Biomedical subjects

Masamichi Goto

Publications and source records attributed to Masamichi Goto.

At least 19 recordsLinked to original sources

PubMed2006

MUC4 expression correlates with poor prognosis in small-sized lung adenocarcinoma.

The mortality of lung cancer remains high, despite improved diagnostic techniques that allow small lung tumors to be detected. In this study, we evaluated the prognostic significance of the tracheal mucin MUC4 by immunohistochemical investigation of the expression profiles of MUC4, ErbB2, p27 and MUC1 in lung adenocarcinoma specimens (non-bronchiolo-alveolar type, < or =3cm) from 185 patients. MUC4 is a membrane mucin, similarly to MUC1, and in addition MUC4 functions as an intra-membrane ligand for receptor tyrosine kinase ErbB2 and is associated with regulation of p27. However, MUC4 expression was found to be unrelated to expression of MUC1, ErbB2 and p27 in small-sized lung adenocarcinomas. The disease-free interval (DFI) and survival rate of 25 patients with high MUC4 expression (> or =25% of neoplastic cells stained) were significantly lower than those of 160 patients with low MUC4 expression (<25% of neoplastic cells stained) (P<0.05), whereas ErbB2 and p27 expression showed no significant correlation with DFI and survival. Univariate analysis showed that high MUC4 and p27 expression correlated with blood vessel invasion (P=0.0004), and MUC4 expression was frequently detected in regions of stromal invasion. In addition, the survival rate of stage IA patients with high MUC4 expression was significantly lower than that of stage IA patients with low MUC4 expression (P<0.05). In conclusion, high MUC4 expression in small-sized lung adenocarcinomas correlates with a short DFI and a poor survival rate. Therefore, MUC4 expression might be a new independent factor for prediction of outcome and indication of poor prognosis in lung adenocarcinoma.

Adenocarcinoma↗

PubMed2006

MUC2 expression is regulated by histone H3 modification and DNA methylation in pancreatic cancer.

Mucins are highly glycosylated proteins that play important roles in carcinogenesis. In pancreatic neoplasia, MUC2 mucin has been demonstrated as a tumor suppressor and we have reported that MUC2 is a favorable prognostic factor. Regulation of MUC2 gene expression is known to be controlled by DNA methylation, but the role of histone modification for MUC2 gene expression has yet to be clarified. Herein, we provide the first report that the histone H3 modification of the MUC2 promoter region regulates MUC2 gene expression. To investigate the histone modification and DNA methylation of the promoter region of the MUC2 gene, we treated 2 human pancreatic cancer cell lines, PANC1 (MUC2-negative) and BxPC3 (MUC2-positive) with the DNA methyltransferase inhibitor 5-azacytidine (5-aza), the histone deacetylase inhibitor trichostatin A (TSA), and a combination of these agents. The DNA methylation level of PANC1 cells was decreased by all 3 treatments, whereas histone H3-K4/K9 methylation and H3-K9/K27 acetylation in PANC1 cells was changed to the level in BxPC3 cells by treatment with TSA alone and with the 5-aza/TSA combination. The expression level of MUC2 mRNA in PANC1 cells exhibited a definite increase when treated with TSA and 5-aza/TSA, whereas 5-aza alone induced only a slight increase. Our results suggest that histone H3 modification in the 5' flanking region play an important role in MUC2 gene expression, possibly affecting DNA methylation. An understanding of these intimately correlated epigenetic changes may be of importance for predicting the outcome of patients with pancreatic neoplasms.

Azacitidine↗

PubMed2006

MUC4 is a novel prognostic factor of extrahepatic bile duct carcinoma.

PURPOSE: Many of the patients with extrahepatic bile duct carcinoma (EHBDC) show a poor outcome. We have reported that MUC4 is a novel prognostic factor of pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to evaluate the prognostic significance of MUC4 expression in EHBDC. EXPERIMENTAL DESIGN: We examined the expression profile of MUC4 in EHBDC tissues from 70 patients using immunohistochemistry. MUC4 is a membrane mucin like MUC1. In addition, MUC4 is an intramembrane ligand for receptor tyrosine kinase ErbB2 and is related with regulation of p27. We compared the MUC4 expression with MUC1, ErbB2, or p27 expression in EHBDC. RESULTS: MUC4 was expressed in 36 of the 70 patients with EHBDC. There was no significant correlation between the MUC4 expression and MUC1, ErbB2, or p27 expression. The survival of 19 patients with high MUC4 expression (>or=20% of carcinoma cells stained) was significantly worse than that of the 51 patients with low MUC4 expression (under 20% of carcinoma cells stained; P = 0.0072). The univariate analysis showed that high MUC4 expression (P = 0.0072), high MUC1 expression (P = 0.0092), histologic grading (P = 0.0029), surgical margin involvement (P = 0.0137), and nodal metastasis (P = 0.0036) were statistically significant risk factors. The backward stepwise multivariate analysis showed that high MUC4 expression (P = 0.0195) and surgical margin involvement (P = 0.0358) were statistically significant independent risk factors. CONCLUSIONS: MUC4 expression in EHBDC is a new independent factor for poor prognosis and predicts the outcome of patients with EHBDC.

