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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 685 records · Page 38Linked to original sources

Transcription factor E4TF1 contains two subunits with different functions.

The transcription factor E4TF1 stimulates transcription from the adenovirus early region 4 promoter by binding to a specific promoter element. E4TF1 has been purified to homogeneity from HeLa cells by sequence-specific DNA affinity chromatography and characterized. E4TF1 is composed of at least two distinct subunits identified as 60 kd and 53 kd polypeptides. The 60 kd protein alone is able to bind to the specific DNA sequence but not to stimulate transcription in vitro. The 53 kd protein alone neither binds to DNA nor stimulates transcription in vitro. However, the 53 kd protein is able to interact with the 60 kd protein and the interaction confers the ability to stimulate transcription in vitro and to increase the DNA binding affinity of the 60 kd protein. This study provides evidence that the interaction between the two different subunits of E4TF1 is required for it to function as a transcription factor, and that one of the subunits binds to a specific DNA sequence and the other works as a modulator.

Base Sequence↗

The specificity of antiglobulin autoantibodies in patients with primary Sjögren's syndrome.

Antiglobulin autoantibodies have already been demonstrated in the sera of patients with primary Sjögren's syndrome (primary SS). In our study, the specificity of primary SS antiglobulins for different regions of IgG molecules was examined by employing both direct binding and competitive inhibition enzyme-linked immunosorbent assay. We found that a considerable amount of total antiglobulins in primary SS was specific for the Fab portion, although the remainder was specific for the Fc portion, namely rheumatoid factor (RF). In contrast, most of the antiglobulins in RA were specific for the Fc portion of IgG. These results indicate that in primary SS, antiglobulins directed against epitopes different from those of RF are produced. These antiglobulins may prove to have a different role in primary SS than that ascribed to RF in RA.

Antibodies, Anti-Idiotypic↗

Expression of human epidermal growth factor and its receptor in esophageal cancer.

The expression of human epidermal growth factor (hEGF) was examined immunohistochemically in 86 esophageal cancer lesions, comprising 67 primary tumors and 19 metastatic lymph nodes. In the normal esophagus, the parabasal and intermediate cell layers showed a weak expression of hEGF, however, hEGF-positive tumor cells were detected in 62 (92.5 per cent) of the 67 primary esophageal carcinomas and in 18 (94.7 per cent) of the 19 metastatic lymph nodes. In this study, the immunoreactivity of hEGF was classified into 4 grades according to the number of stained tumor cells. A significant correlation was observed between the histologic type and the grade of hEGF immunoreactivity (Chi-square test, p less than 0.01). hEGF immunoreactivity in well differentiated squamous cell carcinomas was significantly higher than in other squamous cell carcinomas, although there were no correlations between other pathological findings and hEGF immunoreactivity. Patients with hEGF immunoreactivities of grades II or III had much worse prognoses than those with grades 0 or I (p less than 0.05). In 22 esophageal carcinomas and 10 normal esophageal mucosae, EGF receptor (EGFR) contents were measured by the competitive binding assay. The average EGFR content (101.3 +/- 35.7 fmol/mg protein, mean +/- SE) of the esophageal carcinomas was significantly higher than that (5.3 +/- 1.2) of the normal esophageal mucosae (p less than 0.05). Moreover, in hEGF negative tumors, EGFR contents were lower than in hEGF positive tumors. These results suggest that hEGF and EGFR show increased production in squamous cell carcinomas and could to be useful prognostic factors in patients with esophageal cancer.

Carcinoma, Squamous Cell↗

Growth fractions of breast cancer in relation to epidermal growth factor receptor and estrogen receptor.

Growth fractions detected by a monoclonal antibody, Ki-67, were examined in 40 human breast cancer tissues and the results compared with the immunocytochemical reactivities of epidermal growth factor receptor (EGFR) and estrogen receptor (ER). The proportion of proliferating cells displaying Ki-67 positive staining was significantly higher in the EGFR positive tumors than in the EGFR negative tumors (p less than 0.01). The average percentage of Ki-67 positive cells in the EGFR positive tumors was 19.9 per cent, whereas that in the EGFR negative tumors was 8.0 per cent. By contrast, an inverse relationship between the proportion of proliferating cells and ER positive cells detected by anti-ER monoclonal antibody was observed. This data indicated the difference in growth fractions with relation to the EGFR and ER status of breast cancer.

