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Biomedical subjects

K Tanimoto

Publications and source records attributed to K Tanimoto.

At least 19 recordsLinked to original sources

A combination of upstream and proximal elements is required for efficient expression of the mouse renin promoter in cultured cells.

Renin, a key enzyme controlling blood pressure, is produced mainly in the kidney. To identify the transcriptional regulatory elements of the mouse Ren-1c gene, the promoter regions were fused to the CAT reporter gene and transfected into embryonic kidney-derived 293 cells and four extrarenal cell lines, HeLa, HepG2, HT1080 and NIH3T3 cells. Transient transfection assay showed that sequences from -365 to +16 of the renin gene could direct transcription of the CAT hybrid gene only in 293 cells. Deletion analysis identified two transcriptionally active regions; the renin upstream-promoter element (RU-1 element; position -224 to -138) and the renin proximal-promoter element (RP-2 element; position -75 to -47). Although the RU-1 element functioned as an activator, depending on its orientation, it failed to trans-activate the renin promoter when the RP-2 element was deleted. By contrast, the proximal element alone exhibited a weak trans-activator property. Gel shift assay identified RU-1 element-binding factors in both 293 and HeLa cells, whereas 293 cell-dominant factors were shown to bind only to RP-2 element. Therefore, both RU-1 and RP-2 elements were found to be necessary for efficient CAT expression from the renin promoter in 293 cells, suggesting that activation of the Ren-1c promoter requires combined action between cell type-dominant and ubiquitous nuclear factors.

Animals

Regulation of activin beta A mRNA level by cAMP.

We demonstrated the presence of five species of the activin beta A mRNA in human placenta and one major RNA associated with two minor RNAs of the activin in the fetal membrane. We investigated the effect of 8-bromo-cAMP (8-Br-cAMP) on accumulation of activin beta A subunit mRNA in human fibrosarcoma HT1080 cells. Although low levels of the activin mRNA were detectable in the untreated cells, the one main RNA species was predominantly accumulated by 8-Br-cAMP. We propose that generation of multiple activin mRNAs in the fetal membrane and cAMP-treated HT1080 cells is presumably due to a cell-specific alternative polyadenylation.

8-Bromo Cyclic Adenosine Monophosphate

Mother-to-infant transmission of hepatitis C virus.

Prospective studies of an infant of a mother infected with hepatitis C virus indicated that an HCV infection developed in the infant in early life. Perinatal transmission appeared to be the most likely explanation.

Female

Structure and expression of the mouse angiotensinogen gene.

Angiotensinogen is a precursor of the multifunctional octapeptide hormone, angiotensin II. We have isolated the overlapping clones containing angiotensinogen gene locus from C57BL/6 mouse genomic DNA library and analyzed them by restriction enzyme mapping. The gene exhibited a structural organization similar to those of the human, rat and balb/c mouse angiotensinogen genes. Using a genomic DNA fragment of the mouse angiotensinogen gene as a probe, we have investigated the tissue distribution of angiotensinogen messenger RNA (mRNA) in C57BL/6 mouse. The angiotensinogen mRNA was highest in the liver and detectable in such tissues as brain, kidney, submandibular gland, ovary and heart. However, it was undetectable in lung and spleen under the condition used. Optimal alignments of the 5'-flanking regions among the human, rat and mouse angiotensinogen genes disclosed several deletions in the mouse sequence. To assay the promoter activity, the 5'-flanking region of the mouse angiotensinogen gene was ligated to the bacterial chloramphenicol acetyltransferase (CAT) gene, then transfected into different cultured cells. The angiotensinogen gene sequences elicited preferential expression of CAT activity when introduced into HepG2 cells derived from liver and 293 cells from kidney but not in HeLa cells from uterus, suggesting the presence of a cell type-specific promoter within the sequences. These findings on the structure and expression of the mouse angiotensinogen gene should prove useful in studying the function and control of the angiotensin.

