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T Sugimura

Publications and source records attributed to T Sugimura.

At least 415 records · Page 23Linked to original sources
PubMed1991

Mechanisms of action of okadaic acid class tumor promoters on mouse skin.

Okadaic acid, dinophysistoxin-1 (35-methylokadaic acid), and calyculin A are the okadaic acid class of non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, which do not bind to the phorbol ester receptors in cell membranes or activate protein kinase C in vitro. They have potent tumor-promoting activities on mouse skin, as strong as TPA-type tumor promoters, such as TPA, teleocidin, and aplysiatoxin. DNA samples isolated from tumors induced by dimethylbenz[alpha]anthracene and each of the okadaic acid class tumor promoters had the same mutation at the second nucleotide of codon 61 (CAA to CTA) in the c-H-ras gene. Okadaic acid receptors, protein phosphatases 1 and 2A, are present in the particulate as well as cytosolic fractions of various mouse tissues. The apparent "activation" of protein kinases by the okadaic acid class tumor promoters, after their incubation with 32P-ATP, protein kinases, and protein phosphatases, was observed. This activation was caused by inhibition of protein phosphatases 1 and 2A by the okadaic acid class tumor promoters. Treatment of primary human fibroblasts and human keratinocytes with the okadaic acid class tumor promoters induced the hyperphosphorylation of a 60-kDa protein in nuclear and cytosolic fractions, due to the inhibition of protein phosphatases. The 60-kDa protein is a proteolytic fragment of nucleolin, a major nonhistone protein and is designated as "N-60." The mechanisms of action of the okadaic acid class tumor promoters are discussed with emphasis on the inhibition of protein phosphatase activity.

Animals↗
PubMed1991

Coronary artery distensibility in Kawasaki disease--evaluation by intracoronary infusion of isosorbide dinitrate in long-term follow-up.

The coronary artery lesions in Kawasaki disease (KD) are thought to be a possible risk factor for atherosclerosis in the long term from the pathological point of view. Here we report results of a comparative control study to investigate the distensibility of the coronary artery in KD. A total of 146 patients were divided into 5 groups as follows. (I) Normal group (N); consisting of 44 patients with a known history of KD but with no coronary artery lesion. Among this group of patients those who each showed a regression in their coronary artery aneurysms were divided into 2 subgroups according to the time since onset of KD. (II) A group in the early stage after regression (ER); consisting of 18 patients with a known history of KD followed for 1.8 +/- 0.6 years. (III) A group in the later stage after regression (LR); consisting of 22 patients with a known history of KD followed for 9.4 +/- 2.8 years. (IV) an abnormal group (A); consisting of 21 patients followed for 7.9 +/- 4.0 years with a persistent aneurysm and/or stenosis in a coronary artery at the time of this study. And (V) a control group (C); consisting of 41 patients with a congenital heart disease such as a small ventricular septal defect or mild pulmonary stenosis or patent ductus arteriosus and no history of KD. In each case, the coronary artery diameter was measured by angiography before and after intracoronary infusion of isosorbide dinitrate (ISDN).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Detection of retTPC/PTC transcripts in thyroid adenomas and adenomatous goiter by an RT-PCR method.

A reverse transcriptase-polymerase chain reaction (RT-PCR) method was adopted for detecting transcripts specific for retTPC/PTC, an activated form of the ret proto-oncogene reported to be found specifically in human papillary thyroid carcinomas. By this sensitive method retTPC/PTC transcript could be detected in about 500 fg of total RNA of TPC-1, a retTPC/PTC transcript-positive cell line. In Japanese patients, one of 11 papillary thyroid carcinomas, four of 19 follicular adenomas and one of two adenomatous goiters were positive for the transcript, indicating that the involvement of retTPC/PTC is not specific to papillary thyroid carcinomas. In several independent RT-PCR experiments using different portions of the same positive carcinoma tissue, retTPC/PTC transcript was always detected. On the other hand, the transcript was not always positive in different RNA samples from benign cases, suggesting that positive carcinomas are probably composed of clonal cell populations all expressing retTPC/PTC, whereas adenomas and adenomatous goiter comprise heterogeneous populations: both positive and negative for retTPC/PTC transcript. Activation of the ret proto-oncogene might therefore be involved in malignant conversion to thyroid carcinomas.

