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Biomedical subjects

K Tada

Publications and source records attributed to K Tada.

At least 55 records · Page 3Linked to original sources

Cytogenetic analysis of esophageal squamous cell carcinoma cell lines by comparative genomic hybridization: relationship of cytogenetic aberrations to in vitro cell growth.

Cancer is characterized by autonomous growth of cells, and it is widely accepted that cell proliferation is primarily influenced by individual cell genetics. To elucidate the mechanisms of cancer cell proliferation, we studied differences in genetic aberrations for different type of tumors with different proliferation characteristics. We employed comparative genomic hybridization (CGH) to detect genetic aberrations in six cell lines of esophageal squamous cell carcinoma (ESCC). Three cell lines (YES-1, -2, and -3) grow in culture without fetal calf serum (group A), while others require serum to be maintained in vitro (group B). Both groups showed very similar cytogenetic aberrations: over-representations of 11q13 (6/6), 8q23-qter (5/6), Xq25-qter (5/6), 3q26-qter (4/6), 5p (4/6), 7p15-pter (4/6), 8q21.3-q22 (4/6), 17p (4/6), and 20q13 (4/6), and under-representations of 18q21-qter (6/6), 4q28-q33 (4/6), and 9p21 (4/6). Six amplification loci were mapped to chromosomal regions of 6q23 (1 case), 7p12 (2 cases), 9p21 (1 case), 11p11.2-12 (3 cases), 11q13 (2 cases), and 17p12 (2 cases). However, some differences were detected. DNA copy number increases at 7p12-p13, 11q14-q22, and 11q22-qter and under-representations of 4p, 8p, and 11p14-pter. In contrast, gains at 12p and 20p, and losses at 3p and 5q were detected only in group-B cell lines. These observations suggest that cytogenetic differences between the two groups may be linked to differences in cell growth characteristics in vitro, and that the genes in these chromosomal regions may play important roles in cell proliferation.

Carcinoma, Squamous Cell↗

Enhancement of retrovirus-mediated gene transfer to rat liver in vivo by infusion of hepatocyte growth factor and triiodothyronine.

BACKGROUND/AIMS: Gene transfer using recombinant Moloney murine leukemia viruses (rMoMuLV) requires mitosis of the target cell. Previously, we and others have used partial hepatectomy for induction of hepatocellular proliferation for gene transfer to the liver in vivo by exsanguineous perfusion with rMo-MuLV. We hypothesized that induction of hepatocellular proliferation by combined administration of two hepatocellular mitogens, hepatocyte growth factor (HGF) and triiodothyronine (T3), should permit rMo-MuLV-mediated gene transfer into liver without invasive approaches. METHODS: HGF (1 mg/kg) was perfused continuously into the portal vein of Wistar male rats and T3 (2 mg/kg) was injected subcutaneously. Twenty-four hours after injecting HGF and T3, the state of proliferation of hepatocytes was estimated from the incorporation of 5'-bromo-2'-deoxy-uridine (BrdU). The amphotropic retroviral receptor (Ram-1) expression of liver was evaluated at different time points after injecting HGF and T3 by means of Northern blotting using Ram-1 cDNA probe. In order to evaluate the role of hormone treatment on gene transfer, the liver was perfused exsanguineously with rMoMuLV 24 h after injection with hormones. RESULTS: Rats treated with a combination of HGF and T3 expressed BrdU and beta-galactosidase in 8.3% and 0.7% of hepatocytes, respectively. On the other hand, there was near absence of gene transfer in untreated rats perfused with rMoMuLV Twenty-four hours after the initial manipulation, abundant expression of Ram-1 mRNA was observed in rat hepatocytes treated with HGF plus T3. CONCLUSIONS: Stimulation of hepatocellular mitosis and upregulation of Ram-1 expression by HGF and T3 augment retrovirus-mediated gene transfer into hepatocytes.

Animals↗

Production of highly concentrated xylitol by Candida magnoliae under a microaerobic condition maintained by simple fuzzy control.

Microbial production of xylitol from xylose was investigated using Candida magnoliae. In particular, the effect of the oxygenation condition on the xylitol production yield was examined and the significance of maintaining a microaerobic condition was demonstrated. A simple system of fuzzy logic control (FLC) was devised to maintain the microaerobic condition in the xylitol production phase by regulating the proportion of air (air flow rate) supplied to the fermentor. The input variables to the fuzzy control system were the dissolved oxygen (DO) concentration in the culture broth and the CO2 concentration in the exit gas. A batch cultivation test using the FLC system confirmed the importance of maintaining a constant microaerobic condition throughout the xylitol production phase, and indicated it would be advantageous for this phase to be prolonged. An intermittent fed-batch culture was therefore carried out. The FLC system allowed a constant microaerobic condition to be maintained, resulting in minimal cell mass production and constant xylitol accumulation in the culture medium. As a consequence, a very high xylitol concentration of 356 g/dm3 could be attained. The xylitol yield in the fed-batch culture was 0.75, which corresponded to 82% of the theoretical yield.

