A rapid test of alloreactivity based on interleukin-2 mRNA expression might identify liver transplant recipients with donor-specific hyporesponsiveness

BACKGROUND: Immunosuppression withdrawal is feasible in some liver transplant (OLT) recipients but may lead to severe rejection in others, underlying the need for reliable biomarkers to identify patients with tolerant profile in whose weaning/withdrawal could be safely proposed. We evaluated the value of real-time polymerase chain reaction (PCR)-based measurement of interleukin (IL)-2 mRNA in mixed lymphocyte reaction (MLR) to monitor in vitro anti-donor reactivity in OLT patients. METHODS: MLR were performed in three patients undergoing living donor OLT using a tolerogenic protocol including donor stem cells. IL-2 mRNA production in MLR was measured by PCR at several intervals after OLT. RESULTS: In the early posttransplant period, three patients presented with global immunodeficiency, as indicated by low IL-2 mRNA production against both donor and third-party antigens. In the two patients who has immunosuppression successfully withdrawn, donor-specific hyporesponsiveness was observed thereafter: IL-2 mRNA production against donor cells remained low, while IL-2 mRNA production against a third-party antigen-presenting cells progressively recovered. No such modulation of the anti-donor response was observed in the patient in whom withdrawal led to rapid rejection. CONCLUSION: Measurement of IL-2 mRNA production in MLR might prefer a tool to monitor anti-donor reactivity after OLT for decisions to minimize or withdraw immunosuppression in patients displaying donor-specific hyporesponsiveness.     

Genotype of subjects with borderline hemoglobin A2 levels: Implication for, β-thalassemia carrier screening

In this study, we have defined by molecular analysis, the α, β, and δ globin genotype in a group of individuals with normal or thal-like red cell indices but borderline hemoglobin (Hb)A2 levels, who were identified in a program for β-thal carrier screening. In 37 of 125 individuals with borderline HbA2 levels, we detected a molecular defect in the β, in both the δ and the β, or in the α globin gene. Specifically seven of these subjects were carriers of the ?101 C T mutation, ten of the IVSI nt6 T C mutation, 16 were double heterozygotes for δ and β thal, and two had the triple α globin gene and two the single α globin gene deletion. From these results, we may conclude that subjects with borderline HbA2, particularly when they marry a typical β-thal carrier, should be extensively investigated in order not to miss heterozygous β-thalassemia. © 1994 Wiley-Liss, Inc.     

Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation

In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated upon interaction with both receptor tyrosine kinases (RTK) and G- proteins resulting in the production of moieties involved in the inositol phospholipid signalling pathway. As G proteins, RTK and the inositol phospholipids have all been implicated in the human sperm acrosome reaction, experiments were carried out to determine whether PI 3-kinase was also involved in this phenomenon. Wortmannin is a selective inhibitor of PI 3-kinase and was shown to significantly inhibit the acrosome reaction induced by both mannose-bovine serum albumin (mannose-BSA) (10, 50 and 100 nM) and a polyclonal antibody raised against an extracellular region of the sperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did not inhibit the A23187- or progesterone-induced acrosome reaction. These results suggest that PI 3- kinase is involved in the human sperm acrosome reaction. The levels of tyrosine phosphorylation of sperm proteins as detected by Western blotting using antiphosphotyrosine antibodies was not affected by wortmannin in agonist (A23187 and mannose-BSA)-stimulated spermatozoa. This indicated that PI 3-kinase operates downstream of tyrosine phosphorylation in the signal transduction cascade which leads to the human sperm acrosome reaction.      

Simultaneous 99mTc double labelling of the hepatic reticuloendothelial system and of the red blood cells: a simplified method for the detection of liver hemangiomas

Sonographic images of liver hemangioma are not specific. Causal detection imposes further investigations (angiography, CT, NMR) which are not always practicable. 99mTc-red blood cells study after 99mTc colloid liver scintigraphy has been already proposed. Ten patients with hepatic hemangiomas were evaluated by simplified, simultaneous in vivo double labelling of the reticuloendothelial system and red blood cells by means of successive i.v. injections of SnCl2, 99mTc colloid albumin and 99mTc-pertechnetate. Focal colloid defects filled with the labelled RBC were revealed in 9/10 liver hemangiomas. Angioscintigraphy showed decreased perfusion and RBC scintigraphy an increased blood volume in the focal colloid defects due to the hemangiomas.     

Unusual clinical presentation of Mycobacterium fortuitum infection in an immunocompetent woman

The Mycobacterium fortuitum group of rapidly growing nontuberculous mycobacteria is an uncommon cause of renal infection, particularly in otherwise healthy hosts. We describe a case of nephritis due to M. fortuitum in an immunocompetent woman with a clinical and radiological diagnosis of renal tuberculosis.