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Biomedical subjects

Y Kitagawa

Publications and source records attributed to Y Kitagawa.

At least 289 records · Page 16Linked to original sources
PubMed1989

[Multiple primary neoplasms in patients with multiple myeloma and primary macroglobulinemia].

A review of 65 patients with multiple myeloma (MM) and 10 patients with primary macroglobulinemia (PM) seen at our clinic from 1972 through 1988 revealed further cancers that were found in 11 patients with MM and in 2 patients with PM. In 4 of 13 patients with multiple primary neoplasms, either MM or PM was an antecedent. In 6 patients, MM or PM was coincident with the cancers. In 3 patients, the cancer was antecedent. Only one patient with multiple myeloma developed secondary leukemia following treatment with alkylating agents.

Adult↗
PubMed1989

Role of protein phosphatases in malignant transformation.

Many oncogene products are protein kinases and signals are transduced via phosphorylation of proteins. Similarly, protein-dephosphorylation may play a critical role in malignant cell transformation. We have cloned two catalytic subunits of ser/thr protein phosphatase (PP) type 2A, PP2A alpha, and PP2A beta, from a rat liver cDNA library. Both cDNAs encode peptides of 309 amino acids with a difference of only 8 amino acids between the two. All primary hepatocellular hyperplastic nodules or carcinomas, which were induced by a food carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline, showed up-regulation of expression of the mRNAs of both PP2A alpha and PP2A beta. NIH3T3 cell transformants obtained by introducing activated c-raf, ret-II or Ki-ras oncogenes also showed high levels of PP2A alpha transcripts. Okadaic acid, a non-TPA type tumor promoter, was found to be a potent inhibitor of PP1 and PP2A. Its IC50 for PP1 was much higher than that for PP2A with phosphorylase a as a substrate. When raf and ret-II transformants were cultured with okadaic acid at 8 ng/ml for 2 days, both transformants became flattened and showed strict contact inhibitions. This flat cell morphology was stable for at least one month in the presence of okadaic acid, but in its absence, the cells reverted to their original transformed shape within 7-10 days. Colony formation by raf and ret-II transformants in soft agar was inhibited dose-dependently by okadaic acid; very few colonies grew in the presence of the acid at 8 ng/ml. Okadaic acid had less effect on a transformant of the Ha-ras gene, causing only 50% inhibition of colony formation at 8 ng/ml. The role of protein phosphatases in cellular transformation by certain oncogenes is suggested.

Animals↗
PubMed1989

[A case report of leiomyosarcoma of the rectum].

A case of leiomyosarcoma of the rectum and a review of the relevant Japanese literature is reported. A 33-year-old man, suspected of having a rectal tumor was admitted to out hospital for though examination. The tumor was located at the anterior wall of the rectum behind the prostatic gland. A preoperative perineal biopsy was done and the pathological diameters was a leiomyosarcoma. The abdominoperineal resection was performed but the nerve was able to be preserved. The postoperative quality of life has been good. The difficulties in arriving at a histological differentiation of a simple tumors of the rectum from a malignant smooth muscle tumor of the rectum is discussed.

Adult↗
PubMed1989

[Adrenoleukodystrophy with high signal intensity areas in bilateral pyramidal tracts from internal capsule through medullary pyramids on MRI].

We reported a case of adrenoleukodystrophy in which MRI showed high signal intensity areas in the pyramidal tracts from the internal capsule through the medullary pyramids. A 20-year-old man was admitted with complaints of slowly progressive spastic paraparesis of one and a half year duration. He had no mental deterioration, visual disturbance or sensory impairment. His maternal cousin died of adrenoleukodystrophy at the age of 13 years old, after showing progressive visual disturbance, dementia and quadriplegia. On admission, neurological examination revealed spastic tetraparesis and exaggerated deep tendon reflexes with pathological reflexes. Examination of the mental function and cranial nerves were normal. There were no sensory abnormalities in all modalities. Routine laboratory data including hematological studies, urinalysis, serum electrolytes and enzymes were all normal. Endocrinological examinations showed no adrenocortical insufficiency, and testicular function was normal. Cerebrospinal fluid, EEG, needle EMG and nerve conduction studies were also normal. CT scan showed a mild ventricular enlargement and no low density areas were seen in the cerebral white matter. Spin-echo MRI (SE 2,000/100, 2,000/40) revealed continuous high signal intensity areas in the pyramidal tracts from the internal capsule through medullary pyramids bilaterally. There were no abnormal findings in the spinal cord on MRI. Electrophysiologically, the brain-stem auditory evoked potentials (BAEPs) were abnormal and suggested the presence of bilateral dorsal brain stem lesions. Short latency somatosensory evoked potentials (SEPs) obtained by the bilateral tibial nerve stimulation revealed slowing of the central conduction time, showing delayed P37 latency and normal peripheral conduction time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenoleukodystrophy↗
PubMed1988

