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Biomedical subjects

S Kitano

Publications and source records attributed to S Kitano.

At least 163 records · Page 9Linked to original sources

NF-kappaB inhibitors stimulate apoptosis of rabbit mature osteoclasts and inhibit bone resorption by these cells.

Interesting, recent studies have suggested a possibility that transcriptional factor NF-kappaB may play a functional role in the survival of mouse osteoclasts. However, it has not been known whether NF-kappaB is involved in apoptosis of and bone resorption by mature osteoclasts. Thus, using NF-kappaB inhibitors, we examined the functional role of NF-kappaB in the induction of apoptosis in rabbit mature osteoclasts. PDTC, a potent inhibitor of NF-kappaB, stimulated markedly apoptosis of the osteoclasts and inhibited bone resorption by these cells. These effects also was observed when three other inhibitors of NF-kappaB were used. And a gel mobility shift assay showed that PDTC also inhibited NF-kappaB binding to its consensus sequence in the cells. These results suggest a regulatory role for NF-kappaB in apoptosis in and bone resorption by rabbit mature osteoclasts.

Animals↗

Functional role of endogenous CD14 in lipopolysaccharide-stimulated bone resorption.

Lipopolysaccharide (LPS) is a bacterial cell component that plays multifunctional roles in inflammatory reactions, and one of these roles is that of a powerful stimulator of bone resorption. However, the mechanism by which LPS stimulates bone resorption is not yet understood. In the present study, we show, by using mouse embryonic calvarial cells, that endogenous CD14 and interleukin-1 beta (IL-1 beta) play an important role in the LPS-mediated bone resorption and that interferon-gamma (IFN-gamma) functions as a strong inhibitor of this resorption by suppressing LPS-stimulated expression of CD14 and IL-1 beta genes in the calvarial cells. We observed that LPS-stimulated differentiation of osteoclastic cells and bone resorption were markedly neutralized by anti-mouse CD14 antibody and were clearly inhibited by anti-sense CD14 oligonucleotide treatment. In addition, because LPS stimulated CD14 gene expression in the calvarial cells, these observations demonstrate the precise role of endogenous CD14 in LPS-stimulated differentiation of osteoclastic cells and bone resorption. However, the stimulation of the differentiation of osteoclastic cells and bone resorption was also inhibited by anti-mouse IL-1 beta antibody. Interestingly, anti-sense CD14 oligonucleotide inhibited LPS-stimulated expression of the IL-1 beta gene in the calvarial cells. These observations suggest a functional role of endogenous CD14 in LPS-stimulated expression of the IL-1 beta gene in the cells. Because IFN-gamma is a potent inhibitor of bone resorption stimulated by IL-1, in additional experiments, we examined whether IFN-gamma is able to inhibit LPS-stimulated differentiation of osteoclastic cells and bone resorption. We found that IFN-gamma inhibited these stimulations by suppressing CD14 and IL-1 beta genes in the calvarial cells. The present study thus clearly demonstrates a functional role of endogenous CD14 in LPS-stimulated bone resorption.

Acid Phosphatase↗

The significance of esophageal variceal pressure in patients with cirrhosis.

We measured the portal circulatory hemodynamic parameters in 10 cirrhotic patients with portal hypertension and esophageal varices to determine the significance of esophageal variceal pressure. In 4 patients (group I), the temporary portal vein occlusion produced significant elevations in both the esophageal variceal pressure and the portal venous pressure. The results of the portal circulatory hemodynamic assessment in this group were consistent with the predominance of the backward flow mechanism. In the remaining 6 patients (group II), however, portal vein clamping resulted in a slightly increased esophageal variceal pressure with an enormous increase in the portal pressure. The forward flow mechanism thus appeared to be predominant in group II. In other words, the results of the pressure measurements were consistent with the functional separation of the hemodynamics in the esophageal varices and portal trunk in group II and the functional hemodynamic continuity in group I. This functional separation between the esophageal varices and the portal trunk in group II might therefore have resulted from the increased blood flow in the lesser splanchnic region.

Blood Pressure↗

Laparoscopic splenectomy for splenic hamartoma.

Advances in imaging techniques have made pre-operative diagnosis of splenic tumors possible. A case of successful laparoscopic splenectomy for splenic hamartoma is described here and the indications of this technique are discussed.

Hamartoma↗

Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells.

Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by AII, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2-induced enhancement of DNA synthesis induced by AII. These findings suggest that autocrine HB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC.

Angiotensin II↗

Morphogenesis and development of superficial spreading tumor of the colon and rectum.

