C7 complement deficiency in an Israeli Arab village

Deficiencies of terminal complement components, particularly the latter ones, are often detected because of increased susceptibility to Neisserial infections. Herein we document the first report of C7 deficiency among a highly inbred Arab population living in the lower Galilee region of Israel. Both biochemical and molecular analysis were performed on samples from infected survivors and parents of children who succumbed to Neisserial infections in a 4-year period. Only the index case who suffered recurrent infections and a sibling who had not suffered an infection during the outbreak were found to be C7-deficient. The mutation was found to be the one previously described to be prevalent among Israeli Jews of Moroccan ancestry (mutation G1135C). The implications of this finding are discussed in the context of family pedigree, the protective effect of complement deficiency, and the clinical outcome.     

Palmitic acid metabolism in the soleus muscle in vitro in hypo- and hyperthyroid rats

The aim of this study was to establish whether the rate of fatty acid (FA) incorporation and its utilization by the isolated soleus muscle is modified under conditions of thyroid hormone deficit or excess. The rate of palmitic acid (PA) uptake, oxidation and incorporation into intramuscular lipids with increasing PA concentration (0.5–1.5 mM) in the incubation medium were determined. In hypothyroid rats intramuscular triacylglycerol (TG) synthesis was increased, while the rate of PA oxidation to CO₂ and incorporation into mono- and diacylglycerols (MG/DG) and phospholipids (PL) remained unchanged. In rats with triiodothyronine (T₃) excess the rate of all processes studied was enhanced, although the percentage incorporation of PA into different classes of intramuscular lipids was fairly constant and, independently of thyroid state and FA concentration in the medium, was 56–66% for TG, 9-14% for MG/DG and 24–32% for PL. Our results thus indicate that even short-term T₃ excess accelerates the rate of FA uptake and metabolism in the oxidative soleus muscle, whereas in hypothyroid rats only intramuscular TG synthesis is affected.     

The hypotransferrinaemic mouse: Ultrastructural and laser microprobe analysis observations

Homozygote hypotransferrinaemic mice (hpx/hpx) have cytopathological features similar to those of human congenital atransferrinaemia, genetic haemochromatosis, and neonatal haemochromatosis. These conditions all have in common high levels of cytotoxic non-transferrin-bound serum iron. This study describes the ultrastructural features of iron overload in liver, pancreas, heart, and small intestine of 2- and 12-month-old hypotransferrinaemic mice. Electron microscopic studies of unstained sections showed early parenchymal cell siderosis, with accumulation of numerous ferritin particles and clusters in the cytosol, as well as ferritin and haemosiderin in lysosomes (siderosomes). In the 12-month-old animals, iron was also found in Kupffer cells and macrophages in other tissues. In addition, there were conspicuous iron-containing compounds in the bile canaliculi, and marked iron deposition in the pancreas and heart. Laser microprobe mass analysis (LAMMA) enabled localization and relative quantitation of iron deposition in subcellular compartments providing in situ documentation of iron accumulation in siderosomes and contributed in assessing total cytosolic iron in various cell types. Moreover, it demonstrated the importance and magnitude of the biliary route for iron excretion in these animals.     

Polypeptides of mammalian oncornaviruses. III. Localization of p 15 and reactivity with natural antibody.

Antiserum to p15 of Friend murine leukemia virus (FLV) reacted with intact MuLV's in radioimmunoprecipitation (RIP) assays. The antigen-antibody complexes formed by this reaction were isolated and shown to contain p15 after analysis by SDS polyacrylamide gel electrophoresis. Natural antibody in mice to MuLV reacted in a similar fashion with p15, but in addition, also with the virus glycoproteins (gp71, gp45). Biological studies indicated that gp71 rather than p15 is principally involved in the virus-neutralization reaction. These and other studies indicate that p15 is localized on the virus surface and is recognized by natural antibodies in mice to MuLV.     

