The murine Tcl1 oncogene: embryonic and lymphoid cell expression

In human leukemias and lymphomas nonrandom chromosomal rearrangements cause changes in cell growth and/or survival in such a way as to promote malignancy. The detailed study of the biochemical and genetic pathways altered in human cancer requires the identification or development of models to allow the study and manipulation of cancer gene function. Recently, the breakpoint gene TCL1, involved in chromosome translocations observed mostly in mature T-cell proliferations and chronic lymphocytic leukemias (CLL), was isolated and characterized, and showed to be part of a new gene family of proteins involved in these tumors. The murine Tcl1 gene, is similar in sequence to the murine and human MTCP1 gene also involved in T cell leukemias. The murine Tcl1 gene was shown to reside on mouse chromosome 12 in a region syntenic to human chromosome 14. Furthermore, we show that the murine Tcl1 gene is expressed early in mouse embryonic development and demonstrates expression in fetal hematopoietic organs as well as in immature T and B cells. Characterization of the murine Tcl1 gene will help in developing a mouse model of CLL and would provide the best opportunity to study and decipher the role of TCL1 in malignant transformation.     

Chorionic gonadotropin inhibits rat mammary carcinogenesis through activation of programmed cell death

Human chorionic gonadotropin (hCG) inhibits the progression of 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinomas. In order to determine whether this phenomenon was mediated by induction of programmed cell death or apoptosis, 45-day-old virgin Sprague-Dawley rats received 8 mg DMBA/100 g body weight; 20 days later they were injected daily with 100 IU hCG for 40 days (DMBA + hCG group). Age-matched untreated, hCG- and DMBA + saline treated rats were used as controls. Tissues were collected at the time of DMBA administration and at 5, 10, 20 and 40 days of hCG injection. RNA from mammary glands, adenocarcinomas and ovaries was probed for transforming growth factors (TGF) alpha and beta, and the apoptotic genes TRPM2, ICE, bcl2, bcl-XL, bcl-XS, p53 and c-myc. The mammary glands of hCG-treated animals with or without DMBA exhibited elevated expression of TRPM2, ICE, bcl-XS, c-myc and p53; and elevation in the apoptotic index. Mammary adenocarcinomas developed in those animals treated with hCG showed an elevation in the expression of p53, c-myc and ICE genes in comparison with the levels detected in the adenocarcinomas developed by the animals treated with DMBA alone. No significant alterations in the expression of any of the genes tested was observed in ovarian RNAs. These results led us to conclude that hCG induces programmed cell death in the mammary gland initiated in the carcinogenic process, that this process is p53 dependent, and is modulated by c-myc expression. Our data also indicate the possibility that a cell death program dependent on the bcl2 family exists, because of the potential involvement of p53, bcl-XS and Bax in apoptosis. This additional mechanism of tumor inhibition makes hCG treatment a useful approach for the prevention and therapy of breast cancer.     

Catheter-based radiotherapy to inhibit restenosis after coronary stenting

BACKGROUND: In animal models of coronary restenosis, intracoronary radiotherapy has been shown to reduce the intimal hyperplasia that is a part of restenosis. We studied the safety and efficacy of catheter-based intracoronary gamma radiation plus stenting to reduce coronary restenosis in patients with previous restenosis. METHODS: Patients with restenosis underwent coronary stenting, as required, and balloon dilation and were then randomly assigned to receive catheter-based irradiation with iridium-192 or placebo. Clinical follow-up was performed, with quantitative coronary angiographic and intravascular ultrasonographic measurements at six months. RESULTS: Fifty-five patients were enrolled; 26 were assigned to the iridium-192 group and 29 to the placebo group. Angiographic studies were performed in 53 patients (96 percent) at a mean (+/-SD) of 6.7+/-2.2 months. The mean minimal luminal diameter at follow-up was larger in the iridium-192 group than in the placebo group (2.43+/-0.78 mm vs. 1.85+/-0.89 mm, P=0.02). Late luminal loss was significantly lower in the iridium-192 group than in the placebo group (0.38+/-1.06 mm vs. 1.03+/-0.97 mm, P=0.03). Angiographically identified restenosis (stenosis of 50 percent or more of the luminal diameter at follow-up) occurred in 17 percent of the patients in the iridium-192 group, as compared with 54 percent of those in the placebo group (P= 0.01). There were no apparent complications of the treatment. CONCLUSIONS: In this preliminary, short-term study of patients with previous coronary restenosis, coronary stenting followed by catheter-based intracoronary radiotherapy substantially reduced the rate of subsequent restenosis.     

