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Biomedical subjects

S Kitano

Publications and source records attributed to S Kitano.

At least 199 records · Page 11Linked to original sources

[Quantitative measurements of regional cerebral blood flow using technetium-99m-L,L-ECD SPECT activated with acetazolamide: fundamental study of measurement's accuracy, comparison with 123I-IMP ARG method].

We measured regional cerebral blood flow before and after acetazolamide administration using a serial noninvasive method with 99mTc-ECD developed by Matsuda and Takeuchi et al., and compared the accuracy of measured values with those obtained by the conventional 123I-IMP ARG method. When the regional cerebral blood flow was measured for 80 brain regions in 5 subjects without scatter correction, a differential of 0.5 +/- 8.4% was obtained between values measured before and after physiological saline administration as a placebo. A differential of -0.2 +/- 12.6% was obtained when the same regions were measured with scatter correction. These findings indicated that placebo administration did not affect measured values, regardless of whether scatter correction was performed. When 64 regions in 4 subjects at rest were measured on two successive days, a differential of -1.1 +/- 9.0% was obtained between the values measured on the two days. A differential of -4.0 +/- 11.7% was obtained for the same regions following acetazolamide administration. These findings showed that measurements were reproducible both when subjects were at rest and when they were administered acetazolamide. The above two methods were used for measurement of 80 brain regions in the same 5 subjects for comparison. Measurements of subjects at rest and with acetazolamide administration were performed on separate days. The regression line y = 0.99x + 1.47, r = 0.80, was obtained for the subjects at rest, and y = 0.86x + 7.76, with r = 0.76, for the subjects following acetazolamide administration. These findings demonstrated a good correlation between the values obtained using the two methods. The values obtained using the method of Matsuda and Takeuchi et al., before and after acetazolamide administration were thus consistent with those reported previously using the conventional method, and the former method proved to be both simple and reliable.

Acetazolamide↗

Transcriptional regulation by transforming growth factor beta of the expression of retinoic acid and retinoid X receptor genes in osteoblastic cells is mediated through AP-1.

We now report that transforming growth factor beta1 (TGF-beta1), a potent regulatory cytokine of bone remodeling, is a powerful stimulator for gene expression of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in osteoblastic MC3T3-E1 cells. TGF-beta1 transcriptionally stimulated the expression of RARalpha, RARgamma, and RXRalpha genes, but did not do so for RARbeta, RXRbeta, and RXRgamma genes. We also observed that AP-1, a transcriptional factor, plays an important role in the signal pathway for expression of RARalpha, RARgamma, and RXRalpha genes stimulated by TGF-beta1 because stimulation of the expression of these genes in the cytokine-treated cells was markedly inhibited by a mixture of antisense c-fos and c-jun. A gel mobility shift assay demonstrated that TGF-beta1 is able to increase, in a dose-dependent manner, the binding of nuclear proteins to direct repeat 5, a consensus sequence with high affinity for RAR-RXR heterodimers. The mobility shift assay, using specific antibody for each receptor, showed that direct repeat 5-binding proteins may be RAR and RXR isoforms. The stimulated binding to direct repeat 5 was inhibited strongly by H-7, an inhibitor of serine/threonine kinase, and by curcumin, an inhibitor of AP-1. The present study suggests a novel pathway for TGF-beta1 action in osteoblastic cells via stimulation of RAR-RXR transcriptional activity in a ligand-dependent fashion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Effect of aging on regulation of sdi-1 in rat hepatocytes.

We examined basal and EGF stimulated DNA synthesis as well as sdi-1 mRNA and protein in primary hepatocyte cultures, and basal levels of sdi-1 mRNA and protein in whole liver homogenates from 6 and 24 month old rats. Since EGF stimulated DNA synthesis decreases with age, it was hypothesized that basal and EGF stimulated levels of sdi-1 mRNA and protein, an inhibitor of DNA synthesis, might increase. Surprisingly, however both sdi-1 mRNA and protein actually decreased both in cells and homogenates of old rats. These results indicate that the age-related impairment in EGF stimulated DNA synthesis in hepatocytes appears to occur prior to or parallel with sdi-1 expression and cannot be explained on the basis of increased inhibition due to elevated levels of this protein.

