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Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 487 records · Page 27Linked to original sources

Interactions of thyroid hormones with L-(3H) glutamate binding sites, with special reference to N-methyl-D-aspartate receptors.

An L-(3H)glutamate binding assay was developed in which 82% of the specific binding is to a site that corresponds to the N-methyl-D-aspartate receptor. The effects of various anticonvulsants and thyroid hormones were investigated with this assay. Anticonvulsants did not affect L-(3H)glutamate binding, while L- and D-isomers of triiodothyronine and thyroxine inhibited L-(3H)glutamate binding significantly. Scatchard analysis showed that thyroid hormones interacted with L-(3H)glutamate binding competitively. The interactions of thyroid hormones with NMDA-sensitive L-(3H)glutamate binding may be one of the mechanisms by which these hormones affect the central nervous system.

Amino Acids↗

[Clinical study of large doses of vecuronium; duration of initial and additional doses].

Neuromuscular blockade by large doses of vecuronium was investigated clinically and the duration of action of initial doses (0.2 mg.kg-1 and 0.3 mg.kg-1) and additional doses (0.01 mg.kg-1 and 0.02 mg.kg-1) were measured under enflurane-nitrous oxide anesthesia using a neuromuscular transmission monitoring system (Accelograph). In group A (initial dose = 0.2 mg.kg-1, additional dose = 0.02 mg.kg-1), the time of spontaneous recovery to 25% of control twitch height (T25) and 50% of control (T50) were 63.1 and 82.0 minutes respectively. The T50 interval of the two adjacent added doses (given at the time point of 50% recovery from the previous dose) was 31.1 minutes. Reversal time from TOF ratio = 25% to 75% after administration of edrophonium was 6.1 minutes. In group B (initial = 0.3 mg.kg-1, add. = 0.01 mg.kg-1), T25, T50, T50 interval and reversal time were 122.6, 159.4, 39.2 and 4.6 minutes respectively. In group C (initial = 0.3 mg.kg-1, add. = 0.02 mg.kg-1), above values were 119.2, 145.8, 48.4 and 6.7 minutes respectively. In this study there was no obvious side effect associated with administration of large doses of vecuronium. These methods will be very useful for long surgical procedures.

Female↗

Glanzmann's thrombasthenia associated with a transient deficiency of factor XIII.

A three-year-old girl suffering from ecchymoses developed severe epistaxis. The diagnosis of thrombasthenia was made on the basis of platelet aggregation studies, flow cytometric analysis with monoclonal antibodies and gel electrophoretic analysis. In addition, coagulation studies at the time of epistaxis repeatedly showed a transient deficiency of factor XIII activity and antigen.

Blood Platelet Disorders↗

[Ultrasonographic evaluation of the endometrium in postmenopausal women to select the high risk group of endometrial carcinoma of the uterus].

We examined the usefulness of ultrasonography (USG) for endometrial cancer screening in postmenopausal women. 207 postmenopausal women were ultrasonographically examined. The endometrial echo was classified into 4 types: 1, anechoic; 2, hair-line; 3, linear; and 4, navicular, and was compared with histological findings. No abnormal histological findings were observed in the cases showing type 1 and 2. On the other hand, abnormal histological findings including endometrial hyperplasia, atypical hyperplasia, and endometrial cancer, were seen in 57.7% (15/26) of type 3 cases, and 65.6% (21/32) of type 4 cases. Furthermore, type 3 and 4 women had enlargement of the uterus, and an increased incidence of postmenopausal bleeding. Positive rates in the progesterone challenge test (PCT) and karyopicnotic index (KPI) were higher in type 3 and 4 cases than in type 1 and 2. It was concluded that USG is able to accurately determine the endometrial condition and is useful for identifying high-risk patients in endometrial cancer screening.

Aged↗

[Evaluation of the 1987 revised ARA criteria for rheumatoid arthritis in Japan].

