Fine mapping of the dyskeratosis congenita locus in Xq28

Dyskeratosis congenita (DC) is characterised by reticulate skin pigmentation, mucosal leucoplakia, and nail dystrophy. Bone marrow failure occurs in 50% of patients and is the principal cause of early mortality. In the majority of families the pattern of inheritance of DC is compatible with an X linked recessive trait. The locus for the X linked recessive form of DC has been linked to Xq28. We have now extended our earlier studies by investigating five families with additional Xq28 polymorphic markers; analysis of recombination events in these families has located the DC1 locus between GABRA3 and DXS1108, an interval of approximately 4 Mb.     

Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK

Growth factors activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs) and Jun kinases (JNKs). Although the signaling cascade from growth factor receptors to ERKs is relatively well understood, the pathway leading to JNK activation is more obscure. Activation of JNK by epidermal growth factor (EGF) or nerve growth factor (NGF) was dependent on H-Ras activation, whereas JNK activation by tumor necrosis factor alpha (TNF-alpha) was Ras-independent. Ras activates two protein kinases, Raf-1 and MEK (MAPK, or ERK, kinase) kinase (MEKK). Raf-1 contributes directly to ERK activation but not to JNK activation, whereas MEKK participated in JNK activation but caused ERK activation only after overexpression. These results demonstrate the existence of two distinct Ras-dependent MAPK cascades--one initiated by Raf-1 leading to ERK activation, and the other initiated by MEKK leading to JNK activation.     

Clinical evaluation of the BDProbeTec strand displacement amplification assay for rapid diagnosis of tuberculosis

The reliability of the BDProbeTec MTB Test (Becton Dickinson, Sparks, Md.) for direct detection of Mycobacterium tuberculosis in respiratory specimens was evaluated by comparing results to those of conventional mycobacterial culture, with the BACTEC TB 460 and Middlebrook 7H11 biplates. Patients known to have tuberculosis were excluded from analysis. Of 523 specimens from 277 patients, 53 grew a mycobacterium: 24 specimens of M. tuberculosis and 29 specimens of nontuberculous mycobacteria. After initial testing, 42 specimens were positive by the BDProbeTec, for overall sensitivity, specificity, and positive and negative predictive values of 95.8, 96. 2, 54.8, and 99.8%, respectively. After resolution of discrepancies, 28 specimens were positive by the BDProbeTec, for overall sensitivity, specificity, and positive and negative predictive values of 100, 99.2, 85.7, and 100%, respectively. These same values were 100, 80.8, 93.4, and 100%, respectively, for smear-positive samples and 100, 99.4, 75.0, and 100%, respectively, for smear-negative specimens.     

The presence of cytoplasmic lipid droplets is not sufficient to account for neutral lipid signals in the 1H MR spectra of neutrophils

Stimulation of human peripheral blood neutrophils with lipopolysaccharide (LPS), arachidonic acid (AA) and oleic acid (OA) resulted in significant increases in cytoplasmic lipid droplets. This phenomenon was also observed in enucleated and degranulated cytoplasts prepared from neutrophils stimulated with LPS. In contrast, only LPS and high concentrations of OA (10 microM) produced an increase in the lipid intensities of the MR spectra of neutrophils as determined by COSY cross peak volume measurements. Lipid intensities in cells stimulated with OA (2.5 microM) and AA (2.5 microM) and phorbol myristate acetate (20 nM) were not elevated. LPS stimulation of resting cytoplasts resulted in increased lipid droplets but not MR lipid intensities. These data suggest that while cytoplasmic lipid droplets may correlate with MR lipid intensity under some circumstances, their presence is not sufficient to account for increased neutral lipid signals.     

Neuropeptide Y antibody attenuates 2-deoxy-D-glucose induced feeding in rats

2-deoxy-D-glucose (2-DG) has been shown to induce increased feeding responses in animals. Recent studies suggest the possible involvement of neuropeptide Y (NPY) in 2-DG-induced feeding. The present study examined the effect of immunoneutralization of endogenous NPY on 2-DG-induced feeding. NPY antibody injected into the paraventricular nucleus of the rats significantly attenuated 2-DG-induced feeding, suggesting that hypothalamic NPY may mediate, at least partly, the effect of 2-DG on food intake.     