Toxicological effects of beryllium on platelets and vascular endothelium

The crystal structure of rabbit muscle pyruvate kinase complexed with Mn2+, K+, and pyruvate revealed a binding site of K+ [T. M. Larsen, L. T. Laughlin, H. M. Holden, I. Rayment, and G. H. Reed (1994) Biochemistry 33, 6301-6309]. Sequence comparisons of rabbit muscle pyruvate kinase and pyruvate kinases from Corynebacterium glutamicum and Escherichia coli, which do not exhibit a requirement for activation by monovalent cations, indicate that the only substitutions in the K+ binding site are conservative. Glu 117 in the rabbit muscle enzyme, which is close to the K+ site, is, however, replaced by Lys in these two bacterial pyruvate kinases. The proximity of Glu 117 to K+ in the structure of the rabbit enzyme and conservation of the binding site in the bacterial enzymes which lack a dependence on monovalent cations suggested that a protonated epsilon-amino group of Lys 117 in these bacterial enzymes may provide an "internal monovalent cation." Site-specific mutant forms of the rabbit enzyme corresponding to E117K, E117A, E117D, and E117K/K114Q pyruvate kinase were examined to test this hypothesis. The E117K pyruvate kinase exhibits 12% of the activity of the fully activated wild-type enzyme but is > 200-fold more active than the wild-type enzyme in the absence of activating monovalent cations. Moreover, the activity of E117K pyruvate kinase exhibits no stimulation by monovalent cations in the assay mixtures. Both E117A and E117D pyruvate kinases retain activation by monovalent cations but have reduced activities relative to wild type. The results are consistent with the hypothesis that pyruvate kinases that do not require activation by monovalent cations supply an internal monovalent cation in the form of a protonated epsilon-amino group of Lys. The results also support the assignment of the monovalent cation in the active site of pyruvate kinase.     

Myringoplasty in children: factors influencing surgical outcome

Experiments were designed to evaluate whether guanosine 3',5'-cyclic monophosphate (cGMP)-mediated mechanisms contribute to vasodilation via propofol in rat mesenteric resistance arteries. Ring segments were suspended in the myograph system for isometric tension recording, and responses to propofol were tested in the presence and absence of methylene blue (MB), an inhibitor of guanylate cyclase. At concentrations > or = 1 microM, propofol caused concentration-dependent relaxation of vessel rings precontracted with U46619 (a thromboxane analog). The effect was not affected by N-monomethyl-L-arginine (L-NMMA; 50 microM). MB (5 microM) reversed propofol-induced vasodilation by 30% (p < 0.001). In contrast, MB has no effect on nifedipine-inhibited vasocontraction. The propofol-induced relaxation was further tested in rings incubated in Ca2+-free solution. U46619-induced contractions were significantly reduced by propofol (40 microM) but not by nifedipine (1 microM). Propofol reduced to a similar degree the contractions obtained to exogenously added calcium chloride in the absence and the presence of MB. Furthermore, propofol (10-100 microM) increased cGMP content in cultured bovine vascular smooth-muscle cells. Soluble guanylate cyclase inhibitors, such as MB and LY83583, attenuated this effect. This investigation suggests that propofol-induced relaxations in small arteries, in addition to inhibition of calcium influx, are mediated by increases of cGMP in the smooth muscle cells.     

