharmacokinetic parameters were calculated using a two-compartment open model. C max, AUC, t1/2 alpha and t1/2 beta of total-Pt were 1. 27 +/- 0.21 micrograms/ml, 95.28 +/- 16.93 micrograms.hr/ml, 1.91 +/- 0.76 hr and 190.2 +/- 125.6 hr, respectively. Total-Pt concentration at 120 hr, after administration was 0.54 +/- 0.14 microgram/ml. This result suggests that intraperitoneal low-dose CDDP administration is a promising method for 1-FP therapy for outpatients, because the plasma total-Pt level is maintained at a sufficiently high level for a long period.

Aged↗

PubMed1997

ADP-ribosylation of tuftsin suppresses its receptor-binding capacity and phagocytosis-stimulating activity to murine peritoneal macrophages.

Arginine-specific ADP-ribosyltransferase present in granules of chicken polymorphonuclear leukocytes (so-called heterophils) is released into the extracellular space by stimulus of calcium ionophore A23187 or opsonized zymosan [Terashima et al. (1996) J. Biochem. 120, 1209-1215]. In the present work, we examined extracellular targets of the released transferase and identified tuftsin, a phagocytosis-stimulating tetrapeptide derived from leukokinin, as a preferential substrate of the enzyme in chicken plasma. Specific binding of FITC-tuftsin to murine peritoneal macrophages, observed under a fluorescent microscope, was impaired by ADP-ribosylation of the labelled peptide. Phagocytic assay analyzed by flow cytometry revealed that ADP-ribosylation of tuftsin decreased its phagocytosis-stimulating activity towards the macrophages. Thus, the ADP-ribosylation of tuftsin apparently decreases its biological activity and ADP-ribosylation may possibly be involved in inflammatory processes through alterations in tuftsin activity.

Adenosine Diphosphate Ribose↗

PubMed1997

Vesicular anthracycline accumulation in doxorubicin-selected U-937 cells: participation of lysosomes.

The U-A10 cell line, a doxorubicin-selected variant of human U-937 myeloid leukemia cells, exhibits a redistribution of anthracyclines into a expanded vesicular compartment. The acidic nature of this compartment was confirmed by vital staining with a pH sensitive dye, LysoSensor yellow/blue DND-160. Identification of the vesicular compartment was performed by immunofluorescence analysis. Staining for the LAMP-1 and LAMP-2 antigens showed that the vesicles are enlarged lysosomes that are eccentrically placed near the nucleus of U-A10 cells. By contrast, the expression of the multidrug resistance-associated protein and the P-glycoprotein was observed predominately on the plasma membrane of the drug-resistant cells. The accumulation of daunorubicin into cellular compartments was quantified using radiolabeled drug. Exposing cells to 3[H]-daunorubicin and then isolating intact nuclei showed that nuclei from U-A10 cells accumulated twofold to threefold less anthracycline than nuclei from U-937 cells. However, when nuclei were isolated first and then exposed to 3[H]-daunorubicin, little difference in net nuclear drug accumulation was detected. Cytoplasts prepared from U-A10 and U-937 cells were exposed to 3[H]-daunorubicin to measure cytoplasmic drug accumulation. At external daunorubicin concentrations of 100 ng/mL or higher, cytoplasts from U-A10 cells accumulated significantly more daunorubicin than cytoplasts from U-937 cells. Moreover, studies with the lysosomotropic agent chloroquine showed that U-A10 cells accumulated twofold more chloroquine and showed twofold enhanced sensitivity to this agent as compared with parental U-937 cells. Fluorescence microscopy showed that chloroquine affects vesicular anthracycline sequestration in U-A10 cells with an associated increase in daunorubicin nuclear fluorescence. Although chloroquine did not alter anthracycline cytotoxicity in parental cells, it restored daunorubicin and doxorubicin sensitivity to U-A10 cells. Taken together, these studies demonstrate that U-A10 cells exhibit a redistribution of the lysosomal compartment. The trapping of drug into an expanded acidic vesicular compartment results in decreased nuclear drug accumulation and decreased cytotoxicity. Lysosomotropic agents, such as chloroquine, warrant further study as modulators of this acquired drug-resistance phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Microvessel count predicts metastasis and prognosis in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: In order to evaluate the clinical relevance of angiogenesis in patients with gastric cancer, we investigated the microvessel count in gastric cancer tissues and compared the results with several clinicopathologic factors and prognosis. METHODS: A total of 55 patients with gastric cancer were included in this study. Microvessel count was determined by immunohistochemical staining using antifactor VIII-related antigen antibody. Histologically recognizable blood vessels within tissue sections served as internal control for immunostaining. Normal mouse IgG diluted to an equivalent protein concentration was used as a negative control in place of the primary antibody in each experiment. RESULT: The microvessel count ranged from 4.4 to 39.8 and the median count was 15.6. Microvessel count was significantly higher in patients with hepatic metastasis, lymph node metastasis, adjacent organ invasion, and lymphatic invasion. In patients who had undergone a curative operation, survival time in the hypervascular group was significantly shorter than that in the hypovascular group. CONCLUSIONS: Microvessel count correlated well with tumor progression and may serve as a useful prognostic factor in patients with gastric cancer.