Adult↗

PubMed2006

RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells.

MUC1 is a highly glycosylated, type I transmembrane protein expressed by normal ductal epithelial cells of the pancreas, breast, lung, and gastrointestinal tract, and overexpressed in many cases of adenocarcinoma. We down-regulated MUC1 expression by RNA interference and investigated the effects on malignant and metastatic potential of a human pancreatic cancer cell line, S2-013. MUC1-suppressed clones, S2-013.MTII.C1 and S2-013.MTII.C2, were established by targeting a sequence 3,151 bp from the initiation codon and characterized in vitro for proliferation, invasion, and adhesion. We evaluated the effects of MUC1 suppression in vivo on tumor growth and metastatic properties following implantation into the cecum or pancreas of athymic mice. MUC1-suppressed clones showed significantly decreased proliferation in vitro and in vivo. Global gene expression was evaluated by oligonucleotide microarray analysis. Surprisingly, genes predicted to increase doubling times (cyclin B1 and cyclin D3) were overexpressed in MUC1-suppressed clones. There were alterations in expression of several genes that may affect the malignant properties of pancreatic cancer. Adhesion of MUC1-suppressed cells in vitro to type IV collagen and fibronectin was slightly increased, and adhesion was slightly decreased to type I collagen and laminin. Results of implantation to cecum and pancreas showed significant reduction of metastasis to lymph nodes, lung, or peritoneal sites compared with S2-013.gfp-neo control cells. These results support the hypothesis that MUC1 contributes significantly to growth and metastasis, and that down-regulation of MUC1 protein expression decreases the metastatic potential of pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMed2006

Epstein-Barr virus-associated enteritis with multiple ulcers after stem cell transplantation: first histologically confirmed case.

The present case involves unique enteritis forming multiple ulcers associated with Epstein-Barr virus (EBV). A 57-year-old man had undergone a reduced intensity allogeneic stem cell transplantation for a relapse of multiple myeloma following sequential autologous peripheral blood stem cell transplantation. The ileum, resected for massive melena, showed multiple irregular ulcers with occasional cobblestone-like appearance. There was inflammation including numerous plasma cells in the ulcer bases and surrounding areas, where many EBV-infected plasma cells were detected by double staining with EBV-encoded small RNA-1 (EBER-1) in situ hybridization and CD79a, while EBV-infected epithelial cells were not noted. The number of EBER-1-positive cells in the ileum (mucosa, 1451 cells/mm(2); submucosa, 465 cells/mm(2)) was much larger than in control samples (malignant lymphoma or leukemia after allogeneic stem cell transplantation, n = 4, range 0-113 cells/mm(2); malignant lymphoma after chemotherapy, n = 14, range 0-0.89 cells/mm(2); colon cancer, n = 12, range 0-3.5 cells/mm(2)). In the mucosa near the ulcers, EBER-1-positive cells often surrounded and involved the glandular epithelium, forming lymphoepithelial-like lesions. The histological findings differ from post-transplant lymphoproliferative disorders or intestinal thrombotic microangiopathy, and this is the first case of EBV-associated enteritis with ulcers characterized by numerous plasma cells and lymphoepithelial-like lesions after stem cell transplantation.

CD79 Antigens↗

PubMed2006

Nerve damage in Mycobacterium ulcerans-infected mice: probable cause of painlessness in buruli ulcer.