Three hundred and sixty two Japanese patients with rheumatoid arthritis (RA) and 455 patients with other rheumatic diseases (SLE 233, PSS 63, MCTD 51, PM-DM 41 Behcet's disease 33 and OA 33) were examined for the evaluation of the 1987 revised ARA criteria for RA. In our cases sensitivity was slightly decreased and specificity was markedly increased 5 out of 7 criterions compared with the results reported by ARA. In the investigation how many number of criterions at least which the patients with RA should satisfy, 4 out of 7 criterions in the 1987 criteria turned out the highest figure in the accuracy (the mean of sensitivity and specificity values). So the patients who satisfied at least 4 criterions were classified to have RA. Sensitivity of the 1987 criteria decreased to 90% although that of the 1958 ARA criteria was 93%. Specificity were markedly increased from 88% to 95% (the 1958 and 1987 criteria, respectively). These results might be based on the revision of the duration of "morning stiffness" (lasting at least 1 hour) and on the deletion of "joint pain or tenderness" which was relatively less specific for RA.

Arthritis, Rheumatoid↗

[Clinical evaluation of cefodizime in children].

Cefodizime (THR-221, CDZM), a new parenteral cephalosporin, was evaluated for its efficacy and safety in 20 children with bacterial infections (Table 1), and the following results were obtained. 1. CDZM was administered in 3 or 4 divided doses at daily dosages ranging from 54.5 to 84.2 mg/kg administered by 30 minutes drip infusion or intravenous injection to 20 patients (7 cases of acute tonsillitis, 6 cases of pneumonia, 2 cases each of bronchitis and suppurative cervical lymphadenitis, and 1 case each of acute pharyngitis, acute enteritis and furunculosis) and the following clinical results were obtained: excellent, 7 cases; good, 11 cases; fair, 2 cases. The overall efficacy rate was 90% (Table 4). 2. MICs of CDZM against 15 strains of isolated organisms are shown in Table 2. MICs against all 7 strains of Haemophilus influenzae were less than 0.025 micrograms/ml. MIC against 1 out of 5 strains of Streptococcus pneumoniae was 0.05 micrograms/ml and those against 2 strains were 0.10 micrograms/ml and against the other 2 were 0.20 micrograms/ml. MICs against 3 strains of Staphylococcus aureus were 1.56, 25 and higher than 100 micrograms/ml, respectively. 3. No clinical adverse reaction was observed in any of the 20 patients. Eosinophilia was observed in 2 cases. A slight elevation of S-GOT was found in 1 patient (case No. 8) and moderate elevation of S-GOT and S-GPT in another (case No. 18) (Table 4). In case No. 18, the S-GOT and S-GPT activity improved after the administration of the drug was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Mode of action of erythropoietin (Epo) in an Epo-dependent murine cell line. II. Cell cycle dependency of Epo action.

Erythropoietin (Epo), a glycoprotein hormone, regulates the proliferation and differentiation of committed erythroid progenitor cells. We investigated the effect of Epo on the kinetics of an Epo-dependent cell line (DA-1ER), which was cloned from the murine interleukin 3-dependent cell line, DA-1. Flow cytometry and [3H]thymidine incorporation were used to analyze the cell cycle. Removal of Epo from the culture medium resulted in the accumulation of the cells in the G1 phase. Eighteen hours after the removal of Epo, 75%-80% of the cells were arrested in G1 phase. Readdition of Epo to these quiescent cells allowed them to progress from the G1 to the S phase with a lag period of 10 h. Epo was required throughout the lag period in order to achieve maximal DNA synthesis. When the cells were arrested in the G2/M phase or the G1/S interphase by colcemid and thymidine, respectively, and then released from the arrest, they could complete the cell cycle in the absence of Epo. These findings suggest that Epo is only required in the G1 phase for the cells to progress through the cell cycle.

Animals↗

Tissue-type plasminogen activator in patients with intracranial meningiomas.

Three of 13 patients with intracranial meningiomas showed the pre- and postoperative elevation of tissue-type plasminogen activator (t-PA) related fibrinolytic activity in euglobulin fractions (EFA). During operation, two of these three patients showed a significant elevation of the level of fibrin(ogen) degradation products and oozing in the operating field. However, oozing was not observed in the third patient who had been given tranexamic acid preoperatively. Fibrin autography revealed that a broad lytic band of mol wt 50-60 kDa, probably free t-PA, appeared in the plasma obtained from two of the three patients after operation when EFA elevated significantly. In all patients studied, the t-PA antigen levels were normal preoperatively but increased both during and after operation, and correlated mainly with the intensities of a lytic band of mol wt 110 kDa, probably t-PA complexed with its major inhibitor (PAI-1). These results suggest that the excessive fibrinolysis can induce the local hemorrhagic diathesis during operation and may be related to t-PA function in plasma.