Adult↗

PubMed1997

Functional roles of protein domains on rice alpha-amylase activity.

Characteristics of two rice alpha-amylases Amy1A and Amy3D, and those of two chimeric enzymes Amy1A/3D and Amy3D/1A, engineered from the two isozymes, were compared in the light of the functional roles of protein domains in alpha-amylase. The enzymes that have an Amy1A-type N-terminal domain, Amy1A and Amy1A/3D, showed high activity against soluble starch, while the enzymes that have an Amy3D-type barrel structure, Amy3D and Amy1A/3D, showed high activity in oligosaccharide hydrolysis. Rigidity of protein folding also significantly affected the enzyme activity in both soluble starch and oligosaccharide hydrolysis. Thus, the present work suggests that the structure of the N-terminal domain is important for stability and soluble starch hydrolysis, while the barrel structure that forms the active site significantly affects enzyme activities in oligosaccharide degradation. We have already characterized two rice alpha-amylase isozymes, Amy1A and Amy3D, and a chimeric enzyme engineered from these two isozymes, Amy1A/3D (Terashima et al. 1995, 1996a,b). In spite of the high homology (70%) of their amino acid sequences, Amy1A and Amy3D showed distinct differences in their enzymatic characteristics. The chimeric enzyme Amy1A/3D, which consists of an Amy1A-type N-terminal domain and an Amy3D-type barrel structure, inherited enzymatic characteristics from the both isozymes. In this work, one other chimeric enzyme, Amy3D/1A, which is the counterpart of Amy1A/3D, has been characterized. The characteristics of these four enzymes are discussed in the light of the functional roles of protein domains.

Amylases↗

PubMed1997

Purification of alpha-amylase by specific elution from anti-peptide antibodies.

Chimeric alpha-amylase, produced by recombinant yeast cells, was purified by immunoaffinity chromatography by use of an anti-peptide antibody and an eluent containing an antigen peptide. Chimeric alpha-amylase was adsorbed by the antibody against the peptide corresponding to the C-terminal region of target alpha-amylase, and specifically eluted by the eluent containing the antigen peptide used for immunization. A low concentration of the peptide could competitively elute adsorbed alpha-amylase, and the rate-limiting step of the elution was mass transfer of desorbed alpha-amylase. With this specific method, target proteins can be effectively eluted, and highly purified under mild conditions, from the antibody ligand showing a high-affinity for the adsorption step

Adsorption↗

PubMed1997

Mediastinal lymph node metastasis in patients with clinical stage I peripheral non-small-cell lung cancer.

Our aim in this study was to determine the mediastinal areas where lymphadenectomy should be done at the time of surgical resection of clinical stage I lung cancer. Between 1984 and 1994, 575 patients with clinical stage I non-small-cell lung cancer underwent lobectomy and systematic mediastinal lymphadenectomy. Mediastinal lymph nodes were pathologically positive for disease in 79 patients (14%), and positive nodes appeared normal intraoperatively in 54 patients (68%). Thirty-three percent of those patients with positive N2 (mediastinal) nodes had negative lobar (N1) nodes. In cancer of the right upper lobe, all N2 cases had the lymph node metastases in the superior mediastinal compartment. In cancer of the right middle lobe, all N2 cases but one had the metastases in subcarinal or anterior mediastinal nodes. In cancer of the right lower lobe, all N2 cases but one the metastases in subcarinal nodes. In cancer of the left upper lobe, all N2 cases had the lymph node metastases in the subaortic compartment. In cancer of the left lower lobe, all N2 cases but one had the lymph node metastases in the subcarinal area or subaortic compartment. In conclusion, systematic staging of mediastinal lymph nodes is necessary for all patients with resectable clinical stage I lung cancer. The location of the primary tumor determines the mediastinal areas where lymphadenectomy should be done to examine all lymph nodes.

