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1.
Front Immunol ; 12: 798003, 2021.
Article in English | MEDLINE | ID: mdl-34912348

ABSTRACT

Human endogenous retrovirus W family envelope proteins (pHERV-W ENV/syncytin-1) have been repeatedly associated with multiple sclerosis (MS). Here, we have focused on the study of pHERV-W ENV/syncytin-1 expression levels in MS patients (relapsing and progressive forms) and in healthy donors (HD) and on exploring their possible relationship with Epstein-Barr virus (EBV) and human herpesvirus-6A/B (HHV-6A/B). We included blood samples from 101 MS patients and 37 HD to analyze antiviral antibody titers by ELISA and pHERV-W ENV/syncytin-1 expression levels by flow cytometry as well as by qPCR. Patients with relapsing MS forms showed significantly higher pHERV-W ENV/syncytin-1 protein and gene expression levels than HD. Progressive MS patients also showed significantly higher protein and gene expression levels than both HD and relapsing MS patients. Regarding antiviral antibodies titers, anti-HHV-6A/B IgM levels were positively correlated with pHERV-W ENV/syncytin-1 protein expression levels in patients with relapsing MS, while in the progressive forms patients this correlation was found with anti-HHVA/B IgG levels. Therefore, pHERV-W ENV could be involved in MS pathogenesis, playing a role in relapsing and progressive forms. Besides, anti-HHV-6A/B antibodies positively correlated with pHERV-W ENV expression. Further studies are needed to better understand this possible relationship.


Subject(s)
Endogenous Retroviruses/physiology , Epstein-Barr Virus Infections/immunology , Herpesvirus 4, Human/physiology , Herpesvirus 6, Human/physiology , Multiple Sclerosis/immunology , Roseolovirus Infections/immunology , Adult , Antibodies, Viral/blood , Disease Progression , Female , Gene Expression Regulation, Viral , Gene Products, env/genetics , Gene Products, env/metabolism , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Multiple Sclerosis/virology , Pregnancy Proteins/genetics , Pregnancy Proteins/metabolism
2.
Cell Death Dis ; 5: e1268, 2014 May 29.
Article in English | MEDLINE | ID: mdl-24874740

ABSTRACT

Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark feature of CSB patients is neurodegeneration but the precise molecular cause for this defect remains enigmatic. Further, it is not clear whether the neurodegenerative condition is due to loss of CSB-mediated functions in adult neurogenesis. In this study, we examined the role of CSB in neurogenesis by using the human neural progenitor cells that have self-renewal and differentiation capabilities. In this model system, stable CSB knockdown dramatically reduced the differentiation potential of human neural progenitor cells revealing a key role for CSB in neurogenesis. Neurite outgrowth, a characteristic feature of differentiated neurons, was also greatly abolished in CSB-suppressed cells. In corroboration with this, expression of MAP2 (microtubule-associated protein 2), a crucial player in neuritogenesis, was also impaired in CSB-suppressed cells. Consistent with reduced MAP2 expression in CSB-depleted neural cells, tandem affinity purification and chromatin immunoprecipitation studies revealed a potential role for CSB in the assembly of transcription complex on MAP2 promoter. Altogether, our data led us to conclude that CSB has a crucial role in coordinated regulation of transcription and chromatin remodeling activities that are required during neurogenesis.


Subject(s)
Chromatin Assembly and Disassembly/physiology , DNA Helicases/metabolism , DNA Repair Enzymes/metabolism , Neural Stem Cells/metabolism , Neurites/metabolism , Neurogenesis/physiology , Transcription, Genetic/physiology , Adult , Cell Line , DNA Helicases/genetics , DNA Repair Enzymes/genetics , Humans , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Neural Stem Cells/cytology , Poly-ADP-Ribose Binding Proteins
3.
Article in English | MEDLINE | ID: mdl-23440680

