OBJECTIVE: Acute/subacute interstitial pneumonia (A/SIP) in patients with polymyositis/dermatomyositis (PM/DM) is frequently fatal within months despite high dose prednisolone (PSL) therapy. Our objective was to improve the survival rate of patients with A/SIP associated with PM/DM; and to characterize patients with PM/DM who are at high risk of developing A/SIP. METHODS: We conducted a pilot trial of combined immunosuppressive therapy with high dose PSL, 10-30 mg/kg of intravenous pulse cyclophosphamide (IVCYC) every 3-4 weeks, and 2-4 mg/kg/day of cyclosporin A (CSA) for patients with A/SIP. A/SIP was diagnosed based on a history of rapidly worsening respiratory symptoms, progressive radiological findings or hypoxemia, and compatible findings in high resolution computed tomography images. RESULTS: Before December 2000, 12 patients with DM among 83 PM/DM patients developed A/SIP, and 9 patients died despite treatment using high dose PSL with or without a choice of CSA, cyclophosphamide, or azathioprine. Thereafter, 10 patients with DM among 27 PM/DM patients developed A/SIP, and they were given combination therapy with PSL, CSA, and IVCYC. Five patients survived and are doing well for more than 2 years, although the remaining 5 patients died of respiratory failure within 3 months. DM patients with A/SIP showed the following characteristic features: mild myositis, palmar papule, fever, and negative or low titer of antinuclear antibody. CONCLUSION: Immediate institution of intensified immunosuppressive therapy should be considered for patients with A/SIP complicating DM. However, even early recognition of A/SIP and immediate commencement of a regimen including CSA and IVCYC in addition to high dose PSL may not be sufficient for some of those patients.

Acute Disease↗

PubMed2005

[Biological agents targeting on pro-inflammatory cytokines].

Biological agents targeting on pro-inflammatory cytokines are developed, and provide a great impact on the medical management of rheumatoid arthritis (RA). Particularly, biologics against tumor necrosis factor(TNF) can not only induce great clinical improvement, but also halt structural damage on the joints. Now chimeric anti-TNFalpha monoclonal antibody, infliximab, full human anti-TNFalpha monoclonal antibody, adalimumab, and TNF receptor II (p75) -IgGFc fusion protein, etanercept, are widely used in the inflammatory disorders including RA. This review article shows the characteristics of these anti-TNF biologics on RA, and summarizes the efficacy as well as the safety of the agents.

Adalimumab↗

PubMed2005

[Clinical significance of anti-phosphatidylserine-prothrombin complex antibodies in antiphospholipid syndrome].

We clarified the clinical significance of IgG anti-phosphatidylserine-prothrombin complex (PS-PT) antibodies in the antiphospholipid syndrome (APS). The study population consisted of 122 patients with SLE and lupus-like disease. IgG anti-PS-PT antibodies were detected in 44% of 59 patients according to the diagnostic criteria by Harris and Hughes. This frequency was significantly (p < 0.005) higher than the 14% seen in patients without APS. IgG anti-PS-PT antibodies were strongly (p < 0.005) associated with thrombosis. In addition, IgG anti-PS-PT antibodies were positive in 64% of IgG beta2-GPI dependent anti-cardiolipin antibody negative APS patients under the Sapporo criteria. The above findings indicate that IgG anti-PS-PT antibodies as well as beta2,-GPI dependent anti-cardiolipin antibodies should be examined in the diagnosis of APS.

Adult↗

PubMed2005

The Asian center of international parasite control (ACIPAC): five years of achievement. I. Introduction.

ACIPAC has made an effort to promote the concept of the school-based approach to malaria and STH control, mainly through human resource development, which could be eventually extended to any other health promotion program. Implementation of SSPP resulted in the establishment of national policies on parasite control and/or school health in some partner countries. It also provides a good opportunity for the formulation of partnerships among health and education sectors and international partners, although it did cause some problems concerning the enrollment of persons of authority from partner countries, and the staff of JICA resident offices as well. As described in the Joint Evaluation Report, ACIPAC is expected to further contribute to human resource development and to strengthening human resource and information networking at regional and global levels.

Asia↗

PubMed2004

Entamoeba invadens: cysteine protease inhibitors block excystation and metacystic development.

