Biomedical subjects

T Ikebe

Publications and source records attributed to T Ikebe.

At least 37 records · Page 2Linked to original sources

PubMed2000

A study of the association between the prognosis of carcinoma of the mandibular gingiva and the pattern of bone destruction on computed tomography.

OBJECTIVE: To clarify whether the pattern of bone destruction seen on CT is more closely associated with the outcome of carcinoma of the mandibular gingiva than that derived from panoramic radiographs (PR). METHOD: Axial bone window CT scans and PR of 62 patients with carcinoma of the mandibular gingiva were evaluated retrospectively by two oral radiologists for the pattern of bone destruction. Patterns were classified into the three types: erosive, invasive and mixed. The relationship between these patterns with each imaging modality and cumulative recurrence rate, cumulative metastasis rate and cumulative survival rate, calculated by the Kaplan-Meier method, were statistically analysed by the log rank test. RESULTS: The pattern of bone destruction derived from CT was closely associated with the cumulative metastasis rate (P < 0.05), the cumulative recurrence rate and the cumulative survival rate. In contrast, the pattern of bone destruction based on the PR was not associated with the cumulative metastasis rate (P = 0.43), the cumulative recurrence rate (P = 0.44), or the cumulative survival rate (P = 0.5). CONCLUSION: The prognosis of patients with carcinoma of the mandibular gingiva is more closely related to a classification derived from the pattern of bone destruction on CT rather than PR. However, the number of subjects investigated in this study was not large enough to confirm our conclusions statistically. Further studies by other investigators are therefore needed.

Adult↗

PubMed2000

Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats.

Proliferation and activation of hepatic stellate cells (HSCs) are critical steps for the development of postnecrotic fibrosis in the liver. The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP-470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl(4))- and dimethylnitrosamine-induced hepatic fibrosis were used for an in vivo study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg/kg body weight of TNP-470. In CCl(4)-induced fibrosis, factor VIII-related antigen-positive blood vessels, desmin-, or alpha-smooth muscle actin (alphaSMA)-positive mesenchymal cells, bromodeoxyuridine (BrdU)-positive mesenchymal cells also decreased in number by treatment with TNP-470. In in vitro experiments, a supplement of 1,000 ng/mL TNP-470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and/or presence of platelet-derived growth factor (PDGF). Expression of HSC activation markers, i.e., alphaSMA and PDGF receptor beta, was also suppressed. The present results indicate that TNP-470 inhibits HSC proliferation by blocking the cell-cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect.

Actins↗

PubMed2000

Comparison of fatal coronary heart disease occurrence based on population surveys in Japan and the USA.

BACKGROUND: Although vital statistics have indicated large Japanese-American differences in mortality rates for coronary heart disease (CHD), the magnitude of difference has not been documented well using comparable validation of cause of death. METHODS: Population-based fatal CHD data were compared between the Oita Cardiac Death Survey, Japan and the Atherosclerosis Risk in Communities (ARIC) Study, USA. Both studies (population: Oita City 198 093; the ARIC comunities 286 820) identified possible fatal CHD events (International Classification of Diseases, Ninth Revision [ICD-9]: 410-414, 250, 401-402, 427-429, 440, and 798-799) among residents aged 35-74 years during 1992-1993. Comparable criteria for classifying cause of death were applied. Sex-specific, age-adjusted mortality rates of CHD were calculated by place of death. RESULTS: In all, 330 deaths in Oita and 1398 in the ARIC communities had eligible ICD-9 death certificate codes; CHD codes (ICD-9 410-414) comprised 30.6% of investigated deaths in Oita and 58.6% in ARIC. For men, the non-validated rate ratio for CHD deaths (ARIC:Oita City) was 5.9 (95% CI : 4.2-8.5), which fell to 4.7 (95% CI : 3.5-6.4) with validation and inclusion of sudden deaths within one hour of onset as fatal CHD. For women, the overall non-validated rate ratio was 4.6 (95% CI : 2.8-7.6), which fell to 3.9 (95% CI : 2.4-6.3) with validation and but there was little further change when the sudden deaths were added. CONCLUSIONS: Our results suggest that differences in fatal CHD rates between Japanese and Americans were not as large as suggested by vital statistics when events were validated and sudden deaths were included.

Adult↗

PubMed1999

Synthesis and pharmacological evaluation of carboxamide derivatives as selective serotoninergic 5-HT(4) receptor agonists.