ABSTRACT

INTRODUCTION: Acute kidney injury requiring renal replacement therapy is a serious complication following cardiac surgery associated with poor clinical outcomes. Until now no drug showed nephroprotective effects. Fenoldopam is a dopamine-1 receptor agonist which seems to be effective in improving postoperative renal function. The aim of this paper is to describe the design of the FENO-HSR study, planned to assess the effect of a continuous infusion of fenoldopam in reducing the need for renal replacement therapy in patients with acute kidney injury after cardiac surgery. METHODS: We're performing a double blind, placebo-controlled multicentre randomized trial in over 20 Italian hospitals. Patients who develop acute renal failure defined as R of RIFLE score following cardiac surgery are randomized to receive a 96-hours continuous infusion of either fenoldopam (0.025-0.3 µg/kg/min) or placebo. RESULTS: The primary endpoint will be the rate of renal replacement therapy. Secondary endpoints will be: mortality, time on mechanical ventilation, length of intensive care unit and hospital stay, peak serum creatinine and the rate of acute renal failure (following the RIFLE score). CONCLUSIONS: This trial is planned to assess if fenoldopam could improve relevant outcomes in patients undergoing cardiac surgery who develop acute renal dysfunction. Results of this double-blind randomized trial could provide important insights to improve the management strategy of patients at high risk for postoperative acute kidney injury.

4.
Ann Dermatol Venereol ; 131(8-9): 805-9, 2004.
Article in French | MEDLINE | ID: mdl-15505549

ABSTRACT

BACKGROUND: Darier's disease or keratosis follicularis is an autosomal dominant acantholytic disorder that frequently arises as a result of spontaneous mutation. It is either a generalized or localized condition due to a mutation in the SERCA2 12q23-q24,1 resulting in a faulty organization of the tonofilaments. We present two siblings affected with the linear form of this disorder and discuss these cases as an example of the genetic mechanism of loss of heterozygosity. CASE REPORTS: A 7 year-old girl was referred for evaluation of linear lesions present since the first year of age. Examination disclosed red, 1 to 2 mm papules that coalesced to form linear plaques on the left side of the vulvar and perianal areas, and on the left hand and foot. Her older brother had similar lesions in a linear arrangement on the left side of the face neck and homolateral foot. No lesions were found in their parents. Biopsies of both affected children revealed an intraepidermal suprabasal cleft. Dyskeratotic cells were present in the spinous layer, and corps ronds and grains near the granular layer. DISCUSSION: The linear form of Darier's disease could result from genetic mosaicism for this autosomal dominant disorder. As these children have a more pronounced involvement than the usual Darier's disease lesions, disposed in a linear arrangement, they probably represent a type 2 segmental manifestation of the disorder. Likewise, the presence of the same linear disorder in two siblings could be explained by loss of heterozygosity for the Darier's disease gene.


Subject(s)
Darier Disease/genetics , Loss of Heterozygosity , Adolescent , Child , Female , Humans , Male , Mosaicism , Siblings
5.
Int J Obes Relat Metab Disord ; 27(11): 1398-404, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14574352

ABSTRACT

OBJECTIVES: To examine the longitudinal changes in adiposity and related risk variables of Syndrome X from childhood to young adulthood with respect to early onset of menarche. DESIGN: Community-based longitudinal cohort of female subject (65% white, 35% blacks subjects) who participated in two or more surveys from childhood to young adulthood and had reported their menarcheal age (<12 y, n=437 vs > or =12 y, n=1042). RESULTS: In childhood (5-11 y), adolescence (12-18 y), and young adulthood (19-37 y), females with early menarche displayed significantly higher body mass index (BMI) and triceps skinfold thickness; higher stature in childhood and adolescence; higher fasting insulin and homeostasis model assessment index of insulin resistance (HOMA-IR) in childhood and adulthood; and higher fasting glucose in adulthood. Blood pressure and lipoprotein variables showed no early menarche-related differences. Longitudinal rates of change in BMI (P=0.002), triceps skinfold thickness (P=0.05), insulin (P=0.09), and HOMA-IR (P=0.05) were positive and faster among female subjects with early menarche; fasting glucose decreased slowly in this group (P=0.006). In a multivariate analysis, body fatness and insulin related independently to early menarche (P<0.001). This association was stronger in white subjects (P=0.0008). In adulthood, the prevalence of clustering of three to four risk factors of syndrome X (highest quartile of: (1) BMI, (2) fasting insulin, (3) systolic or mean arterial pressure, and (4) total cholesterol to HDL cholesterol or triglycerides to HDL cholesterol ratio specific for age, race, and study year) was higher among those with early menarche (10.7 vs 6.2%, P=0.002). The odds for developing such clustering in adulthood among those with early menarche was 1.54 (95% CI=1.14-2.07), regardless of race. CONCLUSION: Early menarche is characterized by excess body fatness and insulin beginning in early childhood and higher prevalence of clustering of adverse levels of risk variables of metabolic Syndrome X in young adulthood.


