Surgical treatment of aortic coarctation associated with multi-vessel brachiocephalic involvement in takayasu's arteritis.

In Takayasu's arteritis (TA), both atypical coarctation (CO) and brachiocephalic involvement are common features that occasionally require operative correction. A combination of these abnormalities could duplicate underlying illness in patients, posing an increased risk of operative morbidity. We present, herein, two TA patients in which hypertensive heart disease secondary to CO was surgically corrected. Both patients had multi-vessel brachiocephalic disease. One patient who showed occlusion of all brachiocephalic arteries underwent aorto-aortic bypass, while another with two-vessel lesion underwent axillo-bifemoral bypass grafting. Subclavian reconstruction was supplemental to each procedure, resulting in relief of neurologic stigmata. Strategies to avoid intraoperative cerebral ischemia played an important role in the surgical repair of such TA-related extensive vascular lesions.     

Hepatocyte growth factor in polymorphonuclear leukocytes is increased in patients with systemic inflammatory response syndrome

BACKGROUND: Hepatocyte growth factor (HGF) has a significant effect on the regeneration of epithelial and endothelial cells. Studies have also shown an important role of HGF in wound healing and organ regeneration. Because recent studies indicate that polymorphonuclear leukocytes (PMNLs) store HGF in their specific granules and that HGF can be degranulated in the inflammatory tissue in which activated PMNLs migrate, we evaluated the storage and release of HGF in PMNLs from patients with systemic inflammatory response syndrome (SIRS) and attempted to examine the role of HGF from PMNLs in the systemic inflammatory process. METHODS: Twenty-four patients with SIRS (serum C-reactive protein, 20.2 +/- 12.4 mg/dL [mean +/- SD]) and 18 healthy volunteers were studied. HGF in PMNLs was measured by flow cytometry by using a monoclonal antibody to HGF. The oxidative activity in PMNLs was also measured by flow cytometry. Serum HGF, interleukin (IL)-6, and IL-8 levels in each patient were measured by enzyme-linked immunosorbent assay. HGF degranulation from PMNLs was evaluated in 10 patients. RESULTS: Immunocytochemistry under fluorescence microscopy revealed enhanced expression of HGF in the granules of PMNLs. HGF in PMNLs significantly increased in patients with SIRS compared with PMNLs from healthy volunteers (SIRS, 171.0 +/- 6.6 fluorescence/cell; control, 130.7 +/- 3.8 fluorescence/cell). N-formylmethionyl-leucyl-phenylalanine and lipopolysaccharide stimulation induced further increase of HGF fluorescence in PMNLs from patients. HGF degranulation from PMNLs was also significantly enhanced in patients. Moreover, oxidative activity in PMNLs was significantly enhanced in patients with SIRS. Plasma HGF (pHGF) correlated positively with IL-6 and IL-8 levels in patients (pHGF and IL-6, gamma = 0.635, p < 0.05; pHGF and IL-8, gamma = 0.827, p < 0.01), but these values did not correlate with HGF in PMNLs. CONCLUSION: Activated PMNLs in SIRS patients increased HGF in their granules and demonstrate enhanced degranulation of HGF. The release of HGF from migrated PMNLs in the inflammatory tissue may play an important role in wound healing and organ regeneration under those conditions.     

Citrullination of fibronectin in rheumatoid arthritis synovial tissue

OBJECTIVES: Citrullination, catalysed by peptidylarginine deiminase (PAD), is the post-translational modification of peptidylarginine to citrulline, which is intimately involved in the pathogenesis of rheumatoid arthritis (RA). Fibronectin (Fn), a large glycoprotein, is expressed at high levels in arthritic joints and it mediates various physiological processes through interactions with cell-surface integrin receptors and growth factors. We investigated the citrullination of Fn and its potential contribution to the pathogenesis of RA. METHODS: We localized Fn expression and citrullination in RA synovial tissue by immunohistochemistry, immunoprecipitation and western blotting. We also determined levels of citrullinated Fn in plasma from RA patients using sandwich enzyme-linked immunosorbent assay (ELISA). After incubating Fn with rabbit skeletal muscle PAD, we examined the binding ability of citrullinated Fn to vascular endothelial growth factor (VEGF) and integrin beta1 using a solid-phase receptor binding assay as well as the effect of the citrullinated Fn on apoptosis using cultured HL-60 cells. RESULTS: Immunohistochemistry and western blotting analysis indicated that Fn formed extracellular aggregates that were specifically citrullinated in RA synovial tissue. No Fn deposits were observed in synovial tissues of osteoarthritis (OA). Sandwich ELISA detected higher levels of citrullinated Fn in plasma from patients with RA than from healthy controls or those with systemic lupus erythematosus. Following citrullination in vitro, the affinity of Fn for VEGF increased, but binding activity to integrin beta1 decreased and Fn no longer stimulated the apoptosis of monocytes induced from cultured HL-60 cells. CONCLUSIONS: Our results suggest that the citrullination of Fn is a specific event for RA synovium, although others have detected citrullinated total proteins in inflamed synovial tissue of RA and non-RA patients. Citrullination of Fn could alter interactions between Fn and its receptors and growth factors, consequently contributing to mechanisms of RA pathogenesis such as perturbed angiogenesis and apoptosis.     