3T3 Cells↗
PubMed1991

[The effect of conservative and surgical management for secondary hyperparathyroidism and their problems].

We compared the effect of conservative treatment with that of surgical treatment after applying them on secondary hyperparathyroidism patients (2nd HPT) in order to study the application of surgery on 2nd HPT patients. We selected the test subject of 39 maintenance dialysis patients with complications of 2nd HPT. The conservative treatments were; elcitonine administration (40 u x 3/W) (group 1), ipriflavon administration (200 mg x 3/day) (group 2), and pulse treatment (1.25 (OH)2D3 6 micrograms/W) (group 3). For surgical treatment, we adopted total parathyroidectomy with auto-transplantation into the arm (PTX). The transition of serum parathyroid hormone (PTH-C), alkali-phosphatase (ALP), bone scintigraphy of every 6 months, and change of bone mineral content (BMC) were compared to judge the effects of treatments. We measured 1/3, 1/6 radial region with single photon absorptiometry (SPA) and L3 region with dual photon absorptiometry (DPA) to obtain BMC. We were forced to transfer the patients in groups 1 and 2 (conservative treatment) to pulse treatment or PTX as 12 months later they showed increase in serum PTH-C, ALP and significant drop (P less than 0.05) in BMC average change rate (1/3). In group 3 of pulse treatment, though significant decrease in serum ALP (P less than 0.01) was detected for 10 cases out of 12, serum PTH-C was either unchanged or increased for 4 cases with the value of more than 30 ng/ml. Furthermore the average change rate of BMC stayed at the same level.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1991

Expression of the ret proto-oncogene in human neuroblastoma cell lines and its increase during neuronal differentiation induced by retinoic acid.

Previously we observed specific expression of the ret proto-oncogene (proto-ret) in human neuroblastoma cell lines. A neuronal subline and non-neuronal sublines were isolated from the SK-N-SH cell line, which is composed of a heterogeneous cell population. Expression of proto-ret was detected in the neuronal subline, named SH-4305, but not in three non-neuronal sublines. Expression of proto-ret in the SH-4305 cells increased markedly after treatment with retinoic acid for 1 day, with concomitant morphological change, namely neurite outgrowth, and induction of neurofilament mRNA expression. Induction of proto-ret expression seemed to be correlated with neurite outgrowth and increase of neurofilament mRNA expression. These data suggest that the proto-ret product plays a role in neuronal differentiation.

Blotting, Northern↗
PubMed1991

[Research on the treatment of secondary hyperparathyroidism as a complication of chronic renal failure].

The effects of internal treatment were compared with those of surgical procedures on secondary hyperparathyroidism as a complication of chronic renal failure patients in order to study their applications and problems. Maintenance hemodialysis patients complicated with 2HPT were selected as test subjects. The following internal treatment was administered. 1) Elcitonine to 6 cases and 2) Ipriflavon to 5 cases respectively and applied 3) pulse therapy of 1.25(OH)2D3 to 12 cases. On the other hand, total parathyroidectomy and autotransplantation were carried out as surgical procedures. The results of the treatment were evaluated by comparing serological data including tartrate resistant acid phosphatase (TAP) measured with the passage of time, bone scintigram findings, and change of bone mineral content (BMC) measured by single photon absorptiometry and dual photon absorptiometry. In the pulse therapy group, an oral tolerance test of 6 micrograms of 1.25(OH)2D3 was carried out to investigate its relation to long term prognosis. Furthermore, in both the pulse therapy group and PTX group, serum aluminum (A1) and delta A1 calculated by Defferoxamine (DFO) tolerance test were measured. The results are as follows. 1) In Elcitonine and Ipriflavon administration groups, increase of ALP and PTH and decrease of BMC (p less than 0.05) were recognized. 2) In the pulse therapy group, although the patients with PTH-C less than 30 ng/ml showed decrease in PTH both in short and long terms, cases with PTH-C more than 30 ng/ml kept the same level in PTH. Regardless of the change of PTH and ALP, there was no significant change observed in BMC. 3) In the PTX group, ALP/TAP ratio rose by 900% temporarily and BMC increased (p less than 0.01) in all regions measured. 4) Serum A1 and delta A1 were decreased (p less than 0.01) in PTX cases and in the pulse therapy cases in which ALP was decreased. In recent years, internal treatments on 2HPT patients have become diversified. However, exacerbation of 2HPT considered as an escape phenomenon caused the decrease in BMC after exclusive calcitonine preparatives administration. Pulse therapy, which is regarded at present as most effective in reducing PTH, ALP, did not work to increase BMC efficiently. In other word, in order to attain efficient BMC increase action, it is necessary to transfer from bone resorption phase to formative phase rapidly with drastic decrease of PTH and TAP observed in PTX.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗
PubMed1991

Genetic alterations in human gastric cancer.

