T lymphocyte response to H-2 mutants: cytotoxic effectors are Ly-1+2+.

The lymphocyte differentiation (Ly) antigen phenotype of cytotoxic effector T cells specific for H-2 mutant alloantigens was determined. Cytotoxic effectors generated in primary mixed lymphocyte culture and specific for H-2Kba and H-2Dda alloantigens are sensitive to both anti-Ly-1 and anti-Ly-2 serum plus complement. Reconstitution analysis demonstrated that the mutant-specific T cells were Ly-1+2+. These observations and those previously reported, which indicated that H-2K/D mutant-specific T cells proliferating in mixed lymphocyte culture were Ly-1+2+, demonstrated that Ly-1+2+ T cells are immunocompetent. Furthermore, the nature of the stimulating H-2 complex alloantigen determines the Ly phenotype of responsive T cells.     

A molecular basis for hemoglobin-H disease in American blacks

We have applied gene counting and restriction endonuclease mapping techniques to the study of two American black families in which there were one or more cases of HbH disease. We found deletions of three of the four normal alpha-globin genes in individuals with HbH disease. In two of these individuals, the chromosome containing the single alpha gene could have originated by crossing over between mispaired alpha genes, resulting in a deletion of about 4.2 kilobases (kb).     

Carrier detection in the Wiskott Aldrich syndrome

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease characterized by immunodeficiency and severe thrombocytopenia in affected males, but no demonstrable clinical abnormalities in carrier females. Through analysis of the methylation patterns of X-linked genes that display restriction fragment length polymorphisms (RFLPs), we studied the pattern of X-chromosome inactivation in various cell populations from female relatives of patients with WAS. The peripheral blood T cells, granulocytes, and B cells of eight obligate WAS carriers were found to display specific patterns of X-chromosome inactivation clearly different from these of normal controls. Thus, carriers of WAS could be accurately identified using this analysis.     

HLA-identical marrow transplantation during accelerated-phase chronic myelogenous leukemia: analysis of survival and remission duration

Results of HLA-identical allogeneic marrow transplantation were analyzed for 66 patients with accelerated-phase chronic myelogenous leukemia (CML). Multivariate proportional hazards regression models were used to determine disease-related and transplant-related factors associated with posttransplant mortality and relapse. The projected 5- year survival rate was estimated at 18% by the product-limit method. The major causes of death were interstitial pneumonia, infection, and relapse. Splenomegaly at initial diagnosis and longer time interval from diagnosis to transplant were associated with decreased overall survival and event-free survival. Sixteen patients have relapsed between 17 and 1,569 days (median, 486) posttransplant. The use of T- cell-depleted marrow and older age of the donor or recipient were associated with an increased probability of leukemic relapse. Ten of the 16 relapses occurred among the 15 patients who received T-cell- depleted marrow. The actuarial relapse risk 2.5 years posttransplant was 100% in patients administered T-cell-depleted marrow as compared with 25% in patients administered unmodified marrow. The data in this report emphasize the increased risks and relatively poor results that occur when marrow transplantation is deferred until after signs of acceleration appear. When compared with results for patients who received transplants during chronic phase, the poor results seen here in patients administered unmodified marrow stem primarily from increased transplant-related mortality rather than increased relapse risk. The strikingly increased relapse rate associated with the use of T-cell depletion would discourage its use for graft-v-host disease prevention in patients who receive transplants for CML.     

The cleaved peptide of PAR1 is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin

PURPOSE: Platelet-endothelial cell adhesion is an important pathologic response to vessel injury or inflammation. On binding to its endothelial or platelet G protein-linked seven-transmembrane domain receptor, protease-activated receptor-1 (PAR1), thrombin releases a 41-amino acid peptide (TR(1-41)). We examined the effect of TR(1-41) on platelet activation and on platelet-endothelial cell adhesion. METHODS: A monolayer of confluent human saphenous vein endothelial cells was incubated with washed human platelets. Platelets were stimulated with either TR(1-41), TR(21-41), scrambled TR(1-41), adenosine diphosphate (ADP)-epinephrine (EPI), thrombin, or thrombin receptor activating peptide (TRAP). Platelet activation was identified with flow cytometry. The magnitude of platelet-endothelial cell adhesion was determined with a laser scanning cytometer that scanned the monolayer of endothelial cells and identified fluorescently bound platelets. RESULTS: Maximal thrombin stimulation (0.1 U/mL) induced a threefold increase in platelets bound to endothelial cells compared with buffer alone. Stimulation with TR(1-41) (20 mmol/L) tripled the number of platelets bound to endothelial cells compared with thrombin. Scrambled sequence of TR(1-41) (20 mmol/L) and TR(21-41) (20 mmol/L), neither of which induces platelet activation, had minimal effect on platelet adhesion. Both TRAP (20 mmol/L) and ADP-EPI (20 mmol/L) induced less platelet-endothelial cell adhesion than did thrombin. TR(1-41)-induced platelet-endothelial cell adhesion was partially blocked by glycoprotein (GP)IIb-IIIa-specific monoclonal antibody, 10E5 (10 mg/mL). CONCLUSIONS: TR(1-41), the cleaved peptide of PAR1, is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin, TRAP, or ADP-EPI, and this adhesion is at least in part mediated by the platelet GPIIb-IIIa receptor.     