Adult↗

Molecular cloning of rat phosphoprotein phosphatase 2A beta cDNA and increased expressions of phosphatase 2A alpha and 2A beta in rat liver tumors.

A cDNA clone coding for an isotype of the catalytic subunit of rat phosphoprotein phosphatase 2A was isolated. The deduced amino acid sequence of the clone was different at 8 positions from that of rat phosphatase 2A alpha determined in a previous study. The deduced amino acid sequence of the clone was, however, identical to that of human phosphatase 2A beta and differed only at one position from that of rabbit 2A beta. Thus, the isolated cDNA was identified as a clone coding for rat phosphatase 2A beta. Using a 2A beta specific probe, two kinds of transcripts were detected in rat liver: a major 2.0 kb mRNA transcript and a minor 1.4 kb mRNA transcript. These transcripts were both greatly increased in rat liver tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) regardless of the carcinoma or hyperplastic nodule.

Amino Acid Sequence↗

Increasing incidence of hepatocellular carcinoma possibly associated with non-A, non-B hepatitis in Japan, disclosed by hepatitis B virus DNA analysis of surgically resected cases.

At the National Cancer Center Hospital in Japan, the total number of surgically treated hepatocellular carcinomas (HCCs) has been increasing steadily and rapidly over the last 10 years, whereas the number of cases positive for hepatitis B surface antigen in sera (HBsAg) has remained almost stable. Thus, the relative percentage of HCC cases with serum HBsAg has shown a marked decrease. In order to examine whether this increased proportion of HBsAg-seronegative patients carries hepatitis B virus (HBV) DNA in the liver, we extracted DNA from the formalin-fixed and paraffin-embedded cancerous and noncancerous liver tissues of 79 patients with HCC. The HCCs examined included 49 specimens resected during a period from 1970 to 1980 and 30 resected in 1986 and 1987. We were able to detect reliably the presence of HBV DNA by dot-blot hybridization. The presence of HBV DNA in liver tissues showed a good correlation with positivity for serum HBsAg in both examined groups. In total, HBV DNA was detected in 81% (21 of 26) of HBsAg-seropositive cases and in only 8% (4 of 53) of HBsAg-seronegative cases, indicating that the increased number of HBsAg-seronegative cases had no HBV involvement. Among these HBsAg-seronegative HCC patients, 89.7% showed a histology of cirrhosis or chronic active hepatitis in the noncancerous liver and 29.1% had a history of blood transfusion. These results suggest an increasing incidence of non-A, non-B hepatitis-associated HCCs in Japan and the possible transmission of factors by means other than blood transfusion.

Carcinoma, Hepatocellular↗

Modification of N-methyl-N'-nitro-N-nitrosoguanidine-induced forestomach and glandular stomach carcinogenesis by phenolic antioxidants in rats.

The modifying effects of five phenolic antioxidants on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated forestomach and glandular stomach carcinogenesis were investigated in male F344 rats. Groups of 20 rats were given an intragastric dose of 150 mg/kg body weight MNNG, and starting from 1 week later received diet supplemented with 0.8% catechol (CC), 1.0% 2-tert-butyl-4-methylphenol, 1.5% p-tert-butyl-phenol, 1.5% methylhydroquinone, 1.5% 4-methoxyphenol (4MP), or basal diet alone for 51 weeks. Further groups of 10-15 rats were maintained as controls without prior treatment with MNNG. The incidences of squamous cell carcinoma of the forestomach in MNNG-treated animals were significantly elevated by the diets containing CC (P less than 0.001), 2-tert-butyl-4-methylphenol (P less than 0.001), or p-tert-butylphenol (P less than 0.01), while the development of carcinoma in situ was inhibited by 4MP (P less than 0.01). Treatment with CC, 2-tert-butyl-4-methylphenol, p-tert-butylphenol, or 4MP alone induced forestomach hyperplasia at incidences of 86.7, 40, 93.3, and 100%, respectively. In the pyloric region of the glandular stomach, the development of adenomatous hyperplasia and adenocarcinoma after MNNG treatment was significantly enhanced by diet containing CC (P less than 0.001). Moreover, treatment with CC alone induced 100% adenomatous hyperplasia and induced adenocarcinoma in 20% of animals. These results clearly demonstrated that while antioxidants causing proliferation in forestomach epithelium can markedly enhance carcinogenesis in this tissue, others displaying the same or greater potential for generating a hyperplastic response, like 4MP, can exert an inhibitory effect. In addition, it was shown that CC, which is widely present in our environment, is an unequivocal glandular stomach carcinogen also possessing strong enhancing activity for MNNG-induced lesion development.