Breast Neoplasms↗

Significance of adenocarcinoma-associated antigen YH206 levels in the pancreatic juice.

We measured the pancreatic juice levels of antigen YH206, which is a new tumor marker of adenocarcinomas detected by monoclonal antibody YH206 (Hinoda et al., Int. J Cancer 24(5):653-658, 1988). Sandwich enzyme immunoassay revealed that samples from patients with pancreas cancer (n = 21) showed significantly higher values (P less than 0.01) than those of healthy controls (n = 15). Eight out of 21 (38.1%) samples from patients with pancreas cancer showed more than 100 U/ml, whereas only one out of 20 (5.0%) from patients with chronic pancreatitis exhibited more than 100 U/ml of antigen YH206. Simultaneous measurement of antigen YH206 and CA19-9 demonstrated that although a higher incidence of positivity in the case of pancreas cancer was obtained for both antigens, antigen YH206 showed much lower incidence of positivity (14%) than CA19-9 (57%) in patients with chronic pancreatitis. Therefore, the measurement of antigen YH206 in the pancreatic juice could be of use for the diagnosis of pancreas cancer.

Adenocarcinoma↗

An experimental evaluation of the order of revascularization after interrupting hepatic afferent blood flow.

The purpose of this study was to investigate the influence of the order of revascularization on hepatic metabolic function after interruption of hepatic afferent blood flow to reconstruct the portal vein and the hepatic artery. Hepatic ischemia was induced in male rabbits by clamping the afferent hepatic blood supply. In the cases in which portal blood flow was released after 15 min of hepatic ischemia and hepatic arterial blood flow was released 15 min later, hepatic metabolic function, which was assessed by arterial ketone body ratio, plasma lactate, and hepatic energy charge levels, recovered immediately. When hepatic arterial blood flow was released in the reverse order, the recovery of hepatic function was delayed. In the cases in which portal and hepatic arterial blood flow were released simultaneously after 30 min of hepatic ischemia, hepatic function did not recover even 180 min after reperfusion. In contrast, the venous bypass was established during portal clamping, restoration of hepatic function was accelerated, and there was no significant difference in restoration between the methods of releasing portal blood flow first or releasing hepatic arterial blood flow first. In the method of simultaneous releasing, however, it was most delayed, probably due to the prolonged ischemic time. These results suggest that releasing first the portal or hepatic arterial blood flow with the establishment of venous bypass during the portal clamping would be the best order of revascularization for hepatic function when reconstructing the portal vein and the hepatic artery.

Animals↗

Effect of a platelet activating factor antagonist (CV6209) on shock caused by temporary hepatic inflow occlusion.

Platelet activating factor (PAF) is a newly discovered inflammatory chemical mediator, which was reported to play a pivotal role in various types of shock. There is also a great possibility that PAF plays an important role in the shock caused by hepatic inflow occlusion. In the present study, the effect of CV6209, a PAF antagonist, on the shock caused by the occlusion was investigated. Intravenous 3 micrograms/kg of PAF caused hypotension in Wistar rats (n=6), and pretreatment with intravenous 3 mg/kg of CV6209 significantly (p less than 0.01) prevented the hypotension (n=6). Forty-five minutes of hepatic inflow occlusion caused hypotension in rats during the occlusion period, and the hypotension continued even after restoration of blood flow in control group (pretreated with saline i.v. only, n=5). In contrast, this hypotension was significantly (p less than 0.01) reversed in PAF antagonist group (pretreated with 3 mg/kg of CV6209 i.v., n=5). In sham-operated rats (n=6), arterial pressure remained unchanged and not hypotensive during the monitoring period. The survival rate of rats 90 minutes after declamp was 30% in control group (n=20), and that was significantly (p less than 0.05) improved to be 65% in PAF antagonist group (n=20). In conclusion, PAF plays an important role in the shock and death caused by temporary hepatic inflow occlusion, and a PAF antagonist could be a therapeutic drug against temporary hepatic inflow occlusion.

