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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 397 records · Page 22Linked to original sources
PubMed1997

[Tissue polypeptide antigen as a biological marker of malignant pleural mesothelioma].

To evaluate the role of tissue polypeptide antigen (TPA) as a biological marker of malignant pleural mesothelioma (MPM), we used immunohistochemical techniques to detect TPA in tumor cells, and we measured the content of TPA in serum from patients with MPM. In 14 of 16 patients with MPM, TPA was detected in the cytoplasm of tumor cells. Epithelial-type cells from 11 of 12 patients were stained positively (91.7%), and sarcomatous-type cells from 7 of 8 patients were stained positively (87.5%). Serum TPA levels were abnormally high in 7 of 9 patients. Two of three patients with stage-I disease had normal serum TPA levels, and all patients whose disease was at stage II or higher had abnormal serum TPA levels. Serum TPA levels increased as MPM progressed. These results suggest that the serum TPA level can be used as a biological marker of MPM.

Adult↗
PubMed1997

[Long-term results of preoperative hyperthermo-chemo-radiotherapy (HCR) for patients with esophageal carcinoma invading neighboring structures (T4)].

PATIENTS: A total of 180 patients with esophageal carcinoma invading the neighboring structures (T4) were surgically treated by esophagectomy and reconstruction in the Department of Surgery II, Kyushu University from January 1965 to April 1997. Any of these cases with distant node metastasis and demonstrating organ metastasis or a combined resection of adjacent structures were excluded from this study. As a result, twenty-six patients treated with preoperative hyperthermo-chemo-radiotherapy (HCR Group), 39 treated either with preoperative radiotherapy or preoperative chemo-radiotherapy (R or CR Group) and 23 non-treated patients (Non-tx Group) were thus entered in this study. RESULTS: The 3-year survival rates after esophagectomy in HCR Group, R or CR Group and Non-tx Group were 26.5%, 0% and 9%, respectively, while the 5-year survival rate of the HCR group was 15.9%. The group with preoperative HCR thus showed a significantly more favorable outcome than R or CR Group and Non-tx Group. (p < 0.05). DISCUSSION: The significant difference observed in the prognosis was thought to be due to the reinforced effect of local regulation due to hyperthermia. Our data thus suggest that preoperative HCR contributes to the prolonged post-operative survival for carcinoma of the esophagus invading the neighboring structures.

Aged↗
PubMed1997

Plasma adrenomedullin in cerebrovascular disease: a possible indicator of endothelial injury.

BACKGROUND: Cultured vascular endothelial and smooth muscle cells actively produce adrenomedullin, a novel vasodilator peptide discovered in human pheochromocytoma tissue. This present study was designed to determine whether the plasma level of adrenomedullin is a useful indicator for estimating the degree of endothelial injury in patients with atherosclerotic disease. METHODS: We used a radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in 10 subjects without symptomatic cerebrovascular disease. We also measured the plasma concentrations of thrombomodulin and endothelin as markers of endothelial injury. The patients were divided into three groups (A, B, and C) on the basis of the number of risk factors for atherosclerosis: hypertension, hyperlipidemia, smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2 years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more risk factors. RESULTS: The plasma concentration of adrenomedullin in these patients showed a significant positive correlation with age (r=0.33, p<0.05), as well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be higher in Group B and to be significantly higher in Group C as compared to Group A. Plasma adrenomedullin concentrations did not, however, significantly differ between the infarction and haemorrhage patients. CONCLUSIONS: These findings suggest that the plasma adrenomedullin concentrations reflect the degree of endothelial injury in patients with atherosclerotic disease.

Adrenomedullin↗
PubMed1996

Assignment of the CD45-AP gene to the centromeric end of mouse chromosome 19 and human chromosome 11q13.1-q13.3.

CD45-AP is a recently identified phosphorylated protein that specifically associates with the leukocyte-specific transmembrane glycoprotein CD45. The gene for CD45-AP, Ptprcap (protein tyrosine phosphatase, receptor type c polypeptide associated protein), was mapped in mouse by typing the progeny of two multilocus crosses using the mouse CD45-AP cDNA as a Southern hybridization probe. The CD45-AP gene mapped to the centromeric region of Chr 19 proximal to the genes Fth, Cd5, and Pcna-rs. The gene for the human CD45-AP homologue, PTPRCAP, was localized to chromosome band 11q13.1-q13.3 by fluorescence in situ hybridization using human genomic CD45-AP DNA as a hybridization probe. The genetic mapping of the Ptprcap/PTPRCAP genes extends the previously defined synteny conservation of various genes that have been assigned to these regions of the mouse and the human chromosomes.