Subject(s)
Menarche/physiology , Metabolic Syndrome/physiopathology , Adolescent , Adult , Age Factors , Blood Glucose/metabolism , Body Height , Body Mass Index , Child , Cross-Sectional Studies , Female , Humans , Insulin/blood , Insulin Resistance/physiology , Longitudinal Studies , Metabolic Syndrome/blood , Risk Factors , Skinfold Thickness
6.
Hypertension ; 38(5): 1112-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11711507

ABSTRACT

Alcohol drinking has been associated with increased blood pressure in epidemiological studies. We conducted a meta-analysis of randomized controlled trials to assess the effects of alcohol reduction on blood pressure. We included 15 randomized control trials (total of 2234 participants) published before June 1999 in which alcohol reduction was the only intervention difference between active and control treatment groups. Using a standard protocol, information on sample size, participant characteristics, study design, intervention methods, duration, and treatment results was abstracted independently by 3 investigators. By means of a fixed-effects model, findings from individual trials were pooled after results for each trial were weighted by the inverse of its variance. Overall, alcohol reduction was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressures of -3.31 mm Hg (-2.52 to -4.10 mm Hg) and -2.04 mm Hg (-1.49 to -2.58 mm Hg), respectively. A dose-response relationship was observed between mean percentage of alcohol reduction and mean blood pressure reduction. Effects of intervention were enhanced in those with higher baseline blood pressure. Our study suggests that alcohol reduction should be recommended as an important component of lifestyle modification for the prevention and treatment of hypertension among heavy drinkers.


Subject(s)
Alcohol Drinking/adverse effects , Blood Pressure/drug effects , Adult , Female , Humans , Hypertension/prevention & control , Male , Middle Aged , Publication Bias , Randomized Controlled Trials as Topic , Regression Analysis
7.
Eur J Dermatol ; 11(5): 453-7, 2001.
Article in English | MEDLINE | ID: mdl-11525956

ABSTRACT

We describe a girl with motor and mental retardation, macrocephaly, a "coarse" face, choanal atresia, postnatal feeding difficulty, redundant skin with deep palmar and plantar creases, and histopathological evidence of altered elastic fibers, who died at the age of 11 months. We believe this represents another case of Costello syndrome. Lacking papillomata, she had choanal atresia and underwent a fatal outcome at an early age. The differential diagnosis of cutis laxa in association with postnatal growth retardation and developmental delay and with cardio-facio-cutaneous and Noonan syndromes is discussed.


Subject(s)
Abnormalities, Multiple/pathology , Choanal Atresia/pathology , Intellectual Disability/pathology , Craniofacial Abnormalities/pathology , Fatal Outcome , Female , Humans , Infant , Psychomotor Disorders/pathology , Syndrome
8.
J Clin Epidemiol ; 54(8): 817-22, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11470391

ABSTRACT

The development of obesity in childhood is considered a major determinant of cardiovascular risk. Currently the body mass index (BMI = weight/height(2)) is widely used as a measure of obesity. However, since BMI is associated with height during childhood, a weight for height index (weight/height(p)) that is independent of height is thought to be more appropriate. Therefore, to compare the utility of such weight/height(p) index with BMI in assessing adiposity and its relation to cardiovascular risk variable data from the Bogalusa Heart Study participants aged 6 months to 21 years were examined. A total of 31,796 observations on 12,827 subjects was used in the data analysis. Study variables include height, weight, subscapular and triceps skinfolds, blood pressure, serum lipids and lipoproteins, and plasma glucose and insulin. The optimal exponential for the weight/height(p) index started from 2.42 in the 6 month olds, decreased to 1.86 in 2 to 3 year olds, increased to 3.29 among 10 to 11 year olds, and then decreased to 2.15 in the 20 to 21 year olds. The BMI showed slightly higher correlations than weight/height(p) index with subscapular skinfold in children. Both in children and young adults BMI also showed a slightly higher correlation with other cardiovascular risk factor variables regardless of age-race-sex groups. These results indicate that weight/height(p) index is not superior to BMI as an indicator of adiposity and related cardiovascular risk factors during childhood.


