Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency

While the presence of a lipoyl-containing protein (protein X) separate from lipoyl transacetylase in the pyruvate dehydrogenase complex (PDC) has been known for some time, until recently only the cDNA for the yeast enzyme has been cloned. We have cloned, sequenced and characterized the cDNA encoding the human protein X and localized the protein X gene to chromosome 11p13. We also report here a new case of protein X deficiency identified immunologically, with decreased activity of PDC and without mutations in the E1alpha subunit or E1beta subunit. We report that the cDNA and gene of this patient for protein X has a homozygous 4 bp deletion, specifically in the putative mitochondrial targeting signal sequence which results in a premature stop codon. This is the first documented case of a molecular defect in pyruvate dehydrogenase protein X.      

Radiographic damage in large joints in early rheumatoid arthritis: relationship with radiographic damage in hands and feet, disease activity, and physical disability

An assessment of the onset of radiographic damage in the large joints (hip, knees, shoulders, elbows, ankles and tarsus) in patients with early rheumatoid arthritis, and the relationship of the progression of large joint damage with joint damage in hands and feet, with physical disability, and with cumulative disease activity, was performed in a prospective 6 yr follow-up study. Large joint damage appeared to be an early phenomenon with 20% of the patients having some damage in at least one large joint within 1 yr, and 50% of the patients within 6 yr after disease onset. Radiographic damage in large joints was significantly related to the damage in hands and feet, the physical disability index, and the cumulative disease activity. The initial disease activity at study entry was the only prognostic factor that reached significance.      

Bcl2 inhibits apoptosis associated with terminal differentiation of HL- 60 myeloid leukemia cells

The Bcl2 protein inhibits apoptosis (programmed cell death) induced by a variety of noxious stimuli. However, relatively little is known about its effect on apoptosis that occurs after terminal differentiation. Bcl2 protein levels decrease during differentiation of myeloid cells into granulocytes that subsequently undergo apoptosis, but the potential role of Bcl2 in coupling survival and differentiation remains undefined. To ascertain the relationship between decreasing Bcl2 levels and the onset of apoptosis in differentiating myeloid cells, Bcl2 was hyperexpressed in the HL-60 cell line after retroviral gene transfer. After treatment of HL-60/BCL2 cells with all-trans retinoic acid or phorbol myristic acid, Bcl2 levels did not decrease as in normal HL-60 cells but, rather, increased because of activation of the viral promoter. Differentiation of the Bcl2-overexpressing cells was similar to that of normal HL-60 cells, but they showed little evidence for apoptosis and had a prolonged survival. These studies show that the survival-enhancing properties of Bcl2 counteract programmed cell death that accompanies terminal differentiation; however, Bcl2 has no significant effect on differentiation itself, suggesting that apoptosis and differentiation are regulated independently in myeloid cells.     

Fibrinogen potentiates the effect of interleukin-3 on early human hematopoietic progenitors

The effect of human fibrinogen on the proliferation of purified SBA- CD34+ human bone marrow progenitors was investigated in clonal cultures. Fibrinogen alone or in combination with erythropoietin had no significant effect. However, in the presence of recombinant human interleukin-3 (IL-3), fibrinogen increased significantly in a dose- dependent manner the number of mixed and burst-forming unit-ethrocyte-- derived colonies, whereas the number of other colonies did not significantly change. In the presence of fibrinogen, low concentrations of IL-3 (0.17 U/mL) produced three times more mixed colonies than without fibrinogen, reaching the number of colonies obtained with optimal concentrations of IL-3 (1.67 U/mL). Fibrinogen fragment D had the same effect in the presence of IL-3 as intact fibrinogen, whereas fibrinogen fragment E and human collagen IV did not. This effect was not mediated by integrins, because peptides or monoclonal antibodies that block fibrinogen binding on integrins alpha IIb beta 3, alpha v beta 3 (RGD-peptides), alpha m beta 2 (OKM-1), and alpha x beta 2 (HC1/1) did not affect the observed mitogenic effect. The mitogenic effect of fibrinogen and its D fragment was not mediated by induction of IL-6 or granulocyte--colony-stimulating factor secretion, because it was not inhibited by blocking antisera against these two growth factors. Our results indicate that fibrinogen potentiates the effect of IL-3 on primitive hematopoietic progenitors and suggest that the mitogenic effect of fibrinogen could be mediated via a specific mitogenic receptor that does not belong to the integrin family.     

Systemic inflammatory response syndrome in adult patients with nosocomial bloodstream infections due to enterococci

Background  

Enterococci are the third leading cause of nosocomial bloodstream infection (BSI). Vancomycin resistant enterococci are common and provide treatment challenges; however questions remain about VRE's pathogenicity and its direct clinical impact. This study analyzed the inflammatory response of Enterococcal BSI, contrasting infections from vancomycin-resistant and vancomycin-susceptible isolates.