We examined the effects of six cysteine protease inhibitors on the excystation and metacystic development of Entamoeba invadens. Excystation, which was assessed by counting the number of metacystic amoebae after the induction of excystation, was inhibited by the cysteine protease inhibitors Z-Phe-Ala-DMK and E-64d in a concentration-dependent manner during incubation compared to the controls. Neither inhibitor had a significant effect on cyst viability; thus, their inhibitory effects were not due to the toxic effect on cysts. Metacystic development, when determined by the number of nuclei in amoeba, was also inhibited by these protease inhibitors, because the percentage of 4-nucleate amoebae was higher than in the controls on Day 3 of incubation. Although other cysteine protease inhibitors, Z-Phe-Phe-DMK, E-64, ALLM, and cathepsin inhibitor III, had a weak or little effect on the excystation, they inhibited cysteine protease activity in the lysates of E. invadens cysts. Broad bands with gelatinase activity of metacystic amoebae, as well as cysts and trophozoites, were detected in the gelatin substrate gel electrophores and were inhibited by Z-Phe-Ala-DMK. There was a difference in the protease composition between cysts and trophozoites, and the protease composition of metacystic amoebae changed from cyst-type to trophozoite-type during development. These results strongly suggest that cysteine proteases contribute to the excystation and metacystic development of E. invadens, which leads to successful infection.

Animals↗

PubMed2004

IL-7 exacerbates chronic colitis with expansion of memory IL-7Rhigh CD4+ mucosal T cells in mice.

We have previously demonstrated that mucosal CD4(+) T cells expressing high levels of IL-7 receptor (IL-7R(high)) are pathogenic cells responsible for chronic colitis. Here we investigate whether IL-7 is directly involved in the expansion of IL-7R(high) memory CD4(+) mucosal T cells and the exacerbation of colitis. We first showed that CD4(+) lamina propria lymphocytes (LPLs) from wild-type, T cell receptor-alpha-deficient (TCR-alpha(-/-)), and recombinase-activating gene (RAG)-2(-/-)-transferred mice with or without colitis showed phenotypes of memory cells, but only CD4(+) LPLs from colitic mice showed IL-7R(high). In vitro stimulation by IL-7, but not by IL-15 and thymic stromal lymphopoietin, enhanced significant proliferative responses and survival of colitic CD4(+), but not normal CD4(+) LPLs. Importantly, in vivo administration of IL-7 mice accelerated the expansion of IL-7R(high) memory CD4(+) LPLs and thereby exacerbated chronic colitis in RAG-2(-/-) mice transferred with CD4(+) LPLs from colitic TCR-alpha(-/-) mice. Conversely, the administration of anti-IL-7R monoclonal antibody significantly inhibited the development of TCR-alpha(-/-) colitis with decreased expansion of CD4(+) LPLs. Collectively, the present data indicate that IL-7 is essential for the expansion of pathogenic memory CD4(+) T cells under pathological conditions. Therefore, therapeutic approaches targeting the IL-7R pathway may be feasible in the treatment of human inflammatory bowel disease.

Animals↗

PubMed2004

Different effects of cytochalasins on the growth and differentiation of Entamoeba invadens.

The effect of five different cytochalasins on the growth, encystation and excystation of Entamoeba invadens was examined. At 10 microM, cytochalasins B, D, E and dihydrocytochalasin B markedly inhibited growth. Encystation was inhibited by cytochalasin D at 1 microM but not by other cytochalasins at the same concentration, whereas it was inhibited by 10 microM of cytochalasins B, E and dihydrocytochalasin B as well as cytochalasin D. Excystation, which was assessed by counting the number of metacystic amoebae after inducing excystation, was markedly enhanced by cytochalasin D as previously demonstrated, whereas the enhancing effect of cytochalasins A, B and dihydrocytochalasin B was weak. In contrast, cytochalasin E at 10 microM inhibited excystation and metacystic development. These results indicate that there is a difference in the effect of different cytochalasins on the growth and differentiation of E. invadens, depending on differences in their chemical structure.

Animals↗

PubMed2004

[Collagen diseases and rheumatic diseases].

Explore the source record for details and available documents.

Antibodies, Monoclonal↗

PubMed2004

Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti-IL-6 receptor antibody, MRA, in patients with RA. METHODS: In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria. RESULTS: Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients. CONCLUSION: Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.

Adult↗

PubMed2004

Molecular characterization of peroxiredoxin from Entamoeba moshkovskii and a comparison with Entamoeba histolytica.

Peroxiredoxin of the pathogenic parasite, Entamoeba histolytica, is thought to be involved in protection from oxidative attack by host phagocytic cells and endogenously generated hydrogen peroxide. In this study, we cloned peroxiredoxin genes from the nonpathogenic ameba, Entamoeba moshkovskii, and characterized the peroxiredoxin protein. The open reading frame of three cloned cDNAs was demonstrated to encode a polypeptide of 218 or 217 amino acids. Identity of the amino acid sequence of peroxiredoxins between E. moshkovskii and E. histolytica was considerably high (77-81%), but the N-terminus portion of E. moshkovskii peroxiredoxin was shorter than that of E. histolytica. A recombinant peroxiredoxin of E. moshkovskii expressed in Escherichia coli exhibited hydrogen peroxidase activity. Its K(m) and V(max) values of 35 microM and 0.07 micromol/min/mg protein were approximately 1 and 1.5 times greater than E. histolytica peroxiredoxin, respectively. In addition, the protective effect of E. moshkovskii peroxiredoxin against oxidative-nicking of supercoiled plasmid DNA was shown to be greater than that of E. histolytica peroxiredoxin. Confocal laser scanning microscopy, using polyclonal antibody against the recombinant E. moshkovskii peroxiredoxin, demonstrated that this protein was localized in the nucleus and cytoplasm of trophozoites, supporting its function as a protectant against DNA damage. Southern blot and real-time reverse transcription PCR analyses of the E. moshkovskii peroxiredoxin gene demonstrated that it was a multi-copy gene and its expression was comparable to that of E. histolytica. These results suggest that the antioxidant peroxiredoxin is important for protection against endogenously generated hydrogen peroxide in the nonpathogenic ameba.