A number of new carboxamide derivatives were synthesized. The affinity of these compounds for the serotoninergic 5-HT(4) receptor was evaluated by use of radioligand-binding techniques. The agonistic activity was evaluated as the contractile effect of the ascending colon isolated from guinea-pigs. Among these compounds, 4-amino-5-chloro-2-methoxy-N-[1-[2-[(methylsulfonyl)amino]ethly]-4-piperidinylmethyl]benzamide (24) showed a high affinity for the 5-HT(4) receptor (Ki = 9.6 nM). Compound 24 displayed a higher affinity for 5-HT(4) receptors than the other receptors, including, 5-HT(3) and dopamine D(2) receptors. In addition, compound 24 was confirmed to be a potent 5-HT(4) receptor agonist (ED(50) = 7.0 nM). An interaction model between compound 24 and 5-HT(4) receptor was proposed.

Journal Article↗

PubMed1999

Clinical significance of prior hepatitis B virus infection in patients with hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND: The effect of prior hepatitis B virus (HBV) infection on the clinicopathologic findings for patients with hepatitis C virus (HCV) RNA and hepatocellular carcinoma (HCC) is still unclear. METHODS: Of 59 patients who underwent liver resection for HCV-related HCC (</=2.0 cm in greatest dimension) without metastases between 1990 and 1997, 38 patients had anti-HB core antibody (anti-HBc) and did not have HB surface antigen in their sera (Group 1). Their clinicopathologic findings and outcomes after surgery were compared with those of the remaining 22 patients without anti-HBc (Group 2). RESULTS: The proportion of well-differentiated HCC was significantly lower in Group 1 than in Group 2 (P = 0.0214). The percentage of patients with cirrhosis was significantly lower in Group 1 than in Group 2 (P = 0.0228). The cumulative survival rate was significantly lower in Group 1 than in Group 2 (P = 0.0224). The risk ratio of anti-HBc for shorter survival time was 3.817. CONCLUSIONS: HCC more often developed before cirrhosis in patients with HCV RNA and anti-HBc than in patients positive for HCV RNA alone. Prior HBV infection was a risk factor for poor outcome after liver resection for patients infected with HCV.

Aged↗

PubMed1999

Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence of osteoblasts/stromal cells.

Interleukin-1 (IL-1) is one of the most potent bone-resorbing factors involved in bone loss associated with inflammation. We previously reported that IL-1 prolonged the survival of multinucleated osteoclast-like cells (OCLs) formed in cocultures of murine osteoblasts/stromal cells and bone marrow cells via the prevention of spontaneously occurring apoptosis. It was reported that macrophage colony-stimulating factor (M-CSF/CSF-1) prolongs the survival of OCLs without the help of osteoblasts/stromal cells. The present study was conducted to determine whether IL-1 also directly induces the multinucleation and activation of OCLs. Mononuclear osteoclast-like cells (prefusion osteoclasts; pOCs) were purified using the "disintegrin" echistatin from cocultures of murine osteoblastic cells (MB 1.8 cells) and bone marrow cells. Both IL-1 and M-CSF prolonged the survival and induced the multinucleation of pOCs through their respective receptors. However, actin ring formation (a functional marker of osteoclasts) by multinucleated cells was observed in the pOC cultures treated with IL-1, but not those treated with M-CSF. We previously reported that enriched multinucleated OCLs as well as pOCs placed on bone/dentine slices formed few resorption pits, but their pit-forming activity was greatly increased by the addition of osteoblasts/stromal cells. Here, pit-forming activity of both pOCs and enriched OCLs placed on dentine slices was induced by adding IL-1, even in the absence of osteoblasts/stromal cells. M-CSF failed to induce pit-forming activity in pOC and enriched OCL cultures. These results indicate that IL-1 induces the multinucleation and bone-resorbing activity of osteoclasts even in the absence of osteoblasts/stromal cells.

Animals↗

PubMed1999

Immunohistochemical study of sialyl Le(a) and sialyl Le(x) antigen in oral squamous cell carcinoma: the association of sialyl Le(a) expression with the metastatic potential.

