Sjögren's Syndrome with Chronic Pancreatitis, Sclerosing Cholangitis, and Pulmonary Infiltrations

We report a patient with Sjögren's syndrome and multiple gastrointestinal manifestations who successfully responded to therapy with ursodeoxycholic acid. Our patient had sialoadenitis with dry mouth, dry eyes, arthralgia, chronic pancreatitis, sclerosing cholangitis, and pulmonary inflitrations. The first signs of disease were the symptoms of chronic pancreatitis followed by icterus, caused by extrahepatic bile duct obstruction. Sclerosing cholangitis was diagnosed by liver biopsy and endoscopic retrograde cholangiography. Sialoadenitis, causing dry mouth, was verified by buccal biopsy. Pulmonary infiltrations were seen on standard chest x-ray, and also shown by high-resolution computed tomography examination. Obstructive icterus and even pulmonary infiltration responded successfully to treatment with ursodeoxycholic acid.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

A T-helper cell epitope overlaps a major B-cell epitope in human papillomavirus type 18 E2 protein.

Cultivated CD4+ T-helper cells from two patients with cervical adenocarcinoma showed responses to a peptide EKTGILTVTYHSETQRTK derived from an E2 protein of human papillomavirus type 18 (HPV 18), but not to a corresponding HPV 16 peptide (HKSAIVTLTYDSEWQRDQ). Serum antibodies in the HPV 18 peptide were also demonstrated in these patients. The GILT motif resembles a common pattern present in many T-cell epitopes, and is located at the beginning of an 11-amino acid-long A-helix structure close to the carboxyterminal end of HPV 18 E2. We conclude that two epitopes (a T-helper cell epitope and a B-cell epitope) overlap in the HPV 18 E2.     

Application of markers of collagen metabolism in serum and synovial fluid for assessment of disease process in patients with rheumatoid arthritis.

OBJECTIVE--To assess the potential of markers of collagen metabolism to reflect disease processes in rheumatoid arthritis (RA). METHODS--Serum (S) and synovial fluid (SF) from 59 patients with RA, and a knee joint effusion and serum from 90 control subjects were studied with radioimmunoassays for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP, respectively). The breakdown of type I collagen was quantified with a radioimmunoassay for the cross linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS--About 50% of the patients had increased S-ICTP and S-PIIINP values, whereas S-PINP was increased in only 20% of the patients. The mean SF:S ratios of these markers varied between 4 (for ICTP) and 340 (for PIIINP), indicating that markers of collagen metabolism are formed locally and then released into the circulation. SF-PINP and SF-PIIINP correlated with each other (rs = 0.86, p < 0.001) and with SF-ICTP (rs = 0.69, p < 0.001, and rs = 0.65, p < 0.001, respectively). SF-ICTP was clearly related to radiographic findings in the corresponding knee joint, patients with gross bone deformation having the greatest SF-ICTP concentrations. S-ICTP and S-PIIINP also correlated with conventional markers of disease activity, such as C reactive protein and joint swelling score. CONCLUSION--Markers of collagen metabolism both in serum and synovial fluid can be measured to provide an assessment of disease process in patients with RA. ICTP and PIIINP are the most informative.     

Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.     

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced thoracic cavity. In the most common subtype (TD1), femurs are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were identified in both subtypes. While TD2 was accounted for by a single recurrent mutation in the tyrosine kinase 2 domain, TD1 resulted from either stop codon mutations or missense mutations in the extracellular domain of the gene. Here, we report the identification of FGFR3 mutations in 25/26 TD cases. Two novel missense mutations (Y373C and G370C) were detected in 8/26 and 1/26 TD1 cases respectively. Both mutations created cysteine residues in the juxta extramembrane domain of the receptor. Sixteen cases carried the previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically homogeneous condition and give additional support to the view that newly created cysteine residues in the extracellular domain of the protein play a key role in the severity of the disease.      

Interactions between synthesis of platelet-activating factor and leukotriene B4 in isolated human polymorphonuclear leukocytes

The aim of the present work was to study interactions between the synthesis of platelet-activating factor (PAF) and leukotriene B₄ (LTB₄) in human polymorphonuclear leukocytes (PMNs) in vitro. PAF, at nanomolar concentrations, stimulated calcium ionophore A23187-activated PMNs to release LTB₄ and 5-hydroxyeicosatetraenoic acid (5-HETE). This seems to be a receptor-mediated process as it was blocked by a PAF receptor antagonist WEB 2086 (IC₅₀ 6.6±3.9M). Moreover, LTB₄ stimulated the formation of PAF in activated PMNs. WEB 2086 did not, however, alter PMN migration towards either LTB₄ or the chemotactic peptide FMLP. This suggests that the enhancement of PAF synthesis in response to LTB₄ is a concomitant event rather than a mediating process in LTB₄-induced chemotactic movement of PMNs. These effects are implicated in the complex network of interactions between inflammatory mediators that results accumulation and activation of PMNs in the exacerbation of inflammatory processes.