Expression of CD4 on peripheral blood granulocytes. a novel finding in a case of myelodysplastic syndrome in association with t(5;12)

Myelodysplastic syndromes (MDS) are associated with cell maturation defects that can manifest as abnormal surface antigen expression. We describe a patient with refractory anemia with excess blasts, who presented with infection and extensive dysplastic features in peripheral blood granulocytes. The granulocytes expressed CD11b, CD13, CD15, CD33, and CD43. The granulocytes also expressed CD4 antigen. Cytogenetic analysis showed a clonal t(5;12)(q33;p13). The patient improved on antibiotics with partial improvement in the dysplastic features. However, shortly after, the patient experienced paravertebral extramedullary blast transformation followed by a leukemia phase of acute monoblastic leukemia. The patient died a few days later. This is the first report describing anomalous expression of CD4 on granulocytes in MDS. Since the breakpoint on chromosome 12 is near the CD4 gene, which is mapped to 12p12, we hypothesize that dysregulation of the CD4 gene may have occurred resulting in its persistent expression on mature and maturing granulocytes.     

Cell-mediated immune responses to chlamydial antigens in guinea pigs injected with inactivated chlamydiae

Cell-mediated immunity (CMI) to chlamydial antigens was readily induced in guinea pigs by a single injection of Betaprone-inactivated chlamydiae in complete Freund adjuvant. The CMI was measured in vivo by delayed hypersensitivity skin tests, and in vitro by inhibition of migration of peritoneal exudate cells and by proliferation of lymph node lymphocytes. There was an overall correlation between in vivo and in vitro responses. Of the in vitro assays, migration inhibition reflected the state of sensitization, as judged by skin tests, more uniformly than lymphocyte stimulation. Extensive inter- and intra-species cross-reactivity was noted between LB-1, a strain ofC. trachomatis, and three strains ofC. psittaci, 6BC, GPIC, and 562F. Cross-reactivity between LB-1 and 6BC was one-way only, by all three parameters: LB-1 elicited strong cross-reactions in 6BC-immunized animals but not vice versa. Antichlamydial antibodies could not be demonstrated in any of the animals by microimmunofluorescence.     

Evidence for association and epistasis at the DAOA/G30 and D-amino acid oxidase loci in an Irish schizophrenia sample.

The D-amino acid oxidase (DAO) signaling pathway has been implicated in schizophrenia pathogenesis. This may be mediated through modulation of NMDA function by DAO, which is in turn activated by DAO activator (DAOA, formerly G72). Chumakov et al. (2002); PNAS 99: 13675-13680, identifying the novel schizophrenia susceptibility gene DAOA/G30 and a number of independent studies have since reported evidence of association between the DAOA and DAO genes and schizophrenia. However, at least two studies have failed to replicate the epistatic interaction between these loci described in the original report and there have been differences in the associated alleles/haplotypes reported at each locus. In this study, we performed association and epistasis analyses of the DAOA/G30 and DAO loci in a sample of 373 cases with DSM-IV schizophrenia/schizoaffective disorder and 812 controls from the Republic of Ireland. Corrected for the number of tests performed, we found evidence for association between markers at both genes and schizophrenia: DAOA/G30 (P = 0.005, OR = 1.34 (1.09, 1.65)) and DAO (P = 0.003, OR = 1.43 (1.12, 1.84). The data suggest that evidence for association at DAO (marker rs2111902) is more consistent than previously realized, particularly in Caucasian schizophrenia populations. We identified evidence for epistatic interaction between the associated SNPs at DAOA and DAO genes in contributing to schizophrenia risk (OR = 9.3 (1.4, 60.5). Based on these data, more systematic investigation of genes involved in DAO signaling is required.     