Aging↗

Alteration of beta-catenin expression in colonic epithelial cells of familial adenomatous polyposis patients.

It has been found that beta-catenin, a key regulator of the cadherin-mediated cell adhesion system, forms complexes with adenomatous polyposis coli (APC) tumor suppressor protein, and beta-catenin expression levels are affected by exogenously induced APC protein. The effects of intrinsic APC protein alteration on beta-catenin expression levels and its subcellular localization were examined in colonic epithelia of eight patients with familial adenomatous polyposis. In all eight patients, beta-catenin was immunostained at the membranes of the cell-to-cell borders in normal epithelial cells, whereas the nuclei and cytoplasms stained intensely in addition to the membranes in both adenoma and cancer cells. beta-Catenin expression levels in tumor tissues were over three times higher than those in corresponding normal mucosae of all of the three patients, whose resected specimens were available for quantitative immunoblot analysis. In these three patients, mutant truncated APC proteins were detected and shown to have lost the central region, including a known beta-catenin binding domain. beta-Catenin was not coimmunoprecipitated with these mutant APC proteins in tumor tissues but was able to be coprecipitated with glutathione S-transferase-fused APC protein containing a beta-catenin binding domain. These results suggest that the absence of wild type APC protein affects the subcellular localization and expression levels of beta-catenin in human tissues.

Adenomatous Polyposis Coli↗

Prostaglandin E2 stimulates osteoclast formation via endogenous IL-1 beta expressed through protein kinase A.

The present study was conducted to determine whether endogenous IL-1 is involved as a potent mediator of PGE2-stimulated osteoclast formation in 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3)-primed calvarial cells from mouse embryos. PGE2 induced IL-1 beta gene expression in the primed calvarial cells. IL-1 beta gene expression was also induced in a dose-dependent manner by forskolin and dibutyryl cAMP. PGE2-induced IL-1 beta gene expression was markedly inhibited by H-89, a potent inhibitor of protein kinase A. On the other hand, osteoclast formation in 1 alpha,25-(OH)2D3-primed calvarial cells was also stimulated by forskolin and dibutyryl cAMP, and their stimulatory effects were dose dependent. H-89 also inhibited PGE2-stimulated osteoclast formation. The presence of the IL-1 beta gene product in the conditioned medium of 1 alpha,25-(OH)2D3-primed calvarial cells treated with PGE2 was proved by the results of an immunoprecipitation assay using anti-mouse IL-1 beta Ab. The addition of anti-mouse IL-1 beta Ab to 1 alpha,25-(OH)2D3 primed calvarial cell cultures markedly inhibited PGE2-stimulated osteoclast formation. The stimulatory effect of conditioned medium of primed calvarial cells treated with PGE2 on osteoclast formation was also inhibited by anti-IL-1 beta Ab pretreatment. Furthermore, we found that endogenous IL-6 is partially involved in PGE2-stimulated osteoclast formation.

24,25-Dihydroxyvitamin D 3↗

Hypoxic and excitotoxic damage to cultured rat retinal ganglion cells.

The cytotoxic effects of hypoxia and excitatory amino acids on cultured retinal ganglion cells were studied. The influence of coculture with retinal Müller glia and cortical astrocytes on cell survival was evaluated, as were the effects of the N-methyl-DL-aspartate inhibitor, MK-801. Dissociated retinal neurons from 7-day-old Sprague-Dawley rats were plated on a laminin substrate, neocortex-derived glial monolayers, or Müller cell monolayers. Ganglion cells were labeled by injection of DiI into the superior colliculus 2 days prior to dissociation. Exposure of cultured ganglion cells to glutamate and N-methyl-DL-aspartate showed a time- and concentration-dependent survival rate. Exposure of cells to hypoxia demonstrated a survival rate that was dependent on time and O2 concentration. Excitotoxic and hypoxic damage was entirely blocked by the specific non-competitive inhibitor of N-methyl-DL-aspartate, MK-801. Retinal ganglion cells cultured on cortical astrocytes and retina-derived Müller glia showed significantly better survival rates (P < 0.001) than cells cultured on laminin-coated dishes under control conditions, in hypoxia (9% to 15% O2), and after exposure to 200 microM glutamate. Retinal ganglion cells cultured on Müller glia showed significantly better survival rates (P < 0.01) than those cultured on cortical astrocytes under conditions of hypoxia (9% to 15% O2) and exposure to 200 microM glutamate. The results demonstrate that excitotoxic and hypoxic damage to cultured retinal ganglion cells is moderated by NMDA receptor blockade and by the presence of glial cells, especially retinal Müller cells. This system may provide a useful model for studying the pathophysiology of excitotoxicity and hypoxia on cultured retinal ganglion cells, and may be used to help identify potentially clinically useful therapeutic agents.