Journal Article↗

Randomized comparison of intra-arterial versus intravenous infusion of ACNU for newly diagnosed patients with glioblastoma.

This prospective randomized trial was performed to compare the effectiveness of intra-arterial ACNU with intravenous ACNU in newly diagnosed patients with supratentorial glioblastoma. The primary end points were overall survival and progression-free survival. Within 3 weeks after surgery, patients were randomly assigned to receive either intravenous or intra-arterial ACNU (80 mg/m2) once every 6 weeks concomitant with radiotherapy. Intraarterial ACNU was administered for the first 3 courses followed by intravenous administration. Eighty-four patients were enrolled onto this study and among them 82 patients who passed eligibility criteria were analyzed. Patients characteristics were not different significantly between 2 treatment arms. Median survival and progression-free survival time was 59 and 24 weeks, respectively for intra-arterial arm and 56 and 45 weeks, respectively for intravenous arm. There was no significant difference respectively between two treatment arms. Among the prognostic variables including age, Karnofsky performance status, extent of surgery and treatment arm, Cox's proportional hazards model showed that age was the only significant factor for both survival and progression-free survival (P = 0.003 and 0.016, respectively). With regard to toxicity, there was no significant difference between two treatment arms. Leukoencephalopathy was not observed in intra-arterial arm. In conclusion, intra-arterial ACNU when administered by the method in this study does not increase the survival and progression-free survival of newly diagnosed patients with glioblastoma over that afforded by intravenous ACNU.

Adolescent↗

Schnurri interacts with Mad in a Dpp-dependent manner.

BACKGROUND: Decapentaplegic (Dpp) is a member of the transforming growth factor-beta superfamily. Dpp governs various developmental processes in Drosophila through the transcriptional regulation of a variety of genes. Signals of Dpp are transmitted from the cell membrane to the nucleus by Medea and Mad, both belonging to the Smad protein family. Mad was shown to bind to the Dpp-responsive element in genes such as vestigial, labial, and Ultrabithorax. The DNA binding affinity of Smad proteins is relatively low, and requires other nuclear factor(s) to form stable DNA binding complexes. schnurri (shn) was identified as a candidate gene acting downstream of Dpp receptors, but its relevance to Mad has remained unknown. RESULTS: We characterized the biochemical functions of Shn. Shn forms homo-oligomers. Shn is localized in the nucleus, and is likely to have multiple nuclear localizing signals. Finally, we found that Shn interacts with Mad in a Dpp-dependent manner. CONCLUSIONS: The present results argue that Shn may act as a nuclear component of the Dpp signalling pathway through direct interaction with Mad.

Animals↗

Elevation of total nitrite and nitrate concentration in vaginal secretions as a predictor of premature delivery.

We measured the total concentration of nitrite and nitrate, metabolites of nitric oxide, in vaginal secretions from pregnant women at 22 to 32 weeks' gestation. Total nitrite and nitrate concentrations in patients with preterm premature rupture of membranes and in those with preterm labor and subsequent premature delivery were significantly higher than concentrations in patients who were delivered at term. Elevated total nitrite and nitrate concentration may predict premature delivery.

Biomarkers↗

The presence and role of the dopamine DA-2 receptor in the human decidua.

OBJECTIVES: Our objectives were to identify the presence of the dopamine DA-2 receptor in human decidua and to study its function in human parturition. METHODS: Human term decidual tissues were obtained during vaginal delivery and then homogenized. The P3 fraction was prepared for a radiolabeled receptor assay with [3H] spiperone as the ligand. Human decidual tissues obtained at cesarean section before the onset of labor were incubated in Krebs-Ringer buffer at 37 degrees C for 30 minutes in the presence of dopamine with or without (-)-sulpiride. The level of prostaglandin (PG) F in the medium was measured with a RIA kit. Differences were assessed with the Wilcoxon non-parametric test. RESULTS: Scatchard analysis showed a single class of binding sites having an equilibrium dissociation constant (Kd) of 2.25 +/- 0.59 nM (mean +/- SD) and a maximum binding capacity (Bmax) value of 166.5 +/- 77.7 fmol/mg protein (n = 3). Dopamine significantly increased the production of PGF. This stimulatory effect of dopamine was suppressed by (-)-sulpiride (p < 0.05; n = 7). CONCLUSION: The DA-2 receptor was demonstrated in the human decidua. Dopamine can stimulate PGF production via this receptor.

Decidua↗

[A case of pulmonary Nocardia farcinica infection in a patient with non-tuberculous mycobacteriosis].