BACKGROUND: Carbohydrate antigens in cancer cells are considered to be involved in the binding of cancer cells to the endothelium during metastasis. METHODS: Seventy cases of primary oral squamous cell carcinoma (SCC) were obtained from biopsy specimens and were analyzed immunohistochemically using an antibody against sialyl Lewis (Le)a or sialyl Le(x). Flow cytometry was performed to detect the sialyl Le(a) or sialyl Le(x) expressed on oral SCC cell lines. RESULTS: The expressions of sialyl Le(a), but not sialyl Le(x), of primary tumors significantly correlated to nodal metastasis; 71% of the metastatic cases express sialyl Le(a) and the cases with positive sialyl Le(a) and no sialyl Le(x) demonstrated a high incidence of metastasis (80%). A flow cytometric study demonstrated the oral SCC cell line, which can metastasize in nude mice, to express a high level of sialyl Le(a). CONCLUSION: The high expression of sialyl Le(a) in primary tumors may thus be involved in nodal metastasis and therefore predict a poor prognosis in oral SCC.

Animals↗

PubMed1999

Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis.

BACKGROUND: Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential. MATERIALS AND METHODS: This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined. RESULTS: First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases. CONCLUSION: These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.

Adult↗

PubMed1999

Influence of histological inflammatory activity on regenerative capacity of liver after percutaneous transhepatic portal vein embolization.

Percutaneous transhepatic portal vein embolization (PTPE) produces regenerative hypertrophy in the nonembolized part of the liver, but the regenerative capacity after PTPE in patients with chronic hepatitis is unknown. We studied 34 patients with hepatocellular carcinoma and chronic hepatitis who underwent PTPE at the right portal vein. Hepatic lobular volumes were calculated by computed tomography before and 2 weeks after PTPE. The increase in left lobular volume was analyzed using a stepwise multiple regression method incorporating 11 factors: age; portal venous pressure; proportional volume of the right lobe; indocyanine green retention test; platelet count; serum levels of aspartate transaminase, alanine transaminase, total bilirubin, and albumin; and histological inflammatory grade and stage of fibrosis, according to the criteria of the International Association for the Study of the Liver recommended at their 1994 meeting. The median volume of the left lobe had increased from 405 to 554 cm3 (P < 0.0001) by 2 weeks after PTPE. Inflammatory grade was the only independent factor predicting regenerative hypertrophy (regeneration ratio (%) = 80.3 - 20.1 x grade; standard correlation coefficient = -0.566; P = 0.0014). Histological inflammatory activity was the essential factor regulating liver regeneration after PTPE in patients with chronic hepatitis.

Aged↗

PubMed1999

Gelatinolytic activity of matrix metalloproteinase in tumor tissues correlates with the invasiveness of oral cancer.

We examined whether or not the gelatinolytic activity in tumor tissue was associated with the invasion and metastasis of oral squamous cell carcinoma (OSCC). Tissue homogenates were prepared from 57 biopsy specimens of OSCC. The gelatinolytic activities in the homogenates were measured by gelatin zymography and its densitometric analysis. The Immnunoblot findings revealed the major gelatinolytic activities to be due to matrix metalloproteinase (MMP)-2 and -9. The zymography-detected gelatinolytic activities of MMP-2 and MMP-9 in the tissue specimens significantly correlated with the degree of immunohistochemical staining detected in frozen sections of the same biopsy specimens. According to a histopathological analysis of the mode of invasion, highly invasive cases showed the increased gelatinolytic activities of MMP-2 as well as MMP-9 in the tissue specimens. Although no significant differences were observed in the gelatinase activities between the metastatic cases and the non-metastatic cases, the levels of tissue inhibitor of MMP (TIMP)-1 in the tumor tissue specimens were higher in the non-metastatic cases than in the metastatic cases. The cases with the high levels of MMPs and low levels of TIMP-1 thus seemed to have a high potential to metastasize. As a result, the zymographic measurement of the gelatinolytic activity in biopsy tissue specimens may therefore be useful in predicting the behavior and prognosis of OSCC.

Carcinoma, Squamous Cell↗

PubMed1999

Expression of integrins in squamous cell carcinoma of the oral cavity. Correlations with tumor invasion and metastasis.