Animals↗

Laparoscopic repair of a colonic perforation sustained during colonoscopy.

A patient who sustained a colonic perforation during therapeutic colonoscopy was treated successfully by laparoscopic repair. Laparoscopy was performed 5 h after polypectomy. Fecal matter was not identified in the peritoneal cavity. Local peritonitis was mild. The laceration was oversewn with five sutures using the extracorporeal endoscopic knot technique. The appendix epiploica was then anchored over the lesion. The postoperative recovery was rapid and uneventful. Laparoscopic surgery may become a useful tool for the safe, effective, and minimally invasive management of iatrogenic colonic perforation.

Colon↗

Extreme hyperbilirubinemia induced by endoscopic injection sclerotherapy in a patient with esophageal varices and thalassemia: report of a case.

We describe herein the case of a 57-year-old man with thalassemia who developed acute liver failure after undergoing endoscopic injection sclerotherapy (EIS) to control hemorrhage from a ruptured esophageal varix. The patient, who had been confirmed as having liver cirrhosis due to chronic hepatitis C with thalassemia in 1989, was admitted to our department to undergo EIS for esophageal varices, at which time his serum total bilirubin level was 5.5 mg/dl. As a small amount of hematemesis occurred just after a percutaneous transhepatic portography was performed, emergency EIS was carried out, following which the serum total bilirubin level markedly increased, mainly with a direct fraction, until it reached 70 mg/dl. The patient eventually died from acute liver failure with extreme hyperbilirubinemia on the 27th day after experiencing hematemesis despite all treatment. This unfortunate case demonstrates that sclerotherapy could be an inappropriate method of treatment for patients with hemolytic disease.

Biopsy↗

Noninvasive variceal pressure measurement may be useful for predicting effect of sclerotherapy for esophageal varices.

This study assessed the relationship between variceal pressure and morphological findings and hemodynamics of esophageal varices as well as the effect of sclerotherapy. Esophageal variceal pressure was measured in 40 patients with portal hypertension, using a noninvasive method. Esophageal variceal pressures were significantly higher in moderate or large varices than they were in small varices. Variceal pressures were significantly higher in patients with red color signs on the varices than in those without. According to the percutaneous transhepatic portography, the structure of the esophageal varices was classified into two types: the bar type and the palisading type. The maximum variceal pressure was significantly higher in the bar type than in the palisading type. In patients who underwent more than five sessions of sclerotherapy, the variceal pressure was significantly higher than in those receiving less than four sessions. These results suggest that variceal pressure may well reflect the vascular pattern and be useful for predicting the effect of sclerotherapy.

Blood Pressure Determination↗

A new sealing device (Sandwich-disc) for rapid recreation of pneumoperitoneum during laparoscopic assisted surgery.

We have developed a new device which enables rapid sealing of a minilaparotomy during laparoscopic assisted surgery to recreate an airtight condition. This device consists of a center rod and two discs (7 cm in diameter) which form an airtight condition by compressing the inner and outer surfaces of the abdominal wall. Advanced laparoscopic procedures requiring both pneumoperitoneum and minilaparotomy are facilitated with the use of this device. This new device is called the Sandwich-disc: Takasago Medical Industry Co., Ltd.

Colonic Neoplasms↗

Interleukin-1 beta and tumor necrosis factor-alpha stimulate synergistically the expression of monocyte chemoattractant protein-1 in fibroblastic cells derived from human periodontal ligament.

