Search PubMed⌕ Search

Biomedical subjects

S Kitano

Publications and source records attributed to S Kitano.

At least 181 records · Page 10Linked to original sources

Porphyromonas gingivalis lipopolysaccharide-stimulated bone resorption via CD14 is inhibited by broad-spectrum antibiotics.

In the present study, we examined mechanisms of Porphyromonas gingivalis lipopolysaccharide (P-LPS)-stimulated bone resorption via CD14, one of the lipopolysaccharide (LPS) receptors, and also assessed the inhibitory action of several kinds of antibiotics on the LPS-induced stimulation. First, we observed by using mouse embryonic calvarial cells that P-LPS stimulated bone resorption through the action of endogenous interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) via CD14 because (i) P-LPS-stimulated expression of IL-1beta and IL-6 genes in calvarial cells was inhibited by an anti-mouse CD14 antibody, (ii) stimulated bone resorption was markedly inhibited by both IL-1beta and IL-6 antibodies, and (iii) P-LPS-stimulated bone resorption was clearly neutralized by an anti-mouse CD14 antibody. Next, we examined the effects of several kinds of antibiotics on P-LPS-stimulated bone resorption via CD14. Two of them, chloramphenicol and erythromycin, inhibited P-LPS-stimulated bone resorption in a dose-dependent manner. In an additional experiment, we observed that chloramphenicol clearly inhibited P-LPS-stimulated expression of the CD14, IL-1beta, and IL-6 genes in calvarial cells. These results suggest that chloramphenicol might be a useful antibiotic as an anti-inflammatory agent against P-LPS-stimulated periodontal destruction occurring via CD14 in periodontal disease.

Ampicillin↗

MR cholangiopancreatography and MR urography: improved enhancement with a negative oral contrast agent.

At magnetic resonance (MR) cholangiopancreatography and MR urography with an oral negative contrast agent, low signal intensity was produced in phantoms. In 20 patients suspected of having biliary tract and pancreatic diseases and in 20 healthy volunteers, the signal intensity in the gastrointestinal tract was almost completely eliminated with the negative contrast agent. Differences in image quality between pre- and postcontrast images were statistically significant.

Administration, Oral↗

Parathyroid hormone-related protein upregulates interleukin-1beta-induced nitric oxide synthesis.

The effect of parathyroid hormone-related protein on interleukin-1beta-induced nitric oxide production was studied in rat vascular smooth muscle cells. Interleukin-1beta time- and dose-dependently enhanced the production of nitrite, a stable metabolite of nitric oxide. Parathyroid hormone-related protein(1-34) alone up to 10(-7) mol/L had no obvious effect, but significantly increased the cytokine-induced nitrite production. RNA analysis revealed that the synergistic effect of parathyroid hormone-related protein(1-34) resulted from a potentiation of the expression of inducible nitric oxide synthase and GTP-cyclohydrolase I, the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, which is a cofactor of nitric oxide synthase. The increased nitric oxide release induced by interleukin-1beta or interleukin-1beta with parathyroid hormone-related protein(1-34) was completely inhibited by coincubation with 3x10(-3) mol/L N(G)-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase, or with 10(-3) mol/L 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTP-cyclohydrolase I. Endothelin-1 potentiated interleukin-1beta induction of nitric oxide, which might be mediated by endogenous parathyroid hormone-related protein. Neutralization of exogenous or endogenous parathyroid hormone-related protein with antibody attenuated the synergistic effect of parathyroid hormone-related protein, but did not affect interleukin-1beta induction of nitric oxide. These results suggest that locally produced parathyroid hormone-related protein acts as a synergistic regulator upregulating interleukin-1beta-induced nitric oxide synthesis in the cardiovascular system, and thereby may affect vascular tone and/or vascular remodeling after vascular injury in some pathological processes such as atherosclerosis and hypertension.

Animals↗

Limb salvage using distraction osteogenesis. A classification of the technique.

We report the results of distraction osteogenesis (callotasis) for the reconstruction of extensive defects after the excision of skeletal tumours in the limbs. Bone transport was performed in ten patients (five osteosarcomas and five giant-cell tumours), shortening-distraction in three (two osteosarcomas and one Ewing's sarcoma), and distraction osteogenesis combined with an intramedullary nail to reduce the time of external fixation in six (three osteosarcomas, two chondrosarcomas, and one malignant fibrous histiocytoma). The mean length of the defects after excision of the lesion was 8.4 cm. The mean external fixation index was 39.5 days/cm for the group treated by bone transport, 34.1 days/cm for the shortening-distraction group, and 24.0 days/cm for the group treated by distraction and an intramedullary nail. Functional evaluation gave excellent results in 12 patients, good in five and fair in two. There were ten complications in 19 patients, all of which were successfully treated. We also classified reconstruction using distraction osteogenesis into five types based on the location of the defects after resection of the tumour: type 1, diaphyseal; type 2, metaphyseal; type 3, epiphyseal; type 4, subarticular reconstruction; and type 5, arthrodesis. Our results suggest that reconstruction using distraction osteogenesis provides bone which will develop sufficient biomechanical strength and durability. It is beneficial in patients with an expectation of long-term survival and in growing children.

