Murine thymic lymphoma is associated with a species-specific hematopoietic progenitor cell subpopulation

Many strains of laboratory mouse are uniquely susceptible to the development of T cell lymphoma/leukemia, either spontaneously or as a result of chemical or radiation exposure. In contrast, T cell leukemias or lymphomas which are relatively uncommon in human populations, are not easily induced by radiation, and are not generally associated with chemotherapy or chemical exposure. Evidence is presented to suggest that differences in the susceptibility to the development of these malignancies is related to subtle but important variations in the regulation of hematopoietic stem cell differentiation between these two species.     

Identification of in vitro phosphorylation sites in the growth cone protein SCG10. Effect Of phosphorylation site mutants on microtubule-destabilizing activity

SCG10 is a neuron-specific, membrane-associated protein that is highly concentrated in growth cones of developing neurons. Previous studies have suggested that it is a regulator of microtubule dynamics and that it may influence microtubule polymerization in growth cones. Here, we demonstrate that in vivo, SCG10 exists in both phosphorylated and unphosphorylated forms. By two-dimensional gel electrophoresis, two phosphoisoforms were detected in neonatal rat brain. Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A, Ser-62 and Ser-73 for mitogen-activated protein kinase and Ser-73 for cyclin-dependent kinase. We also show that overexpression of SCG10 induces a disruption of the microtubule network in COS-7 cells. By expressing different phosphorylation site mutants, we have dissected the roles of the individual phosphorylation sites in regulating its microtubule-destabilizing activity. We show that nonphosphorylatable mutants have increased activity, whereas mutants in which phosphorylation is mimicked by serine-to-aspartate substitutions have decreased activity. These data suggest that the microtubule-destabilizing activity of SCG10 is regulated by phosphorylation, and that SCG10 may link signal transduction of growth or guidance cues involving serine/threonine protein kinases to alterations of microtubule dynamics in the growth cone.     

Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.     

Construction of recombination-deficient strains of Streptococcus gordonii by disruption of the recA gene

Degenerate oligonucleotide primers were used in a polymerase chain reaction (PCR) to amplify a region of the recA sequence of Streptococcus gordonii Challis. The resulting PCR fragment was cloned into the suicide vector pAM6199 and introduced into strain Challis, giving rise to recombination-deficient strains in which the recA gene was specifically inactivated.     

The current aspects of seroepidemiological research in combined foci of leishmaniasis

The accuracies of ultrasonography (US) and computed tomography (CT) for determining tumor invasion of the chest wall in lung cancer were compared in a retrospective study of 120 patients. US findings were evaluated preoperatively according to the following criteria: disruption of pleura, extension through the chest wall, and fixation of tumor during breathing. CT findings were evaluated with the following criteria: obtuse angle of the mass to the pleural surface, more than 3 cm contact with the pleural surface, and visible pleural thickening associated with the mass. Chest wall invasion was judged as positive when at least two of the three findings were present with either technique. Nineteen of the 120 patients had chest wall invasion by tumor. The sensitivity of US was 100% and the specificity was 98%. The sensitivity of CT was 68% and the specificity was 66%. The accuracy of US and CT were 98% and 67%, respectively.     

Non-destructive testing of rock bolts using guided ultrasonic waves

The research outlined in this paper is aimed at the development of a portable non-destructive testing instrument for evaluating the condition of rock bolts. In applications such as coal mine roof reinforcement, the opportunities for rock bolt inspection are currently limited to destructive techniques such as the pull-out test. It is proposed that guided ultrasonic waves can be used to solve this inspection problem, using a pulse-echo test carried out from the free end of the bolt. Suitable test frequencies have been identified through the use of modelling software, and successful laboratory and site trials have been undertaken. The research has shown that the proposed approach is capable of determining the bolt length, and of identifying major defects such as necking, deformation, and loss of resin encapsulation.     

Metastatic parathyroid carcinoma in the MEN2A syndrome

We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.     