A 64 years old woman without systemic immunological disorders was admitted to our hospital because of a productive cough, low grade fever and bloody sputum. Chest X-ray revealed multiple nodules with calcification, infiltrates and bronchiectasis. Laboratory findings showed mild hypoproteinemia and elevated sedimentation rate. Both Nocardia farcinica and Mycobacterium intracellulare were isolated from the bronchial lavage fluid. Administration of sulfamethoxazole-trimethoprim improved her symptoms. In a recurrent study of bronchial lavage N. farcinica was not isolated, but M. intracellurale was still isolated. We believe that N. farcinica may cause infectious exacerbation of chronic lung disease: non-tuberculous mycobacteriosis and bronchiectasis.

Female↗

L-Lysine production by exponential feeding of L-threonine.

The effect of L-threonine feeding in the production phase on L-lysine production by Brevibacterium flavum, which requires L-homoserine or L-threonine for cell growth, was investigated considering the concerted inhibition by L-threonine plus L-lysine, and the metabolism related to lysine production. Exponential feeding of L-threonine increased L-lysine production to 70 g/l about three times that without feeding. From the analysis of the metabolic flux, carbon flux of L-lysine synthesis pathway in the production phase after L-threonine feeding was higher than that in the growth phase. The results show that feeding of an inhibitory substance may increase the production, especially when the substance is necessary for the continuation of cell growth and/or production.

Journal Article↗

Gene delivery with optimized electroporation parameters shows potential for treatment of gliomas.

Electroporation, a standard laboratory method of introducing exogenous molecules into cells, has been gaining importance as a very effective non-viral physical technique of gene delivery. In this study, we have used subcutaneous model of the C6 rat glioma cells and established an optimal condition to obtain very high gene expression in tumor tissues using both reporter and functional genes. Tumors grown on the flanks of Wistar rats are exposed and directly injected with plasmid DNA having the constructs of luciferase, green fluorescent protein and, the fragment of the diphtheria toxin, DT-A. The tumors are then subjected to square wave pulses from an electroporator. Gene expression is found to be several orders of magnitude higher when the tumors are pulsed with the optimized electrical parameters compared to the controls. For luciferase, the enhancement is approximately 135-fold, for the green fluorescent protein, gene expression is seen over a wide area within the sections examined, as contrast to a few punctate dots in the control specimens, and finally, DT-A shows massive death in the tumor tissue. A special circular array of six needles through which pulses are delivered with rotating electric field is found to be highly efficient in transferring genes inside the tumor. Direct injection of plasmid DNA followed by electroporation allows very high in vivo gene transfer and its subsequent expression into tumor tissues. This method may be applicable to any solid tumor.

Animals↗

[Esophageal dilation therapy for achalasia of the esophagus].

Esophageal dilation therapy for esophageal achalasia has a 300-year history and remains the first-line therapy because of its low cost, progressively decreasing morbidity and mortality, and possibility of surgery for patients who do not improve. Another advantage is the feasibility of repeated trial even after surgery. The aim of this procedure is to produce a controlled tear in the lower esophageal sphincter muscle. Precise esophagographic, endoscopic, and manometric diagnosis is necessary for successful esophageal dilation therapy. In addition, the exclusion of pseudoachalasia using echogram or CT scan is important. The procedure should be carried out accurately to prevent complications. If perforation occurs, appropriate, timely management is required.

Catheterization↗

[Sjögren's syndrome with malignant lymphoma, interstitial pneumonia, and pulmonary hypertension].

A 62-year-old woman was admitted to our hospital for further examination of cough and dyspnea on exertion. She had suffered xerostomia and xerophthalmia for 7 years. Physical examinations showed purpura on the lower extremities, Raynaud's phenomenon, and swelling of the parotid glands. Laboratory data disclosed thrombocytopenia, hypergammaglobulinemia, and high titers of anti-nuclear antibody, anti SS-A, and anti SS-B antibodies. Sicca symptoms, a positive Schirmer's tear test, and laboratory findings together yielded a diagnosis of Sjögren's syndrome. Chest X-P and computed tomographic films demonstrated diffuse reticulonodular shadows and multiple nodules in the left lower lung. Echocardiography and right cardiac catheterization revealed enlargement of the right ventricle, tricuspid regurgitation, and elevated pulmonary arterial pressure. Histologic findings from an open-lung biopsy specimen revealed accumulation of inflammatory cells and fibrosis around broncho-vascular bundles, and diffuse large cell lymphoma. Despite a favorable response to chemotherapy, the patient died of right ventricular failure.

Female↗

[Social phobia with somatic symptoms including nausea and urgency of micturition].

