Crystal structure of cytoplasmic Escherichia coli peptidyl-prolyl isomerase: evidence for decreased mobility of loops upon complexation

Ryanodine receptors (RyRs), a class of intracellular calcium release channels, are the largest ion channels known. Recently, cryoelectron microscopy and image reconstructions of isolated receptors have shown that most of the protein mass forms a porous, multidomain cytoplasmic assembly. Evidence is mounting that suggests that the cytoplasmic assembly communicates with the transmembrane regions over distances of 100 or greater. RyRs are centrally important in excitation-contraction coupling, which occurs at specialized regions where the sarcoplasmic reticulum, containing the RyRs, and the plasma membrane/transverse-tubule system form junctions. Numerous proteins are present at these junctions, some of which interact directly with the RyR.     

Effects of environmental conditions on food consumption in female and male rats

The present experiment examined food and water consumption under different housing conditions in 20 female and 20 male Wistar rats. Food and water consumption were measured for 6 h a day following an 18-h same-sex crowded or individual housing period for each of 6 days. All subjects were individually housed during the 6-h measurement period and had access to food and water. Female rats consumed more food and water than did male rats during the 6-h period, regardless of their 18-h housing condition. In addition, previously crowded rats consumed more food and water during the 6-h period than did rats that were previously individually housed. During the 18-h period, when subjects were differentially housed, males consumed more food and water than did females; crowded rats ate less than did individually housed rats; and crowded rats drank more water than did individually housed rats. Based on plasma corticosterone data, the female and male rats were differentially affected by housing conditions. The present results are discussed with regard to housing conditions per se and sex differences in stress responses to housing.     

Plants transformed with a mutant alfalfa mosaic virus coat protein gene are resistant to the mutant but not to wild-type virus

Transgenic tobacco plants expressing the wild-type (wt) coat protein (CP) gene of alfalfa mosaic virus (AIMV) have been shown to be resistant to infection with viral particles and RNAs or to infection with viral particles only. The difference in resistance of these plants to RNA inocula was found to correlate with a difference in the expression level of the transgene. Plants expressing a mutant AIMV CP with the N-terminal serine residue changed to glycine have been shown to be susceptible to infection with wt viral particles or RNAs. By site-directed mutagenesis of AIMV cDNA a viable mutant virus encoding CP with the same N-terminal mutation was obtained. Plants expressing wt or mutant CP were resistant to the mutant virus, demonstrating that a single amino acid substitution in CP did not permit the virus to overcome CP-mediated resistance. Although the mutant CP did not confer resistance to wt virus when expressed in transgenic plants, it was still effective in classical cross-protection: plants infected with the mutant virus were resistant to severe strain of AIMV. A model to explain the data is discussed.     

Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder

OBJECTIVE: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. METHOD: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. RESULTS: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. CONCLUSIONS: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.     

Thoracic spinal stenosis: diagnostic and treatment challenges

Thoracic stenosis may be defined by a narrowing of the anteroposterior (AP) diameter of the thoracic spinal canal to < 10 mm. Primary thoracic stenosis, documented when myelography is carried beyond the thoracolumbar junction into the upper thoracic canal, is most frequently associated with lumbar stenosis, whereas secondary stenosis, attributed to endocrinopathies and systemic diseases, more typically involves the entire spinal canal. Recognition of the presence of primary or secondary thoracic stenosis and the entire extent of attendant disease in the adjacent cervical or lumbar regions is essential to proper surgical management. Nine cases of primary and one instance of secondary thoracic spinal stenosis were reviewed. Seven of nine patients with primary thoracic stenosis had accompanying lumbar involvement, whereas one patient with secondary stenosis attributed to acromegaly had cervical, thoracic, and lumbar stenosis.     

