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Biomedical subjects

S Hirose

Publications and source records attributed to S Hirose.

At least 235 records · Page 13Linked to original sources

Rheumatoid arthritis complicated by pachy- and leptomeningeal rheumatoid nodule-like granulomas and systemic vasculitis.

Rheumatoid nodule is a frequent and characteristic extra-articular manifestation of rheumatoid arthritis (RA). Its involvement of central nervous system is a rare occurrence with only a few reported cases. A 78-year-old man with severe arthritis showing the formation of rheumatoid nodule-like granulomas in the dura and subarachnoid space along with the spleen is presented. The characteristic morphological finding of the granulomas was the presence of neutrophils and the absence of definite fibrinoid necrosis, which differed from the typical features of rheumatoid nodules previously described. The diagnosis should be based on the exclusion of diseases that may cause similar granulomatous reactions including infectious diseases. Additionally, there was systemic necrotizing vasculitis in the dura and multiple cerebral infarcts, although the association between vasculitis and cerebral infarcts was not clear.

Aged↗

Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.

The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Acute Disease↗

Regulation of the EDG84A gene by FTZ-F1 during metamorphosis in Drosophila melanogaster.

The transcription factor FTZ-F1 is a member of the nuclear hormone receptor superfamily and is transiently expressed during the mid- and late prepupal periods in Drosophila melanogaster. A putative pupal cuticle gene, EDG84A, is expressed slightly following FTZ-F1 expression during the prepupal period and carries a strong FTZ-F1 binding site between bases 100 and 92 upstream of its transcription start site. In this study, EDG84A mRNA was found to be prematurely expressed upon heat induction of FTZ-F1 in prepupae carrying the heat shock promoter-FTZ-F1 cDNA fusion gene construct. Transgenic fly lines having the 0.8-kb region of the EDG84A promoter fused to lacZ expressed the reporter gene in a tissue- and stage-specific manner. Base substitutions in the FTZ-F1 binding site within the 0.8-kb promoter abolished expression of lacZ. These results strongly suggest that the EDG84A gene is a direct target of FTZ-F1. Deletion studies of the cis-regulatory region of the EDG84A gene revealed that space-specific expression in imaginal disc-derived epidermis is controlled by the region between bp -408 and -104 from the transcription start site. The region between bp -408 and -194 is necessary to repress expression in a posterior part of the body, while the region between bp -193 and -104 carries a positive element for activation in an anterior part of the body. These results suggest that FTZ-F1 governs expression of the EDG84A gene in conjunction with putative tissue-specific regulators.

Animals↗

cGMP produced in response to ANP and CNP regulates proliferation and differentiation of osteoblastic cells.

The effects of natriuretic peptides on the proliferation and differentiation of osteoblast-like cells from rat calvariae were examined. Natriuretic peptides are physiological agonists that activate receptor guanylate cyclases, namely, natriuretic peptide receptor (NPR)-A and NPR-B. Exposure of cells to atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) resulted in large increases in the rate of intracellular production of guanosine 3',5'-cyclic monophosphate (cGMP). Moreover, CNP-like immunoreactivity was detected in the conditioned medium from osteoblast-like cells, while ANP was undetectable. In cells exposed to natriuretic peptides, a dose-dependent reduction in the rate of DNA synthesis was observed. Natriuretic peptides also stimulated the activity of alkaline phosphatase (ALPase) and the expression of mRNA for ALPase and osteocalcin and the mineralization of nodules by the cultured cells. These results could be reproduced by treating cells with 8-bromo-cGMP. Endothelin-1, whose physiological functions are the opposite of those of natriuretic peptides, decreased the ALPase activity and the mineralization of nodules. In the present study, natriuretic peptides were demonstrated to promote bone formation via the action of cGMP in a signal-transduction pathway mediated by specific receptors in osteoblast-like cells.

Alkaline Phosphatase↗

Whole body autoradiography and microautoradiography in eels after intra-arterial administration of 125I-labeled eel ANP.

