T-Lymphoblasts with Erythropoietic Helper Function in Acute T-Cell Leukemia

A patient with acute T-lymphoblastic leukemia was found to maintain a normal hemoglobin concentration both at presentation and preterminally several months later, despite a replaced bone marrow and over 80% circulating lymphoblasts on both occasions. Cell surface marker analysis demonstrated the T-lymphoblasts both at presentation and preterminally to belong to the T-helper subpopulation. In vitro culture studies demonstrated that the patient's T-lymphoblasts, as well as conditioned medium derived from these lymphoblasts, significantly stimulated normal bone marrow erythroid colony growth (CFU-E). These findings suggest that in this patient the preservation of erythropoiesis resulted from a helper effect exerted by his T-lymphoblasts.     

Bone marrow transplantation in Fanconi anemia using matched sibling donors

Eighteen patients with Fanconi anemia (FA) with evidence of bone marrow (BM) aplasia underwent allogenic BM transplants (BMT) from matched sibling donors (MSD). Median age at BMT was 7.6 years. Conditioning consisted of low-dose cyclophosphamide (CY; 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI; 400 cGy). Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A and prednisone. In addition antithymocyte globulin (ATG) was administered in the pretransplant period to promote engraftment and in the posttransplant period for additional GVHD prophylaxis. Engraftment occurred rapidly (median, 12 days for an absolute neutrophil count > or = 0.5 x 10(9)/L; median, 22 days for platelet count > or = 50 x 10(9)/L). Seventeen patients have sustained engraftment and are transfusion-independent, with Lansky scores of 100% at median follow-up of 27 months. One patient developed graft failure 4 months after initial engraftment and required a second BM infusion. None of the patients developed acute GVHD; 3 patients (16%) developed chronic GVHD. BMT is a feasible option for FA patients having an MSD and should be performed at a young age and early in the course of the disease, before the development of complications. We believe the addition of ATG to the transplant regimen of low-dose CY, TAI, and cyclosporin was responsible for improvement in the survival of FA patients undergoing BMT. The regimen was well tolerated and was associated with a low incidence of complications including GVHD.     

Notch activation results in phenotypic and functional changes consistent with endothelial-to-mesenchymal transformation

Various studies have identified a critical role for Notch signaling in cardiovascular development. In this and other systems, Notch receptors and ligands are expressed in regions that undergo epithelial-to-mesenchymal transformation. However, there is no direct evidence that Notch activation can induce mesenchymal transdifferentiation. In this study we show that Notch activation in endothelial cells results in morphological, phenotypic, and functional changes consistent with mesenchymal transformation. These changes include downregulation of endothelial markers (vascular endothelial [VE]-cadherin, Tie1, Tie2, platelet-endothelial cell adhesion molecule-1, and endothelial NO synthase), upregulation of mesenchymal markers (alpha-smooth muscle actin, fibronectin, and platelet-derived growth factor receptors), and migration toward platelet-derived growth factor-BB. Notch-induced endothelial-to-mesenchymal transformation does not seem to require external regulation and is restricted to cells expressing activated Notch. Jagged1 stimulation of endothelial cells induces a similar mesenchymal transformation, and Jagged1, Notch1, and Notch4 are expressed in the ventricular outflow tract during stages of endocardial cushion formation. This is the first evidence that Jagged1-Notch interactions induce endothelial-to-mesenchymal transformation, and our findings suggest that Notch signaling may be required for proper endocardial cushion differentiation and/or vascular smooth muscle cell development.     

Intestinal fungal and parasitic infections in kidney transplant recipients: a multi-center study

Kidney transplant recipients are susceptible to various infections due to the use of immunosuppressive drugs. The present study was performed as studies on the prevalence of intestinal fungal and parasitic infections in kidney transplant recipients are limited. A total of 150 kidney transplant recipients and 225 matched immunocompetent outpatients, who were referred to the laboratory of Noor Hospital, Isfahan, were studied. After recording demographic characteristics, direct test and specific laboratory cultures were carried out on the stool specimens. Patients were instructed on sanitary rules and, during each medical visit, they were reminded of the same. The overall prevalence of intestinal parasitic and fungal infections was 33.3% and 58.7%, respectively, in transplant recipients and 20% and 51%, respectively, in the control group; the difference was not statistically significant. The most prevalent intestinal parasite was Entameba coli, which was seen in 9.3% of the study patients and 6.7% of the controls. The most prevalent fungus was Candida sp., which was seen in 22% of the study patients and 24.4% of the control group. Co-existing infection with two or more fungi was seen in 14.8% and 3.4% in the case and control groups, respectively; P <0.001. Interestingly, there was no significant difference in the prevalence of infection by a single organism between the two groups. However, co-existing infection with two or more species was more prevalent in transplant recipients. We conclude that further investigations are needed to evaluate the pathogenesis of infection with these microorganisms.     