Detection of clonal platelet antibodies in immunologically-mediated thrombocytopenias: association with circulating clonal/oligoclonal B cells

Aware that T and B cells in autoimmune thrombocytopenia are abnormal, including the existence of clonal B cell populations, we sought to characterize this clonal phenomenon in various immunological thrombocytopenias using platelet antibody light chain analysis, flow cytometry, Southern blot analysis, and PCR. Using a monoclonal antibody-antigen capture ELISA, we analysed sera from 21 of 26 patients with autoimmune, alloimmune, or drug-induced immunological thrombocytopenia for the light chain phenotypes of their platelet antibodies. Alloantibodies and drug-dependent antibodies from four and 14 patients, respectively, were found that expressed a predominant type of light chain, suggesting that these platelet-reactive antibodies were monoclonal or oligoclonal in nature. 14 of the 26 patients were available for light chain B cell phenotyping studies. Of these 14 patients, thrombocytopenia was due to autoimmunity in two, drug-induced immunity in four, and alloimmunity in eight. We detected clonal populations of B cells in all 14 patients by flow cytometry. Although six of these latter patients possessed platelet antibodies with clonal characteristics, light chain phenotypes of antibodies in five patients were opposite to those of their B cells. Eight of these patients were further examined for immunoglobulin gene rearrangement using Southern and/or polymerase chain reaction analysis. In all eight patients we detected clonal or oligoclonal B cell populations. Only two of these patients had malignancies (chronic lymphocytic leukaemia) that would be expected to have detectable clonal B cells, and thus the mechanism for clonal expansion in the other six patients did not appear to be related to an obvious neoplastic process. Prior to these studies, detection of clonal B cells in thrombocytopenic patients without known malignancies was limited to individuals with autoimmune thrombocytopenia, prompting the speculation that this particular autoimmune disorder arises from B cell dysregulation, rather than from expansion of specific autoantibody producing B cell clones. In contrast, the current studies provide evidence that clonal B cells are common to patients with any form of immunologically-mediated thrombocytopenia. Moreover, the majority of the platelet antibodies (86%) present in these disorders exhibited monoclonal characteristics in that there was an apparent restriction in light chain usage.     

Orthopaedic aspects of prune belly syndrome

Prune belly syndrome is a relatively uncommon disorder that is characterized by intrauterine urinary obstruction associated with cryptorchisdism, oligohydramnios, and orthopaedic deformations. The oligohydramnios is believed to produce limited intrauterine space, which in turn leads to fetal compression and the resultant deformities. The deformities observed in our patients were developmental dislocation of the hip (DDH), clubfeet, metatarsus adductus, vertical talus, and congenital muscular torticollis. These deformations should be treated aggressively because children with prune belly syndrome may be expected to have a relatively normal life if their renal function is good. The one exception is that as infants these children are very susceptible to pulmonary infections because of their inability to cough. Therefore, treatment of the hip and other deformations should be delayed until the children are old enough to be able to clear pulmonary secretions easily.     

ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer

Overexpression of the erbB-2 gene contributes to aggressive behavior of various human adenocarcinomas, including breast cancer, through an unknown molecular mechanism. The erbB-2-encoded protein is a member of the ErbB family of growth factor receptors, but no direct ligand of ErbB-2 has been reported. We show that in various cells ErbB-2 can form heterodimers with both EGF receptor (ErbB-1) and NDF receptors (ErbB-3 and ErbB-4), suggesting that it may affect the action of heterologous ligands without the involvement of a direct ErbB-2 ligand. This possibility was addressed in breast cancer cells through either overexpression of ErbB-2 or by blocking its delivery to the cell surface by means of an endoplasmic reticulum-trapped antibody. We report that ErbB-2 overexpression enhanced binding affinities to both EGF and NDF, through deceleration of ligand dissociation rates. Likewise, removal of ErbB-2 from the cell surface almost completely abolished ligand binding by accelerating dissociation of both growth factors. The kinetic effects resulted in enhancement and prolongation of the stimulation of two major cytoplasmic signaling pathways, namely: MAP kinase (ERK) and c-Jun kinase (SAPK), by either ligand. Our results imply that ErbB-2 is a pan-ErbB subunit of the high affinity heterodimeric receptors for NDF and EGF. Therefore, the oncogenic action of ErbB-2 in human cancers may be due to its ability to potentiate in trans growth factor signaling.