Amino Acid Sequence↗

PubMed2004

Genotypic variation among lineages of Trypanosoma cruzi and its geographic aspects.

Isozyme analysis with 18 enzyme loci was conducted on 146 isolates of Trypanosoma cruzi from Mexico, Guatemala, Colombia, Ecuador, Peru, Brazil, Bolivia, Paraguay and Chile. Forty-four different MLGs (groups of isolates with identical multilocus genotypes) were identified and a phylogeny was constructed. The phylogenetic tree consisted of two main groups (T. cruzi I, T. cruzi II), and the latter was further divided into two subgroups (T. cruzi IIa, T. cruzi IIb-e). Evidence of hybridization between different MLGs of T. cruzi II was found, which means that genetic exchanges seem to have occurred in South American T. cruzi. On the other hand, the persistence of characteristic T. cruzi I and T. cruzi II isozyme patterns in single small villages in Bolivia and Guatemala suggested that genetic exchange is very rare between major lineages. A significant difference in genetic diversity was shown between T. cruzi I and T. cruzi II from several indices of population genetics. Two possibilities could explain this genetic variation in the population: differences in evolutionary history and/or different tendencies to exchange genetic material. Broad-scale geographic distributions of T. cruzi I and T. cruzi IIb-e were different; T. cruzi I occurred in Central America and south to Bolivia and Brazil, while T. cruzi IIb-e occurred in the central and southern areas of South America, overlapping with T. cruzi I in Brazil and Bolivia.

Animals↗

PubMed2004

Bacterial expression of a human monoclonal antibody-alkaline phosphatase conjugate specific for Entamoeba histolytica.

We previously produced human monoclonal antibody Fab fragments specific to Entamoeba histolytica in Escherichia coli. In order to use these Fab fragments for diagnostic purposes, an expression vector to produce a fusion protein of Fab and alkaline phosphatase (PhoA) in E. coli was designed and constructed. The E. coli PhoA gene was fused to the 3' terminus of the gene encoding the heavy-chain Fd region. The kappa and Fd genes from a previously prepared antibody clone, CP33, which is specific for the 260-kDa lectin of E. histolytica, were used as human antibody genes. When the fusion protein of CP33 and PhoA was incubated with paraformaldehyde-fixed trophozoites of E. histolytica and developed with a substrate, the trophozoites appeared to be stained. These results demonstrate the feasibility of bacterial expression of a human monoclonal antibody-PhoA conjugate specific for E. histolytica and that the antibody can be used to detect E. histolytica antigen without the use of chemically conjugated secondary antibodies.

Alkaline Phosphatase↗

PubMed2004

Evaluation of recombinant fragments of Entamoeba histolytica Gal/GalNAc lectin intermediate subunit for serodiagnosis of amebiasis.

We have recently identified a 150-kDa surface antigen of Entamoeba histolytica as an intermediate subunit (Igl) of galactose- and N-acetyl-D-galactosamine-inhibitable lectin, which is a cysteine-rich protein consisting of 1,101 amino acids (aa) and containing multiple CXXC motifs in amino acid sequences. In the present study, full-length Igl except for the signal sequences (aa 14 to 1088) and three fragments of Igl-the N-terminal part (aa 14 to 382), the middle part (aa 294 to 753), and the C-terminal part (aa 603 to 1088)-were prepared in Escherichia coli, and the reactivity of these recombinant proteins with sera from patients with amebiasis was examined by means of enzyme-linked immunosorbent assay (ELISA). Sera from 57 symptomatic patients with amebic liver abscess or amebic colitis, sera from 15 asymptomatic cyst passers, sera from 40 individuals with other protozoan infections, and sera from 50 healthy controls were used. The sensitivity and specificity of the recombinant full-length Igl in the ELISA were 90 and 94%, respectively. When three fragments were used as antigens in the ELISA, the sensitivities were 56% in the N terminus, 92% in the middle part, and 97% in the C terminus. The specificities of the three antigens were 96% in the N terminus and 99% in both the middle and C-terminal fragments. These results demonstrate that Igl is well recognized in not only symptomatic but also asymptomatic patients with E. histolytica infection and that the carboxyl terminus of Igl is an especially useful antigen for the serodiagnosis of amebiasis.

Animals↗