Effect of treatment with 13-cis-retinoic acid and ara-C on the hematopoietic stem cells of patients with myelodysplastic syndromes

PURPOSE: To assess the "in vivo" effect of 13-cis-retinoic acid and low dose Ara-C in MDS as well as to establish "in vitro" advantage of retinoid dose-related growth pattern on bone marrow cultures as defined by culture timing and CFU-GM proliferative response. PATIENTS AND METHODS: We evaluated 28 patients diagnosed of MDS according to FAB classification, of whom 4 cases had RA, 8 cases SRA, 14 cases RAEB and 2 cases RAEB-T. Patients who had RA and SRA were treated with oral 13-cis-retinoic acid at doses of 20-40 mg daily for 4 months and those cases with RAEB and RAEB-T had subcutaneous Ara-C at doses of 3 mg/m2 twice a day for 21 days. The "in vivo" and "in vitro" effect of retinoic acid on the haemopoietic differentiation was evaluated by the growth CFU-GM in semisolid cell culture methods. RESULTS: Increasing in vitro concentrations of 13-cis retinoic acid did not enhance the growth of myelodysplastic progenitors. Nevertheless, our study did not find any beneficial therapeutic effect of retinoic compounds in MDS patients. In this study, low-dose Ara-C (3 mg/m2) showed similar effects when compared with higher doses reported by others. Furthermore, in terms of CFU-GM proliferation the concentration of colonies before and after treatment were fairly similar in all but two patients. CONCLUSIONS: The results drawn from our study demonstrated that there is no beneficial advantage of 13-cis-retinoic acid as a differentiation inducing agent on myelodysplastic patients. In contrast, lower doses of Ara-C showed similar effects on haemopoiesis of MDS patients than standard doses of 10-20 mg/m2 but with less side effects.     

Calcium chloride in vitro effects on isolated myofibrillar proteins

The objective of this study was to determine the effect of 30 mM CaCl(2) on the solubilization of those structural proteins that contribute to myofibril stability. Ovine M. longissimus dorsi (longissimus) samples were obtained immediately post-exsanguination, myofibrils were isolated, glycerated, and frozen until needed. Myofibrils were washed, diluted and incubated in 0·1 m KCl, 10 mm Tris, pH 7·0 buffer for 24, 48 and 72 h. Treatments consisted of: (1) control, (2) 1 mm E(64), (3) 30 mm CaCl(2), and (4) 1 mm E(64) + 30 mm CaCl(2). Results (SDS-PAGE) indicated that myosin heavy chain (though not to a great extent), M-protein, C-protein, α-actinin, actin, troponin-T, tropomyosin isoforms, troponin-I and 72, 70, 62, 33, 32, 30, and 22 kDa unidentified bands were solubilized from myofibrils incubated in KCl buffer for 72 h. The addition of CaCl(2) hastened the appearance of some of the proteins in the supernatant fractions, but no differences were observed at 72 h among the treatments. The addition of E(64) had no effect on which proteins were released. Thus, in the absence of proteolysis it appears that a general solubilization of thick-and-thin filament ancillary proteins occurs in the presence of 30 mm CaCl(2). However, the contribution to tenderness should be minimal, because solubilized proteins are not part of the cytoskeletal elements that are responsible for maintaining structural integrity of the tissue.     

Simflowny: A general-purpose platform for the management of physical models and simulation problems

Simflowny is a software platform which aims to formalize the main elements of a simulation flow. It allows users to manage (i) formal representations of physical models based on Initial Value Problems (hyperbolic, parabolic and mixed-type partial differential equations), (ii) simulation problems based on such models, and (iii) discretization schemes to translate the problem to a finite mesh. Additionally, Simflowny generates automatically code for general-purpose simulation frameworks. This paper first presents an introductory example of such problems. Then, formal representations are explained. Afterwards, it summarizes the platform’s architecture. Finally, validation results are provided.     

Effect of pH and ionic strength on bovine m-calpain and calpastatin activity

The effects of bovine skeletal muscle m-calpain and calpastatin on the degradation of casein and isolated bovine myofibrils were characterized under various pH values (7.0, 6.2, 5.7) and ionic strengths (32 to 400 mM KCl) at 25 degrees C. Caseinolytic assays indicated that m-calpain activity increased with increasing pH (P < .01) but decreased with increasing ionic strength (P < .01). Regardless of the presence of m-calpain, SDS-PAGE of myofibrils showed increased solubilization of myofibrillar proteins as pH and ionic strength increased. However, only in the presence of m-calpain were changes normally observed during postmortem storage reproduced. Protein release attributed to m-calpain activity increased with pH, but the effects of elevated ionic strength on the ability of m-calpain to hydrolyze myofibrillar proteins were not evident from SDS-PAGE, except for the decreased troponin-T degradation by m-calpain at the higher ionic strengths. A pH x ionic strength interaction was observed for calpastatin activity determined by caseinolytic assays (P < .01). No changes in m-calpain inhibition were detected at pH 7.0 and 6.2 at different ionic strengths. However, at pH 5.7 the ability of calpastatin to inhibit m-calpain decreased with increasing ionic strength. No changes in m-calpain inhibition could be detected with SDS-PAGE. Based on these results, it can be concluded that although m-calpain and calpastatin activities decrease with increasing ionic strength, their activities in the presence of myofibrils were not affected by ionic strengths typically found in postmortem muscle.     

Chemical and thermal characterization of high‐ and low‐density irradiated polyethylenes

A comparative study of the dynamic mechanical relaxation spectra of high‐ and low‐density polyethylenes irradiated with γ‐radiation from a Co⁶⁰ source was performed. The irradiation doses ranged from 0 to 100 Mrad. All the samples were previously characterized by determination of the molecular weight distribution, the number of functional groups, and the crystalline fraction. All the relaxation zones between ?145°C and the melt were studied in the frequency range from 0.3 to 30 Hz. The changes observed in the mechanical relaxation spectra were related to modifications in the chemical structure and morphological parameters attributed to the exposure of the samples to the γ‐radiation. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1953–1958, 2002     

Parental attachment, self-esteem, and antisocial behaviors among African American, European American, and Mexican American adolescents.

This study examined the relation of mother and father attachment to self-esteem and self-reported involvement in antisocial behaviors among African American (n=488), European American (n=661), and Mexican American (n=434) high school students. The attachment dimensions of anxiety and avoidance were examined using self-report scales that were developed and validated with participants in the study. Findings indicated that adolescents from the 3 ethnic/racial groups did not differ greatly in their reported attachment to father and mother. Consistent with theoretical formulations, securely attached adolescents from the 3 ethnic groups had a more positive sense of self-esteem and reported less involvement in antisocial behaviors than their less securely attached peers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lymphocele: an unusual mass in the right upper quadrant

A patient with a palpable right upper abdominal mass eight years after cholecystectomy was found to have a subhepatic lymphocele. Although this is an uncommon location, the presence of a sonolucent mass in an area of previous surgery suggests lymphocele.     

It's in Your Nature: I'm Lost in Paris

R&Sie(n)'s installation I'm Lost in Paris (2008), a disturbing take on the ecological house, epitomises the preoccupation of the French architect François Roche with the contradictions of modern nature. Javier Arbona tracks how Roche's notion of nature as ‘a partly human artifice’ which is both alien and personalised play out in his various projects, capitulating between attempts at overcoming alienation and heightening it. Copyright © 2010 John Wiley & Sons, Ltd.