Interposition grafting for reoperation on the common femoral artery

PURPOSE: This report details our experience with common femoral artery resection and Dacron interposition grafting in the management of vascular reoperations involving the common femoral artery. DESIGN: Retrospective review. SETTING: University teaching hospital. SUBJECTS: Consecutive reoperative patients who had common femoral artery interposition grafting for arteriosclerotic occlusive disease from 1986 to 1997. INTERVENTIONS: Common femoral artery resection and interposition grafting. MAIN OUTCOME MEASURES: Operative morbidity and mortality rates and long-term patency, limb salvage, patient survival, freedom-from-graft-infection, and freedom-from-reoperation rates. RESULTS: Ninety-nine common femoral arteries (16 bilateral) were resected and replaced with Dacron interposition grafts in 83 patients (50 male, 33 female; mean age, 65 years) who had had 237 previous ipsilateral common femoral artery operations (mean, 2.4 operations; range, 1-9 operations). Simultaneous infrainguinal bypass grafts were performed in 52 operations (53%), and 60 operations (61%) were performed in patients who had had previous ipsilateral proximal bypass grafts. Operative mortality was 2%, with a 14% rate of perioperative wound complications. Mean follow-up time was 22 months. One- and 3-year assisted primary patency rates for the interposition grafts were 90% and 77%, respectively. Both 1- and 3-year life-table-determined limb salvage rates were 95%. One- and 3-year life-table-determined freedom-from-reoperation rates were 74% and 43%, respectively. One- and 3-year life-table-determined freedom-from-infection rates were 99% and 92%, respectively. One- and 3-year life-table-determined survival rates were 82% and 73%, respectively. CONCLUSIONS: Common femoral artery resection and Dacron interposition grafting are safe, and they obviate many difficulties associated with reoperative common femoral artery surgery with satisfactory long-term results.     

On the reorganization of sensory hand areas after mono-hemispheric lesion: a functional (MEG)/anatomical (MRI) integrative study

The topography of primary sensory cortical hand area following a monohemispheric lesion (sudden = stroke; progressive = neoplasm) was investigated in relationship with clinical recovery of sensorimotor deficits. Twenty seven patients with monohemispheric lesions were studied in a clinically stabilized condition. Functional informations from magnetoencephalography (MEG) were integrated with anatomical data from magnetic resonance imaging (MRI). MEG localizations of the neurons firing at early latencies in primary sensory cortex after separate stimulation of median nerve, thumb and little fingers of each hand were carried out. Characteristics of cerebral equivalent current dipoles (ECDs) activated by each contralateral stimulation, the 'hand extension' (i.e., the distance in millimetres between ECDs of first and fifth digits), as well as interhemispheric differences of the tested parameters were investigated. Finally, ECDs' locations were integrated with MRI. Lesions involving cortical (C) or subcortical (s.c.) areas receiving sensory input from the hand were often combined to increase interhemispheric asymmetry of the tested parameters (22% for C and 49% for s.c. lesions). This might be due to an activation of neuronal districts which in the affected hemisphere (AH) differ from those normally activated in the unaffected hemisphere (UH) and in the control population. Moreover, the 'hand extension' was enlarged on the AH--more frequently after a SC lesion--mainly due to a medial shift of the little finger ECD, combined to a tendency of both finger ECDs to shift frontally. After a C lesion, responses from the AH were often stronger than normal. Spatial reorganizations were also seen in the UH (7% of C and 14% of SC lesions). 'Hand extension' in the UH was selectively enlarged for the P30m only when combined with a similar enlargement in the AH. Significant interhemispheric asymmetries due to neuronal reorganization in the AH were associated with worse clinical outcomes compared to patients without asymmetries.