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↗
PubMed1988

Molecular cloning of cDNA for the catalytic subunit of rat liver type 2A protein phosphatase, and detection of high levels of expression of the gene in normal and cancer cells.

A cloned cDNA encoding a catalytic subunit of type 2A protein phosphatase from a rat liver cDNA library was obtained by use of a synthetic oligonucleotide corresponding to the tryptic peptide sequence of the purified enzyme. There was only a single amino acid difference between the deduced amino acid sequence of the clone obtained and those of the catalytic subunits, 2A alpha, of the rabbit skeletal muscle, porcine kidney and human liver enzymes, suggesting that this clone was a rat 2A alpha cDNA. On Northern blot analysis using a cDNA fragment as a probe, three mRNA species were detected in rat liver: a major mRNA of 2.0 kb and a minor one of 2.7 kb under high stringency conditions, and also a 1.1 kb mRNA under low stringency conditions. The 2A alpha gene was found to be highly expressed in various tissues of rat, especially the brain. High levels of expression of the gene were also detected in mouse NIH3T3 cells and their transformants, and in human cancer cell lines as well as a human immortalized cell line.

Amino Acid Sequence↗
PubMed1988

Enhanced synthesis and secretion of type IV collagen and entactin during adipose conversion of 3T3-L1 cells and production of unorthodox laminin complex.

Synthesis and secretion of basement membrane proteins by 3T3-L1 adipocytes were studied by metabolic labeling of the cells with [35S]methionine. Enhanced synthesis and secretion of many polypeptides of high molecular weight were observed by stimulating the adipose conversion of 3T3-L1 fibroblasts with dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Among these polypeptides, alpha 1(IV) and alpha 2(IV) chains of collagen were identified based on specific immunoprecipitation and digestion with bacterial collagenase. Synthesis and secretion of alpha 1(IV) and alpha 2(IV) chains were negligible in the fibroblasts, but remarkably enhanced in adipocytes. Based on specific immunoprecipitation of a sulfated polypeptide of 150 kDa, enhanced (6-fold) synthesis and secretion of entactin were also demonstrated. Immunoprecipitation with anti-laminin antiserum showed synthesis of three polypeptides with sizes corresponding to B subunits but failed to demonstrate synthesis of the A subunit. Synthesis of these laminin-related polypeptides remained constant during the conversion. Nonreducing sodium dodecyl sulfate electrophoresis showed intracellular assembly of three laminin-related polypeptides into binary and ternary complexes in a similar sequence of AB1B2 formation via B1B2 in embryonal carcinoma F9 (Morita, A., Sugimoto, E., and Kitagawa, Y. (1985) Biochem. J. 229, 259-264). The ternary complex of laminin in 3T3-L1 cells had a size significantly smaller than AB1B2 complex in F9 cells. In this complex, a novel subunit appears to take the place of the A subunit. Thus, a novel laminin complex is produced by 3T3-L1 cells.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Tyrosine sulfation is not the last modification of entactin before its secretion from 3T3-L1 adipocytes.

Tyrosine sulfation of entactin was studied by labeling of 3T3-L1 adipocytes with [35S]methionine or H2 35SO4 in the presence or absence of tunicamycin or monensin. Four precursors (EN1-4) at different steps of modification were detected in addition to mature entactin. Under normal conditions, EN2 and mature entactin were intracellular species, and the latter was sulfated and secreted. Inhibition of co-translational transfer of N-linked oligosaccharides by tunicamycin produced EN1 and EN3 as intracellular species, and EN3 was sulfated and secreted. Interruption of protein transport from medial to trans (distal) Golgi cisternae by monensin, and consequent blockage of terminal glycosylation caused intracellular accumulation of EN4. EN4 was sulfated and of different size compared to mature entactin. These facts suggested that tyrosine sulfation of entactin occurs in medial Golgi cisternae and is not the last modification before its secretion. Our results appeared inconsistent with recent observations by Baeuerle and Huttner [(1987) J. Cell Biol. 105, 2655-2664] that tyrosine sulfation of IgM occurred within the trans (distal) Golgi cisternae as the last modification before its exit from the Golgi complex.