The present study demonstrates that interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) induce and synergistically stimulate monocyte chemoattractant protein-1 (MCP-1) expression in fibroblasts from human periodontal ligament. IL-1 beta and TNF-alpha induced in a dose-dependent manner the expression of the MCP-1 gene in the fibroblasts from the human periodontal ligament. However, such an inducing effect was not observed with IL-6 and interferon-gamma. The peak expression of the MCP-1 gene by IL-1 beta or TNF-alpha was observed at 3 h after initiation of their treatment. Furthermore, IL-1 beta in combination with TNF-alpha synergistically stimulated the MCP-1 gene expression in the cells. We also observed significant chemotactic activity for human monocytes in conditioned medium of fibroblasts from the human periodontal ligament treated with both cytokines. The stimulated chemotactic activity induced by these cytokines depended on both dose and treatment time. The chemotactic activity in conditioned medium of IL-1 beta-treated fibroblasts from the human periodontal ligament was neutralized by antiserum specific for MCP-1 protein. The MCP-1 gene product in conditioned medium of IL-1 beta-treated fibroblasts from the human periodontal ligament was shown to have a molecular mass of 11,000 Da by immunoprecipitation with the specific antiserum, and IL-1 beta also stimulated synergistically MCP-1 protein expression in combination with TNF-alpha. These results suggest that IL-1 beta and TNF-alpha may contribute to the infiltration of monocytes into inflammatory sites of periodontal ligament tissues via the MCP-1 gene product produced by fibroblasts from the human periodontal ligament.

Chemokine CCL2↗

CD14-mediated signal pathway of Porphyromonas gingivalis lipopolysaccharide in human gingival fibroblasts.

Lipopolysaccharide (LPS) induces expression of inflammatory cytokines in monocytes/macrophages via CD14, one of the LPS receptors, which is expressed predominantly in these cells. It has been demonstrated that Porphyromonas gingivalis LPS (P-LPS) also is able to induce inflammatory cytokines in human gingival fibroblasts. Therefore, it is important to determine whether CD14 is expressed in gingival fibroblasts and to define the P-LPS-mediated signal-transducing mechanism in the cells. In this study, we observed unexpectedly by immunohistochemical, Western blotting (immunoblotting), and Northern (RNA) blotting assays that CD14 is expressed at high density in human gingival fibroblasts. P-LPS-induced expression of the monocyte chemoattractant protein 1 (MCP-1) gene in the cells was inhibited markedly by treatment with anti-human CD14 antibody and was completely inhibited by herbimycin A, a potent inhibitor of tyrosine kinase. The inhibitor also dramatically inhibited monocyte chemotactic activity of and MCP-1 production by the cells. Furthermore, P-LPS-induced expression of the MCP-1 gene in the cells also was blocked by inhibitors of two transcription factors, i.e., curcumin, an inhibitor of AP-1, and pyrolidine dithiocarbamate, an inhibitor of NF-kappaB. Both inhibitors inhibited monocyte chemotactic activity in the culture supernatant of P-LPS-treated cells. Gel shift mobility assay showed stimulation of the AP-1 and NF-kappaB contents in P-LPS-treated cells. This study is the first to demonstrate the expression of CD14 in human gingival fibroblasts and to show that the signal-transducing pathway of P-LPS in the cells is mediated by CD14.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Porphyromonas gingivalis fimbrillin is one of the fibronectin-binding proteins.

In this study, we demonstrate that Porphyromonas gingivalis fimbrillin, a major component of bacterial fimbriae, is one of the fibronectin-binding proteins and that fibronectin is a potent inhibitor of the adherence of the bacteria to host cells and of the pathogenesis of the bacterium that acts by binding to the fimbriae. A Western blotting (immunoblotting) assay showed that fibronectin binds strongly to P. gingivalis fimbrillin. The fimbrial binding to fibronectin was also evidenced by a binding assay involving 125I-labeled fimbriae. Furthermore, fibronectin markedly inhibited the fimbria-induced expression of interleukin-1beta and neutrophil-specific chemoattractant KC genes in macrophages. The inhibitory action depended on the fimbrial interaction with heparin-binding and cell attachment domains in the fibronectin structure. The binding of P.gingivalis to mouse peritoneal macrophages via its fimbriae was inhibited by fibronectin. Fibronectin also inhibited the bacterial cell-induced expression of interleukin-1beta and KC genes in the macrophages. These results demonstrate the importance of fibronectin as a modulator of the pathogenic mechanism of P. gingivalis, a pathogen that causes adult periodontal disease.

