Expression of Bcl-2 by human bone marrow mast cells and its overexpression in mast cell leukemia

Bcl-2 protein plays a major role in the prevention of programmed cell death of differentiating cells. In the present study, the expression of cytoplasmic bcl-2 by human Bone Marrow Mast Cells (BMMC) from both normal and pathological bone marrow samples was examined. A total of 35 subjects corresponding to 9 healthy volunteers, 8 cases of adult indolent systemic mast cell disease (SMCD), 4 cases of pediatric mastocytosis (PM), 11 cases of hematological malignancies (HM), 2 cases of reactive bone marrow, and 1 case of mast cell leukemia (MCL) were analyzed. The expression of bcl-2 was studied using quantitative three-color flow cytometry. We also studied the molecular configuration of the bcl-2 gene and other relatives by Southern blot and polymerase chain reaction (PCR) in the MCL case. Bcl-2 expression was detected in BMMC from all samples analyzed. No significant differences on the expression of bcl-2 were detected between BMMC from healthy subjects and patients with SMCD, PM, HM, and reactive bone marrow. By contrast, bcl-2 protein was overexpressed in BMMC from MCL patient without gene rearrangement. Our results show that bcl-2 protein was constitutively expressed by BMMC. BMMC from MCL display overexpression of bcl-2, which could not be related to molecular rearrangements involving the bcl-2 gene. The expression of this protein by mature MC may play a role in the prevention of MC apoptosis and thus help to explain the long survival of these cells. The overexpression of bcl-2 by BMMC in MCL may help to explain their resistance to chemotherapy-induced apoptosis.     

Usefulness of NTproBNP in the emergency management of patients with severe dyspnea and an uncertain heart failure diagnosis

INTRODUCTION AND OBJECTIVES: Measurement of N-terminal pro-B-type natriuretic peptide (NTproBNP) helps in diagnosing heart failure (HF). The test's usefulness may be greatest in patients with severe dyspnea of uncertain origin. However, NTproBNP has not been evaluated specifically in this setting. PATIENTS AND METHOD: This prospective emergency department study included 70 patients with shortness of breath at rest as their chief complaint. In the attending physician's opinion, both HF and a non-cardiac cause were equally probable. Blinded NTproBNP measurement was carried out in blood samples collected on admission. Patients were monitored and their final diagnoses were based on clinical findings, therapeutic responses, and cardiac and noncardiac tests performed during hospitalization. RESULTS: The NTproBNP level was higher in the 49 patients (70%) with a final diagnosis of HF (P = .006); the area under the ROC curve was 0.72 (0.60-0.82). The optimum diagnostic cut-off value was 900 pg/mL, which had an accuracy of 87%, a sensitivity of 98%, and a negative predictive value of 92%. The NTproBNP level was significantly higher in the 6 patients (9%) who died during hospitalization (P = .009); the area under the ROC curve was 0.87 (0.76-0.93) and the optimum cut-off value for predicting death was 5500 pg/mL, which had an accuracy of 77%, a sensitivity of 100%, and a positive likelihood ratio of 4.2. CONCLUSIONS: In patients with severe dyspnea and an uncertain diagnosis of HF, an NTproBNP level < 900 pg/mL helps exclude the presence of HF, whereas a NTproBNP level > 5500 pg/mL identifies patients at an increased risk of death.     

Valvuloplasty with balloon catheter in biologic prosthesis. Reality or illusion

We performed catheter balloon valvuloplasty (CBV) on 8 stenotic operatively-excised bioprosthetic valves (2 Hancock and 6 Ionescu Shiley). Pathology of valves before CBV included degenerative changes: commissural fusion by mounds of calcific deposits (2 valves), fibrotic and focally calcified leaflets (7 valves) and stiff and thick valves (1 valve). Inflation of the balloon resulted in commissural splitting (2 valves), leaflet cracks and fractures (3 valves). Removal of the deflated balloon catheter was associated with debris dislodgement (3 valves). In one case the valve was unable to close with potential for acute regurgitation. Thus, CBV of bioprosthetic valves can split fused commissures by similar mechanisms as in native valves. CBV may fracture calcific deposits causing acute emboli. It can also disrupt the leaflets causing acute insufficiency. The findings suggest a limited role of CBV in the treatment of stenotic bioprosthetic valves in mitral and aortic position.     

Lung scintigraphy with technetium 99m depreotide in the assessment of solitary pulmonary nodules

A solitary pulmonary nodule (SPN) is defined as a parenchymal lesion measuring less than 3 cm in diameter that is not associated with other lesions. Ninety percent of SPNs are discovered incidentally and most are benign. The management of radiographically indeterminate SPNs has not been established and invasive procedures must be undertaken in order to understand the nature of the nodule. We review our experience with the use of somatostatin receptor scintigraphy with technetium Tc99m depreotide in 10 patients with suspected malignant SPN. We discuss the limitations and applications of this technique in the evaluation of whether SPNs are benign or malignant for the purpose of identifying patients for biopsy. For this application, this technique can be considered an alternative to positron emission tomography using fluorine-18 fluordeoxyglucose.     

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics

Mutations in the glucokinase (GCK) gene are considered to be a possible cause of maturity-onset diabetes of the young. The purpose of this study was to evaluate the contribution of this gene to the development of post-renal transplantation diabetes mellitus (PTDM). Identification of the GCK mutation was attempted in 58 selected renal allograft recipients with PTDM and 45 normal controls. The exons in the GCK gene were examined using polymerase chain reaction (PCR), followed by an analysis of single-stranded DNA conformational polymorphism (SSCP). The abnormal bands were then confirmed by DNA sequencing analysis. The family members of the patients affected with GCK mutation were also examined. Two of the 58 PTDM patients (3.4%) were found to have GCK mutations. One had the mutation on exon 5 and the other on intron 7. One control subject had the mutation on intron 9. The mutation on exon 5 was identified as a substitution of CCT (proline) for CTT (leucine) at codon 164, which has never been reported before. The family members of the PTDM patient with a mutation on exon 5 were analyzed by PCR, followed by SSCP, and two of them had the same mutation. The abnormal band seen on SSCP analysis of exon 7 was identified as the C→T substitution at the 39th nucleotide in intron 7. Two of the family members also displayed the same bands on the SSCP. One of the 45 normal controls had a known polymorphism located at the 8th nucleotide in intron 9. We found a GCK mutation on the exon in subjects with PTDM and we speculate that this mutation may be one of the possible contributing factors of PTDM, although variations of the GCK gene are not common causes of PTDM.