Animals↗

Differential expression of c-myc and the transferrin receptor in G1 synchronized M1 myeloid leukemia cells.

We have studied the transcriptional activity, steady-state mRNA levels, and steady-state protein levels of the c-myc and transferrin receptor (TfR) genes in murine M1 myeloid leukemia cells arrested in G1 phase of the cell cycle by different methods. When cells are growth-arrested by density inhibition, a technique that places the majority of cells in early G1, c-myc protein, as detected by Western analysis, is expressed at 80% of the level seen in proliferating cells. Steady-state mRNA levels and, to a lesser extent, transcriptional activity of the c-myc gene, parallel the protein findings. Under these conditions, TfR gene expression is much lower than in normally cycling cells. We have previously demonstrated that density-inhibited M1 cells, released from density inhibition and treated with the DNA polymerase alpha inhibitor aphidicolin, remain in G1, but at a point temporally closer to S phase. Cells treated in this manner demonstrate reduced transcriptional activity and expression of the c-myc gene, but TfR gene expression approximates the level found in proliferating cells. These data suggest that neither c-myc nor TfR gene expression is constant throughout the G1 phase of the cell cycle in M1 cells. c-myc gene expression is highest in early G1 and falls to low levels by late G1, while the reverse is true for TfR gene expression.

Animals↗

Alteration of cell cycle progression in human leukemia cell line (KOPM-28) induced by 12-o-tetradecanoylphorbol-13-acetate.

Terminal cell differentiation usually results in an irreversible arrest in the G1 phase of the cell cycle and loss of cell renewal ability. Human promyelocytic leukemia HL-60 cells induced with 12-o-tetradecanoylphorbol-13-acetate (TPA) differentiate into monocytes/macrophages and accumulate in G1. We determined the effect of TPA on the growth kinetics of a human leukemia cell line (KOPM-28), which developed several of the characteristics of megakaryocytes in response to TPA, such as the surface antigen complex IIb/IIIa, platelet peroxidase and polyploidy. Cell growth was immediately and completely inhibited by TPA. Flow cytometric analysis of cellular DNA content revealed a gradual decrease in cells in G1 and an accumulation of cells in G2. These data suggest that TPA prolonged G1 and rapidly arrested the cells in G2. Synchronized cells were utilized to further analyze the rapid G2 arrest. Cells arrested with aphidicolin at the G1/S interphase were released, and the effects of TPA (added at different intervals) on cell cycle progression were examined 14 h after release. The results showed that TPA added at the end of the S phase, as well as at the G1/S interphase incompletely but distinctly arrested cells in G2. Moreover, G2 arrest was observed when TPA was added to cells released from a colcemid-induced G2/M block, suggesting that cells already in G2 were inhibited by TPA from moving through M to G1. Since some cells became multi-nucleated in the course of incubation with TPA, this G2 accumulation may have resulted at least in part from a prolongation of the phase or a transient G2 block. These changes in cell cycle progression induced by TPA may be characteristic of and/or related to megakaryocytic differentiation of hemopoietic precursor cells.

Cell Cycle↗

Histopathological classification of malignant lymphomas in slaughtered swine.