Bufferless broadcasting: a low power distributed circuit techniquefor broadcasting 10-Gb/s chip input signals

Bufferless distributed circuit (BDC) broadcasting is proposed as a technique for broadcasting high-speed chip input signals to a series of on-chip destination cells as needed in crosspoint switch, parallel multiplier, distributed amplifier, etc., chip designs. In contrast with conventional techniques that use an on-chip buffer to assist broadcasting, BDC broadcasting offers the advantage of lower signal delay and power dissipation. In an experimental GaAs heterojunction bipolar transistor (HBT) 8×4 crosspoint switch assembly, BDC broadcasting was found to achieve a 40% power savings with little or no penalty in jitter or bit error rate performance at a 10-Gb/s data rate     

Electroconvulsive therapy of acute manic episodes: a review of 50 years' experience

OBJECTIVE: The most common indication for electroconvulsive therapy (ECT) is major depression. It is less recognized that ECT is effective also in the treatment of acute mania. This article aims to provide a comprehensive and critical review of the literature on the use of ECT for manic patients. METHOD: All published papers in the English language on the use of ECT in acute mania that could be found were reviewed with regard to efficacy, frequency and number of treatments, bilateral versus unilateral electrode placement, predictors of antimanic response, stability of therapeutic response, cognitive consequences, and other relevant issues. RESULTS: The evidence indicates that ECT is associated with remission or marked clinical improvement in 80% of manic patients and that it is an effective treatment for patients whose manic episodes have responded poorly to pharmacotherapy. Manic patients do not require a high frequency or prolonged course of treatments to respond to ECT. The seizure threshold appears to be lower in manic patients than in depressed patients. The issues of relapse following response to ECT, cognitive consequences of ECT, and the relative merits of unilateral versus bilateral ECT in manic patients require further study. CONCLUSIONS: ECT is an effective and safe treatment for acute mania. Remission of mania following ECT reflects a primary therapeutic effect rather than a secondary consequence of an ECT-induced organic brain syndrome.     

Expansion in bioreactors of human progenitor populations from cord blood and mobilized peripheral blood

Umbilical cord blood (UCB) and mobilized peripheral blood (MPB) provide an alternate source to bone marrow for transplantation. Expansion in vitro of stem/progenitor cell populations from these sources may provide adult-sized grafts otherwise not attainable because of the limited cell numbers available in the case of UCB or because of numerous rounds of apheresis required for sufficient MPB cells. We asked whether continuous perfusion culture could be employed in ex vivo expansion to produce clinically relevant numbers of stem/progenitor cells from these sources. To evaluate MPB, 1-10 million leukocytes, from patients who had received either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF), were inoculated into bioreactors, with or without irradiated, allogeneic stroma. The growth factor combination in the perfusion medium consisted of interleukin-3 (IL-3), stem cell factor (SCF), GM-CSF and erythropoietin (Epo). Under the best conditions tested, total cell numbers, granulocyte-macrophage colony-forming units (CFU-GM), and long-term culture-initiating cell (LTC-IC) populations were expanded by about 50-, 80-, and 20-fold, respectively, over 14 days. At low cell inocula (1 million), the presence of stroma enhanced the expansion of total cells and CFU-GM but not of LTC-IC. When SCF was not included in the medium, both total cells and CFU-GM expanded to a much lesser extent, but again the expansion of LTC-IC was not affected. At the higher cell inoculum (10 million), expansions of total cells and CFU-GM were equivalent with or without stroma. To evaluate UCB, cells were placed into bioreactors with or without irradiated, allogeneic stroma, and the bioreactors were perfused with medium containing the four standard growth factors. After 6-14 days, in several independent experiments, 20-24 million cells were harvested from bioreactors perfused with SCF-containing medium, irrespective of the presence or absence of preformed stroma. Similarly, in reactors perfused with SCF-containing medium (with or without stroma), an average 40- to 60-fold expansion of CFU-GM was obtained, yielding an average of 1.5-1.8 x 10(5) CFU-GM per reactor. Harvested cells were thus up to 40-fold enriched in CFU-GM in comparison to the inoculum. In the absence of SCF, cell expansions averaged 1.5- to 2-fold, and CFU-GM were expanded only 10- to 14-fold by day 14. As before, the presence of preformed stroma did not affect either cell or CFU-GM yields, provided the cell inoculum was at least 4.5 million cells.(ABSTRACT TRUNCATED AT 400 WORDS)