Buruli ulcer is an emerging chronic painless skin disease found in the tropics and caused by Mycobacterium ulcerans; however, it remains unknown why the large and deep ulcers associated with this disease remain painless. To answer this question, we examined the pathology of BALB/c mice inoculated in the footpads with M. ulcerans African strain 97-107. On days 54 to 70 after inoculation, extensive dermal ulcers, subcutaneous edema, and numerous acid-fast bacilli were noted at the inoculate region. Nerve invasion occurred in the perineurium and extended to the endoneurium, and some nerve bundles were swollen and massively invaded by acid-fast bacilli. However, Schwann cell invasion, a characteristic of leprosy, was not observed. Vacuolar degeneration of myelin-forming Schwann cells was noted in some nerves which may be induced by mycolactone, a toxic lipid produced by M. ulcerans. Polymerase chain reaction analysis of microdissected nerve tissue sections showed positive amplification of M. ulcerans-specific genomic sequences but not of Mycobacterium leprae-specific sequences. Behavioral tests showed decrease of pain until edematous stage, but markedly ulcerated animals showed ordinary response against stimulation. Our study suggests that the painlessness of the disease may be partly due to intraneural invasion of bacilli. Further studies of nerve invasion in clinical samples are urgently needed.

Animals↗

PubMed2006

[Guideline for the treatment of Hansen's disease in Japan (Second edition)].

ad hoc committee of Japanese Leprosy Association recommends revised standard treatment protocol of leprosy in Japan, which is a modification of World Health Organization's multidrug therapy (WHO/MDT, 1997). For paucibacillary (PB) leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough. However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment seems insufficient. Thus, (A) For MB with bacterial index (BI) > or = 3 before treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is necessary. When BI become negative and active lesion is lost within 2 years, no maintenance therapy is necessary. When BI is still positive, one year of MDT/MB is added (3 years in total), followed by maintenance therapy by dapsone and clofazimine until BI negativity and loss of active lesions. (B) For MB with BI < 3 or fresh MB (less than 6 months after the onset of the disease) with BI > or = 3, 1 year treatment by MDT/MB is necessary. When BI become negative and active lesion is lost within one year, no maintenance therapy is necessary. When BI is still positive or active lesion is remaining, additional therapy with MDT/MB for one more year is recommended. This is a simplification of first version in 2000. Brief summary of diagnosis, purpose of therapy, character of drugs, and prevention of deformity is also described.

Clofazimine↗

PubMed2005

Mapping of the methylation pattern of the MUC2 promoter in pancreatic cancer cell lines, using bisulfite genomic sequencing.

Expression of the MUC2 gene is controlled by the methylation of CpG sites in the promoter region, but the detailed methylation status of this region has yet to be reported. We have mapped the complete methylation status of the MUC2 promoter from position -1989 to position +288 upstream, a region that contains 59 CpG sites, using bisulfite genomic sequencing in two pancreatic cancer cell lines (PANC1, BxPC3) and in isolated normal colon crypts as a control. The MUC2 promoter in PANC1, a cell line that does not express MUC2, was highly methylated (average 87%, complete methylation at 28 of the 59 CpG sites), while the promoter region in the MUC2-expressing BxPC3 cell line (average 43%, complete methylation at 2 of 59 CpG sites) and in MUC2-expressing normal colon crypts (average 33%, no CpG site was completely methylated) were only partially methylated (P<0.0001). 5-Aza-2'-deoxycytidine treatment of PANC1 cells reduced the methylation level (average 36%) and induced MUC2 mRNA expression. However, mRNA expression of AP2, SP1 and CDX2 was not affected by this treatment. Our data provide the first detailed methylation map of the MUC2 promoter region for the first time, using the conversion-specific bisulfite genomic sequencing. Previously unproven methylation sites were detected, and some AP2 and SP1 binding sites showed different methylation levels among PANC1, BxPC3 and colonic crypt cells. Our mapping data provide an essential basis for further studies of methylation-regulated MUC2 inactivation.

Azacitidine↗

PubMed2005

Aberrant expression of pyloric gland-type mucin in mucin-producing bile duct carcinomas: a clear difference between the core peptide and the carbohydrate moiety.

The authors have recently defined the clinopathological entity of a mucin-producing bile duct tumor (MPBT), and divided MPBT into two distinct subtypes: 'columnar-type' and 'cuboidal-type' MPBT. Mucin core protein 6 (MUC6), which is present in normal pyloric glands, had higher expression levels in cuboidal-type tumors than in columnar-type tumors. In the pyloric glands, a carbohydrate antigen detected by monoclonal antibody HIK1083 (CA/HIK1083) is also expressed. In order to evaluate the coexpression pattern of MUC6 and CA/HIK1083 in MPBT, expression profiles were evaluated in 38 surgically excised mucin-producing bile duct carcinomas (MPBC; cuboidal-type, n = 15; columnar-type, n = 23), using immunohistochemistry. The staining rate was graded as follows: -, <5% of neoplastic cells stained; +, 5% to <20%; + +, 20% to <50%; + + +, > or =50%. In cuboidal-type MPBC, MUC6 was positive in all cases (+ + +, 13/15; + +, 1/15; +, 1/15), whereas CA/HIK1083 was negative in all cases (-, 15/15; P < 0.0001). In columnar-type MPBC, MUC6 was positive in 65% of cases (+ + +, 6/23; + +, 8/23; +, 1/23; -, 8/23), and CA/HIK1083 was positive in 52% (+ +, 3/23; +, 9/23; -, 11/23; not significant). Our results clearly demonstrate that cuboidal-type MPBC have an aberrant pyloric glandular phenotype, that is, MUC6+/CA/HIK1083-. This unique profile may be related to different outcomes of patients with MPBC.

