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We present 2 cases of Aspergillus endocarditis occurring in lung transplant recipients, both of whom were treated with early surgical intervention and triazole anti-fungal agents. Neither had evidence of airway colonization/infection with Aspergillus post-transplant, suggesting hematogenous spread of fungi at the time of surgery as a possible mechanism of infection. One case was successfully treated and discharged from the hospital, but, despite initial recovery, death occurred 10 months later due to a recurrence of Aspergillus endocarditis. Aspergillus endocarditis should be considered a relapsing disease and survivors of the condition should receive ongoing anti-fungal therapy.

The microparticle capture enzyme immuno-assay (MEIA) is an automated system for measuring specific antibody by interaction with antigen-coated particles. An MEIA method for detecting toxoplasma-specific IgM was compared with established reference methods. The MEIA had an acceptable level of sensitivity and reproducibility and was easier to perform than conventional tests, but it required expensive, dedicated equipment and, in our study, false positive results were recorded with 7% of samples. MEIA could be used to investigate immunocompetent patients with suspected toxoplasmosis but positive findings should be confirmed by an alternative form of assay. The technique is not suitable for the investigation of neonates, for which a more sensitive method is required.

Tolerance induction by CD45RB monoclonal antibody (mAb) in murine allograft models is associated with an alteration in the CD45RBlo/CD45RBhi T-cell ratio in favor of CD45RBlo T cells, which can function as regulatory cells and promote tolerance. It has been proposed that inversion of the CD45RBhi/CD45RBlo normal T-cell ratio by mAb can occur by down-regulation of CD45RB surface molecules expressed by T cells. Because CD45RB mAb infusion can lead to a reduction in peripheral T cells, we tested whether other mechanisms might participate in the inversion of the CD45RBhi/CD45RBlo ratio, including apoptosis of CD45RBhi cells. We report that CD45RB mAb led to rapid elimination of both CD4+ and CD8+ T cells in vitro. Importantly, CD45RB mAb selectively eliminated CD45RBhi T cells without affecting the viability of CD45RBlo T cells. Furthermore, the death of T cells occurred with a reduction in mitochondrial transmembrane potential and DNA fragmentation but with little evidence of nuclear condensation and cell shrinkage typically found with cells undergoing apoptosis. We propose that CD45RB mAb therapy may promote a dominant regulatory T-cell population that has the capacity to inhibit rejection by the selective elimination of CD45RBhi effector T cells. This occurs by a process that does not involve the classic morphologic features of apoptosis. Strategies that facilitate an inversion of the CD45RBhi/CD45RBlo T-cell subset ratio may improve the efficacy of CD45RB mAb, and therapeutic measures that prevent deletion of CD45RBhi T cells may need to be avoided to achieve tolerance clinically.

Nitric oxide (NO) is a simple molecule implicated in neuronal transmission, endothelium-dependent vasodilatation, and macrophage immunologic activation. Enzymes responsible for NO synthesis constitute a family with at least three distinct isoforms - neuronal (NOS1), endothelial (NOS3), and inducible tissue. NO synthase enzymatic activity is constitutively expressed but activation of the calcium/calmodulin signaling pathway is required for maximal activity. Constitutive NO synthases contrast with a pathway for NO synthesis evident in macrophages, Kupffer cells, hepatocytes, vascular smooth muscle, and mesangial cells, among others. NO synthase activity is induced in these cell types by cytokines or bacterial wall products over a period of many hours. 14 refs., 1 fig.

A comprehensive analysis of the structure of neuronal nitric oxide synthase (nNOS; EC 1.14.13.39 ) mRNA species revealed NOS1 to be the most structurally diverse human gene described to date in terms of promoter usage. Nine unique exon 1 variants are variously used for transcript initiation in diverse tissues, and each is expressed from a unique 5′-flanking region. The dependence on unique genomic regions to control transcription initiation in a cell-specific fashion burdens the transcripts with complex 5′-mRNA leader sequences. Elaborate splicing patterns that involve alternatively spliced leader exons and exon skipping have been superimposed on this diversity. Highly structured nNOS mRNA 5′-untranslated regions, which have profound effects on translation both in vitro and in cells, contain cis RNA elements that modulate translational efficiency in response to changes in cellular phenotype.

The bio-physiological basis of nuclear medicine imaging is related to the disease process and it has been further developed - this time the target is bacteria and the disease state is infection. It is often than an inflammation may be due to bacterial infection. Conditions like osteomyelitis or endocarditis where long term antibiotic therapy would be appropriate require that the specific presence of a bacterial infection is demonstrated as the cause of inflammation. The available radiopharmaceuticals: Ga-67 citrate, Tc-99m or In-111 human immune globulin, Tc-99m antigranulocyte antibodies or binding peptides or Tc-99m/In-111 labelled leucocytes offer little help to provide this specific information. To address this issue, a search was pursued for an agent which would bind to living bacteria and that can be radiolabelled. This has resulted in development of Tc-99m Infection by Solanki et al [1].