Adolescent↗

[Urinary bacteria in elderly patients with urinary incontinence and low levels of daily activity].

The results of bacteria isolated from the urine of inactive elderly patients with urinary incontinence in 1982, 87, 93 and 95 were compared and the chronological changes of urinary bacteria were analyzed. The following results were obtained: (1) The most common bacteria isolated from the patients in 1995 were D-group Enterococcus, followed by Providencia rettgeri, E. coli, Pseudomonas aeruginosa and Proteus mirabilis. It is thought that the main cause of the more frequent isolation of Enterococcus is an abuse of cephems and fecal contamination. (2) The most common bacteriaisolated from the patients who were managed with an indwelling urethral catheter were Proteus and Providencia species, and their incidence tended to decrease from 1982 to 1995. (3) Infection with Pseudomonas species tended to increase, as did that Staphylococcus species, especially Methicillin-resistant Staphylococcus aureus and then decreased. Based on these findings, it is important to assess and treat dysuria before inserting an indwelling urethral catheter, and to select an antibacterial agent that is effective in elderly patients with urinary incontinence and limited activity.

Activities of Daily Living↗

[Cerebral infarction and asymptomatic arteriosclerosis obliterans in the elderly].

We examined the associations between cerebral infarction (CI), asymptomatic arteriosclerosis obliterans (ASO), and known risk factors for these diseases. The subjects were 67 elderly patients (11 men and 56 women, mean +/- SD age of 79.6 +/- 8.5 years). in 44 patients CI was diagnosed by CT scan; 23 were classified as having cortical infarction and 21 as having lacunar infarction. In 41 patients asymptomatic ASO was diagnosed by an ankle-pressure index (API) of less than 0.9. To identify risk factors for these diseases, we examined the association among these diseases and hypertension (blood pressure > or = 140/90 mmHg), hypercholesterolemia (total cholesterol concentration > or = 220 mg/dl), hypertriglyceridemia (triglyceride concentration > or = 150 mg/dl), low HDL-cholesterolemia (HDL-C concentration < 40 mg/dl), high LDL-cholesterolemia (LDL-C concentration > or = 150 mg/dl), and glucose intolerance (fasting blood sugar concentration > or = 110 mg/dl). The incidence of asymptomatic ASO in the subjects with CI was significantly higher than that in the subjects without CI (chi 2 test; p < 0.05, odds ratio 6.4), including cortical infarction (p < 0.05, odds ratio 8.9) and lacunar infarction (p < 0.05, odds ratio 3.8). Patients with lacunar infarction were more likely to have hypertension than were controls (p < 0.05). Cortical infarction was not associated with these risk factors. Both low HDL-C and high LDL-G were more common in patients with asymptomatic ASO than patients without asymptomatic ASO (p < 0.05). These results indicate that CI and asymptomatic ASO are strongly associated in the elderly, especially in subjects with cortical infarction, and that aging itself contributes to cortical infarction.

Aged↗

Prognostic factors of node-negative gastric carcinoma: univariate and multivariate analyses.

BACKGROUND: The presence or absence of lymph node metastasis closely correlates with survival of patients with gastric carcinoma. Although prognostic significance of the number and level of lymph node metastasis has been clarified, clinicopathologic features and prognostic indicators of node-negative gastric carcinoma have not yet been studied. STUDY DESIGN: The records of 435 patients who underwent curative D2 or D3 gastrectomy for gastric carcinoma between 1977 and 1987 were analyzed retrospectively. Clinicopathologic data of 252 patients having no lymph node metastasis were compared with those of 183 patients with lymph node metastasis. Prognostic factors were investigated by univariate and multivariate analyses. RESULTS: Compared with node-positive cases, node-negative cases were characterized by frequent location in the lower two thirds of the stomach (85 percent), tumor size less than 4 cm (54 percent), grossly superficial type (69 percent), and tumor invasion not beyond the muscularis propria (77 percent). The 10-year-survival rate for patients with node-negative tumors was 93.4 percent. Multivariate analysis demonstrated that depth of wall invasion and age of patient were independent prognostic factors. CONCLUSIONS: Node-negative gastric carcinoma is associated with a favorable outcome because of small progression of the disease. The depth of wall invasion and patient age were the most important prognostic factors.