125I-labeled eel atrial natriuretic peptide (ANP) was administered into the ventral or dorsal aorta of freshwater (FW) and seawater (SW) eels, Anguilla japonica, and the major target organs were explored by whole body autoradiography. Localization of the ANP binding in the target organs was also examined at tissue and cell levels by microautoradiography using tissue sections. Whole body autoradiography revealed that the specific label was accumulated predominantly in the gill, with lesser amounts in the atrium, kidney, liver, and urinary bladder. Autoradiographic grains were most dense in the secondary lamellae of the gill, particularly on the side of the efferent filamental artery. Other binding sites in target tissues were the glomerulus of the kidney, epicardium and endocardium of the atrium, bile duct/blood vessels of the liver, and interrenal cells of the head kidney. There was no difference in the distribution and density of grains between injections into the ventral aorta and dorsal aorta, although, in the former, injected 125I-labeled eel ANP passes through the gill before reaching peripheral target tissues. There was a tendency for downregulation of ANP binding sites in SW eels, especially in the gill. These results show that specific ANP binding sites are present in organs that are implicated in osmoregulation and cardiovascular regulation in eels and further suggest that the number of ANP binding sites varies according to changes in the environmental salinity.

Anguilla↗

Nuclear magnetic resonance studies of sugar metabolism in the human infant lens.

We investigated sugar metabolism in lenses isolated from infants with stage-5 retinopathy of prematurity (ROP). The lenses were incubated in 13C-labeled glucose (35.5 mM) or galactose (30 mM) for 24 h at 37.5 degrees C. Six to 8 lenses were pooled for each experiment. 13C-nuclear magnetic resonance spectroscopy was then performed on perchloric acid extracts of these lenses. Active aldose metabolism was indicated by the production of lactate. However, neither sorbitol nor dulcitol was detected. On the other hand, an experimental aldose reductase inhibitor, sorbinil, caused a decrease in the hexose monophosphate shunt activity suggesting an active polyol pathway. Both polyols therefore appeared to have been metabolized further. In addition, galactose metabolism was unique in that it not only involved a galactose-->glucose epimerization, but also a direct galactose-->ribose conversion, and a production of galactose-3-phosphate. Although it is possible that the ROP lenses have adapted to oxidative stress during the postnatal high-oxygen incubation for premature infants, we believe the observed sugar metabolism is representative of the developing human lens.

Aldehyde Reductase↗

Vascular action of circulating and local natriuretic peptide systems is potentiated in obese/hyperglycemic and hypertensive rats.

Hypertension is commonly associated with diabetes mellitus. The aim of the present study was to explore the pathophysiological significance of the natriuretic peptide (NP) system in hypertension associated with genetically obese/hyperglycemic Wistar fatty rats. The messenger RNA (mRNA) levels of the two biologically active NP receptors, NP-A receptor [more specific for atrial natriuretic peptide (ANP)] and NP-B receptor [more specific for C-type natriuretic peptide (CNP)], and CNP mRNA levels were determined in the aorta and kidney by ribonuclease protection assay. Plasma ANP levels were determined by RIA. Both NP-A and NP-B receptor mRNA levels in the aortae of Wistar fatty rats were double those in Wistar lean rats. Plasma ANP levels and CNP mRNA levels in the aorta of Wistar fatty rats were also significantly higher than those in Wistar lean rats. In contrast, there was no significant difference in renal levels of the mRNA for both NP receptors and CNP between the two strains. Administration of a NP-A and -B receptor antagonist, HS-142-1, to Wistar fatty rats resulted in a significant increase in systolic blood pressure and a larger decrease in plasma cGMP level than that in Wistar lean rats, with no difference in the extents of decrease in urine volume and urinary sodium excretion between the two strains. These results suggest that both the ANP/NP-A system and the CNP/NP-B system in vessels are up-regulated at the level of gene expression and may, thus, play an important role in counteracting the hypertension associated with diabetes mellitus.

Animals↗

Angiotensin II-dependent down-regulation of vascular natriuretic peptide type C receptor gene expression in hypertensive rats.

