Study of a human minor alloantigen in relation to clinical graft-versus-host disease

Sixty-seven pairs of HLA matched siblings, each comprising marrow donor and recipient in the Seattle marrow transplant program, were analyzed to establish phenotype for a newly described minor H antigen, W1. The test for phenotype entailed cold target inhibition of cytotoxicity, directed at this antigen and mediated by specifically stimulated T cell lines. There were 58 compatible and six W1 incompatible pairs. The low frequency of W1 mismatch is due to the strong preponderance of W1-positive individuals in the general population. Severe graft-versus-host disease (GVHD), both acute and chronic, was observed among the 58 recipients of marrow from W1 matched donors. These results do not reveal any particular importance for W1 incompatibility in human GVHD and indeed indicate that other systems are involved. Even if some cases are triggered by incompatibility at W1, the maximum frequency with which this could occur would be about 10%, due to the limited polymorphism of this alloantigenic system.     

Lower Extremity Geometry in Morbid Obesity—Considerations for Total Knee Arthroplasty

Background

Obesity has been associated with varying adverse outcomes related to total knee arthroplasty (TKA) and has long been associated with various mechanical complications. Computational modeling holds promise for investigating biomechanical aberrations related to TKA in obese patients. However, basic anthropometric information regarding the shape of the lower extremity in obese patients is lacking. We, therefore, developed a method to determine lower extremity shape both generally and subject specific as a function of body mass index (BMI) and sex.

Longitudinal analysis of T-cell receptor gene use by CD8(+) T cells in early human immunodeficiency virus infection in patients receiving highly active antiretroviral therapy

The effects of early antiretroviral therapy on the peripheral CD8(+) T-cell population were assessed by sequentially determining the T-cell receptor (TCR) repertoire complexity in a cohort of 15 individuals recently diagnosed with human immunodeficiency virus infection. Analysis was based on quantitative TCR variable B gene (TCRBV) usage and complementary-determining region 3 length assessment. Repertories were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. Early administration of highly active antiretroviral therapy has a positive effect on the preservation and homeostasis of the CD8(+) cell repertoire. Nevertheless, differences from average baseline and control TCR profiles and initial development of repertoire perturbations were observed. The findings suggest that additional therapeutic protocols will be required during primary infection to significantly prevent long-term erosion of the T-cell-mediated immune response.     

Combined Procedures with Laparoscopic Cholecystectomy

With advancement in laparoscopic surgery a number of surgical procedures can be performed combined with laparoscopic cholecystectomy in a single surgery. We evaluate the safety & efficacy of such surgeries. A retrospective review of all patients who had undergone combined procedures with laparoscopic cholecystectomy during January 2005 to June 2009 was performed. 3144 laparoscopic cholecystectomies were performed in the period from January 2005 to June 2009. Of these, 401 cases were combined with another procedure. The mean operative time was 80 min (range 50–270 min). The mean hospital stay was 3.2 days (range 1–5 days). The mean no. of days injectable analgesics was required was 2 days (range 1 day–4 days). Combined procedures provide patients with all the benefits of minimal invasive surgery and also give the benefit of single time anaesthesia without adding to post operative morbidity & hospital stay.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.