Integrins are cell adhesion molecules that mediate the cell to extracellular matrix interactions. We sought to determine whether the integrin expression on tumor cells is associated with invasive and metastatic potential. First, in 8 cell lines of oral squamous cell carcinoma, 4 of which were metastatic in nude mice and 4 of which were not, integrin expression was examined. When these cell lines were cultured in vitro or transplanted into the tongues of nude mice, the metastatic cell lines tended to show a stronger expression of alpha 2, alpha 3, alpha 5, and alpha 6 integrins than did the nonmetastatic cell lines. Second, integrin expression was immunohistochemically examined in 65 biopsy specimens of primary oral squamous cell carcinoma. In invasive or metastatic cases, a marked expression of alpha 2, alpha 3, alpha 5, and alpha 6 integrins was frequently observed. The association of integrin expression with the mode of tumor invasion and nodal involvement was found to be statistically significant. These results suggest that integrin expression is closely associated with tumor invasion and nodal involvement in oral squamous cell carcinoma.

Animals↗

PubMed1999

Relationship between multicentric occurrence of hepatocellular carcinoma and histology of noncancerous hepatic tissue in patients with chronic hepatitis C.

The relationship between multicentric occurrence of hepatocellular carcinoma (HCC) and the histology of noncancerous hepatic tissue was investigated in 252 patients infected with hepatitis C virus (HCV) and surgically treated for HCC. One type of multicentric HCC had at least one tumor consisting of well-differentiated HCC, together with moderately or poorly differentiated HCC located in a separate region. The other type had an area of well-differentiated component around HCC with less differentiation in all occurrences. Noncancerous hepatic tissues were assessed using a histologic activity index score. Serum alanine aminotransferase (ALT) activity, the concentration of type 4 collagen, the grading score (severity of active hepatitis), and the staging score (degree of fibrosis) were significantly higher in patients with multicentric HCCs than in those without them. Platelet count was significantly lower in patients with multicentric HCCs. The prevalence of multicentric HCCs increased as the grading score and staging score increased. On univariate analysis, a low platelet count and high grading and staging scores were risk factors for multicentric HCCs. A high ALT activity and a high concentration of type 4 collagen tended to be risk factors. On multivariate analysis, high grading score and high staging score were independent risk factors. These findings indicate that active hepatitis and extensive fibrosis are responsible for the development of multicentric HCCs. Measurement of platelet count, ALT activity, and the concentration of type 4 collagen, and histologic assessment of noncancerous hepatic tissue provide information useful for estimation of the potential for multicentric carcinogenesis.

Alanine Transaminase↗

PubMed1999

Correlation of clinicopathologic features of resected hepatocellular carcinoma with hepatitis C virus genotype.

Clinicopathologic findings in patients with hepatocellular carcinoma complicating hepatitis C virus and outcomes after liver resection were compared between different viral genotypes. One hundred and forty-seven patients with both anti-hepatitis C virus antibody and hepatitis C virus RNA in their sera underwent curative resection for hepatocellular carcinoma in our department between 1991 and 1997. Of these patients, 115 were infected with hepatitis C virus genotype 1b (group 1), and 32 were infected with 2a or 2b (group 2). Clinicopathologic findings and outcomes after operation were compared between the two groups. Alanine aminotransferase activity was significantly higher in group 2 than in group 1. Genotypes did not differ concomitantly with histopathologic features of the carcinoma or adjacent hepatic tissue. Although the tumor-free survival rate did not differ significantly between the two groups, recurrence was not detected during the period beyond 3 years following operation in group 2, while recurrences arose during that period in 16 group 1 patients, most of whom continued to manifest active hepatitis. In 7 of these 16 patients, the recurrent tumors were histologically multicentric in origin. The cumulative survival rate was significantly lower in group 1 than 2. Multivariate analysis indicated that genotype 1b was an independent risk factor for short survival. Patients infected with genotype 1b may have a relatively high risk of ongoing hepatocarcinogenesis and more aggressive progression of associated liver dysfunction, resulting in a poorer outcome than with other genotypes.

Aged↗

PubMed1999

Effects of continuous hepatitis with persistent hepatitis C viremia on outcome after resection of hepatocellular carcinoma.