Biological actions of natriuretic peptide (NP) are determined by the condition of the receptor as well as that of the hormone. Although we previously demonstrated in hypertensive rats the up-regulation of NP-A receptor that mediates various biological actions of NPs, the pathophysiologic significance of NP-C receptor, another subtype thought to be related to clearance of NPs and possibly to biological actions, remains unknown. In the present study, we determined NP-C receptor messenger RNA (mRNA) level in the aortic tissue of stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and in cultured aortic smooth muscle cells by ribonuclease protection assay. The aortic NP-C receptor mRNA level in SHR-SP/Izm was significantly lower than that in the control WKY/Izm. Oral administration of an angiotensin (Ang) II receptor (AT1) antagonist, TCV-116, but not a calcium channel blocker, manidipine, reversed the down-regulated NP-C receptor mRNA in SHR-SP/Izm to the level in WKY/Izm, whereas the latter was more potent in decreasing the blood pressure. In cultured aortic smooth muscle cells, the NP-C receptor was the predominant subtype. Ang II decreased the NP-C receptor mRNA level in a dose-dependent manner, but this effect was reversed by an AT1 antagonist, CV-11974. Neither the NP-A nor NP-B receptor mRNA level was altered by Ang II. These findings indicate that vascular NP-C receptor is down- regulated via Ang-II-mediated mechanism in SHR-SP/Izm. The phenomenon, together with the up-regulation of the NP-A receptor, may play an important role in counteracting hypertension by enhancing the action of NPs.

Angiotensin II↗

Determination of wing cell fate by the escargot and snail genes in Drosophila.

Inset appendages such as the wing and the leg are formed in response to inductive signals in the embryonic field. In Drosophila, cells receiving such signals initiate developmental programs which allow them to become imaginal discs. Subsequently, these discs autonomously organize patterns specific for each appendage. We here report that two related transcription factors, Escargot and Snail that are expressed in the embryonic wing disc, function as intrinsic determinants of the wing cell fate. In escargot or snail mutant embryos, wing-specific expression of Snail, Vestigial and beta-galactosidase regulated by escargot enhancer were found as well as in wild-type embryos. However, in escargot snail double mutant embryos, wing development proceeded until stage 13, but the marker expression was not maintained in later stages, and the invagination of the primordium was absent. From such analyses, it was concluded that Escargot and Snail expression in the wing disc are maintained by their auto- and crossactivation. Ubiquitous escargot or snail expression induced from the hsp70 promoter rescued the escargot snail double mutant phenotype with the effects confined to the prospective wing cells. Similar DNA binding specificities of Escargot and Snail suggest that they control the same set of genes required for wing development. We thus propose the following scenario for early wing disc development. Prospective wing cells respond to the induction by turning on escargot and snail transcription, and become competent for regulation by Escargot and Snail. Such cells initiate auto- and crossregulatory circuits of escargot and snail. The sustained Escargot and Snail expression then activates vestigial and other target genes that are essential for wing development. This maintains the commitment to the wing cell fate and induces wing-specific cell shape change.

Animals↗

The expression of lymphocyte function associated antigen-1, intercellular adhesion molecule-1 on peripheral blood lymphocytes in patients with systemic lupus erythematosus.

The ratios of CD11a, CD18, HLA-DP on T cells and CD54 on B cells of 54 patients with active systemic lupus erythematosus (SLE) were examined. The ratios of LFA-1 alpha, beta, ICAM-1, HLA-DP among SLE patients were significantly higher when compared with normal healthy controls, and the significant correlation between the ratio of LFA-1+ T cells and HLA-DP+ T cells, and LFA-1+ T cells and ICAM-1+ B cells was recognized. These results may suggest that LFA-1, ICAM-1 is related to the mutual action between activated T cells and B cells.

Adolescent↗

[A case of bronchiolo-alveolar carcinoma with high production of carbohydrate antigen (CA19-9)].