Adenocarcinoma, Mucinous↗

PubMed2005

[Pathological diagnosis of leprosy in developing countries].

In the developing countries where leprosy is prevalent, diagnosis of leprosy is made from clinical signs and symptoms. However, when difficult and doubtful cases increase after the advance of leprosy control programs, definitive diagnosis of leprosy by histopathology become necessary. This report describes our experience of technical support to re-establish histopathology service and introduction of immunohistochemistry in the leprosy referral center of Myanmar, and we discuss the ideal way of international technical support. This activity was performed as a part of leprosy control and basic health services project of Japan International Cooperation Agency (JICA) since 2000 to 2005.

Clinical Laboratory Techniques↗

PubMed2004

MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type.

Complete surgical resection of the tumor is the sole approach to improve the cure rate of patients with intrahepatic cholangiocarcinoma-mass forming type (ICC-MF). Although patients are treated by curative resection, many of them show poor outcome. Mucin (MUC)4 expression has been implicated as a marker for diagnosis and progression of pancreatic adenocarcinomas, but there is no study of the relationship between MUC4 expression and patient's prognosis in ICC-MF. In the present study, we examined the expression profile of MUC4 in ICC-MF tissue from 27 patients using immunohistochemistry. MUC4 was expressed in the carcinoma tissues of 10 (37%) of the 27 ICC-MF tumors, whereas it was not expressed in normal liver tissue. Because MUC4 is an intramembrane ligand for receptor tyrosine kinase ErbB2 and is related with regulation of p27, we also compared the MUC4 expression with ErbB2 and p27 expressions in ICC-MFs. The patients with MUC4 and ErbB2 double positive expression showed a short survival period compared to non-expressing patients. MUC4 and p27 showed no relationship. The univariate analysis showed that tumor size, intrahepatic metastasis, lymph node metastasis, MUC4 expression, and MUC1 expression were statistically significant risk factors affecting the outcome of the patients with ICC-MF. The multivariate analysis demonstrated that MUC4 expression, as well as surgical margin, were statistically significant independent risk factors. In conclusion, the results suggest that expression of MUC4 in ICC-MF is a new independent factor for poor prognosis and is a useful marker to predict the outcome of the patients with ICC-MF.

Aged↗

PubMed2004

Traumatic injury-induced midkine expression in the adult rat spinal cord during the early stage.

Spinal cord injury is a debilitating condition. Midkine (MK) is involved in the generation of the central nervous system during development; however, the role of MK in the mature spinal cord has not been clarified. We examined the expression of MK, which has neurotrophic activity, before and after traumatic injury to the adult rat spinal cord. Following laminectomy, the rat spinal cord was injured at the T-9 level by applying extradural static weight-compression, in which a cylindrical compressor was used to induce complete and irreversible transverse spinal cord injury with paralysis of the lower extremities. The expression of MK was examined up to 14 days after the injury by immunohistochemical and Western blot analyses. Intense MK immunoreactivity was observed in the gray matter around the injury site but not in the necrotic lesion 1-7 days postinjury, although it was slightly positive 14 days after the injury. MK immunoreactivity was not detected in the normal spinal cord. The expression of MK was an early event, and its expression was compared to the increased production of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, that was elevated at 2 days postinjury and continued over a 14 day period following the injury. Double immunostaining with anti-MK and anti-GFAP showed the existence of MK in the astrocytic cytoplasm. These findings suggest that MK was produced in astrocytes approximating the damaged region and may represent a reparative neurotrophic factor during the early phase of traumatic injury of the spinal cord.

Animals↗

PubMed2004

Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms.