A histological classification of 36 cases of malignant lymphoma in slaughtered swine is reported. All the lymphomas observed were diagnosed as diffuse types and were further classified into four types by their histological characteristics based on the classification of the Japanese Lymphoma Study Group (Suchi et al., 1979). The cases consisted of 16 of the Burkitt type, 2 of the immunoblastic type, 3 of the medium-sized cell type and 15 of the mixed cell type. The histological appearances of these lymphomas were compared with those of human lymphomas. All tumours closely resembled non-Hodgkin's diffuse type of B cell lymphoma and differed from tumours in other sites such as the liver and kidneys.

Animals↗

Clonal origin of atypical adenomatous hyperplasia of the liver and clonal identity with hepatocellular carcinoma.

We present details of two separate nodular lesions of atypical adenomatous hyperplasia, within one of which a small area of overt hepatocellular carcinoma was detected. The patient was positive for serum hepatitis B surface antigen, and Southern blot analysis revealed that deoxyribonucleic acid from the lesions of hepatocellular carcinoma and surrounding atypical adenomatous hyperplasia showed the same restriction pattern of integrated hepatitis B virus deoxyribonucleic acid, indicating that the two lesions were derived from an identical clone. It was also indicated that the two separate lesions of atypical adenomatous hyperplasia were independently derived through clonal expansion of different cells.

Blotting, Southern↗

Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S-transferase placental form positive foci in rats--an approach for a new medium-term bioassay system.

A large series of assays of the hepatocarcinogenic potential of 112 different compounds were carried out using a rapid bioassay system developed in this laboratory based on the two-step concept of hepatocarcinogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p. and starting 2 weeks later were treated with test compounds for 6 weeks and then killed, all rats being subjected to two-thirds partial hepatectomy (PH) at week 3. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive (GST-P+) foci in the liver with those of the corresponding control group given DEN alone. Positive was scored for a significant increase in the value of GST-P+ foci, negative for no change or a decrease. Results were compared to reported Salmonella/microsome and long-term carcinogenicity test findings. Of the liver carcinogens, 10 out of 11 (90.9%) mutagenic, and 11 out of 13 (84.6%) non-mutagenic compounds gave positive results (mean, 87.5%). Carcinogens other than the hepatocarcinogens gave less positive results (two out of 17, 11.8%). None of the compounds reported as non-carcinogenic demonstrated positivity suggesting that the assay system does not suffer from the disadvantage of false-positive results. The protocol system also provided information concerning the inhibitory potential of compounds such as anti-oxidants. It is concluded that the present experimental protocol which requires far fewer animals and shorter duration than a long-term carcinogenicity test has practical applications for the rapid and economical screening of environmental hepatocarcinogens and their inhibitory agents.

Animals↗

Effect of modifying agents on the phenotypic expression of cytochrome P-450, glutathione S-transferase molecular forms, microsomal epoxide hydrolase, glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase in rat liver preneoplastic lesions.

The expression of A and P forms of glutathione S-transferase (GST-A and P), two cytochrome P-450 isoenzymes (P-450 PB3a and P-450 MC2), microsomal epoxide hydrolase (mEHb), glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyltranspeptidase (gamma-GT) was compared in preneoplastic liver lesions and background parenchyma of F344 rats post-treated with butylated hydroxyanisole (BHA), ethoxyquin (EQ) or acetaminophen (AAP). These latter three compounds have been shown to inhibit hepatocarcinogenesis after initial treatment with N-ethyl-N-hydroxyethylnitrosamine (EHEN) and a significant decrease in the number of enzyme-altered foci and nodules positive for GST-P, GST-A, G6PD and gamma-GT and negative for P-450 PB3a, P-450 MC2 was associated with their administration. Whereas in the foci case the decrease was most prominent for non-discrete (heterogeneous) type lesions, the results of quantitation of nodules revealed a most significant alteration in the discrete homogeneously staining population. This indicates that BHA, EQ and AAP have the potential to inhibit the growth of the phenotypically stable lesions thought most likely to be the immediate precursors of hepatocellular carcinomas. The two anti-oxidants were associated with periportal increase of all enzymes investigated, whereas AAP induced GST species and mEHb in the perivenular zone. Irrespective of slightly elevated enzyme levels in surrounding parenchyma, mEHb antibody binding levels within lesions showed a reciprocal shift from positive to negative in rats treated with BHA, EQ and AAP.

Animals↗