Subject(s)
Body Mass Index , Cardiovascular Diseases/etiology , Obesity/complications , Adolescent , Adult , Body Height , Body Weight , Child , Child, Preschool , Female , Humans , Infant , Linear Models , Louisiana , Male , Risk Factors , Skinfold Thickness
9.
Atherosclerosis ; 155(1): 201-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11223443

ABSTRACT

Elevated serum triglyceride level is increasingly being recognized as an important indicator of cardiovascular risk. The distribution and correlates of serum triglycerides were examined in a biracial (black-white) community-based sample of 1342 young adults (30% black) aged 20-37 years. Triglyceride levels showed significant race (white>black) and sex (male>female) differences. Black females, despite their relatively increased body fatness, had lowest triglyceride levels. In terms of conjoint trait of dyslipidemia based on the National Cholesterol Education Program cutpoints, 9% of white males displayed high triglyceride (> or =200 mg/dl) in combination with low high-density lipoprotein (HDL)-cholesterol (<35 mg/dl). In comparison, none of the black females fell into this category. Serum triglycerides even at levels between 100 and 150 mg/dl were significantly adversely associated with risk variables of insulin resistance syndrome such as adiposity and visceral fatness measures, HDL-cholesterol, insulin, and systolic blood pressure, especially among whites. Visceral fatness as measured by waist circumference (except black males) and insulin were the major predictors of triglyceride levels. Overall, triglyceride levels above 150 mg/dl were associated with increased risk of hypertension (odds ratio (OR)=1.8, 95% confidence interval (CI)=1.8-3.0), type 2 diabetes (OR=3.1, CI=1.4-6.9), parental history of hypertension (OR=1.3, CI=1.0-1.8) and parental history of type 2 diabetes (OR=1.7, CI=1.2-2.3). Thus, serum triglyceride levels may be valuable in the assessment of cardiovascular risk during young adulthood.


Subject(s)
Black or African American , Cardiovascular Diseases/ethnology , Triglycerides/blood , White People , Adult , Cardiovascular Diseases/blood , Cardiovascular Diseases/genetics , Cholesterol, HDL/blood , Cross-Sectional Studies , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/genetics , Female , Humans , Hypertension/ethnology , Hypertension/genetics , Louisiana/epidemiology , Male , Risk Factors
10.
Pediatr Dermatol ; 16(3): 222-7, 1999.
Article in English | MEDLINE | ID: mdl-10383782

ABSTRACT

Blue rubber bleb nevus (BRBN) syndrome is a rare disorder characterized by distinctive cutaneous and gastrointestinal vascular malformations. The latter may lead to bleeding complications. We followed four affected children for at least 5 years. The evolution of their disease and the value of pharmacologic agents (steroids, interferon) in the management of some of these patients are discussed.


Subject(s)
Gastrointestinal Hemorrhage/pathology , Gastrointestinal Neoplasms/pathology , Nevus, Blue/pathology , Skin Neoplasms/pathology , Anal Canal , Child , Child, Preschool , Female , Foot , Humans , Infant , Male
11.
J Mol Biol ; 286(2): 327-37, 1999 Feb 19.
Article in English | MEDLINE | ID: mdl-9973554

ABSTRACT

NF-Y is a conserved trimeric transcriptional activator with an extremely high specificity for CCAAT boxes. The NF-YB and NF-YC subunits have histone fold motifs with a high degree of homology to NC2alpha/beta, a TBP-binding repressor. The histone fold is composed of three alpha helices, alpha1, alpha2, alpha3, separated by short loops. Structural data on core histones showed that alpha1 are involved in DNA-binding. To understand the molecular basis of NF-Y sequence-specificity, we constructed deletion and swapping mutants, in which the alpha1 of NC2 and archeal HMfB, a bona fide histonic protein, was placed in NF-YB and NF-YC. Our analysis indicates that (i) subunit interactions are normal; (ii) NF-YB-NF-YC and NC2alpha/beta do not form heterodimers and NC2 cannot associate NF-YA. (iii) None of the NF-Y swaps can complex with TBP on a TATA box. (iv) Specific residues, R47 and K49 in NF-YC and N61 in NF-YB, are crucial for CCAAT-binding. We conclude that specificity of the NF-Y trimer is not due to NF-YA only, but stems in part from the contribution of the histone fold alpha1, particularly that of NF-YB.