The aim of this study was to clarify the morphogenesis and mechanism of a wide intramucosal extension of a superficial spreading (epithelial) tumor (SST; defined as an epithelial tumor with wide intramucosal spreading involving a diameter of 30 mm or more) in the colon and rectum. For this purpose favorable sites, histological components, and histological growth patterns were compared between 95 cases of SST (16 adenomas and 79 carcinomas) and 2356 non-SST cases, which served as controls. The frequency of SST was significantly higher in the cecum and rectum, and lower in the sigmoid colon when compared to the locations of the control. Among the SST cases, 82.3% of superficial spreading carcinoma (SSC) had an adenomatous component and 96.2% had a cytologically low-grade carcinoma (CAL). In intramucosal SSC, the adenomatous and/or CAL component was predominant, and the proportion of high-grade carcinoma (CAH) was significantly smaller in intramucosal SSC in comparison with the control group. In the mucosal spreading area of SST, 78.9% were tubulovillous in histological type and 86.3% showed a replacing growth pattern. These results indicate that an SST initially develops as an adenoma in at least 85.3% of cases and CAL in 14.7% cases at most; spreads superficially in the mucosa by a replacing growth mechanism that forms a tubulovillous and villous structure; and is affected by intestinal peristalsis less than non-SST.

Adenoma↗

Sarcomatoid hepatocellular carcinoma with osteoclast-like giant cells: case report and immunohistochemical observations.

Hepatocellular carcinoma (HCC) with osteoclast-like giant cells (OGC) developed in the cirrhotic liver of a 42-year-old male. Serum protein induced by vitamin K absence or antagonist II was elevated preoperatively. The patient died of the disease on the 28th postoperative day. Histologically, the tumor consisted of OGC and mononuclear cells (MC). The OGC were characterized by benign-appearing nuclei, whereas the MC had atypical nuclei with a considerable number of mitoses. A vaguely trabecular pattern was observed in the focal area of the tumor, but no evidence of overt HCC was found. Immunohistochemical analysis revealed that both OGC and MC were diffusely positive for histiocytic and mesenchymal markers. Some MC were focally positive for cytokeratins 7, 8 and 19, and for albumin. Our clinical, histological and immunohistochemical findings suggest that the MC were derived from hepatocytes, with some mesenchymal features, but the OGC were non-neoplastic and reactive histiocytes.

Adult↗

Interleukin-6 production in human fibroblasts derived from periodontal tissues is differentially regulated by cytokines and a glucocorticoid.

Interleukin-6 (IL-6) is thought to be a major mediator of the host's defense against infection, and it regulates immune responses in inflamed tissue. In this study, we investigated the regulation of IL-6 production in human gingival fibroblasts (HGF) and human periodontal ligament fibroblasts (HPLF). Pro-inflammatory cytokines including interleukin (IL)-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha stimulated IL-6 production in HGF and HPLF in a time- and dose-dependent manner. This IL-1 alpha, IL-1 beta, or TNF-alpha-induced IL-6 production was enhanced, but the cAMP accumulation they induced was inhibited by the addition of indomethacin. This result suggests that endogenous prostaglandin E2 (PGE2) partially inhibits IL-1 or TNF-alpha-induced IL-6 production and that the enhancement of IL-6 production by IL-1 or TNF-alpha may not be caused through endogenous PGE2-induced cAMP-dependent pathway. Dexamethasone (DEX), a glucocorticoid which is a inhibitor of nuclear factor kappa B (NF-kappa B activation, markedly inhibited IL-1 (alpha or beta) or TNF-alpha-induced IL-6 production; so this production may be partially mediated through NF-kappa B. IL-1 (alpha or beta) and TNF-alpha enhanced IL-6 production synergistically. IL-6 production in HGF or HPLF stimulated with IL-1 beta was augmented by the addition of interferon (IFN)-gamma, but was slightly suppressed by the addition of IL-4. Endogenous IL-6 enhanced IL-1 (alpha or beta)-induced IL-6 production in the presence of IL-6 soluble receptor (IL-6sR). Accordingly, in inflamed periodontal tissues, gingival fibroblasts and periodontal ligament fibroblasts stimulated with pro-inflammatory cytokines such as IL-1 or TNF-alpha, may produce IL-6, and this production can be differentially modulated by endogenous PGE2, IL-6sR, T cell-derived cytokines such as IFN-gamma or IL-4, and glucocorticoids.

Anti-Inflammatory Agents, Non-Steroidal↗

Porphyromonas gingivalis fimbria-stimulated bone resorption is inhibited through binding of the fimbriae to fibronectin.

Our most recent study demonstrated that fibronectin is one of the Porphyromonas gingivalis fimbria-binding proteins. In this present study, we demonstrate with mouse embryonic calvarial cells that P. gingivalis fimbria-stimulated bone resorption is inhibited by human fibronectin. The fibronectin inhibition was dose and culture time dependent and was completely neutralized by antifibronectin antibody. The inhibitory action of fibronectin depended on fimbrial interaction with the heparin-binding and cell-attachment domains in the fibronectin structure.

Animals↗

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↗