Analysis of Variance↗

Antineoplastic effect of erbstatin on human mammary and esophageal tumors in athymic nude mice.

The growth of MCF-7, a human mammary carcinoma, in athymic nude mice was inhibited by intraperitoneal administration of erbstatin for 14 days in combination with an iron chelator, foroxymithine, which inhibits the decomposition of erbstatin. Another human mammary carcinoma, Br-10, was not affected. Foroxymithine alone had no anti-tumor activity. In four esophageal tumors, erbstatin retarded tumor growth. There were no side-effects in any erbstatin-treated group. Levels of epidermal growth factor receptors were not changed throughout treatment with erbstatin at any dose. Erbstatin, a tyrosine kinase inhibitor, may have an antineoplastic effect against human mammary and esophageal tumors.

Animals↗

Clinical correlations with chemosensitivities measured in a simplified tritiated thymidine incorporation assay in patients with malignant effusion.

Utilizing a simplified tritiated thymidine incorporation assay, in vitro chemosensitivity of tumor cells obtained from malignant effusions was assessed and, in these patients, chemotherapeutic drugs were administered directly into the peritoneal or pleural cavity. Then, correlations between in vitro sensitivity and clinical response were investigated. Fifteen (88%) of 17 patients with various carcinomas gave evaluable chemosensitivity results. All 15 patients were evaluable for in vitro-in vivo correlations. This assay had an accuracy of 75% for prediction of response (3 of 4) and an accuracy of 82% for prediction of resistance (9 of 11), when the peak achievable plasma concentrations were selected as the concentrations used for in vitro sensitivity testing, adopting 80% inhibition of thymidine incorporation as cutoff level.

Adult↗

Increased gamma-aminobutyrate aminotransferase activity in brain of patients with Alzheimer's disease.

In order to search for more proximal factors in the pathogenesis of Alzheimer's disease, we studied the activities of various enzyme in the brains of patients, as well as control cases, by postmortem autopsy. In addition to the findings already known, such as the increase in prolyl endopeptidase (post-proline cleaving enzyme, PPCE) activity and the decrease in kallikrein activity, we found, anew, an increase in aminobutyrate aminotransferase (GABA-T) activity in the Alzheimer brain. This may be an important impetus for the reduction of gamma-aminobutyric acid (GABA) in the brain, one of the neurotransmitters. It has to be determined whether the former two abnormalities offer a background for such an abnormality of the neurotransmitter.

4-Aminobutyrate Transaminase↗

Increase in aminobutyrate aminotransferase and cholineacetyltransferase in cerebrum of aged rats.

We previously reported an increase in aminobutyrate aminotransferase (GABA-T) activity in the cerebrum of Alzheimer patients. In the present study, we investigated whether such findings are common in the usual aging process as well. We examined the activity of various enzymes, which were examined in the previous study, in the cerebrum of Wistar-Kyoto rats and spontaneously hypertensive rats. In the two strains, we compared the enzyme activities between the two groups of animals, 5 weeks and 13 weeks of age. In both strains, the older animals had significantly higher activities of GABA-T and choline acetyltransferase (ChAc-T). In spite of other enzymatic changes coexisting, the above two enzymes were suggested by discriminant function analysis to be playing a major role in the multiple enzymatic changes in the cerebrum of the animals.

4-Aminobutyrate Transaminase↗

Anti-receptor antibodies reverse the phenotype of cells transformed by two interacting proto-oncogene encoded receptor proteins.

The neu oncogene product, p185neu, is a tyrosine kinase receptor with structural similarity to the epidermal growth factor (EGF) receptor. We have recently described that coexpression of EGF receptors and high levels of normal p185c-neu lead to transformation of rodent fibroblasts. Anti-EGF receptor and anti-p185neu monoclonal antibodies inhibited tumorigenic growth of these transformants implanted into nude mice. These monoclonal antibodies also suppressed focus formation of the cells transformed by the synergistic action of these receptor proteins in vitro. However, EGF enhanced focus formation and stimulated cell growth when added to cells transfected just with the EGF receptor encoding cDNA. These data suggest that receptor specific effectors may have potentially useful applications in cancer therapy for neoplasms which demonstrate increased receptor densities. In addition the data suggest novel differences in the actions of tyrosine kinases when acting alone or in concert with other receptors.