Adult↗

PubMed1997

GTP-dependent modification of a 21-kDa substrate with NAD+ in bovine brain soluble fraction is not ADP-ribosylation of small G-protein but tailing of tRNA.

Labeling of 21-kDa material was observed when bovine brain soluble fraction was incubated with [adenylate-32P]NAD+ in the presence of GTP. The 21-kDa substrate, slightly smaller than C3 substrate in size, was labeled even without C3 exoenzyme. GTP could be replaced by nucleoside triphosphates other than ATP while ATP inhibited the GTP-induced labeling of 21-kDa substrate. After incubation of the soluble fraction with [adenylate-32P]NAD+ in the presence of GTP, [32P]ADP and [32P]ATP were detected in addition to [32P]AMP and [32P]ADP-ribose while only the last two nucleotides were observed without GTP. The 21-kDa substrate was labeled with [alpha-32P]ATP even in the absence of GTP, suggesting adenylylation rather than ADP-ribosylation. The labeled 21-kDa substrate, was extractable by phenol, disappeared with RNase treatment but not with tryptic digestion. Alkaline treatment of the phenol extract yielded an equal mixture of 3'-[32P]CMP and 2'-[32P]CMP. From these results we concluded that the 21-kDa labeling is a result of tRNA tailing with [alpha-32P]ATP generated from the [32P]AMP moiety of [adenylate-32P]NAD+. Results from reconstitution experiments using enzymes and tRNA purified from bovine brain soluble fraction, which are involved in this pathway, confirmed our conclusion.

ADP Ribose Transferases↗

PubMed1997

The usefulness of the ATP assay with serum-free culture for chemosensitivity testing of gastrointestinal cancer.

In order to predict a patient's response to a drug prior to chemotherapy for gastrointestinal cancer, we developed an adenosine triphosphate (ATP) assay with serum-free culture (SF-ATPA) which enables fibroblast overgrowth to be suppressed. A total of 244 gastrointestinal cancer tissue samples were obtained from surgical resection. After enzymatic digestion, cells (2 x 10(4)/well) were cultured for 72 h with continuous exposure to drugs (single or combined use), and cell viability was evaluated by measuring the intracellular ATP level. 208 of 244 samples (85%) were considered to be evaluable in terms of drug response. There were no differences in the evaluability rates among the tumour types. A drug was judged as active using the criterion of < or = 50% reduction of the intracellular ATP level in a single-agent treated group compared with the level of the control. Similarly, in the combined drug treated group, drugs were considered as active using two different criteria (< or = 30% reduction of the intracellular ATP level for two drugs and < or = 20% for three drugs). Each tumour type had its own spectrum for chemosensitivity. Of 25 patients evaluated for assay-clinical correlations, 16 were examined by both single-agent and combined drug administration and the predictive accuracy of the assay was higher for the combined drug than for the single agent (88% versus 69%, respectively). In 25 patients, the true positive rate was 64% and the true negative rate was 100%, yielding an overall predictive accuracy of 84%. These results suggest that SF-ATPA may be useful for predicting drug response in patients with gastrointestinal cancer.

Adenosine Triphosphate↗

PubMed1997

Commonly deleted region on the long arm of chromosome 7 in differentiated adenocarcinoma of the stomach.

Loss of heterozygosity (LOH) at several chromosomal loci is a common event in human malignancies. Frequent LOH on the long arm of chromosome 7 has been reported in various human malignancies, and investigators have identified the most common site of LOH as 7q31.1. We have identified ten chromosomal loci, including chromosome 7q, that have been shown by previous allelotype study to be sites of frequent LOH in differentiated adenocarcinoma of the stomach. In the present study, we performed a polymerase chain reaction (PCR) microsatellite analysis to define the common deleted region on 7q, using 14 polymorphic microsatellite markers in matched tumour and non-tumour DNAs from 53 patients with primary gastric carcinoma of the differentiated type. LOH at any locus on 7q occurred in 34% (18 out of 53) of the tumours. Although many tumours exhibited total or large interstitial deletions, we determined the smallest common deleted region to be at D7S480 (7q31.1). This is identical to the region identified for other human malignancies. These observations indicate that a putative tumour suppressor gene at 7q31.1 may be involved in the pathogenesis of differentiated adenocarcinoma of the stomach.