Subject(s)
Bacterial Proteins/chemistry , DNA-Binding Proteins/chemistry , Histones/chemistry , Protein Structure, Secondary , Regulatory Sequences, Nucleic Acid , Amino Acid Sequence , Archaea/genetics , Binding Sites , CCAAT-Enhancer-Binding Proteins , DNA/metabolism , DNA-Binding Proteins/metabolism , Dimerization , Molecular Sequence Data , Mutagenesis, Site-Directed , Phosphoproteins/metabolism , Protein Binding , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolism , Sequence Deletion , Substrate Specificity , Transcription Factors/metabolism
12.
Pediatr Dermatol ; 12(3): 228-30, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7501552

ABSTRACT

Aplasia cutis congenita is a rare disorder characterized by localized absence of skin at birth. Type V in Frieden's classification, which is associated with fetus papyraceous or placental infarcts, occurs as a large cutaneous defect on the trunk and extremities. The patient we report had a lesion affecting the trunk and extremities symmetrically, with no family history of the disorder or chromosomal abnormalities. In our opinion, despite the absence of fetus papyraceous or placental infarct, this patient's condition can be classified as type V.


Subject(s)
Ectodermal Dysplasia , Ectodermal Dysplasia/complications , Ectodermal Dysplasia/pathology , Humans , Infant, Newborn , Male , Placenta/pathology
13.
Am J Trop Med Hyg ; 47(3): 310-6, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1524144

ABSTRACT

We evaluated four baits for the delivery of oral rabies vaccines to dogs. In a controlled study in a town in rural Mexico, 177 randomly selected dogs were assigned to receive one of four experimental baits (two of which were developed by the Denver Wildlife Research Center [DWRC]): one of two cylindrical polyurethane sponges with a corn meal coating (one fried in corn oil [DWRC-corn], the other in fish oil [DWRC-fish]), a fish-flavored polymer bait, or a wax bait. Each dog was also offered a commercial dog biscuit. We recorded whether or not the bait was completely consumed, and used the following measures to estimate the amount of oropharyngeal contact with each bait: total chewing time, presence of pieces of bait on the ground following administration, the total area of ground surrounding the location of ingestion that was covered with green dye contained in each bait, and condition of ampules that contained the dye. The dog biscuits were completely consumed significantly more often than the baits (155 of 176 [88%] for the biscuits versus 89 of 176 [50.5%] for the four baits; P less than 10(-6)), but were chewed for a significantly shorter time than the baits (mean time 34 sec for the biscuit versus 60-82 sec for the four baits: P less than 0.001). The ideal bait would probably combine the attractiveness of the commercial biscuit and the ability of the sponge baits to promote contact with the mucous membranes.


Subject(s)
Dog Diseases/prevention & control , Rabies Vaccines/administration & dosage , Rabies/veterinary , Vaccination/veterinary , Administration, Oral , Animal Feed , Animals , Developing Countries , Dogs , Evaluation Studies as Topic , Female , Male , Mexico , Rabies/prevention & control , Rural Health , Vaccination/methods
14.
Am J Trop Med Hyg ; 47(3): 317-27, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1524145

ABSTRACT

We compared three vaccination strategies in three rural communities in Mexico to determine the factors associated with the success of vaccination programs in areas where canine rabies is poorly controlled. In town A, intensive publicity and community participation were used; owners were instructed to bring their dogs to temporary centralized clinics for vaccination. In town B, only brief precampaign publicity was used, followed by vaccination at a centralized site. Minimal publicity was also used in town C, but the vaccination campaign was conducted house to house. A total of 5,426 residents and 1,597 dogs were counted in the three towns (mean human:dog ratio 3.4:1). In Town A, 70.1% (472 of 673) of the dogs were vaccinated; the campaign required 40 person-minutes per dog. Significantly greater proportions were vaccinated in town B (262 of 318 [82.4%]; P less than 0.001) and town C (483 of 561 [86.1%]; P less than 0.00001); each of these latter campaigns required 10 person-minutes per dog. The following factors were positively associated (by multivariate analyses) with vaccination of individual dogs: non-intensive publicity, house-to-house vaccination, dogs owned by a single member of the household, and dogs acquired greater than 15 days after birth. Intensive publicity did not increase the overall success of the vaccination program; the efficiency of centralized versus and house-to-house vaccination was comparable.


Subject(s)
Dog Diseases/prevention & control , Rabies Vaccines , Rabies/veterinary , Vaccination/veterinary , Administration, Oral , Adolescent , Adult , Age Factors , Aged , Animals , Bites and Stings/epidemiology , Child , Child, Preschool , Dog Diseases/epidemiology , Dogs , Housing , Humans , Infant , Mexico/epidemiology , Middle Aged , Rabies/epidemiology , Rabies/prevention & control , Rabies Vaccines/administration & dosage , Rural Population
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