Clinicopathological features of serrated lesions of the colorectum

We reviewed 428 subjects with colorectal serrated lesions resected endoscopically or surgically at our institution. Colorectal serrated lesions were pathologically divided into 3 groups: hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA). SSA/P was detected frequently in the right colon and SSA/P was mainly flat-elevated. Cancers occurring in SSA/P were found more frequently than HP or TSA. The incidence of cancer in SSA/P was equivalent to that of cancer in traditional adenoma. Further studies are warranted to clarify clinicopathological features of serrated lesions of the colorectum.     

Pseudomembranous colitis after Helicobacter pylori eradication therapy

A 69-year-old woman with gastritis was prescribed a 1-week triple regimen therapy of Amoxicillin, Clarithromycin, and Lansoprazole to eradicate Helicobacter pylori (H. pylori) starting on March 7, 2005. H. pylori was detected on the gastric mucosa by the urease test. Twenty days after eradication therapy, she began to suffer from profuse watery diarrhea. Colonoscopy on April 12 showed multiple pseudomembranes in the cecum and the transverse colon, leading to a diagnosis of pseudomembranous colitis. Because she had not taken Vancomycin (VCM) (500 mg/day) as directed, she had a relapse of watery diarrhea and was admitted on April 30. A stool test for Clostridium difficile (CD) toxin was positive, although colonoscopy showed only a few aphthoid erosions in the cecum and the transverse colon on May 6. She was treated with oral VCM (2000 mg/day) from May 6, and diarrhea disappeared by May 11. The stool test for CD toxin was negative, so VCM was discontinued. Care must thus be taken in H. pylori eradication to ensure that the triple regimen therapy does not lead to pseudomembranous colitis.     

Analysis of single-nucleotide polymorphisms in Japanese rheumatoid arthritis patients shows additional susceptibility markers besides the classic shared epitope susceptibility sequences

OBJECTIVE: To examine the entire HLA region for loci (other than the DRB1 locus) associated with rheumatoid arthritis (RA) susceptibility, by typing HLA-DRB1 alleles and multiple single-nucleotide polymorphisms (SNPs) in the Japanese population. METHODS: The HLA-DRB1 alleles and 88 SNPs distributed over the HLA gene complex were genotyped, for 828 patients with RA and 1,032 control subjects. The data were evaluated for linkage disequilibrium, and case-control associations were analyzed in 2 ways, in the presence or absence of the disease-susceptibility DRB1 allele, to detect loci independent of the DRB1 allele. RESULTS: HLA-DRB1 alleles *0405, *0401, *0901, *0101, *1401, *1602, *0403, and *1405 were significantly associated with RA in the Japanese population. The smallest P value (P = 1.4 x 10(-27)) was observed in association with an intronic SNP of the NOTCH4 gene, which was due to strong linkage disequilibrium with the HLA-DRB1 allele. A strong association that was independent of HLA-DRB1 shared epitope alleles was observed in 2 SNPs: one in the intron of the MICA gene, the other in the intron of the HLA-DQB2 gene. Their association with RA, independent of HLA-DRB1 shared epitope alleles, was suggestive (P = 0.0024 [corrected P (P(corr)) = 0.068, and P = 0.00037 [P(corr) = 0.012], respectively). CONCLUSION: These findings suggest that 1 or more other loci besides the HLA-DRB1 or other DRB1 (non-shared epitope, non-*0901) alleles are involved in RA susceptibility/protection.