Most types of human tumors display a consistent set of genetic alterations that are thought to play a role in tumor development and progression. In the case of gastric carcinomas, consistent genetic changes have been difficult to identify because (1) the tumor DNA samples are often heavily contaminated with DNA from normal stromal cells and (2) the tumors are heterogeneous in origin. However, with the recent application of more refined molecular genetic techniques, it has become clear that gastric carcinomas display some of the same genetic alterations observed in other common carcinomas. These changes include point mutation of the ras oncogene and the p53 tumor suppressor gene, gene amplification, and chromosomal loss of heterozygosity.

Chromosome Deletion↗
PubMed1990

The zinc fingers of human poly(ADP-ribose) polymerase are differentially required for the recognition of DNA breaks and nicks and the consequent enzyme activation. Other structures recognize intact DNA.

The recognition of double-stranded DNA breaks and single-stranded nicks by human poly(ADP-ribose) polymerase and the consequent enzymic activation were examined using derivatives of the enzyme expressed in Escherichia coli. The N-terminal 162 residues encompass two zinc fingers. Deletion or mutation of the first finger results in a loss of activation by DNA with either single-stranded or double-stranded damage. Destruction of the second finger reduces activation by double-stranded DNA breaks only slightly, but eliminates activation by single-stranded DNA nicks. These data suggest that activation by single-stranded DNA nicks requires two zinc fingers, but activation by double-stranded DNA breaks requires only the finger closer to the N terminus. Variant proteins that lack both zinc fingers are enzymically inactive but still exhibit weak DNA binding, which is independent of DNA damage. Thus, other regions are also capable of binding intact DNA, but the recognition of a strand nick or break which occasions the synthesis of poly(ADP-ribose) specifically requires the zinc fingers.

Amino Acid Sequence↗
PubMed1990

Point mutation of the p53 gene resulting in splicing inhibition in small cell lung carcinoma.

The p53 gene is functionally inactivated mostly by point mutations resulting in amino acid substitutions in a wide variety of human cancers. We found a novel mutation of the p53 gene in a small cell lung carcinoma cell line, Lu-143. One of the allelic p53 genes was lost accompanied by loss of heterozygosity for chromosome 17. In the remaining allelic p53 gene, there was a single-base substitution of G to T at position 1 within the splice donor site of intron 7, and the mutated intron was not spliced out during the mRNA maturation process. As a result of this mutation, larger sized p53 mRNA was expressed and no p53 specific protein was detected in this cell line. These results suggest that mutations causing splicing abnormalities are one of the molecular mechanisms for the p53 gene inactivation in human cancer.

Alleles↗
PubMed1990

Striking similarity of the distribution patterns of the poly(ADP-ribose) polymerase and DNA polymerase beta among various mouse organs.

The expression level of poly(ADP-ribose) polymerase mRNA as well as the level of enzymatic activity were examined in various mouse organs by northern blot and activity gel analyses. High levels of the mRNA expression and enzymatic activity were observed in testis, thymus, spleen, and brain. On the other hand, low levels of the mRNA expression and enzymatic activity were observed in liver and kidney. These findings suggest that the expression of the poly(ADP-ribose) polymerase is mainly regulated by transcription. Striking similarity was observed between the patterns of organ distribution of enzymatic activities of poly(ADP-ribose) polymerase and DNA polymerase beta in various mouse organs.

Animals↗
PubMed1990

Protein phosphatases possibly involved in rat spermatogenesis.

