Sodium current-induced calcium signals in isolated guinea-pig ventricular myocytes.

1. Na+ current (INa)-induced Ca2+ transients were studied in ventricular myocytes isolated from adult guinea-pig hearts. The fluorescent Ca2+ indicator fluo-3 or a mixture of fluo-3 and fura-red were used in conjunction with confocal microscopy to follow the intracellular Ca2+ concentration while membrane currents were measured simultaneously with the whole-cell configuration of the patch-clamp technique. 2. Ca2+ release from the sarcoplasmic reticulum (SR) could be triggered either by Ca2+ current (ICa) or Na+ current (INa). Analysis of INa-induced Ca2+ signals at higher temporal resolution revealed a faster upstroke of these transients when compared with those triggered by ICa. 3. In the presence of 20 microM ryanodine to block SR Ca2+ release ICa elicited a verapamil-sensitive Ca2+ transient with a slow upstroke. INa also induced a residual Ca2+ transient that was insensitive to 10 microM verapamil and characterized by a rapid upstroke. 4. The existence of a residual Ca2+ transient in the absence of SR Ca2+ release and L-type ICa indicates that INa is indeed able to evoke an increase in [Ca2+]i without uncontrolled activation of Ca2+ channels. 5. Substitution of extracellular Na+ by Li+ suppressed INa-induced Ca2+ transients, suggesting that the Ca2+ release and the residual Ca2+ transient can only be elicited by influx of Na+ and not by Li+. This result supports the notion that both the residual Ca2+ transient as well as the INa-induced Ca2+ release are mediated by the Na(+)-Ca2+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)     

伴近视的鞍区肿瘤眼部病变特点

目的：探讨近视患者的鞍区肿瘤眼部病变的临床特点。方法：回顾分析了18例伴近视的鞍区肿瘤的视力、视野及眼底等情况。结果：18例初诊时,19眼（占52.8%）视力低下4.0,仅5例（占27.8%）视野缺损呈典型的视交性单、双颞侧偏盲,10例（占55.6%）双眼视神经不同程度萎缩,4例（占22.2%）单眼视神经萎缩。结论：伴近视的鞍区肿瘤眼部病变常很严重,容易被误诊为青光眼性视神经萎缩,视乳头炎、缺血性视神经病变。     

The MLL recombinome of acute leukemias.

Chromosomal rearrangements of the human MLL gene are a hallmark for aggressive (high-risk) pediatric, adult and therapy-associated acute leukemias. These patients need to be identified in order to subject these patients to appropriate therapy regimen. A recently developed long-distance inverse PCR method was applied to genomic DNA isolated from individual acute leukemia patients in order to identify chromosomal rearrangements of the human MLL gene. We present data of the molecular characterization of 414 samples obtained from 272 pediatric and 142 adult leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) was determined and several new TPGs were identified. The combined data of our study and published data revealed a total of 87 different MLL rearrangements of which 51 TPGs are now characterized at the molecular level. Interestingly, the four most frequently found TPGs (AF4, AF9, ENL and AF10) encode nuclear proteins that are part of a protein network involved in histone H3K79 methylation. Thus, translocations of the MLL gene, by itself coding for a histone H3K4 methyltransferase, are presumably not randomly chosen, rather functionally selected.     

Clinical study of FK506 in patients with myasthenia gravis

Focal demyelinating lesions typically occur within a 1-cm segment of a nerve. In electrodiagnostic studies, measurements over longer distances decrease the chance of detecting such lesions, but measurements over shorter distances result in greater experimental error. Our objective was therefore to determine the optimal screening distance for ulnar neuropathy at the elbow (UNE) incorporating previously derived experimental errors for calculating nerve conduction velocity (NCV). Using a lesion model wherein prolongation of 0.4 ms was added to the expected latency of a 1-cm nerve segment, new NCVs were derived for distances between 1 and 10 cm for nerves normally conducting between 40 and 65 m/s. Lesion detection, or sensitivity, was defined as the likelihood of calculating a decrease of 10 m/s from the normal NCV while including the experimental error. Specificity was related to the likelihood of an inadvertent calculation of such a decrease in NCV in a segment without a lesion. Sensitivity and specificity were derived at multiple distances with varying NCVs. The total percentage error was the sum of the false-negative and false-positive percentages. The least total percentage error occurred at 3-4 cm, 4-6 cm, and 6-8 cm for nerves normally conducting at 40-50 m/s, 50-60 m/s, and 60-65 m/s, respectively. We conclude that the optimal distance for screening UNE, considering both sensitivity and specificity, is significantly less than 10 cm, perhaps as low as 4-6 cm; considering in addition the likely locations of focal lesions, the best distance is 6-8 cm.     

Meningeal hemangiopericytoma in childhood

Meningeal hemangiopericytoma (MHP) is extremely rare in childhood. Mean age at diagnosis is between 38 and 43 years. We present an 8-year-old boy with MHP of the middle cranial fossa. Imaging findings were indistinguishable from an aggressive bone tumor such as Ewing's sarcoma. Imaging findings are presented and discussed. Our case indicates that MHP should be considered in the differential diagnosis of skull-base tumors despite the fact that MHP is extremely rare in childhood. Received: 8 July 1999; Revised: 28 September 1999; Accepted: 29 September 1999     

Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95

The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and long-term toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups. Estimated 6-year event-free survival (6y-pEFS) for all 2169 patients was 79.6% (± 0.9%). The large standard-risk (SR) group (35% of patients) achieved an excellent 6y-EFS of 89.5% (± 1.1%) despite significant reduction of anthracyclines. In the medium-risk (MR) group (53% of patients), 6y-pEFS was 79.7% (± 1.2%); no improvement was accomplished by the randomized use of additional intermediate-dose cytarabine after consolidation. Omission of preventive cranial irradiation in non–T-ALL MR patients was possible without significant reduction of EFS, although the incidence of central nervous system relapses increased. In the high-risk (HR) group (12% of patients), intensification of consolidation/reinduction treatment led to considerable improvement over the previous ALL-BFM trials yielding a 6y-pEFS of 49.2% (± 3.2%). Compared without previous trial ALL-BFM 90, consistently favorable results in non-HR patients were achieved with significant treatment reduction in the majority of these patients.