Animals↗
PubMed1996

Molecular cloning and analysis of the 5'-flanking region of the rat PP1 alpha gene.

We have cloned an 8 kbp genomic fragment of 5'-flanking region of the gene encoding the catalytic subunit of rat protein phosphatase 1 alpha. Neither CAAT box nor TATA box was detected but a 300 bp high GC region containing nine Sp1 transcription factor binding sites is present immediately upstream of the translation start site, demonstrating that PP1 alpha is a housekeeping gene. Luciferase reporter assay showed that transcription of PP1 alpha is controlled at the high GC region.

3T3 Cells↗
PubMed1996

Adrenomedullin-sensitive receptors are preferentially expressed in cultured rat mesangial cells.

By using cultured rat mesangial cells, we compared the effects on cyclic nucleotide levels of adrenomedullin with those of the structurally related peptides, calcitonin gene-related peptide (CGRP) and amylin. Adrenomedullin potently increased cAMP levels 7-fold in a time- and concentration-dependent manner. Its EC50 was 3 x 10(-9) M. CGRP was less potent (2-fold) with an EC50 of 10(-7) M, and amylin had no effect on cAMP levels. All three peptides failed to increase cGMP levels. Treatment of cells with near maximal concentrations of adrenomedullin (10(-7) M) and CGRP (10(-6) M) had no additive effect on cAMP levels. Human adrenomedullin-(22-52)-NH2, a putative adrenomedullin receptor antagonist, inhibited the production of cAMP elicited by adrenomedullin (IC50: 7 x 10(-8) M) and CGRP (IC50: 5 x 10(-8) M). Human CGRP-(8-37), a CGRP receptor antagonist, conversely, reduced the cAMP elevation caused by these peptides with a lower potency (IC50: 10(-6) M for both peptides). This demonstrated that human adrenomedullin-(22-52)-NH2 was a more effective antagonist for adrenomedullin- and CGRP-specific receptors than human CGRP-(8-37). Results suggest that receptors sensitive to adrenomedullin are preferentially expressed in cultured rat mesangial cells. Immunohistochemical study showed almost no immunoreactive adrenomedullin and CGRP, if any, in the cells. Adrenomedullin may regulate mesangial function as either a paracrine or circulating hormone via a cAMP- but not a cGMP-dependent mechanism.

Adrenomedullin↗
PubMed1996

Mutagenic specificity of N-methyl-N'-nitro-N-nitrosoguanidine in the tonB gene on the chromosome of Escherichia coli recA+ and recA- cells.

DNA base sequence changes induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) mutagenesis has been determined for the endogenous tonB gene of Escherichia coli recA+ strain and its isogenic recA56 strain. In the recA+ strain, base substitutions accounted for 48 mutations among 54 MNNG-induced independent mutations analyzed and consisted of 45 G:C to A:T transitions, two A:T to G:C transitions and one A:T to C:G transversion. In the recA56 strain, 67% (34/51) were base substitutions among which G:C to A:T transition (28/51) predominated, followed by three A:T to T:A transversions, two G:C to T:A transversions, and one A:T to G:C transition. These mutagenic specificities were consistent with the mispairing predicted by the methylation of the O6 position of guanine. In both strains the G:C to A:T mutations were found at guanine residues preceded by either guanine or thymine on the non-transcribed strand of the target gene.

Bacterial Proteins↗
PubMed1996

Autocrine response of Schizosaccharomyces pombe haploid cells to mating pheromones.

The mating response of the fission yeast Schizosaccharomyces pombe is mediated by mating pheromones, M-factor and P-factor, produced by h- and h+ cells, respectively. When the M-factor receptor (Map3) was ectopically expressed in h- cells lacking the P-factor receptor (Mam2), they acquired mating competence in response to M-factor which they secreted. The autocrine response to P-factor in h- cells was so weak that mating competence was not acquired, although expression of the pheromone-responsive gene matl-Pm was detected. These observations support the notion that the intensity of cellular response to mating phermones is different between h- and h+ cells, although downstream pathways of the pheromone receptors are shared by the two mating types.

