Pentoxifylline therapy in human immunodeficiency virus-seropositive persons with tuberculosis: a randomized, controlled trial

Macrophage activation and tumor necrosis factor-alpha (TNF-alpha) production are critical in tuberculosis immunity but may result in increased human immunodeficiency virus (HIV) expression and accelerated HIV disease progression in HIV-infected persons. Pentoxifylline inhibits expression of TNF-alpha and HIV. A double-blind, placebo-controlled study of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-release formulation was done in Ugandan HIV-infected patients with pulmonary tuberculosis. Subjects had early HIV disease (mean CD4 cell count, 380/microL) and did not receive other antiretroviral drugs. Pentoxifylline resulted in decreased plasma HIV RNA and serum beta 2-microglobulin and, in a subset of moderately anemic patients, improved blood hemoglobin levels. Trends were noted toward reduced TNF-alpha production in vitro and improved performance scores, but these did not reach statistical significance. No effect was noted on body mass, CD4 cell count, or survival. Additional studies of more potent TNF-alpha inhibitors in HIV-positive subjects with tuberculosis are warranted.     

Meat tenderness and the calpain proteolytic system in longissimus muscle of young bulls and steers

The objectives of this study were to examine the effects of castration on the calpain proteinase system (mu-calpain, m-calpain, and calpastatin) activities and meat tenderness. Six each, MARC III bulls and steers were slaughtered at approximately 12 mo of age. Longissimus muscle samples were obtained for determining myofibril fragmentation index, Warner-Bratzler shear force, and sensory panel evaluation at 1, 7, and 14 d postmortem, and mu- and m-calpain and calpastatin activities at 24 h postmortem. Bulls produced leaner carcasses with lower (P < .05) quality grades than did steers. Meat from bulls had higher (P < .05) shear force values than meat from steers; however, sensory panelists were unable (P > .05) to detect differences in tenderness or other sensory traits between bulls and steers. Activities of mu- and m-calpain were not affected (P > .05) by castration; however, calpastatin was higher (P < .05) in muscles from the bull carcasses. Lower (P < .05) myofibril fragmentation index values indicate that less proteolysis occurred in muscle from bulls than in muscle from steers during the first 7 d postmortem. Greater calpastatin 24-h activity may be associated with the increased shear force of meat from bulls.     

Abrupt (< 1 day), acute (< 1 week), and early (< 1 month) vessel closure at the angioplasty site. Morphologic observations and causes of closure in 130 necropsy patients undergoing coronary angioplasty

While abundant clinical and angiographic data are available regarding features of acute or abrupt closure at the site of balloon angioplasty, little morphologic information is available. This study discusses morphologic-histologic causes for acute closure after angioplasty in 130 necropsy patients. Intimal-medial flaps, elastic recoil, and primary thrombosis were the three leading morphologic causes for closure. Data were subdivided into time categories: abrupt (< 1 day), acute (< 1 week), and early (< 1 month). Intimal-medial flaps remained the most common cause for angioplasty closure despite time from angioplasty to documented occlusion. Morphologic recognition of types and frequencies of angioplasty closure are discussed, and specific mechanical, pharmacologic, or combined treatments are reviewed.     

Vascular rejection post heart transplantation is associated with positive flow cytometric cross-matching

28 isolates of canine parvovirus type-2 (CPV-2) were obtained from dogs with hemorrhagic gastroenteritis in Italy. The antigenic structure of CPV-2 isolates was characterized, using four discriminating monoclonal antibodies. In addition, four vaccinal strains were examined. Similar to reports from Australia and the United Kingdom, a much higher prevalence of CPV-2a (25/28 isolates) was observed than the other variant type, CPV-2b (3/28 isolates). DNA fragments (2.2 kbp) of representative strains of CPV-2, CPV-2a and CPV-2b were amplified by the polymerase chain reaction (PCR) and the products were digested by the restriction enzymes (RE) RsaI, HpaII, HindIII and PvuII. The RvaI enzyme allows the differentiation of CPV-2 from CPV-2a and CPV-2b.     

Acquired autoimmune thrombocytopenia post-bone marrow transplantation for severe combined immunodeficiency

Children with severe combined immunodeficiency (SCID) have profoundly diminished humoral and cellular immunity resulting in death during infancy unless immune reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post-bone marrow transplantation can be seen in relation to infection, graft-versus-host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune dysregulation. We report two cases of severe AITP following BMT for SCID. Both cases developed large intracerebral hemorrhages from which one died. Autoimmune thrombocytopenia in this setting can be life-threatening and we recommend early and active intervention.     

Immune recognition of viral antigens

The response exhibited by the immune system to viral and other foreign antigens consists of antibody-mediated and T cell-mediated immunity. Structural and molecular biological studies have shown that the antibody response is tailored to provide exquisite specificity by generating binding pockets that are complementary in shape as well as in charge to the antigen. On the other hand, the cellular response uses T-cell receptors (TCRs) and the major histocompatibility complex (MHC) antigens. Structural information on the TCRs is not yet available, but the crystal structures of several MHC class I molecules have shown how one MHC molecule can bind many different peptide sequences that share only the common anchor residue positions that determine allele specificity. MHC class I interactions with the peptide backbone at the N and C termini explain the high specificity of the binding groove for peptide ligands and suggest a universal mode of recognition for peptides to MHC class I molecules. Peptide-MHC class II interactions are less well understood, although recent structural work has shown important differences in the binding clefts of MHC class I and II that lead to longer peptides being bound to class II molecules. Detailed analysis at the molecular level has indicated that conformational changes in both antibodies and MHC molecules occur upon antigen binding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct and GTP-dependent interaction of ADP ribosylation factor 1 with coatomer subunit beta

A site-directed photocrosslink approach was used to elucidate components that interact directly with ADP- ribosylation factor (ARF)-GTP during coat assembly. Two ARF mutants were generated that contain a photolabile amino acid at positions distant to each other within the ARF molecule. Here we show that one of the two positions specifically interacts with coatomer subunit beta both on Golgi membranes and in isolated coat protein complex type I (COPI)-coated vesicles. Thus, a direct and GTP-dependent interaction of coatomer via beta-coat protein complex (COP) with ARF is involved in the coating of COPI-coated vesicles. These data implicate a bivalent interaction of the complex with the donor membrane during vesicle formation.     

Aorto-left atrial fistula in prosthetic aortic endocarditis

Aortic valve endocarditis commonly leads to the formation of a root abscess, but fistulae are uncommon. The echocardiographic findings in a patient with Streptococcus viridans endocarditis of a prosthetic aortic valve associated with a fistula between the aorta and the left atrium are presented. The diagnosis was made by transthoracic echocardiography, although the transesophageal study gave higher resolution views and allowed a more confident exclusion of mitral valve involvement.