Tumors with clinically recognizable mucin production arising from bile duct, "mucin-producing bile duct tumors (MPBTs)," have not been studied yet for their pathologic features and classification in details. The clinical findings of MPBT have a lot of similarities to those of pancreatic intraductal papillary-mucinous neoplasm. In the present study, we examined 30 MPBTs and classified them into two distinct morphologic categories: 22 cases of "columnar type" composed of pseudostratified columnar cells with basophilic cytoplasm and columnar nuclei and 8 cases of "cuboidal type" composed of pancreaticobiliary and/or oncocytic pattern. Pancreaticobiliary pattern showed abundantly branched papillae lined by acidophilic cuboidal cells with round nuclei, whereas oncocytic pattern was characterized by intraepithelial lumina and cribriform pattern composed of abundant oxyphilic cells with round nuclei, and these patterns overlapped frequently. There were significant differences in the clinicopathologic findings including macroscopic findings, morphometric data, mucin expression profiles (MUC2 expression in columnar type and MUC6 expression in cuboidal type), and cell proliferative activities between columnar type and cuboidal type. Patients with columnar type showed significantly poorer survival than those with cuboidal type. We concluded that columnar type and cuboidal type of MBPTs belong to different lineage of neoplasm and that they are counterparts of "intestinal type" and "pancreaticobiliary type" of pancreatic intraductal papillary-mucinous neoplasm, respectively.

Adenocarcinoma, Papillary↗

PubMed2004

Uterine lipoleiomyoma: a histopathological review of 17 cases.

Lipoleiomyoma is a rare uterine tumor. The exact frequency and proliferation activity are not yet known. This study aims to know the frequency and evaluate the relation with renal angiomyolipoma. Lipoleiomyoma cases were immunohistochemically stained by antibodies for Ki-67, melanoma specific antigen HMB45, S-100 protein, and alpha smooth muscle actin (alpha-SMA). Frequency of uterine lipoleiomyoma among uterine myomatous tumor was 17/4904 (0.35%) in the Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School database (1983-2003). Patients ranged from 45 to 74 years of age, and 10 cases were associated with leiomyoma. Six of 17 (35%) cases showed areas with renal angiomyolipoma-like vessels and atypical cellular features. Immunostaining was available in 12 cases. By Ki-67 labeling index, both muscle (average 1.38%) and fat (average 1.17%) portions of the tumor had greater proliferation than normal myometrium (average 0.76%), which suggests that fat portions of the tumor are proliferating adipose tissue rather than fatty degeneration of muscular counterpart. HMB45 antigen, which is positive in renal angiomyolipoma, was negative in three uterine cases having angiomyolipoma-like vessels (3/12). However, HMB45 antigen was positive in spindle-shaped tumor cells of three cases (3/12) which lacked angiomyolipoma-like vessels. Presence of angiomyolipoma-like blood vessels in these tumors is not an uncommon feature. However, the diagnosis of uterine angiomyolipoma should not be based on the result of HMB45 antigen immunoreactivity alone.

Actins↗

PubMed2004

[Guideline for the treatment of leprosy by new quinolones].

Ofloxacin(OFLX) is often applied today as a substitution drug of MDT for drug resistance to dapsone, rifampicin or clofazimine. However, OFLX resistance is also becoming a great concern. Low and/or irregular administration are considered to be the major causes of OFLX resistance. OFLX should be used as a combined therapy, and minimal daily dose of 400 mg of OFLX or 200-300 mg of levofloxacin is required. Quinolone resistance should be considered when no improvement of clinical and/or bacterial index is observed after the treatment for 6 months. In such cases, resistance gene detection is necessary.

Anti-Infective Agents↗

PubMed2004

[Comparison of inhibitory effect of rifalazil and rifampicin against Mycobacterium ulcerans infection induced in mice].