Adenocarcinoma↗

PubMed1997

The best site for bronchial stapling in left and right upper lobectomies: a comparative study.

Bronchial stapling and postoperative bronchoscopy was performed in 22 left upper lobectomies (LUL) and 18 right upper lobectomies (RUL). Seven LUL cases and 15 RUL cases with staples positioned 2 bronchial rings (BR) from the entrance to the upper lobe bronchus (ULB) had no residual cartilaginous rings at the stump (RCRS). Deformity of the residual bronchus (DRB) was found in 6 of these 7 LUL cases, and 3 of these 15 RUL cases (p < 0.01), with a high rate of suffering from a severe cough. The remaining 15 LUL cases and 3 RUL cases had staples positioned 3 to 4 BR from the entrance to the ULB resulting in one or two RCRS. Only one LUL case with one RCRS was accompanied by DRB and coughing. These facts strongly imply a connection between cough and DRB. DRB was frequently seen in LUL cases with no RCRS (86%), was less likely to occur in cases with one RCRS (10%), and was absent in cases with two RCRS (p < 0.01). We conclude that bronchial staples applied during a LUL should be positioned 3 or 4 bronchial rings distal from the entrance to the left ULB.

Aged↗

PubMed1997

Analysis of the DPC4 gene in gastric carcinoma.

Allelic loss on chromosome 18q is involved in the progression of gastric carcinoma. Recently, DPC4 (deleted in pancreatic carcinoma, locus 4), a candidate tumor suppressor gene, has been localized at 18q21.1. This gene is inactivated in nearly one half of pancreatic carcinomas. We tested for DPC4 gene mutations and allelic status at 18q21 in 30 primary gastric carcinomas and 5 gastric carcinoma cell lines. Polymerase chain reaction single-strand conformation polymorphism and sequencing analyses revealed no DPC4 mutations in any of the primary tumors or cell lines. Homozygous deletion of DPC4 was observed in only 1 (MKN-45) of the 5 (20%) cell lines. This suggests that the target gene for loss on 18q is not DPC4. The true tumor suppressor gene, encoded near DPC4, has yet to be identified.

Chromosome Deletion↗

PubMed1997

A pilot phase 2 study of surgical treatment after induction chemotherapy for resectable stage I to IIIA small cell lung cancer.

BACKGROUND: To evaluate the feasibility and efficacy of surgical resection of the primary tumor and regional lymph nodes in patients with resectable stage I to IIIA small cell lung cancer (SCLC) who had responded to induction chemotherapy. METHODS AND RESULTS: Twenty-two patients (age, 39 to 70 years; median, 60.5 years) with resectable stage I to IIIA SCLC were identified as candidates for induction chemotherapy. All patients received two to four cycles of preoperative chemotherapy IV every 3 weeks (CAV II: cisplatin, 80 mg/m2, day 1; doxorubicin hydrochloride (Adriamycin), 30 mg/m2, day 1; etoposide (VePesid), 60 mg/m2 day 1 to 5). The overall response rate to induction chemotherapy was 95.5% (complete response, 5 of 22; and partial response, 16 of 22). After induction chemotherapy, 21 patients (95.5%) underwent a surgical resection (one pneumonectomy, 19 lobectomies, one segmentectomy). The postoperative pathologic study revealed only SCLC in 15 patients, only adenocarcinoma in one patient, and no residual tumor in five patients. The median survival time was 61.9 months for both the 21 surgical patients and all 22 patients, while their actuarial 3-year survival rates were 66.7% and 63.6%, respectively, for a follow-up period from 41.1 to 107.6 months (median, 59.8 months). Patients with clinical stages I and II disease had significantly longer survival times than did those with stage IIIA disease (3-year survival rates, 73.3% and 42.9%, respectively; p=0.018). The major adverse reaction was an operation-related death for one patient with N2 disease, but no other serious side effects were observed. CONCLUSION: This induction chemotherapy followed by surgery is feasible and may be beneficial for the treatment of resectable stage I to IIIA SCLC.

Adult↗

PubMed1997

[The effect of nicardipine hydrochloride upon the pulmonary arterial pressure].