The effect of persistent hepatitis C viremia on the outcome after resection of hepatocellular carcinoma (HCC) was investigated in 59 consecutive patients with a single small HCC (< or = 3.0 cm in diameter). The presence of serum hepatitis C virus (HCV) RNA was evaluated using a reverse transcription polymerase chain reaction method as well as a branched DNA probe method. Clinicopathologic findings were compared between patients with and without viremia and the risk factors for poor outcome were evaluated. Hepatitis C virus (HCV) RNA was not detected in the sera from 7 patients (group 1), but was detected in the sera from the other 52 patients (group 2). Alanine aminotransferase (ALT) activity was significantly higher in group 2 than in group 1. The proportion of patients with active hepatitis was significantly higher in group 2. In group 2, new HCC often developed after the operation and four patients died of liver dysfunction. HCV viremia, high ALT activity, high concentration of total bilirubin, and liver cirrhosis were related to recurrence after the operation. Multivariate analysis indicated that HCV viremia and high ALT activity were independent risk factors for recurrence of HCC. Continuous hepatitis with persistent HCV viremia worsened the outcome after the resection of HCC by causing new development of HCC and deterioration of liver function. In patients with HCV-related HCC, but without HCV viremia, satisfactory results can be expected after liver resection.

Aged↗

PubMed1999

Reevaluation of the promoter structure of the class 3 flagellar operons of Escherichia coli and Salmonella.

Flagellar class 3 operons of Escherichia coli and Salmonella are transcribed by RNA polymerase containing sigma 28. The consensus sequence of the sigma 28-dependent promoters was believed to be TAAA N15 GCCGATAA. In this study, we found that the E. coli genome contains a large number of sequences homologous to this consensus. However, we showed that they do not always exert a sigma 28-dependent promoter activity. We compare more carefully the sequences of the class 3 flagellar promoters and propose a revised structure of the sigma 28-dependent promoters as TAAAGTTT N11 GCCGATAA.

Base Sequence↗

PubMed1999

Promoter analysis of the class 2 flagellar operons of Salmonella.

The Salmonella flagellar operons are divided into three classes with reference to their relative positions in the transcriptional hierarchy. Expression of the class 2 operons requires the class 1 gene products, FlhD and FlhC, and is enhanced by an unknown mechanism in the presence of the class 3-specific sigma factor, FliA, and in the absence of its cognate anti-sigma factor, FlgM. In this study, the transcriptional start site mapping was performed by primer extension analysis for five class 2 operons, flgA, flgB, flhB, fliE and fliL. In all cases, one or a few major transcriptional start sites were identified. These start signals disappeared in the flhDC-mutant background, and their intensity decreased and increased in the fliA-mutant and flgM-mutant backgrounds, respectively. Therefore, we conclude that the FlhD/FlhC-dependent transcription is responsible for the FliA-dependent enhancement. Sequence comparison revealed that an imperfect inverted repetitious sequence is conserved upstream of the class 2 operons. Truncation of this sequence from the flgB promoter reduced its transcriptional activity to the background level, indicating that this is an essential cis-acting element for transcription of the class 2 operons.

Bacterial Proteins↗

PubMed1999

Two novel regulatory genes, fliT and fliZ, in the flagellar regulon of Salmonella.

The flagellar operons of Salmonella are divided into three classes with respect to their transcriptional hierarchy. Expression of the class 2 operons requires the class 1 gene products, FlhD and FlhC, and is increased by mutation in the flgM gene, which encodes a class 3-specific anti-sigma factor. Here we report the identification of two novel regulatory genes for class 2 transcription. Presence of the fliZ and fliT genes on multicopy plasmids enhanced and inhibited, respectively, transcription from a chromosomal class 2 promoter. Disruption of the fliZ and fliT genes on the chromosome decreased and increased, respectively, class 2 expression. These results suggest that the fliZ and fliT genes may encode positive and negative regulatory factors, respectively, for class 2 expression. Enhancement of class 2 expression by the flgM mutation was cancelled by the coexisting fliZ mutation, indicating that FliZ is essential for this enhancement.

Bacterial Proteins↗

PubMed1999

A pancreatic anaplastic carcinoma of spindle-cell form.

A 56-yr-old man with complaint of abdominal pain and body weight loss was admitted to our hospital. Contrast-enhanced computed tomography on admission revealed a pancreatic tumor. Contrast-enhanced computed tomography 1 m.o. after admission revealed rapid growth of this tumor. We performed exploratory laparotomy with only a needle biopsy of the unresectable tumor because of extensive spread, including liver metastases. Further histological and immunohistochemical examination revealed that both the pancreatic tumor and the hepatic metastases featured malignant spindle-shaped cells. Despite radiotherapy, the patient died 40 d after laparotomy.

Biopsy, Needle↗