PURPOSE: Buruli ulcer is a human skin disease caused by Mycobacterium ulcerans infection, which is characterized by massive skin ulceration and persistent necrotic change. In recent years Buruli ulcer has rapidly emerged as an increasingly important cause of human morbidity around the world. The disease is endemic at least 32 countries in Africa, Western Pacific, Asia and South America, and it is considered the third most common mycobacterial infection of humans after tuberculosis and leprosy. An effective chemotherapeutic regimen against Buruli ulcer disease has not been established to date. In this study, the inhibitory effect of rifalazil (RLZ) against M. ulcerans was assessed in experimentally infected mice and compared to that of rifampicin (RFP). MATERIALS AND METHODS: Five-week-old BALB/c female mice were challenged with 25 microliters (CFU = 4 x 10(4) of M. ulcerans cultured in Middlebrook 7H9 broth in bilateral hind footpads. Mice were administered per os with a suspension of RLZ or RFP at 2.5, 5, or 10 mg/kg once daily 5 times per week starting from one day up to 6 weeks after infection. During the treatment, mice were observed weekly for footpad skin lesions and examined for footpad swelling. In addition, CFU enumeration was done on both hind footpads and spleen at 2, 4, and 6 weeks after initiating treatment. RESULTS: In the infected control mice group, slightly erythematous lesions and moderate swelling of footpads were observed 4 weeks after the infection. Ulcerative lesion was observed 6 weeks after the infection. Mean log10 CFU/footpad (FP) was 5.22 on day 1 after the infection and increased to 5.56, 6.29, and 7.33 at 2, 4, and 6 weeks after treatment was initiated in the treated groups. On the other hand, no visible erythema, swelling or ulcerative lesion in footpads were observed in RLZ-administered groups. Furthermore, log10 CFU/FP decreased to 4.14 after only 2 weeks of initiating treatment in 2.5 mg/kg administered group, i.e. the lowest dose employed group. Log10 CFU/FP decreased to < 2.1 in 6 weeks in the 10 mg/kg administered group, which was close to the detection limit (< 1.7) of the CFU assay. By contrast, inhibitory effect on disease progression and reduction of CFU were observed only in the group of mice given 10 mg/kg among RFP-administered groups: the reduction of CFU was not observed in the early period but 6 weeks after initiating treatment. CONCLUSION: These results clearly demonstrate that the in vivo anti-M.ulcerans activity of RLZ is much higher than RFP. RLZ activity against M. ulcerans can be expected to control the disease progression in the clinical applications.

Animals↗

PubMed2003

High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine.

OBJECTIVE: High mobility group box chromosomal protein 1 (HMGB-1), a nuclear DNA binding protein, was recently rediscovered as a new proinflammatory cytokine. The purpose of this study was to demonstrate HMGB-1 expression in vivo and to identify the role of HMGB-1 in the pathogenesis of rheumatoid arthritis (RA). METHODS: HMGB-1 concentrations in synovial fluid (SF) and serum from RA and osteoarthritis (OA) patients were measured by immunoblot analysis. The protein's specific receptor, receptor for advanced glycation end products (RAGE), was examined in SF macrophages (SFMs). We measured levels of proinflammatory cytokines released by SFMs treated with HMGB-1 via enzyme-linked immunosorbent assay and used soluble RAGE (sRAGE) to block the release of tumor necrosis factor alpha (TNFalpha). Immunohistochemical analysis and immunofluorescence assay were employed to examine localization of HMGB-1 in RA synovium and its translocation in SFMs after TNFalpha stimulation. RESULTS: HMGB-1 concentrations were significantly higher in SF of RA patients than in that of OA patients. SFMs expressed RAGE and released TNFalpha, interleukin-1beta (IL-1beta), and IL-6 upon stimulation with HMGB-1. HMGB-1 was found in CD68-positive cells of RA synovium, and TNFalpha stimulation translocated HMGB-1 from the nucleus to the cytosol in SFMs. Blockade by sRAGE inhibited the release of TNFalpha from SFMs. CONCLUSION: HMGB-1 was more strongly expressed in SF of RA patients than in that of OA patients, inducing the release of proinflammatory cytokines from SFMs. HMGB-1 plays a pivotal role in the pathogenesis of RA and may be an original target of therapy as a novel cytokine.

Aged↗

PubMed2003

Cured tuberculoid patients have a greater life expectancy than cured lepromatous patients in Japan.

Leprosy patients lack specific cellular immunity against Mycobacterium leprae, but other immunological functions are thought to be preserved. However, in a leprosy sanatorium in South Japan between 1982 and 2000, we found that the average age at death of cured lepromatous leprosy patients was about 5 yrs younger than that of cured tuberculoid patients; [male/lepromatous, 76.0 +/- 10.0 yrs old vs. male/tuberculoid, 79.7 +/- 9.4 yrs old, p = 0.026], and [female/lepromatous, 78.0 +/- 10.5 vs. female/tuberculoid, 85.3 +/- 9.8, p = 0.0001]. This trend was also observed in autopsy records of two other leprosy sanatoria in Japan. In a prospective study based on their age in 1982, among females in the age group between 60 and 69, lepromatous patients (75.3 +/- 6.0 yrs) died earlier than tuberculoid patients (81.0 +/- 5.1 yrs) (p < 0.01). These findings suggest that lepromatous patients have higher risk of death even in a post-chemotherapy era.

Aged↗