The expression of mRNAs for catalytic subunits of serine/threonine protein phosphatases 1 (PP-1) and 2A (PP-2A) in various rat tissues were examined. Four kinds of probes were used to detect mRNAs for two isotypes of PP-1 (dis2m1 and dis2m2), and two isotypes of PP-2A (PP-2A alpha and PP-2A beta). mRNAs for all of these four catalytic subunits were expressed in almost all tissues at substantial levels. They were expressed in two different sizes in most tissues. Remarkable evidence is that the smaller sized mRNAs of dis2m1 and PP-2A beta, 1.8 kb and 1.4 kb in length, respectively, were specifically highly expressed in testis. Both these smaller sized mRNAs began to be expressed at the age when meiosis started and were detected in testicular germ cells at the pachytene stage of meiotic prophase. Protein phosphatases which have peptides encoded by dis2m1 and PP-2A beta as catalytic subunits may play important roles in spermatogenesis.

Animals↗
PubMed1990

Photoaffinity labeling of protein phosphatase 2A, the receptor for a tumor promoter okadaic acid, by [27-3H]methyl 7-O-(4-azidobenzoyl)okadaate.

The interaction of okadaic acid and a protein phosphatase, which is the receptor for a tumor promoter, okadaic acid, was studied. [27-3H]Methyl 7-O-(4-azidobenzoyl)okadaate was synthesized and protein phosphatase 2A, which consists of two regulatory subunits of 65 kDa and 42 kDa and a catalytic subunit of 37 kDa, was purified from bovine brain. After UV irradiation of the reaction mixture, [3H]methyl 7-O-(4-azidobenzoyl)okadaate covalently bound to the catalytic subunit, but not to the two regulatory subunits. These results strongly suggest that okadaic acid, a potent inhibitor of protein phosphatases, binds specifically to the catalytic subunit rather than to the other regulatory subunits.

Affinity Labels↗
PubMed1990

Tumor-promoting activity of staurosporine, a protein kinase inhibitor on mouse skin.

Staurosporine, which is a potent inhibitor of protein kinases, such as protein kinase C, inhibited both inductions of adhesion of human promyelocytic leukemia cells (50% effective dose = 9.0 nM) and Epstein-Barr virus early antigen in Raji cells (50% effective dose = 3.4 nM) by teleocidin. However, staurosporine induced irritation on mouse ear and histidine decarboxylase activity in mouse skin. It did not induce ornithine decarboxylase activity in mouse epidermis. The two-stage carcinogenesis experiments of staurosporine were carried out at two different doses. Experiment 1 revealed that the group treatment with a single application of 100 micrograms of 7,12-dimethylbenz(a)anthracene, followed by repeated applications of 50 micrograms of staurosporine, resulted in 85.7% of tumor-bearing mice at Wk 30, whereas group treatment with staurosporine alone or 7,12-dimethylbenz(a)anthracene alone gave 6.7% and 0%, respectively. Experiment 2 showed that group treatment with 7,12-dimethylbenz(a)anthracene followed by applications of 10 micrograms of staurosporine resulted in 33% of tumor-bearing mice at Wk 30. In addition, staurosporine treatment reduced the percentages of tumor-bearing mice treated with teleocidin from 100% to 67% in Wk 15. These results demonstrated that staurosporine is a weak tumor promoter of mouse skin compared with teleocidin, but staurosporine has some potency to inhibit tumor promotion by teleocidin.

Alkaloids↗
PubMed1990

Production of shorter mRNA for protein phosphatase 2A beta by alternative poly(A) addition.

Two types of cDNA clones of protein phosphatase 2A beta, PP-2A beta L and PP-2A beta S, were isolated from a rat testis cDNA library. PP-2A beta L was 1.8 kb in length and corresponded to the 2.0 kb mRNA that is the major species expressed in somatic tissues. PP-2A beta S was 1.3 kb in length and corresponded to the 1.4 kb mRNA that is the major species expressed in germ cells of the testis. Nucleotide sequencing of these two clones revealed that their open reading frames were identical. The only difference between these two cDNAs was at the 3' non-coding region due to alternative poly(A) addition: the 1.8 kb cDNA had a consensus poly(A) addition signal, AATAAA, but the 1.3 kb cDNA had an unusual poly(A) addition signal, probably with the sequence AATATA. These data suggest that in germ cells there may be some mechanism that utilizes the specific poly(A) addition signal.

Animals↗