Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis

A nonrandom translocation between chromosomes 3 and 21, t(3;21)(q26.2;q22) has been detected in patients with a myelodysplastic syndrome or acute myeloid leukemia after treatment (t-MDS/t-AML) for a primary malignant disease and in chronic myelogenous leukemia in blast crisis (CML-BC). In these patients, the breakpoint on chromosome 21 is at band 21q22. This band is also involved in the t(8;21)(q22;q22) detected in 40% of the patients with acute myeloid leukemia subtype M2 (AML-M2) de novo who have an abnormal karyotype. In the t(8;21), the AML1 gene is the site of the breakpoint on chromosome 21. The AML1 gene is transcribed from telomere to centromere, and in the t(8;21) the 5' part of AML1 is fused to the ETO gene on chromosome 8 to produce the chimeric AML1/ETO on the der(8) chromosome. We found that AML1 is also rearranged in two t-AML patients and in one CML-BC patient with the t(3;21), but the breakpoints are approximately 40 to 60 kb downstream to those of AML-M2 patients. This region contains at least one additional exon of AML1, as determined by using an AML1 cDNA as a probe in Southern blot analysis. The t(3;21) breakpoints for the remaining patients could not be determined because, by fluorescence in situ hybridization analysis, the breaks are outside of the region covered by the available probes.     

Hypercalcemia and soft tissue calcification owing to sarcoidosis: The sunlight‐cola connection

Hypercalcemia occurs in sarcoidosis because of 1,25‐dihydroxyvitamin D production by pulmonary alveolar macrophages. Long‐standing hypercalcemia and hypercalciuria may cause such complications as nephrocalcinosis, nephrolithiasis, and soft tissue calcification, which can be at least partially reversible with treatment. Here we present a 43‐year‐old African‐American man with diffuse soft tissue calcifications and acute kidney injury owing to sarcoidosis‐induced hypercalcemia, probably exacerbated by sun exposure and phosphorus intake in the form of dietary cola drinks. Soft tissue calcifications resolved and kidney function improved significantly with hydration and glucocorticoid therapy. We discuss the pathophysiology of the hypercalcemia of sarcoidosis and current treatment options. © 2010 American Society for Bone and Mineral Research     

Bioinformatics advances in saliva diagnostics

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic,translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval,integration and analysis of data,we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart.     

Salbutamol for hyperkalaemia in children

Hyperkalaemia is a potentially fatal disorder that demands direct treatment. The efficacy of traditional medical treatment is unpredictable, limited, of short duration or carries the risk of serious adverse events. The administration of salbutamol for hyperkalaemia in children is described in several clinical trials and case reports.

Conclusion: Salbutamol, inhaled or infused, is safe and efficacious and results in a predictable and long-lasting reduction in serum potassium. Salbutamol merits a place as the preferred medication for hyperkalaemia in children without arrhythmias. If follow-up with haemodialysis is required, the administration of salbutamol gives time to make the necessary preparations.     

Nocturnal hypoglycaemia and sleep disturbances in young teenagers with insulin dependent diabetes mellitus

OBJECTIVE: To determine the effect of nocturnal hypoglycaemia on sleep architecture in adolescents with insulin dependent diabetes mellitus (IDDM). DESIGN: 20 adolescents with IDDM (mean age 12.8 years, mean glycated haemoglobin (HbA1c) 8.9%) were studied on one night. Plasma glucose was measured every 30 minutes and cortisol and growth hormone levels every 60 minutes. Sleep was recorded using standard polysomnographic montages, and sleep architecture was analysed for total sleep time, stages 1-4, rapid eye movement, fragmentation, and arousals. RESULTS: Six subjects (30%) became hypoglycaemic (five subjects < 2.5 mmol/l), with one being symptomatic. There were no differences in age, HbA1c, duration of diabetes, or insulin regimen between hypoglycaemic and non-hypoglycaemic subjects. Hypoglycaemia was not predicted by glucose measurements before bed. There was no detectable rise in plasma cortisol or growth hormone concentrations during hypoglycaemia. Sleep architecture was not disturbed by nocturnal hypoglycaemia with no differences found in sleep stages, fragmentation, or arousals. CONCLUSIONS: Nocturnal hypoglycaemia is a common and usually asymptomatic complication of treatment in adolescents with IDDM. Moderate hypoglycaemia has not been shown to affect sleep architecture adversely. These findings are consistent with, and may explain, the observation that severe hypoglycaemia, with consequent seizure activity, is more common at night than during the day. Counterregulatory hormone responses to nocturnal hypoglycaemia may be less marked than with similar degrees of diurnal hypoglycaemia.     

肝素使用和监控指南

1 肝素类药物的基本特性 1.1 肝素的化学性质肝素是天然氨基葡聚糖,由肥大细胞产生。药用的肝素由猪或牛的黏膜中提取。肝素由糖醛酸链和葡糖胺链交替组成, 含多少不等的硫酸根,相对分子质量5 ku～35 ku。现在使用     

Voluntary and involuntary adaptation of gait in Parkinson's disease

Voluntary and involuntary adaptation of gait in Parkinson's disease (PD) were studied in two separate experiments. In the first experiment, effects of changes in voluntary control were studied by asking PD patients and age-matched healthy subjects to adapt their walking pattern to visual cues resulting in spatial constraints, and auditory cues resulting in temporal constraints on stepping movements. In the second experiment, the adaptation to increases in speed during overground and treadmill walking was studied. Most patients were able to adapt their walking patterns in accordance with instructions. Notwithstanding consistent differences in step length, the adaptation to different conditions under study was highly similar in PD patients and healthy subjects. Only during walking with visually guided step length were the observed adaptations in PD patients less consistent. Contrary to these dissimilarities, the involuntary adaptation of timing of support and swing phases within the stride cycle was very similar between groups. In all conditions, only with changes in step length could a change in relative timing be observed. Our findings show that voluntary adaptation of gait is possible in PD and that basic involuntary coordination mechanisms are preserved. The observed disturbances in stride length regulation probably reflect an inability to perform fast movements in PD. Copyright 1998 Elsevier Science B.V.     

The survival motor neuron protein in spinal muscular atrophy

The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non- SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.