Cloning, Molecular↗
PubMed1996

Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway.

Acute promyelocytic leukemia (APL) is associated with a chromosomal translocation t(15;17) and successfully differentiated by all-trans-retinoic acid (ATRA) in vivo as well as in vitro. The PML-retinoic acid receptor alpha (RARA) oncoprotein, which is generated by the translocation, blocks the differentiation, and ATRA is thought to modulate the dominant negative function of PML-RARA. However, the molecular effect of ATRA on PML-RARA is unknown. In this study, we showed by means of immunoblotting that the expression of PML-RARA decreased within 12 h in APL cells treated with ATRA at concentrations greater than 0.1 microM. The decrease of PML-RARA was associated with restoration of the normal subcellular PML localization. PML-RARA transcripts were not down-regulated by ATRA. However, lactacystin, a specific inhibitor of the proteasome, almost completely inhibited the decrease of PML-RARA. These data indicate that the PML-RARA degradation is accelerated by pharmacological concentrations of ATRA, suggesting that ATRA allows APL cells to differentiate by relieving the differentiation block.

Acetylcysteine↗
PubMed1996

Proadrenomedullin N-terminal 20 peptide is rapidly cleaved by neutral endopeptidase.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide which is processed from an adrenomedullin precursor. PAMP is rapidly cleaved by human neutral endopeptidase (NEP), a protease which plays a key role in the degradation of human atrial natriuretic peptide (ANP). A double reciprocal plot indicated that Km of NEP as a substrate of PAMP was 6.1 microM and V(max) was 3.1 mmol/min/mg of NEP. EDTA, phosphoramidon and thiorphan inhibit the proteolysis of PAMP by NEP. NEP cleaves at least 6 peptide bonds in human PAMP; Arg2-Leu3, Glu8-Phe9, Lys12-Trp13, Lys15-Trp16, Trp16-Ala17 and Ala17-Leu18. The present data suggest that NEP may be involved in the circulation control by degrading PAMP as well as ANP.

Adrenomedullin↗
PubMed1996

What is the earliest malignant lesion in the esophagus?

BACKGROUND: The incidence of early esophageal cancer is definitely increasing due to recent advances in diagnostics. When we discuss early carcinoma of the esophagus, however, there is still controversy as to whether dysplasia is either benign or the earliest malignant lesion. METHODS: Nineteen resected esophaguses with both cancer and dysplasia (including 19 cancers concomitant with 26 dysplastic lesions) were studied for expression of p53 protein. RESULTS: Immunohistochemical overexpression of p53 protein in esophageal dysplasia is almost the same as that in cancer. CONCLUSIONS: Esophageal dysplasia should be recognized as the earliest malignant lesion which already demonstrates cancerous features although it is not immediately critical. A routine endoscopic Lugol's solution test is very useful for both detection and following-up of the early nests in the esophagus. These lesions are good candidates for endoscopic mucosal resection for the purpose of accurate diagnosis or curative treatment.

Esophageal Neoplasms↗
PubMed1996

Induction of inducible nitric-oxide synthase by the heterotrimeric G protein Galpha13.

While the functions of several G protein alpha subunits such as alpha(s( and alpha(q) are relatively well understood, the action of others such as alpha13 remain largely undefined. Because of recent interest in regulation of nitric-oxide synthase (NOS) by G protein-coupled signaling systems and findings that receptors for two proinflammatory substances, thrombin and thromboxane couple to alpha13, we studied the effect of alpha13 on NOS activity in a renal epithelial cell line. We found that stable overexpression of alpha13 or its GTPase-deficient mutant, alpha13Q226L, in a continuous renal epithelial cell line (MCT) increased NOS activity. The increased NOS activity was due to increased expression of the macrophage-inducible form of NOS (iNOS). iNOS protein and activity were not increased in similar cells expressing an activated alpha(s) (alpha(s)Q227L) or were minimally increased in cells expressing activated alpha(i1) (alpha-i1Q204L) and alpha(q) (alpha(q)Q209L), members of the three other G protein alpha chain families. Transient co-expression of alpha13 or alpha13Q226L increased the activity of an iNOS promoter-CAT construct demonstrating that alpha13 increases iNOS expression through transcription. Consequently, alpha13 induces iNOS through a novel mechanism that is distinct from that of other G protein alpha chains and that may mediate the actions of G protein-dependent proinflammatory agents.