A 75-year-old female had loss of appetite, left hypochondrial and back pain. An X-ray and a computed tomogram of both lungs showed multiple small granular shadows. By Tc-labelled bone scintigram, multiple uptakes were found. Since high serum CA19-9 was obtained, pancreatic or bile duct cancer with multiple lung and bone metastasis was suspected. The autopsy revealed, small nodules in both lungs were well-differentiated adenocarcinoma, bronchiolo-alveolar type, and immunohistologically, tumor cells were stained positively for CA19-9. Since CA19-9 exists in normal bronchial glands and bronchiole, high level of serum CA19-9 in our patient may be derived from the neoplastic bronchiolar epithelium.

Adenocarcinoma, Bronchiolo-Alveolar↗

[The pathogenesis of idiopathic portal hypertension].

Idiopathic portal hypertension (IPH), so called Banti's disease, is characterized by anemia, splenomegaly and portal hypertension. While sharing certain clinical features, IPH is distinct from liver cirrhosis not only in histopathology and natural history but also in vascular anatomy and portal hemodynamics. Our studies have shown that the majority of patients with IPH have high serum levels of immunoglobulins, including autoantibodies, associated with abnormally high frequencies of activated T cells and the biased usage of particular T cell receptor (TCR) V beta gene segments. These results suggested that IPH was an immunological disorder mediated by a continuous stimulation with either a certain antigen or more likely a superantigen.

Adult↗

[Biliary endoprosthesis using metallic stents in management of malignant biliary strictures].

Metallic stents were placed percutaneous-transhepaticaly in 65 patients for palliation of malignant biliary obstruction. Fifty-five patients were managed without jaundice 1-12 months (median, 6.8 months) after stent placement. Ten patients had recurrent jaundice due to ingrowth of tumor through the stents. No stent-related complications were seen in all patients. The small transhepatic track required makes insertion easier, less painful, and probably safer when compared with plastic stents, and the large internal lumen reduces the rate of occlusion by encrusted bile. The metallic biliary stent is suggested as an effective treatment for malignant biliary obstruction.

Adult↗

Differential gene expression of vascular natriuretic peptide receptor subtype in artery and vein.

Although the vasorelaxation by natriuretic peptide (NP) is much less potent in the vein than in the artery, mechanism underlying the phenomenon remains unknown. Since NP receptor consists of three subtypes with different functions, we determined the mRNA level of each NP receptor subtype in the artery and vein by ribonuclease protection assay. In the aorta, NP-A receptor related to the biological action of NP was the predominant form. By contrast, NP-C receptor related mainly to the clearance of NP was the predominant form in the inferior vena cava: NP-C mRNA level was about two fold higher than in the aorta, while both NP-A and NP-B receptor mRNA levels were about half of that in the aorta. These results provide the molecular basis for the different biological response to NP in the artery and vein. Differential gene expression of NP receptor subtype could be an important determinant of the biological actions of NP.

Animals↗

Reciprocal regulation by cyclic nucleotides of the differentiation of rat osteoblast-like cells and mineralization of nodules.

The effects of cAMP and cGMP on the differentiation of osteoblast-like cells derived from rat calvariae and on the formation of bone in vitro were studied. Continuous culture of osteoblast-like cells in the presence of 8-bromo-cyclic AMP (8-Br-cAMP) resulted in the dose-related inhibition both of the synthesis of cellular alkaline phosphatase (ALPase), which is known as a marker of osteoblastic differentiation, and of the formation of mineralized nodules, which is a model of the formation of bone in vitro. By contrast, 8-bromo-cyclic GMP (8-Br-cGMP) promoted the synthesis of ALPase and the formation of mineralized nodules. Northern blot analysis revealed that these cyclic nucleotides modulated the steady-state levels of mRNAs for ALPase and osteocalcin, a bone-matrix protein that is specifically produced by osteoblast. The present results indicate that cAMP and cGMP act reciprocally to regulate osteoblastic differentiation and the subsequent formation of mineralized nodules.

8-Bromo Cyclic Adenosine Monophosphate↗