This study examines the effects of induced hypotension with intravenous administration of nicardipine hydrochloride (NIC) upon pulmonary arterial pressure (PAP) undergoing modified radical mastectomy with neuroleptanesthesia (NLA-group; 3 cases) and inhalation anesthesia (N2O+ isoflurane; GOI-group; 3 cases). Systolic arterial pressure was reduced and maintained at 80 mmHg. During and after induced hypotension in NLA-group, heart rate (HR), cardiac index, pulmonary arterial pressure (PAP) increased remarkably. On the other hand, systemic vascular resistance index was reduced. In GOI group, no significant changes were seen in PAP. The acceleration of the autonomic baro-reflex induced by decreased blood pressure produced by NIC may be depressed under anesthesia to initiate this difference in response of HR to NIC. The data indicate that this depressive effect of NLA on this reflex is weak, and NIC is a potent systemic vasodilator with hyperdynamic hemodynamic effects in addition to an increase in right ventricular function, and PAP was increased.

Adult↗

PubMed1997

Commonly deleted regions on the long arm of chromosome 21 in differentiated adenocarcinoma of the stomach.

During an allelotype analysis of differentiated adenocarcinoma of the stomach, we observed frequent loss of heterozygosity (LOH) on several chromosomes including the long arm of chromosome 21 (21q). Therefore, we analyzed DNA isolated from 45 tumors for LOH at 10 loci on 21q by using polymorphic microsatellite markers. In 20 (44%) of 45 tumors, we detected LOH at single or multiple loci on 21q. Deletion mapping of these 20 tumors revealed two separate commonly deleted regions. Our findings suggest that 21q contains at least two potential tumor suppressor genes which play crucial roles in the development of differentiated adenocarcinoma of the stomach.

Adenocarcinoma↗

PubMed1997

[A study of the effects of antidepressants on the GABAA receptor and its complex based on the drug actions on the power-spectral changes of rat hippocampal EEG induced by GABA antagonists and inverse agonists].

To analyze the effects of antidepressants on the GABAA receptor, we investigated how the chronic administration of antidepressants (10 mg/kg twice a day for three or seven days, ip) influenced the power-spectral changes induced by pentylenetetrazol (PTZ; a GABA antagonist; 27.5 mg/kg) or beta-carboline-3-carboxylic-acid-methylester (beta-CCM; an inverse agonist; 1 mg/kg) on rat hippocampal EEGs. PTZ and beta-CCM are known to inhibit the chloride ionophore and benzodiazepine receptor (GABAA receptor complex), respectively. After the ip injection of both compounds, the EEG power under 12 Hz increased to about five times that before injection. Between the rats that did not receive any antidepressants and all those injected with the drugs for 3 days or treated with desipramine (DMI) for 7 days, there were no apparent changes in the effect of PTZ or beta-CCM. However, in the rats treated with imipramine, fluoxetine or trazodone for 7 days, the increase in power after the injection of PTZ or beta-CCM was apparently suppressed. In these rats, the power values were less than three times those before the dosing of PTZ or beta-CCM. DMI is known to inhibit the re-uptake of norepinephrine (NE), while the other three antidepressants inhibit that of serotonin (5-HT). Trazodone is also reported to block the 5-HT2 sites. These observations might indicate that the chronic administration of antidepressants prompted the function of the GABAA receptor complex. Moreover, it is also suggested that, to that action, the effect of antidepressants on the 5-HT system or interaction between the 5-HT system and GABA receptors might play some role.

Animals↗

PubMed1997

Analysis of the fragile histidine triad gene in primary gastric carcinomas and gastric carcinoma cell lines.

The FHIT (fragile histidine triad) gene has been isolated from the chromosome region 3p14.2, which includes the fragile site locus FRA3B and the breakpoint of the t(3;8) of familial renal carcinoma. FHIT has been suggested to be a candidate tumor suppressor gene for digestive tract carcinomas. To evaluate the significance of FHIT gene abnormalities in gastric carcinogenesis, we examined the allelic status and transcripts of the gene in 23 primary gastric carcinomas as well as 7 gastric carcinoma cell lines. Four of the seven (57%) cell lines exhibited homozygous deletions of variable sizes at 3p14.2 all of which included D3S1300, which is located close to, or within, FRA3B. However, only 2 of 16 (13%) informative cases showed loss of heterozygosity at D3S1300 in the primary tumors. Direct analysis by reverse transcriptase polymerase chain reaction failed to reveal abnormal transcripts, including exon skipping and sequence changes, in the primary tumors or in the cell lines without homozygous deletions. These results suggest that FHIT gene abnormalities are infrequent in primary gastric carcinomas and that the frequent homozygous deletions seen in cell lines might simply reflect the plasticity of the genome at FRA3B under culture conditions.

Acid Anhydride Hydrolases↗