Animals↗
PubMed1996

Mutagenic specificity of ultraviolet light in the tonB gene on the chromosome of Escherichia coli uvrA cells.

We have analyzed the DNA sequence changes in a total of 60 ultraviolet-induced mutations in the endogenous tonB gene of Escherichia coli uvrA strain. Of the mutations 82% were base substitutions among which G:C-->A:T transition predominated. Three GG-->AA tandem double-base substitutions, which are thought to originate from UV damage, were also observed. The sites where base substitutions occurred were correlated with sequences of adjacent pyrimidines, indicating mutation-targeted UV photoproducts. G:C-->A:T transition in the tonB gene mutation can be exclusively observed at either the 3' side of the TC site which is on the template for the lagging strand of DNA replication or the 5'/3' sides of the CC site on the template for the leading strand. We hypothesize that this extreme strand specificity is due to a difference in fidelity of DNA replication of the leading and the lagging strand.

Adenosine Triphosphatases↗
PubMed1996

Early gastric lymphoma: a clinicopathologic study of ten patients, literature review, and comparison with early gastric adenocarcinoma.

BACKGROUND: Improved diagnostic techniques have increased early detection of gastric lymphoma as well as the early detection of adenocarcinoma. However, clinicopathologic features of early gastric lymphoma are presently undefined. METHODS: Clinicopathologic features of 10 patients with early gastric lymphoma were compared with the same features of 180 patients with early gastric adenocarcinoma. In addition, 46 articles were reviewed to evaluate clinicopathologic differences. RESULTS: Early gastric lymphoma was found in 29.2% of the patients who underwent surgery for gastric lymphoma. Early gastric lymphoma was associated with lymph node involvement in 29.9% of the patients, superficial spreading tumors in 48.6%, and multifocal lesions in 40%. These rates are greater than those in patients with adenocarcinomas (P < 0.05%). The survival rate was identical in both groups. Early gastric lymphoma may develop into large, multifocal tumors, accompanied by lymph node involvement. CONCLUSIONS: Surgical treatment with a wide resection of the stomach and extensive lymph node dissection is necessary for early gastric lymphomas.

Adenocarcinoma↗
PubMed1996

Transcription of the murine iNOS gene is inhibited by docosahexaenoic acid, a major constituent of fetal and neonatal sera as well as fish oils.

Macrophage activation is deficient in the fetus and neonate when the serum concentrations of docosahexaenoic acid (DHA) are 150 microM, or 10-50-fold higher than in the adult. We now show that DHA inhibits production of nitric oxide (NO) by macrophages stimulated in vitro by IFNgamma plus LPS, or by IFNgamma plus TNFalpha. The half-maximal inhibitory activity of DHA was approximately 25 microM. There were strict biochemical requirements of the fatty acid for inhibition. Polyenoic fatty acids with 22 carbons were more inhibitory than those with 20 carbons. Among 22-carbon fatty acids, those with a greater number of double bonds and a double bond in the n-3 position were more inhibitory. DHA was the most inhibitory of the polyenoic acids we tested. Inducible nitric oxide synthase (iNOS) is the enzyme responsible for the production of NO by macrophages. NO production is initiated after new iNOS enzyme is synthesized following transcription of the iNOS gene. In macrophages stimulated by IFNgamma plus LPS, DHA inhibited accumulation of iNOS mRNA, as measured by Northern blotting, and iNOS transcription, as measured by nuclear run-on assays. We transfected RAW 264.7 macrophages with a construct containing the iNOS promoter fused to the chloramphenicol acetyl transferase gene. DHA inhibited activation of this promoter by IFN gamma plus LPS. By inhibiting iNOS transcription in the fetus and neonate, DHA may contribute to their increased susceptibility to infection.

Adult↗