Extensive nodular sarcoidosis in the hand

We report an atypical case of nodular sarcoidosis involving both hands. The pattern of extensive involvement of all digits with lesions extending into the pulp spaces has not been reported previously. The diagnosis of sarcoidosis should be considered even in patients presenting with clinically uncharacteristic manifestations.     

Missense mutation of the cholecystokinin B receptor gene: lack of association with panic disorder

Cholecystokinin tetrapeptide (CCK4) is known to induce panic attacks in patients with panic disorder at a lower dose than in normal controls. Therefore, the cholecystokinin B (CCKB) receptor gene is a candidate gene for panic disorder. We searched for mutations in the CCKB gene in 22 probands of panic disorder pedigrees, using single-strand conformation polymorphism (SSCP) analysis. Two polymorphisms were detected. A polymorphism in an intron (2491 C-->A) between exons 4 and 5 was observed in 10 of 22 probands. A missense mutation in the extracellular loop of exon 2 (1550 G-->A, Val125-->Ile) was found in only one proband. This mutation was also examined in additional 34 unrelated patients with panic disorder and 112 controls. The prevalence rate of this mutation was 8.8% in patients with panic disorder (3/34) and 4.4% in controls (5/112). The mutation did not segregate with panic disorder in two families where this could be tested. These results suggest no pathophysiological significance of this mutation in panic disorder.     

Repair of congenital pulmonary incompetence by bicuspidization of the pulmonary valve

We report the successful repair of pulmonary incompetence in an adult due to the congenital absence of the posterior leaflet of the pulmonary valve. The repair consisted of bicuspidization of the pulmonary valve, which achieved competence and eliminated the symptoms and echocardiographic manifestations of right ventricular overload while preserving the native valve.     

Correction of the copper transport defect of Menkes patient fibroblasts by expression of the Menkes and Wilson ATPases

Menkes' disease is a fatal, X-linked, copper deficiency disorder that results from defective copper efflux from intestinal cells and inadequate copper delivery to other tissues, leading to deficiencies of critical copper-dependent enzymes. Wilson's disease is an autosomally inherited, copper toxicosis disorder resulting from defective biliary excretion of copper, which leads to copper accumulation in the liver. The ATP7A and ATP7B genes that are defective in patients with Menkes' and Wilson's diseases, respectively, encode transmembrane, P-type ATPase proteins (ATP7A or MNK and ATP7B or WND, respectively) that function to translocate copper across cellular membranes. In this study, the cDNAs derived from a normal human ATP7A gene and the murine ATP7B homologue, Atp7b, were separately transfected into an immortalized fibroblast cell line obtained from a Menkes' disease patient. Both MNK and WND expressed from plasmid constructs were able to correct the copper accumulation and copper retention phenotype of these cells. However, the two proteins responded differently to elevated extracellular copper levels. Although MNK showed copper-induced trafficking from the trans-Golgi network to the plasma membrane, in the same cell line the intracellular location of WND did not appear to be affected by elevated copper.     

Identification of ligand binding sites on integrin alpha4beta1 through chemical cross-linking

We have used chemical cross-linking to identify sequences in integrin alpha4beta1 that are involved in its interactions with ligands. A recently described leucine-aspartic acid-valine (LDV)-based small molecule inhibitor of alpha4beta1 (BIO-1494), that contained a single reactive amino group for targeting the cross-linking, was used for these studies. The specificity of the interaction was defined by (i) the ability to block the interaction with a competitive inhibitor lacking the reactive group, (ii) the absolute requirement of divalent cations for cross-linking, and (iii) the lack of cross-linking to the functionally related integrin alpha4beta7. With ANB-NOS as the cross-linker, only the beta1 chain was labeled with BIO-1494, while with the more flexible cross-linker DSS both the alpha4 and beta1 chains were modified. Similar results were obtained when cross-linking was performed on K562 cells expressing alpha4beta1 but not on K562 cells expressing alpha2beta1. The site of cross-linking on the beta1 chain was localized by CNBr peptide mapping within residues 130-146, a region that contains the putative metal binding site DXSXS and for which analogous data had been generated with RGD binding to integrin alphaIIbbeta3. The striking similarity between the data we generated for an LDV ligand and published data for the RGD family supports the notion of a common ligand binding pocket formed by both integrin chains. The cross-linking strategy developed here should serve as a useful tool for studying alpha4beta1 function.     

Lymphocyte response in patients with head and neck cancer: effect of clinical stage and radiotherapy

Ffty-three patients with head and neck cancer tested before radiation treatment to determine numbers of blood lymphocytes and immunologic responses to mitogens of lymphocytes in whole-blood cultures had mean values that were 19% to 26% less than values for healthy individuals. Thirty patients whose disease was in stages III or IV had values similar to those in 23 patients whose disease was in stages I or II. Values for 45 patients tested at end of radiotherapy decreased to about 50% of pretreatment values; however, patients with advanced lesions experienced greater decreases (to 24% to 50%) than patients with localized lesions (to 71% to 84%). Patients with advanced lesions usually received radiation to larger areas than patients with localized lesions; therefore, the extent of decline in laboratory values was most likely dependent on volume of tissue treated.