Influence of hippocampal GABA<Subscript>B</Subscript> receptor inhibition on memory in rats with acute β-amyloid toxicity

The neurotransmitter γ-aminobutyric acid (GABA) is involved in the process of memory. It has been reported that the inhibition of GABA_B receptors has beneficial effects on cognition. The aim of this study was to investigate the role of CGP35348 (a GABA_B receptor antagonist) on dentate gyrus GABA_B receptor inhibition and its effects on learning and memory impairments that had been induced in adult male rats by microinjection of β-amyloid (Aβ). Seventy Wistar male rats were randomly divided into seven groups: control, sham (receiving the Aβ vehicle only), Aβ, Aβ + CGP35348 (1, 10, and 100 μg/μL), and CGP35348 alone (10 μg/μL). Memory impairment was induced by unilateral interventricular microinjection of Aβ (6 μg/6 μL). Rats were cannulated bilaterally in the dentate gyrus, and then, they were treated for 20 consecutive days. Learning and memory were assessed using the novel object recognition and passive avoidance learning tests. The discrimination index and the step-through latency were significantly increased in the Aβ + CGP35348 group in comparison to the Aβ only group (P?<?0.05 and P?<?0.01, respectively). Data showed that the discrimination index was decreased in the Aβ + CGP35348 group in comparison with the control group (P?<?0.05) and sham group (P?<?0.01). Moreover, the step-through latency was significantly decreased in the Aβ + CGP35348 group in comparison to the control and sham groups (P?<?0.01). Data from this study indicated that intra-hippocampal microinjection of the GABA_B receptor antagonist counteracts the learning, memory, and cognitive impairments induced by Aβ. It can be concluded that the GABA_B receptor antagonist is a possible therapeutic agent against the progression of acute Aβ toxicity-induced memory impairment.     

Haemopoietic stem/progenitor cell transplant in Fanconi anaemia using HLA-matched sibling umbilical cord blood cells

Summary There have only been a few reports documenting the use of umbilical cord blood as a source of stem cells for haemopoietic reconstitution. We report our experience with a child with Fanconi anaemia (FA) who underwent a stem cell transplant using umbilical cord blood cells from his HLA matched sibling. Although the engraftment was somewhat slow, it was complete and comparable to other transplants performed in FA patients using HLA matched sibling marrow. There was no graft-versus-host disease. The post-transplant period was uncomplicated and, at a follow-up of 36 months, this child is well with normal blood counts and immune function.     

Androgen dependency in acquired aplastic anemia

We describe three patients with acquired aplastic anemia showing dependency on androgens, with blood counts that correlated directly with variation in oxymetholone dosage. In two of the patients, red cells, neutrophils and platelets showed parallel fluctuations, whereas in one patient the red cells and white cells, but not the platelets, fluctuated in relationship to oxymetholone therapy. There was no hematologic response to dromostanolone in two patients. These results support the benefit of androgen therapy in some patients with acquired aplastic anemia.     

Contingent and non-contingent biofeedback training for Type A and B healthy adults: can Type As relax by competing?

This paper investigates an alternative approach to the modification of cardiovascular reactivity in healthy Type A adults using contingent (true) and non-contingent (false) heart rate biofeedback. Sixteen Type A and sixteen Type B subjects were either given instructions to compete for heart rate reduction or were given no competitive instructions. There were four relaxation sessions. In one, subjects were given contingent heart rate biofeedback and in another they were given no feedback. In two sessions 'feedback' was non-contingent: in one condition feedback suggested that heart rate decreased across the session; in the other the suggestion was of increase. Results showed that overall, biofeedback was an effective method for heart rate reduction but non-contingent feedback (decreased heart rate) was found to be as effective as contingent feedback. Overall, Type A subjects reduced heart rate significantly more than Type Bs. More importantly, Type As reduced heart rate significantly more when competing than when competition was not mentioned. These results suggest that core elements of Type A behaviour, in particular competition, could be exploited in the modification of physiological hyperactivity in healthy Type A individuals.