Acquired homozygosity of the rearranged bcr allele during the acute leukemic phase of a patient with Ph-negative chronic myeloid leukemia

A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML.     

Crossreaction of monoclonal Anti-T-cell antibodies: Implications for classifying B-cell leukemias

Summary Cell samples from 62 patients with B-cell leukemias (33 CLL, 8 IC, 6 PLL, 4 HCL, 2 ALL and 9 other NHL) were tested with a series of monoclonal antibodies (A50, T101, Lyt2, Leu1, M203) directed against T cells and shown to crossreact with B-CLL. The results demonstrate a heterogeneity of B-cell leukemias as all typical cases of CLL were reactive whereas most other cases were negative. Using the fluorescence-activated cell sorter, a somewhat stronger reaction was seen in early or benign cases of CLL, compared to advanced cases. All B-cell leukemias tested expressed the Ia antigen.     

Hepatic apoptosis and proliferation in male and female rats fed alcohol: role of cytokines

Background: The female liver is more sensitive to the toxic effect of chronic alcohol intake than the male liver. The aim of the study was to compare the influence of gender and sex hormonal status on apoptosis and cell proliferation following chronic ethanol intake.
Methods: Male and female rats were pair fed for 8 weeks a liquid diet containing 36% of their total daily calories as ethanol (ETOH group) or sucrose (control group). Liver samples were analyzed for apoptosis and hepatocyte proliferation by immunohistochemistry. The hepatic production of factors able to influence cell death and proliferation, such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) were determined.
Results: In both male and female rats, ethanol intake promoted apoptosis in the liver. This effect of ethanol was more evident in female than male rat livers. Hepatic TNFα levels, which promote apoptosis, are significantly more elevated in female than in male livers. Hepatic IL-6 production, which promotes hepatocyte proliferation, was induced by ethanol only in males, but not female animals.
Conclusion: This observed difference in cytokine responses may contribute to the enhanced sensitivity of female liver to EtOH-induced injury.     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.     

Results of the systematic application of ventricular stimulation methods

This study was undertaken to test the validity of methods of evaluating ventricular tachycardia and in therapeutic surveillance. One hundred and thirty nine patients aged 16 to 84 years, with and without severe ventricular arrhythmias (ventricular tachycardia, VT, and fibrillation, VF) were divided into two groups after clinical, echocardiographic and 24 hour Holter investigations: Group I comprised 26 patients with a least one documented attack of VT or VF; Group II comprised 113 patients without these arrhythmias, who complained of dizziness, syncope, and/or their ECG showed a conduction defect, and so electrophysiological investigation was undertaken. A protocol of ventricular stimulation was undertaken in addition to the usual measurements of conduction times, comprising incremental ventricular stimulation from 100 to 200/min, single and paired extrastimulus in sinus rhythm and during ventricular pacing at rates of 100 and 150/min, the first extrastimulus being programmed 10 ms after the end of the ventricular effective refractory period. Excluding bundle to bundle reentry, the following results were obtained: In Group I: VT was triggered 16 times (61,5 p. 100), and in 4 of these cases VF occurred and required defibrillation. Ten patients had previous myocardial infarction; 5 patients had left ventricular dilatation. In 2 cases runs of 3 or 4 VES were recorded. No arrhythmia could be induced in 8 cases (30,8 p. 100); 5 of these patients had apparently normal hearts. In Group II: VT (greater than 5 VES) was triggered in 22 cases (19,5 p. 100) and in 4 cases this degenerated to VF requiring defibrillation. 11 patients had apparently normal hearts; 6 patients had left ventricular dilatation and 4 patients had previous myocardial infarction. 1 to 4 repetitive VES were observed in 67 cases (59,3 p. 100): the heart was judged to be normal in all patients except those with previous infarction. No correlation was established between the ability to induce VT and age, syncope, or ECG changes (especially bundle branch block). However, a correlation was found between the induction of VT and underlying cardiac disease and the method of induction of VT; in Group II, all episodes of VT were triggered by delivering paired ventricular extrastimuli on a background paced rhythm. These results show that repetitive ventricular responses can easily be triggered and that this has no pathological significance.(ABSTRACT TRUNCATED AT 400 WORDS)