The common symptoms of the social anxiety response include blushing, trembling, feelings of muscular tension of the face, and fear of eye contact. However, the ICD-10 mentions other less familiar symptoms such as nausea, urgency of micturition or defecation, gastrointestinal discomfort, and diarrhea as symptoms of social phobia. Since some of these somatic symptoms are classified as panic-like symptoms in the DSM-IV, it is sometimes difficult to distinguish between social phobia and agoraphobia when these somatic symptoms appear in situations usually associated with agoraphobia. We investigated whether social phobic patients with familiar symptoms (classical group; N = 24) and those with unfamiliar symptoms such as nausea, urgency of micturition or defecation (N/U group; N = 13) could be distinguished on the basis of several selected demographic and psychological tests. Fear of negative evaluation (FNE), social avoidance and distress (SAD), brief social phobia scale (BSPS), and Rosenberg's self esteem score (Se) were compared among these two groups and 82 controls. We also investigated whether they have "fears of making other people feel uncomfortable" which is believed to be a characteristic symptom for what is known in Japanese as "taijin-kyofu-sho." Both groups had higher scores on FNE, SAD, fear and avoidance scores of BSPS, and lower scores on Se as compared with controls. However, neither group differed in demographic variables or results of psychological tests, except for higher scores on the performance score of BSPS and increased rate of "fears of making other people feel uncomfortable" in the classical group. It is suggested that social phobia patients had common social phobic symptomatology and psychopathology irrespective of their somatic symptoms.

Adult↗

Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15A13-15.

To date, three loci for autosomal recessive hereditary spastic paraplegia (ARHSP) linked to chromosomes 8p12-q13, 16qter, and 15q13-15 have been characterized. We have clinically characterized 13 Japanese ARHSP families and performed genetic linkage analyses. All 13 families were classified as having the "complicated" form, which manifests with mental impairment and thin corpus callosum. Linkage to the 8p12-q13 and 16qter loci was excluded, although 10 of the 13 families showed marker data consistent with linkage to the 15q13-15 locus. The multipoint LOD score of the 10 families linked to chromosome 15 was above 9.00 in the 3-centimorgan segment flanked by D15S994 and D15S659, with a maximum multipoint LOD score of 9.68 at a position 1.2 centimorgans telomeric from D15S994 to D15S659. We have shown that ARHSP with thin corpus callosum, a subtype of recessive spastic paraplegia, maps to chromosome 15q13-15.

Adolescent↗

[Measles pneumonia presenting with multiple nodular opacities on chest radiographs].

A 22-year-old woman presented with fever, cough, and maculopapular erythematous rash on hands and feet. These symptoms developed 14 days after the onset of natural measles in the patient's daughter. Chest radiographs obtained on the first examination showed multiple nodular opacities and infiltrates in the left and right lung fields. Serological examinations disclosed elevated levels of the specific IgM antibody and a remarkably elevated hemagglutination inhibition (HI) titer, indicating a recent measles infection. The patient's symptoms, skin eruptions, and abnormal chest radiograph findings disappeared after several days. However, chest computed tomographic scans taken 8 months after the initial examination revealed small, residual nodular opacities. Other than the fact that the patient had received attenuated measles virus vaccine, these findings were typical of the clinical course for atypical pneumonia. We concluded that in the differential diagnosis of multiple nodular opacities on chest radiographs, adequate attention should be given to pulmonary involvement of measles infection.

Adult↗

Tissue factor expressed in pituitary adenoma cells contributes to the development of vascular events in pituitary adenomas.

BACKGROUND: Tissue factor (TF) was initially identified as an important factor in the initiation of coagulation. TF has recently been found to be expressed highly in certain types of malignant tumors. It has also been reported to be involved in systemic coagulopathy in cancer patients and in the proliferative and invasive activities of tumor cells. Tissue factor pathway inhibitor (TFPI) is a strong biologic inhibitor of TF. To the authors' knowledge, this is the first study of the expression of TF and TFPI in human pituitary adenoma. METHODS: The expression of TF and TFPI were analyzed by immunohistochemical methods in human pituitary adenoma samples. To examine whether TF and TFPI expression influence the proliferative and/or invasive character of pituitary adenomas, the authors determined the MIB-1 labeling indices and invasiveness of all the pituitary adenomas they examined. Furthermore, to determine whether TF contributes to coagulation inside adenoma tissues, the incidence of cysts or hematomas in adenomas was analyzed. RESULTS: In cells from 29 of 83 pituitary adenomas, overexpression of TF was observed. This was not the case for normal pituitary gland cells. TFPI was not expressed in either the adenomas or the normal pituitary glands from adenoma-bearing individuals. The expression of TF was significantly correlated with the formation of cysts or hematomas in pituitary adenomas. However, no such correlation with either the proliferative activity or the invasive character of the adenomas was observed. CONCLUSIONS: Locally overexpressed TF in adenoma cells may contribute to the development of vascular events, such as infarction and/or hemorrhagic infarction, in pituitary adenomas.

Adenoma↗