Hydrogenated fat diet intake during pregnancy and lactation modifies the PAI-1 gene expression in white adipose tissue of offspring in adult life

We examine whether feeding pregnant and lactating rats hydrogenated fats rich in trans fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 90-day-old offspring. Pregnant and lactating Wistar rats were fed with either a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). Upon weaning, the male pups were sorted into four groups: CC, mothers were receiving C and pups were kept on C; CT, mothers were receiving C and pups were fed with T; TT, mothers were receiving T and pups were kept on T; TC, mothers were receiving T and pups were fed with C. Pups' food intake and body weight were quantified weekly and the pups were killed at day 90 of life by decapitation. Blood and carcass as well as retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Food intake and body weight were lower in TC and TT, and metabolic efficiency was reduced in TT. Offspring of TT and TC rats had increased white adipose tissue PAI-1 gene expression. Insulin receptor was higher in TT than other groups. Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation could promote deleterious consequences, even after the withdrawal of the causal factor.     

The p53 codon 72 polymorphism and risk of high-grade cervical intraepithelial neoplasia

BACKGROUND: The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated in increasing susceptibility of the cervix to human papillomavirus (HPV) infection and thus altering cancer risk. However, research on this topic has been contentious, which prompted us to carry out a case-control study in the Montreal area. METHODS: Cases were women with histologically-confirmed high-grade cervical intraepithelial neoplasia (HGCIN). Controls were women without a history of cervical abnormalities. From each woman, we obtained a cervical specimen for HPV testing and p53 genotyping, and a questionnaire was completed. DNA sequencing was used to minimize genotype misclassification. A subsample of specimens was also genotyped using the TaqMan assay. RESULTS: There were 357 cases and 760 controls recruited between February 2001 and December 2003. The distribution of Arg/Arg, Arg/Pro and Pro/Pro was 55.2, 36.4 and 8.4%, respectively, among cases, and 52.1, 38.7 and 9.2%, among controls, corresponding to an odds ratio (OR) adjusted for ancestral origin of 1.16 (95% confidence interval (CI): 0.9-1.5) for Arg/Arg versus other genotypes. When restricted to high-risk HPV-positive women, the adjusted ORs were 1.40 (CI: 0.9-2.1) and 2.12 (CI: 1.1-4.2), for Arg/Arg versus other genotypes and versus Pro/Pro, respectively. The findings were comparable with analyses of genotype results that agreed between DNA sequencing and TaqMan. CONCLUSIONS: In this study, we attempted to minimize selection bias, population stratification and genotype misclassification. The results suggest that the role of the p53 codon 72 polymorphism on HGCIN is weak at best. Further research may reveal if the polymorphism has a stronger influence on the risk of invasive cervical cancer.     

The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene

Several tyrosine kinase genes are involved in chromosomal translocations in chronic myeloproliferative disorders, but there are still uncharacterized translocations in some cases. We report two such cases corresponding to atypical chronic myeloid leukaemia with a t(8;9)(p22;p24) translocation. By fluorescence in situ hybridisation (FISH) on the corresponding metaphases with a bacterial artificial chromosome probe encompassing the janus kinase 2 (JAK2) gene at 9p24, we observed a split for both patients, suggesting that this gene was rearranged. The locus at 8p22 contains different candidate genes including the pericentriolar material 1 gene (PCM1), already implicated in reciprocal translocations. The rearrangement of the PCM1 gene was demonstrated by FISH, for both patients. By RT-PCR, we confirmed the fusion of 3' part of JAK2 with the 5' part of PCM1. Sequence analysis of the chimeric PCM1-JAK2 mRNA suggests that the putative protein displays the coiled-coil domains of PCM1 and the tyrosine kinase domain of JAK2. This new translocation identifies JAK2 as a possible therapeutic target for compounds with anti-tyrosine kinase activity.     

Human T-cell leukemia virus type 1 molecular variants, Vanuatu, Melanesia

Four of 391 Ni-Vanuatu women were infected with variants of human T-cell leukemia virus type 1 (HTLV-1) Melanesian subtype C. These strains had env nucleotide sequences approximately 99% similar to each other and diverging from the main molecular subtypes of HTLV-1 by 6% to 9%. These strains were likely introduced during ancient human population movements in Melanesia.     

Nuclear size as a cell-kinetic marker for osteoblast differentiation

A nuclear morphometic assay for preosteoblasts is introduced as a cell-kinetic technique, applicable to routine histological preparations of mineralized tissue. Because this method is a morphological marker for osteoblast precursor cell differentiation, it provides a new dimension for determining the mechanism of osteoblast histogenesis. Osteoblast precursors of the periodontal ligament are a mixed population of progenitors, kinetically separable into two distinct groups according to nuclear size. Preosteoblasts, the immediate proliferating precursors of osteoblasts, have large nuclei (>170 μm³) and are derived from relatively undifferentiated fibroblastlike cells, which have smaller nuclei (<80 μm³). Increase in nuclear volume, during G ₁ phase of the cell cycle, is apparently a morphological manifestation of change in genomic expression. This key event in preosteoblast differentiation is related to mechanical stress/strain and may be an important rate-limiting step in osteoblast histogenesis.     

Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation

OBJECTIVE: Regulatory CD4 T cells that express high levels of CD25 play a vital role in the maintenance of tolerance to self antigens and are required for the induction of nonresponsiveness to alloantigens. The long-term CD4+CD25high T-cell reconstitution after allogeneic stem cell transplantation is unknown. Here, we evaluated whether recovery of this T-cell subset might be linked to the establishment of full donor/recipient tolerance. METHODS: The frequency of CD4+CD25high T cells was determined by Fluorescence Activated Cell Sorter (FACS) analysis in 31 patients, with a mean follow-up of more than 31 months posttransplant. The expression levels of Foxp3 mRNA were assessed by quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: Patients with or without graft-versus-host disease (GvHD) had significant and persistent CD4 T-cell lymphopenia. The relative frequency of CD25high cells and the expression levels of FoxP3 mRNA within this subset were similar between all patients and healthy controls. No significant difference was found in the number of Foxp3-expressing CD4+CD25high T cells in patients with or without GvHD. Finally, younger age and absence of previous GvHD were significantly linked to CD4+CD25high T-cell recovery. CONCLUSION: The low number of Foxp3-expressing CD4+CD25high T cells in grafted patients is not a specific default of this compartment but a consequence of global CD4 T-cell lymphopenia after allogeneic stem cell transplantation. Moreover, levels of Foxp3 mRNA in the CD25+ T-cell compartment do not allow predicting the development of GvHD in the long term.     

Performance of asialotransferrin in detecting alcohol abuse

BACKGROUND: The spectrum of alcohol use disorders covers hazardous use, alcohol abuse, and alcohol dependence. The present study evaluated the performance of asialotransferrin, a newly proposed biomarker for alcohol use disorders, in detecting alcohol abuse and alcohol dependence. METHOD: A 4-month trial was conducted in three groups of participants: alcohol abusers and alcohol-dependent patients, as defined in DSM-IV, and a control group. Asialotransferrin was assayed by capillary zone electrophoresis. RESULTS: Asialotransferrin demonstrated a sensitivity of 0.34 and a specificity of 1.00 for alcohol abuse. The sensitivity of asialotransferrin increased to 0.57 in alcohol-dependent patients. CONCLUSION: Despite the high specificity of asialotransferrin in alcohol use disorders, its sensitivity is too low to make it a useful marker of alcohol abuse.     

Structure-activity relationships of dengue antiviral polycyclic quinones

The virucidal and antiviral photoactivities of three compounds, hypericin, tetrabromohypericin and gymnochrome B, were evaluated against dengue viruses. All the three products were active, and both the virucidal and antiviral activities were enhanced by light. Gymnochrome B was more potent than hypericin and tetrabromohypericin. The presence of the side chains on the hypericin core of gymnochromes appears to be beneficial for both virucidal and antiviral activities. This enhanced activity is likely to be linked to a complementary mechanism independent of photoactivation.     

Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients

BACKGROUND: In newly diagnosed apnoeic patients without a history of hypertension, clinical hypertension is underdiagnosed in at least 40% of the cases. An increase in diastolic blood pressure is the most frequent pattern encountered. OBJECTIVE: To assess clinic and 24-h blood pressure, baroreflex sensitivity and left ventricular mass for identifying the prevalence, the type and the consequences of hypertension in newly diagnosed apnoeic patients. PATIENTS AND METHODS: Fifty-nine unselected patients (age = 48 +/- 12 years, body mass index = 28.1 +/- 4.5 kg/m2) referred to a university hospital sleep laboratory for symptoms suggesting obstructive sleep apnoea were included. Diagnosis of apnoea was accepted when respiratory disturbance index was > or = 15/h of sleep. Blood pressure was considered as normal by their general practitioner and all of them were free of any medication for hypertension. Echocardiography, 24-hour ambulatory blood pressure monitoring and assessment of the baroreflex sensitivity were performed. RESULTS: Forty-two percent of the apnoeic patients demonstrated a clinical hypertension, 34 subjects (58%) had a daytime hypertension, and 45 patients (76%) had a night-time hypertension, using 24-h monitoring. All the daytime hypertensives also had night-time hypertension. Forty-seven of the 59 patients (80%) were hypertensive either in the clinic or using 24-h recording. Diastolic and systolo-diastolic hypertension were the prominent types of hypertension observed both by clinic or ambulatory measurements. Respiratory disturbance index was significantly higher in apnoeic patients suffering isolated diastolic hypertension than in the normotensives (50.9 +/- 26.5/h versus 36.0 +/- 12.3/h, respectively; P = 0.02). The prevalence rate of left ventricular hypertrophy was high (between 15 and 20%) and occurred independently of associated hypertension. Baroreflex sensitivity was altered whatever the type of hypertension and decreased with the severity of obstructive sleep apnoea. CONCLUSION: Hypertension is hugely underdiagnosed in apnoeic patients unknown to be hypertensive. Use of 24-h blood pressure monitoring allowed the diagnosis of twice as much hypertension than did clinical measurement. Even at the beginning of their history of hypertension, apnoeic patients exhibited chronic adaptations of their cardiovascular system, as shown by early changes in baroreflex sensitivity and an increased prevalence of left ventricular hypertrophy.