Evaluation and characterization of micronuclei in early spermatids of mice exposed to 1,3-butadiene

The 18S rRNA gene (Rns) phylogeny of Acanthamoeba is being investigated as a basis for improvements in the nomenclature and taxonomy of the genus. We previously analyzed Rns sequences from 18 isolates from morphological groups 2 and 3 and found that they fell into four distinct evolutionary lineages we called sequence types T1-T4. Here, we analyzed sequences from 53 isolates representing 16 species and including 35 new strains. Eight additional lineages (sequence types T5-T12) were identified. Four of the 12 sequence types included strains from more than one nominal species. Thus, sequence types could be equated with species in some cases or with complexes of closely related species in others. The largest complex, sequence type T4, which contained six closely related nominal species, included 24 of 25 keratitis isolates. Rns sequence variation was insufficient for full phylogenetic resolution of branching orders within this complex, but the mixing of species observed at terminal nodes confirmed that traditional classification of isolates has been inconsistent. One solution to this problem would be to equate sequence types and single species. Alternatively, additional molecular information will be required to reliably differentiate species within the complexes. Three sequence types of morphological group 1 species represented the earliest divergence in the history of the genus and, based on their genetic distinctiveness, are candidates for reclassification as one or more novel genera.     

Age differences and the identity negative priming effect: An updated meta-analysis.

A recent meta-analysis (P. Verbaeghen & L. De Meersman, 1998a) revealed that older adults show a reliable but significantly reduced negative priming effect compared with young adults. The present study provides an updated quantitative review on the effect of aging on the magnitude of the negative priming effect in identity tasks. This analysis demonstrated that the negative priming effect was not significantly different between young and old adults. This result differs from P. Verhaeghen and L. De Meersman's study. The implications of this finding for inhibitory-based theories of cognitive aging are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Negative myoclonic status due to antiepileptic drug tapering: report of three cases

PURPOSE: Epileptic negative myoclonus (ENM) has been increasingly recognized in different epilepsies, but the reasons for its appearance and prognosis remain uncertain. We report 3 patients who developed de novo, almost continuous ENM, triggered by antiepileptic drug (AED) tapering, that resolved with treatment. METHODS: Three patients aged 16, 19, and 65 years with a 13- to 36-year history of partial epilepsy were receiving a therapeutic dosage of carbamazepine or phenobarbital plus either clobazam (CLB) or valproate (VPA). None had previously had ENM. Forty-eight to 72 h after CLB or VPA withdrawal, the habitual seizures recurred. The patient also began to report repetitive postural lapses of one or more limbs that interfered with eating or writing. At this time, each patient underwent polygraphy with simultaneous surface electromyography (EMG) of deltoid, biceps, and triceps muscles and of the wrist extensor and flexor bilaterally. RESULTS: In all patients, EEGs demonstrated almost continuous epileptiform discharges whose spatial distribution was similar to that observed before ENM appearance. Polygraphic recordings showed repetitive loss of postural EMG activity in one or more limbs, 100-400 ms in duration, which occurred in conjunction with the spike-waves. One milligram of clonazepam intravenously always terminated ENM status, which has not recurred in the ensuing 9-36 months. CONCLUSIONS: ENM may emerge as a new type of seizure due to tapering of AED therapy. This effect is possibly related to the great activation of epileptiform activity with consequent interference with cortical activity.     

Role of p53 gene in colorectal neoplasms

A prospective study on the role of the p53 gene in sporadic colorectal neoplasms is presented and the level of mutant p53 protein was measured in the tissue removed during colonoscopy from: patients previously operated for colorectal malignant neoplasms, patients with active neoplasms, first degree relatives and during regular checks. 72% of patients with an active tumour showed a positive p53 and 38% in follow-up checks. Longer follow-up periods and a major number of patients are necessary to assess the prognostic importance of the p53 protein.