Female↗

Preoperative assessment of advanced gastric carcinoma using computed tomography.

OBJECTIVES: The role of computed tomography (CT) for the staging of gastric carcinoma is controversial. The purpose of this study was to evaluate the utility of CT in assessing the perigastric spread of advanced gastric carcinoma. METHODS: The study included 56 patients who underwent dynamic CT and laparotomy for the treatment of node-positive gastric adenocarcinoma. Preoperative CT findings were compared with surgical findings, and diagnostic accuracy was estimated. RESULTS: Sensitivity, specificity, and accuracy of preoperative CT in determining the perigastric tumor spreads were 33, 97, and 73% in pancreatic invasion, 36, 97, and 70% in level III lymph node involvement, and 89, 98, and 96% in liver metastasis. Peritoneal dissemination was not detected in 15 of 56 patients (27%), and stage IV disease was not diagnosed correctly in 18 of 40 patients (45%). CONCLUSIONS: Radiologists and surgeons must remember that pancreatic invasion, extended lymph node metastasis, and peritoneal dissemination are sometimes overlooked in CT examination in patients with advanced gastric carcinoma.

Adenocarcinoma↗

Direct extracranial-intracranial bypass for children with moyamoya disease.

To improve cerebral hypoperfusion in the ischemic type of Moyamoya disease, we have applied superficial temporal artery-middle cerebral artery (STA-MCA) double anastomoses in combination with encephalo-myo-synangiosis (EMS) for 19 hemispheres of 10 children (age from 5 to 11 years at surgery). Two branches of the STA were anastomosed to the two cortical arteries which were selected in the watershed area of the cerebral hemisphere estimated as a hypoperfusion area on the preoperative angiograms. Before surgery transient ischemic attacks (TIAs) developed from every month to every 6 months in association with hyperventilation or sobbing. No perioperative completed stroke or wound complications was observed, although single TIA developed in four patients within 1 month after surgery. Postoperative angiogram demonstrated that, not only the preoperative watershed area, but also the most of the middle cerebral artery territory was oppacified via the 2 branches of the STA in all 19 hemispheres. In a mean follow-up period of 4 years, no ischemic episode was induced by hyperventilation, and there was no mental or neurological deterioration. STA-MCA double anastomoses, to the cerebral watershed area, in combination with EMS are safe and effective even for younger children with Moyamoya disease.

Anastomosis, Surgical↗

[Functions of the transforming growth factor-beta superfamily in eyes].

One human body is composed of 6 x 10(13) cells, and eyes are also composed of many cells of different functions. The cellular functions and intercellular interaction are regulated by many regulators including cytokines and growth factors to maintain the homeostasis. The transforming growth factor-beta (TGF-beta) superfamily, a large family of multifunctional factors, regulates various cellular functions, including cellular proliferation, migration, differentiation, apoptosis and extracellular matrix production. The TGF-beta superfamily contains about 30 multifunctional factors, and is divided into several families according to the sequence homology. The TGF-beta family, the activin family, and bone morphogenic proteins belong to the TGF-beta superfamily. TGF-beta superfamily members transduce signals through type I and type II serine/threonine type transmembrane receptors. The signals are transduced from receptors through nuclei by Smad family members, which are phosphorylated by the activated type I receptors and translocate from cytoplasm into nuclei. TGF-beta family members and the TGF-beta superfamily receptor family are expressed in ocular tissues including the cornea, ciliary epithelium, lens epithelium, retina, and blood vessels. This observation suggests the importance of the TGF-beta superfamily in eyes. Smad family members (Smad 1, Smad 2, Smad 3 and Smad 4) are expressed in the cultured retinal pigmant epithelial cell line (D407), in which TGF-beta and activin A stimulate the translocation of Smad 2, but not Smad 1 into nuclei, whereas bone morphogenetic protein (BMP) stimulates that of Smad 1, but not Smad 2. TGF-beta superfamily members play important roles in the pathogenesis of retinal neovascularization and in the wound healing process of corneal tissue. TGF-beta inhibits the endothelial functions, but, stimulates angiogenesis in vivo. TGF-beta is involved in the formation of abnormal connective tissue in corneal wound healing. In these processes, many cytokines and growth factors are involved, interacting with each other and forming networks. It is mandatory to clarify the networks to investigate molecular pathogenesis and new therapeutic agents.

Diabetic Retinopathy↗

[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↗