Panton–Valentine leukocidin Staphylococcus aureus osteomyelitis of the adult tibia – a case report

Panton–Valentine leukocidin toxin producing Staphylococcus aureus (PVLSA) is known to be responsible for recurrent soft tissue infections and more serious invasive infections including necrotising pneumonia, pyomyositis, and osteomyelitis. Most reported cases involving musculoskeletal infection in adults are associated with methicillin-resistant S. aureus (MRSA) PVL-producing strains. We present the case of an adult male with PVL toxin–producing methicillin-sensitive S. aureus (MSSA) osteomyelitis of the tibia which has not previously been described in adults and highlight issues of recognition, treatment, and surgical management of PVLSA osteomyelitis.     

The relevance of long head biceps degeneration in the presence of rotator cuff tears

Background  

Long head biceps (LHB) degeneration in combination with rotator cuff tears can be a source of chronic shoulder pain. LHB tenotomy is an approved surgical procedure for pain reduction and improvement of joint function, however, the pathophysiology of LHB degeneration is not fully understood. In the literature, neoangiogenesis in tendon tissue has previously been shown to be associated with tendon degeneration. Vascular Endothelial Growth Factor (VEGF) is an important inducer of neoangiogenesis. The hypotheses are first that an elevated VEGF expression and vessel density can be found in degenerated LHB tissue and second that there is a relation between VEGF expression, vessel density and the different types of rotator cuff tears.     

Osteochondritis dissecans of the capitellum in adolescents

Osteochondritis dissecans(OCD)is a disorder of articular cartilage and subchondral bone.In the elbow,an OCD is localized most commonly at the humeral capitellum.Teenagers engaged in sports that involve repetitive stress on the elbow are at risk.A high index of suspicion is warranted to prevent delay in the diagnosis.Plain radiographs may disclose the lesion but computed tomography and magnetic resonance imaging are more accurate in the detection of OCD.To determine the best treatment option it is important to differentiate between stable and unstable OCD lesions.Stable lesions can be initially treated nonoperatively with elbow rest or activity modification and physical therapy.Unstable lesions and stable lesions not responding to conservative therapy require a surgical approach.Arthroscopic debridement and microfracturing has become the standard initial procedure for treatment of capitellar OCD.Numerous other surgical options have been reported,including internal fixation of large fragments and osteochondral autograft transfer.The aim of this article is to provide a current concepts review of the etiology,clinical presentation,diagnosis,treatment,and outcomes of elbow OCD.     

The role of neutropenia on outcomes of cancer patients with community-acquired pneumonia

Although the presence of neutropenia may predispose cancer patients to develop community-acquired pneumonia, the role of neutropenia on their outcomes has not been investigated. The purpose of the present study was to compare clinical outcomes of cancer community-acquired pneumonia patients with and without neutropenia. Patients with cancer, identified in the Community-Acquired Pneumonia Organization database, were divided into two groups according to the type of cancer and the presence of neutropenia: patients with solid cancer without neutropenia versus those with functional or absolute neutropenia. Among the 3,106 community-acquired pneumonia patients enrolled, 135 had cancer without neutropenia and 75 had cancer with neutropenia. No significant difference was found between patients with and without neutropenia regarding mean time to clinical stability (5.4+/-2.7 versus 4.9+/-2.7 days, respectively), mean length of hospital stay (9.2+/-7.7 versus 9.9+/-9.6 days) and in-hospital mortality (18 versus 15%, respectively). Using a multiple logistic regression model, neutropenia was not associated with mortality in cancer patients when adjusting for significant covariates (odds ratio 1.30). Lack of neutropenia, during the initial evaluation of a cancer community-acquired pneumonia patient, should not be considered an indicator of better clinical outcome.     

B-cell Lymphoma in retrieved femoral heads: a long term follow up

Background  

A relatively high incidence of pathological conditions in retrieved femoral heads, including a group of patients having low grade B-cell lymphoma, has been described before. At short term follow up none of these patients with low-grade B-cell lymphoma showed evidence of systemic disease. However, the long term follow up of these patients is not known.