New areas for therapeutic intervention in the treatment of rheumatic disease.

Anti-rheumatic therapy has been targeted against the symptoms arising from chronic inflammation of the joint. This has resulted in the extensive use of non-steroidal anti-inflammatory drugs. It is now becoming apparent that these agents have no beneficial effect on disease progression. This mini review concentrates on the formation and maintenance of pannus, the granulomatous tissue responsible for cartilage and bone erosion. This reveals a number of possible therapeutic targets. Protease inhibitors could be used to interfere with the degradatory processes. The diverse functions of endothelial cells suggest oedema formation, cell accumulation and supply of nutrients to the granulomatous tissue could all be targeted by appropriate therapy. Alternatively the immune processes that control pannus formation and state of activation could be regulated by interfering with antigen presentation and the cytokine network.     

Characterization of bortezomib-adapted I-45 mesothelioma cells

Background  

Bortezomib, a proteasome-specific inhibitor, has emerged as a promising cancer therapeutic agent. However, development of resistance to bortezomib may pose a challenge to effective anticancer therapy. Therefore, characterization of cellular mechanisms involved in bortezomib resistance and development of effective strategies to overcome this resistance represent important steps in the advancement of bortezomib-mediated cancer therapy.     

Congestive gastropathy

15 patients with congestive gastropathy were reported including clinical and pathological characteristics of the disease. Every patient had alcoholic liver cirrhosis and portal hypertension. 6 patient's stomach was resected while in 2 further cases the disease was found at autopsy. In additional 7 cases the characteristic microvascular changes were observed in endoscopic biopsy specimens from the gastric mucosa. The authors presume that this disease has an acute and a chronic stage. In the acute stage dilated capillaries are present under the surface, not related to the inflammation of gastric mucosa. This phenomenon was described in the literature. In the chronic stage there are dilated and tortuous vessels in the submucosal layer surrounded by collagenous connective tissue. The authors suppose that the thick and fibrotic submucosal layer causes microcirculatory disturbances in the gastric mucosa. The impaired microcirculation may cause extensive ulcers with profuse and sometimes lethal bleeding.     

Isolated leukemic iritis in childhood

Case report on a child with acute lymphogenous leukemia. Although there was constant hematological remission she developed an isolated leukemic iritis and secondary glaucoma. The clinical picture showed a characteristic stratification of the hyphema. After the patient had remained seated for a prolonged period of time the leukemic cells settled above the erythrocytes, forming a so-called pseudohypopyon, which diagnostically important. Cytologic examination after anterior chamber paracentesis is indispensable in order to establish the etiology of the disease. Isolated leukemic iritis may be the first sign of a relapse and therefore indicate a need to reinstitute induction therapy.     

The relationship between anti-human eye muscle antibodies and thyroid function, anti-TSH receptor antibodies and eye symptoms in Graves' ophthalmopathy.

Circulating IgG, IgA, and IgM antibodies to human eye muscle cytosol antigens were studied in 60 patients with Graves' ophthalmopathy using the indirect ELISA method. There was a significant difference in the levels of both IgG and IgA antibodies between the patients with Graves' ophthalmopathy and a control group (p < 0.001). IgA antibodies to eye muscle cytosol antigens were raised in 20 out of 29 patients with proptosis (class 3 ophthalmopathy), in comparison with 31 patients out of the total group of 60 with Graves' ophthalmopathy (p < 0.02). Anti-TSH receptor antibodies (TRAK) were not present in over half of the 31 patients with raised IgA antibodies to eye muscle antigens. However, a significant difference was found between the levels of IgG and IgA antibodies in the TRAK-negative patients (p < 0.05). These findings suggests that both IgG and IgA antibodies to eye muscle antigens might be important in the development of ophthalmopathy.     

Simple non-radioactive detection of the CFTR mutation N1303K by artificial creation of a restriction site.

N1303K is one of the most frequent non-delta F508 mutations causing cystic fibrosis in Central Europe. Since no restriction site is altered by this mutation and no other frequent mutations are known so far in exon 21, the detection requires a separate and laborious test. A mismatched primer was used to create an artificial Hin dIII site in amplified wildtype DNA, which is destroyed by the mutation. This allows for rapid and convenient detection by restriction enzyme digestion.