Characterization of the Strain-Specific and Common Surface Antigens of Mycoplasma arginini

A combination of quantitative immunoelectrophoresis and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis was used to determine location and molecular weights of surface membrane antigens of four strains of Mycoplasma arginini. Two major surface antigens were identified for M. arginini by absorption of antiserum with whole cells: one surface antigen was strain specific, electrophoretically fast, and prominently located on the surface, whereas the other surface antigen was common to the four strains and of intermediate electrophoretic mobility. Three of the four strains of M. arginini (G-230, 23243, and 27389) possessed immunologically strain-specific antigens which did not cross-react, whereas the leonis strain lacked an immunologically detectable unique surface antigen. A monospecific antiserum prepared against immune precipitates of the strain-specific antigen of strain G-230 detected three polypeptides of 74,000, 44,000, and 17,000 daltons in SDS-polyacrylamide gels of membrane preparations. All four strains shared the common surface antigen which appeared considerably more hydrophobic than the strain-specific surface antigen because it could only be demonstrated by charge-shift immunoelectrophoretic conditions (addition of deoxycholate to the nonionic detergent). Monospecific antiserum to the common antigen of strain G-230 reacted with all four M. arginini strains, but did not react with two other arginine-utilizing species, and recognized three polypeptides of 40,000, 29,000, and 20,000 daltons in membranes of strain G-230. Whereas the common surface antigen is a likely target for conventional serological reactions used for identification of the species M. arginini, strain-specific antigen cannot fulfill this role but must participate in other surface reactions.     

The expression of B7-H1 on keratinocytes in chronic inflammatory mucocutaneous disease and its regulatory role

PD-1 and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, have been identified recently as CD28-B7 family molecules that are implicated in immune regulation. Lichen planus (LP) is a T cell-mediated chronic inflammatory mucocutaneous disease. We investigated the expression and function of PD-1 and its two ligands in LP. Immunohistochemical examination revealed the abundant expression of PD-1 and B7-H1 in infiltrating T cells and macrophages, and lower-level expression of B7-DC on macrophages in the subepithelium. Interestingly, substantial expression of B7-H1 on keratinocytes (KCs) was found close to the numerous T cell infiltrates in the subepithelium. Unstimulated cultured KCs expressed both B7-H1 and B7-DC, and their expression was upregulated by proinflammatory cytokines, particularly IFN-gamma. The T-cell proliferative responses and IFN-gamma production that were induced by IFN-gamma-treated KCs were augmented preferentially by anti-B7-H1 mAb, but not by anti-B7-DC mAb. These results indicate the regulatory role of B7-H1 on KCs in the interactions with T cells. Our results suggest that the induction of B7-H1 on KCs may play an important role in tolerance induction in the inflamed oral mucosa and skin.     

Criteria for the administration of KI for thyroid blocking of radioiodine

Scientific data are reviewed to evaluate the risks of radioiodine uptake and to compare those risks with the benefits and risks of low milligram doses of stable potassium iodide (KI). The limit of 25 rad to the thyroid due to radioiodine uptake is adopted as the "break-even" point above which 130-mg KI doses should be administered. The biological and radiological kinetics of radioiodine for protracted uptakes were derived from the Medical Internal Radiation Dose Committee (MIRD) model (MIRD75). Resulting calculations yielded estimates of dose commitment rates to the thyroid as a function of thyroidal uptake. The extrapolated value of the 1-hr inhalation curve for 131I with 30% uptake compares well with the established MPCa value and intercepts the origin. The calculated KI-blocking efficiency as a function of time after radioiodine uptake agrees well with previously reported experimental data. The prevention or "blocking" of 25 rad to the thyroid was the criterion used to define critical values of radioiodine in the thyroid. Critical values are functions of isotope, the duration of uptake and the elapsed time between inhalation and assay of thyroid content. The presence of radioiodine in the thyroid in amounts greater than the critical value indicates that more than 25 rad to the thyroid can be averted, and KI should be administered in the absence of contraindications. Critical average concentrations are implicitly defined by the method of calculation used in the derivation. Critical average concentrations are presented as criteria for KI administration when assays of the radioiodine content of the thyroid are unavailable. Illustrative applications of critical values and critical average concentrations are presented in the Appendix.