High IKZF1/3 protein expression is a favorable prognostic factor for survival of relapsed/refractory multiple myeloma patients treated with lenalidomide

The aim of this study is to assess nucleoprotein expression of IKZF1/3 in patients with relapsed/refractory multiple myeloma (MM) who received lenalidomide-based therapy and correlated them with their clinical outcomes. A total of 50 patients diagnosed with MM were entered in the study with the median follow-up of 86.4 months. By immunohistochemistry (IHC), IKZF1 and IKZF3 were expressed in 72 and 58% of the cases, respectively. IKZF1 and IKZF3 expressions were associated with longer median progression free survival (P?=?0.0029 and P?<?0.0001) and overall survival (P?=?0.0014 and P?<?0.0001). IKZF3 expression also appears predicted a favorable response to the lenalidomide-based therapy.     

Infrared spectroscopy and differential scanning calorimetry studies of binary combinations of cis-6-octadecenoic acid and octadecanoic acid

Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies are reported for combinations of cis-6-octadecenoic acid (also termed petroselinic acid, PSA) and octadecanoic acid (also termed stearic acid, SA) across a wide range of binary mole ratio combinations. The data are then used to plot the phase diagram which is found to be montotectic with the PSA reducing the melting temperature of SA at all compositions. The relevance of these experiments to stratum corneum (SC) biophysical behavior, particularly the influence and potential mechanisms of PSA on dermal permeation, is discussed. The potential role of cis-6-octadecenoic acid as a permeation enhancer is discussed in the context of these studies of its interaction with saturated fatty acids.     

Inhibitors of HIV protease: Unique non-peptide active site templates

New templates were designed and prepared which straddle the active site of HIV-1 protease. These templates were designed to be ‘flexible scaffolds’ upon which substituents could be appended to fill the pockets of HIV protease. The new templates prepared and analysed were 4-hydroxy-5H-furan-2-ones, 4-hydroxy-5,6-dihydropyrones, 3-hydroxy-cyclohex-2-enones, and 4-hydroxy-2(1H)-pyridinones, of which the 4-hydroxy- 5,6-dihydropyrones were found to be the most potent inhibitors of HIV-1 protease.     

Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol ester dietary challenge

Twelve obligate heterozygotes from two kindreds were ascertained through phytosterolemic probands homozygous for molecular defects in the ATP binding cassette (ABC) half transporter, ABCG8. The response of these heterozygotes to a Step 1 diet low in fat, saturated fat, and cholesterol, and to 2.2 g daily of plant sterols (as esters) was determined in Protocol I (16 weeks) and Protocol II (28 weeks) during three consecutive feeding periods: Step 1/placebo spread; Step 1/plant sterol spread; and Step 1/placebo spread (washout). At baseline, half the heterozygotes had moderate dyslipidemia and one-third had mildly elevated campesterol and sitosterol levels. On the Step 1/placebo spread, mean LDL cholesterol decreased significantly, 11.2% in Protocol I (n = 12), and 16.0% in Protocol II (n = 7). Substitution with plant sterol spread produced a significant treatment effect on LDL levels in Protocols I and II. Conversely, the mean levels of campesterol and sitosterol increased 119% and 54%, respectively, during the use of plant sterol spread for 6 weeks in Protocol I, an effect mirrored for 12 weeks in Protocol II. During the placebo spread washouts, LDL levels increased, while those of plant sterols decreased to baseline levels in both protocols. In conclusion, phytosterolemic heterozygotes respond well to a Step 1 diet, and their response to a plant sterol ester challenge appears similar to that observed in normals.     

Determination, diversification and multipotency of mammalian myogenic cells

In amniotes, myogenic commitment appears to be dependent upon signaling from neural tube and dorsal ectoderm, that can be replaced by members of the Wnt family and by Sonic hedgehog. Once committed, myoblasts undergo different fates, in that they can differentiate immediately to form the myotome, or later to give rise to primary and secondary muscle fibers. With fiber maturation, satellite cells are first detected; these cells contribute to fiber growth and regeneration during post-natal life. We will describe recent data, mainly from our laboratory, that suggest a different origin for some of the cells that are incorporated into the muscle fibers during late development. We propose the possibility that these myogenic cells are derived from the vasculature, are multi-potent and become committed to myogenesis by local signaling, when ingressing a differentiating muscle tissue. The implications for fetal and perinatal development of the whole mesoderm will also be discussed.     

Weight loss maintenance following a primary care intervention for low-income minority women

Although the primary care setting offers an innovative option for weight loss interventions, there is minimal research examining this type of intervention with low-income minority women. Further, there is a lack of research on the long-term effects of these programs. The purpose of this investigation was to examine the weight loss maintenance of low-income African-American women participating in a primary care weight management intervention. A randomized controlled trial was conducted with overweight and obese women (N = 144) enrolled at two primary care clinics. Women received a 6-month tailored weight loss intervention delivered by their primary care physician and completed follow-up assessments 9, 12, and 18 months following randomization. The weight loss maintenance of the tailored intervention was compared to a standard care comparison group. The weight loss of intervention participants (-1.52 +/- 3.72 kg) was significantly greater than that of standard care participants (0.61 +/- 3.37 kg) at month 9 (P = 0.01). However, there was no difference between the groups at the 12-month or 18-month follow-ups. Participants receiving a tailored weight loss intervention from their physician were able to maintain their modest weight loss up to 3-6 months following treatment. Women demonstrated weight regain at the 18-month follow-up assessment, suggesting that more intensive follow-up in the primary care setting may be needed to obtain successful long-term weight loss maintenance.     

The DNA deaminase activity of human APOBEC3G is required for Ty1, MusD, and human immunodeficiency virus type 1 restriction

Human APOBEC3G and several other APOBEC3 proteins have been shown to inhibit the replication of a variety of retrotransposons and retroviruses. All of these enzymes can deaminate cytosines within single-strand DNA, but the overall importance of this conserved activity in retroelement restriction has been questioned by reports of deaminase-independent mechanisms. Here, three distinct retroelements, a yeast retrotransposon, Ty1, a murine endogenous retrovirus, MusD, and a lentivirus, human immunodeficiency virus type 1 (HIV-1), were used to evaluate the relative contributions of deaminase-dependent and -independent mechanisms. Although human APOBEC3G can restrict the replication of all three of these retroelements, APOBEC3G lacking the catalytic glutamate (E259Q) was clearly defective. This phenotype was particularly clear in experiments with low levels of APOBEC3G expression. In contrast, purposeful overexpression of APOBEC3G-E259Q was able to cause modest to severe reductions in the replication of Ty1, MusD, and HIV-1(ΔVif). The importance of these observations was highlighted by data showing that CEM-SS T-cell lines expressing near-physiologic levels of APOBEC3G-E259Q failed to inhibit the replication of HIV-1(ΔVif), whereas similar levels of wild-type APOBEC3G fully suppressed virus infectivity. Despite the requirement for DNA deamination, uracil DNA glycosylase did not modulate APOBEC3G-dependent restriction of Ty1 or HIV-1(ΔVif), further supporting prior studies indicating that the major uracil excision repair system of cells is not involved. In conclusion, the absolute requirement for the catalytic glutamate of APOBEC3G in Ty1, MusD, and HIV-1 restriction strongly indicates that DNA cytosine deamination is an essential part of the mechanism.