Adhesins, Bacterial↗

Syntheses and anti-inflammatory activities of O-acyloximes. II.

Novel O-acyloximes having an acetyl group or N-protected amino acid as an O-acyl group were synthesized by reaction with acetyl chloride or by a mixed anhydride method. 4'-Morpholinoacetophenone oxime (oxime-2) was determined to be the (E) isomer by X-ray crystal structure analysis. The anti-inflammatory activities of the test compounds were assessed in terms of the inhibitory effect on increased vascular permeability induced by histamine, and several compounds were assessed together by means of the carrageenan-induced paw edema assay. In general, acetyl oximes and tert-butyloxycarbonylphenylalanyl oximes showed inhibitory action on increased vascular permeability. Particularly important for the appearance of anti-inflammatory activity was direct attachment of the acetyl group to the oxime. Of the two isoforms of cyclooxygenase (COX-1 and COX-2), COX-1 activity was inhibited by oxime-2 and 4'-piperidinoacetophenone oxime (oxime-3) with IC50 values of 50 and 130 microM, respectively, while COX-2 activity was not inhibited. The in vitro inhibitory effect of oxime-2 and oxime-3 on COX-1 activity decreased with O-acylation of the oximes.

Animals↗

Non-traumatic arteriovenous fistulas of the scalp treated by a combination of embolization and surgical removal.

Three patients with non-traumatic arteriovenous fistulas (AVFs) of the scalp were treated by embolization using acrylate glue through the transarterial route or by direct puncture of the lesions and then surgical resection. Complete cure was achieved in all three patients. Selective angiography is indispensable in the correct diagnosis of scalp AVFs. Embolization facilitates surgical removal when necessary, and this combination is the treatment of choice for scalp AVFs.

Acrylates↗

Vein of Galen aneurysmal malformation in a neonate treated by endovascular surgery--case report.

A male neonate with vein of Galen aneurysmal malformation developed fetal heart failure after a gestation period of 37 weeks. Labor was induced, but a cesarean section had to be performed because of fetal distress. His Apgar scores were 2/8 at birth. The boy required controlled ventilation due to generalized seizure and cyanosis. Neuroimaging revealed vein of Galen aneurysmal malformation with enormous arteriovenous shunt flows. Transarterial embolization was performed on days 4 and 6 to reduce the progressive high-output congestive heart failure. Three large feeders were occluded with interlocking detachable coils, markedly reducing the shunt flow. Although heart failure improved markedly, he died of pulmonary hemorrhage on day 12. Endovascular surgery can improve the prognosis of heart failure in the neonatal period less invasively than other treatment modalities, and may help to minimize ischemic brain damage and thus increase the possibility of normal brain maturation.

Arteriovenous Fistula↗

[Effective mechanisms of laser photocoagulation for neovascularization in diabetic retinopathy].

Effective mechanisms of laser photocoagulation for neovascularization in diabetic retinopathy were investigated in regard to change in oxygen pressure in the retina and vitreous and cytokines related to ischemia. The mechanism of laser photocoagulation is suggested to be as follows. 1. Destruction of the outer retina, especially of photoreceptors that have high oxygen consumption decreases metabolic function of the outer retina and its oxygen consumption. 2. The destruction allows increase of oxygen diffusion from choroidal vessels to inner retina, which improves the metabolic function by equilibrating oxygen demand and supply in the inner retina. (3) Production and secretion of neovascular factors such as vascular endothelial growth factor (VEGF) is decreased by the improvement of hypoxia. 4. The neovascularization is decreased by the synergistic effect between the neovascular factors and suppressors such an VEGF, fibroblast growth factor (FGF), and transforming growth factor-beta (TGF-beta). The improvement of the retinal ischemia and the decrease of cytokines are implicated in the regression of neovascularization by the laser photocoagulation for diabetic retinopathy.

Animals↗