Angiotensinogen

Endothelial cell destruction by polymorphonuclear leukocytes incubated with sera from patients with systemic lupus erythematosus (SLE).

When normal polymorphonuclear leukocytes (PMN) were incubated with sera from patients with active systemic lupus erythematosus (SLE), a significantly increased cytotoxicity against human cultured vascular endothelial cells (EC), compared with normal control sera, was demonstrated by the standard 51Cr release method. The degree of this cytotoxicity was correlated with the immune complex level in each serum. The cytotoxicity did not correlate with the presence of anti-EC antibody. An absorption study with C1q-Sepharose 4B further suggested that the immune complexes are the factor which induce cytotoxicity. A gel fractionation study, however, indicated the heterogenity of the cytotoxic activity, and suggested the possible contribution of other substances including anti-EC, at least in some of the patients. This type of cytotoxicity may initiate the inflammatory process including vascular damage of the disease.

Adult

Lobenzarit disodium (CCA) inhibits the proliferation of human endothelial cells and the activity of DNA polymerase alpha.

N-(2)-Carboxyphenyl-4-chloroanthranilic acid disodium [Lobenzarit disodium (CCA)] is widely used for the treatment of patients with RA in Japan; however, the pharmacological mechanism of the compound is still unclear. In this report, the effect of CCA on the proliferation and DNA synthesis of endothelial cells was examined. CCA inhibited DNA synthesis in endothelial cells at a rather lower concentration than that in fibroblasts and HeLa cells. The DNA polymerase alpha activity was inhibited by CCA at a lower concentration than E. coli DNA polymerase I and avian myeloblastosis virus reverse transcriptase. Thus, CCA is a potent inhibitor of DNA polymerase alpha and this inhibitory effect could cause the inhibition of endothelial cell proliferation, which may be related to the therapeutic and pharmacological mechanisms of CCA.

Anti-Inflammatory Agents, Non-Steroidal

Preliminary criteria for classification of adult Still's disease.

We have attempted to design classification criteria for adult Still's disease by analyzing the data obtained through a multicenter survey of 90 Japanese patients with this disease and of 267 control patients. The proposed criteria consisted of fever, arthralgia, typical rash, and leukocytosis as major, and sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction, and the absence of rheumatoid factor and antinuclear antibody as minor criteria. Requiring 5 or more criteria including 2 or more major criteria yielded 96.2% sensitivity and 92.1% specificity. However, an exclusion process will be needed for an accurate classification, since this disease is relatively rare.

Adolescent

[Overlapping syndrome].

Overlapping syndrome (OS) is usually used as the term of the combinations of three connective tissue diseases, i.e., systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS) and polymyositis (PM) or dermatomyositis (DM). OS is sometimes confused with mixed connective tissue disease (MCTD) since the definitions of the both diseases have not been established yet. Rheumatoid arthritis (RA) is a distinct disease and only exceptionally associated with the other CTD. These rare cases include destructive arthritis of SLE and PSS, multiple peripheral type of psoriatic arthritis, and arthritis associated with X-linked hypogammaglobulinemia and selective IgA deficiency. The conditions complicated with RA are not uncommon. They are osteoporosis, Sjogren's syndrome, amyloidosis and so on. There are some rare conditions or diseases which will be able to develop to RA. These peculiar cases include juvenile rheumatoid arthritis, adult onset Still's disease, polymyalgia rheumatica and palindromic rheumatism.

Amyloidosis

Transient myopia with severe chemosis associated with exacerbation of disease activity in systemic lupus erythematosus.

A 46-year-old woman with systemic lupus erythematosus (SLE) developed bilateral transient myopia and periorbital edema with severe chemosis. Her myopia was ascribed to a refractive abnormality that was caused by curvature change and anterior displacement of the lenses and the ciliary bodies due to anterior ocular edema. The conditions were not associated with systemic edema or abnormality in the fundi and responded well to the systemic administration of corticosteroid. The course of the ocular symptoms paralleled changes of serum CH50 and anti-dsDNA antibody levels. Thus it was concluded that her ocular symptoms were closely related to activity of her SLE and may be considered a feature of SLE.