Animals↗

Preparation and duplex-to-single strand transition of the fully complementary duplex of d(G4).d(C4) in aqueous solution.

The d(G4) and d(C4) molecules in the single stranded state were synthesized by the phosphotriester method and purified. The full duplex of tetramer d(G4).d(C4) was prepared by expending about a month. The duplex-to-single strand transition was observed by UV-spectroscopy. A standard hypochromic effect was observed, which is different from some experimental results reported previously.

DNA, Single-Stranded↗

Watersoluble synthetic nucleic acid analogs--polyethyleneimine derivatives containing nucleic acid bases--conformation and interactionwith nucleic acids.

Water soluble polyethyleneimine derivatives containing nucleic acid bases were found to interact with polynucleotides, DNA, RNA. The conformational change by formation of complex was observed by CD spectra and was discussed with the hypochromicity in UV spectra. The rates of interactions between nucleic acid bases in polymers were slow as shown by UV spectra, but the conformational changes of the polynucleotides were fast as shown by CD spectra. In the case of the uracil derivative (PEI-Hse-Ura), high value of CD spectra [theta] 2.80 = -8.0 x 10(-4) for the complex with DNA might be caused by psi type conformation of DNA.

Circular Dichroism↗

[A case of recurrence of a metastatic brain tumor which disappeared due to chemotherapy only].

A rare case of recurrence of a metastatic brain tumor which disappeared due to chemotherapy only is reported. A 52-year-old male was noticed to have an abnormal shadow in his chest X-P at a routine medical examination, so a close examination was made. He was diagnosed as having right renal cell carcinoma which had metastasized to the lung. He was treated by intra-arterial infusion of anti-cancer drugs and embolization of the right renal artery. No renal symptom was seen, growth of the primary tumor stopped, and the abnormal shadow in his chest diminished. However, weakness in the left hand appeared 19 months after the first examination and he was admitted to our clinic. He was alert, but slight left hand weakness was observed. CT scan revealed a diffusely enhanced mass in the right parietal lobe. Total removal of the brain tumor was performed and the histology was metastasis of renal cell carcinoma. He was discharged and was able to walk but he had slight left hemiparesis. UFT 6 capsules a day were administrated in our out-patient clinic. However, CT scan revealed recurrence of the tumor 2 weeks after discharge, we followed up with conservative treatment, and no growth of the tumor was seen. It disappeared 5 months after discharge after being treated with UFT only. We regard UFT as having been effective in this case.

Antineoplastic Combined Chemotherapy Protocols↗

Maxillary growth after two-stage palatal closure in complete (unilateral and bilateral) clefts of the lip and palate from infancy until 10 years of age.

The purpose of the study is to clarify the maxillary growth effects following different types of palatal closure in complete clefts of the lip and palate from infancy to 10 years of age. Lip repair, carried out at 5 months in one stage, was accomplished by Tennison's procedure. These patients were then assigned randomly to each of the 4 experimental groups according to the types of clefts and of palatal closure. One group of 14 patients in unilateral cases (Unil-S) and another group of 8 patients in bilateral cases (Bil-S) received mucoperiosteal palatal push-back procedure in a single stage at 20 months. The third group of 16 patients in unilateral cases (Unil-T) and the fourth group of 7 patients in bilateral cases (Bil-T) received the two-stage palatal closure based on Perko technique in which primary veloplasty was accomplished at 20 months and hard palate closure at 5 year 10 months. Non-cleft subjects were served as Controls. A longitudinal maxillary growth was monitored by the measurements of maxillofacial cast models obtained from each of the subjects. The results showed that the growth in depth and height of the maxilla of the Unil-T showed catch-up growth after primary veloplasty and resulted in no significant differences compared to that of the Control in the later phases, however, the Unil-S did not. The maxillary growth inhibition in height was characteristic in both Bil-S and Bil-T after palatal closure. There were no differences between the Bil-S and Bil-T in any dimensions and observation phases. The results indicate that the employment of the two-stage palatal closure is more beneficial for the unilateral cases, however, careful consideration is needed in bilateral cases.

Cephalometry↗