Adipose Tissue↗
PubMed1988

Enhanced transcription of mitochondrial genes after growth stimulation and glucocorticoid treatment of Reuber hepatoma H-35.

When a serum-deprived culture of Reuber hepatoma H-35 cells was stimulated by serum, cells proliferated synchronously showing a peak of [3H]thymidine incorporation within 16 h and doubling of cell number within 24 h. A 5-10-fold increase of mRNAs of mitochondrial genes was observed prior to S-phase by Northern hybridization of total cellular RNA with cloned fragments of rat mitochondrial DNA as probes. In organelle transcription by mitochondria isolated from growth-arrested or growth-stimulated cells suggested that the increase of mitochondrial mRNAs was mainly due to enhanced transcription. Less enhanced transcription was observed by treating the cells with dexamethasone, which causes translocation of large amount of protein into mitochondria. The latter effect was counteracted by insulin.

Animals↗
PubMed1988

Detection of carcinogenic glutamic acid pyrolysis products in Worcestershire sauce by high-performance liquid chromatography.

Commercially available Worcestershire sauce was analyzed for mutagenic and carcinogenic glutamic acid pyrolysis products using high-performance liquid chromatography. These carcinogenic heterocyclic amines were found to be present in all brands of Worcestershire sauce analyzed. The identity of the carcinogens was confirmed by spectrometric analyses and the SOS umu-test. The concentrations of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) in the Worcestershire sauce were 695 +/- 329 pmol/liter (mean +/- SD, n = 5) and 1,839 +/- 1,321 pmol/liter (n = 5), respectively.

Amines↗
PubMed1988

Biphasic response to retinoic acid dose in differentiation of F9 cells into primitive endoderm-like cells.

The differentiation of F9 cells, as monitored by the secretion of basement membrane proteins, was biphasic depending on the dose of retinoic acid (RA) used. Secretion of laminin A reached a plateau at about 10 nM and increased again at more than 100 mM RA. A similar biphasic response was observed in the secretion of tissue-type plasminogen activator as well. In the presence of RA alone, this biphasic pattern of differentiation was stable for a long period of time, but the addition of 1 mM dibutyryl cAMP changed it to monophasic after 12 days of exposure.

Animals↗
PubMed1988

32P-postlabeling analysis of DNA adducts in rat stomach with 1-nitrosoindole-3-acetonitrile, a direct-acting mutagenic indole compound formed by nitrosation.

Modification of DNA by a direct-acting mutagen, 1-nitrosoindole-3-acetonitrile, which is formed from indole-3-acetonitrile upon nitrite treatment, was investigated. 32P-Postlabeling analysis clearly demonstrated the formation of DNA adducts in the stomach of rats after intragastric administration of 1-nitrosoindole-3-acetonitrile. The level of DNA adducts in both the forestomach and glandular stomach 2 h after administration of 100 mg/kg body weight of the compound was about one adduct per 10(7) nucleotides. The DNAs of the forestomach and glandular stomach gave six common spots on two-dimensional chromatography, three of which were also produced by in vitro reaction of this compound with DNA. Thus, 1-nitrosoindole-3-acetonitrile can form DNA adducts in vivo and in vitro. No DNA adducts were detected after treatment with the non-nitrosated compound indole-3-acetonitrile both in vivo and in vitro. These results suggest that 1-nitrosoindole-3-acetonitrile has the in vivo tumor initiating activity in the stomach.

Acetonitriles↗
PubMed1988

Activated K-ras in tumorigenic and non-tumorigenic cell variants from a rat colon adenocarcinoma, induced by dimethylhydrazine.

Using NIH3T3 cell transfection assay, activated c-K-ras was detected in two cell lines, TRb and TSb, obtained from a single colon adenocarcinoma induced in a rat by 1,2-dimethylhydrazine. TRb cells give rise to progressive and metastatic tumors in the syngeneic rats, whereas TSb cells only induce regressive tumors. Levels of K-ras transcripts in TRb and TSb cells were higher than that of NIH3T3 cells, but no difference was found between TRb and TSb cells. No significant difference was observed in expression levels of c-myc in these two cell lines. c-fos expression was, however, significantly lower in TRb than TSb cells.

1,2-Dimethylhydrazine↗