Antibodies, Antinuclear

Early hilar lung cancer: its clinical aspect.

Early hilar lung cancers are rare, but are curable if they are properly diagnosed and treated. In the past 14 years, we have treated 27 patients with early hilar cancers that fulfilled the criteria proposed by the Japanese Lung Cancer Society (JLCS). Eighteen patients presented with symptoms and 9 were detected by the mass screening examination of sputum cytology. All lesions in both groups were finally diagnosed by bronchoscopy. Twenty patients (74%) had positive sputum cytology, whereas only 7 (26%) had positive chest X-ray findings. All the patients underwent surgery, and bronchoplasty was the most frequent operative procedure. The 5-year survival rate was 100%, and the 10-year survival rate was 91.7%, as one patient died of a second primary lung cancer in the 6th postoperative year. In conclusion, the definition of early hilar lung cancer proposed by the JLCS is thought to be reasonable, and early hilar lung cancer is a curable disease, if it is properly diagnosed and treated.

Bronchoscopy

The effect of intracerebroventricular administration of somatostatin on prolactin and TSH release in rats.

We investigated the effect of intracerebroventricular (icv) administration of somatostatin (SRIF) on prolactin (PRL) and thyroid-stimulating hormone (TSH) release in freely moving rats chronically cannulated with an atrial catheter. The plasma PRL levels were significantly elevated following the icv administration of 0.5 microgram SRIF. No further increase in PRL following the icv administration of SRIF were found in the rats in the course of repeated intravenous of injection of 5.0 mg/kg sulpiride, a specific D2 receptor antagonist. On the other hand, the injection of 5.0 micrograms SRIF resulted in no significant change in the plasma TSH levels. These results suggest that the effect of SRIF on PRL release was exerted through brain D2 receptors.

Animals

Effect of size of region of interest on precision of bone mineral measurements of the mandible by quantitative computed tomography.

The effect of size and shape of the region of interest (ROI) on the precision of the measurements of bone mineral content of mandibular bone by quantitative computed tomography (QCT) has been studied. A dry mandible and a series of calcium carbonate rods (density: 119.6 mg cm-3, 461.2 mg cm-3 and 939.0 mg cm-3) were used. The precision of measurements of the ROI for sizes less than 1 cm2 was very low, but the shape did not have any influence on the precision if the material examined was either homogeneous or if it was heterogeneous from always the same area. Higher precision was found when the ROI was more than 1 cm2. The size of ROI is a critical factor in the measurement of bone mineral content in the mandible by QCT.

Bone Density

Image salvage in panoramic radiography using histogram optimization.

Optical density and contrast recovery from poor quality panoramic radiographs was studied using the histogram modification technique. A series of experimental images of varying density and contrast were obtained by exposing a phantom in 4 kV steps between 50 and 94 kV. A standard of good image quality was selected by 10 observers grading the radiographs. Images were processed using the histogram specification technique and re-evaluated. All the processed images were found to be of acceptable quality. This technique was also shown to be applicable for salvaging unacceptable clinical radiographs.

Humans

Structure and sequence analysis of the human activin beta A subunit gene.

The cloned genomic DNA containing the human activin beta A subunit gene were analyzed by restriction endonuclease mapping, Southern blotting and DNA sequencing. The activin gene is composed of two exons interrupted by the 9-kb intron. The TATA, CCAAT and CT-stretch sequences were found in the 5'-flanking region of the gene. An intronic sequence contained SV40 enhancer core element in the vicinity of the exon 1. In the 3'-flanking region, we identified eight consensus polyadenylation sequences, five ATTTA motifs, CA element consisting of (CA)14, AP-1 binding site and two SV40 enhancer core elements. A dot matrix analysis revealed the high degree of conservation between the human and rat sequences within the 3'-flanking region, suggesting a possible functional significance.

Activins