Daniele Loffredo - Academia.edu (original) (raw)

Papers by Daniele Loffredo

$Research paper thumbnail of Phospholipids chiral at phosphorus. Characterization of the subgel phase of thiophosphatidylcholines by use of X-ray diffraction, Phosphorus31 nuclear magnetic resonance, and Fourier transform infrared spectroscopy$

Biochemistry, 1988

A recent study using differential scanning calorimetry (DSC) showed that the thermotropic phase b... more A recent study using differential scanning calorimetry (DSC) showed that the thermotropic phase behavior of 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC) is sensitive to the configuration at phosphorus and that the R P isomer displayed only a broad transition at 45.6 OC [Wisner, D. A., Rosario-Jansen, T., & Tsai, M.-D. (1986) J . Am. Chem. SOC. 108, 8064-80681. We have employed X-ray diffraction, 31P NMR, and Fourier transform infrared (FT-IR) spectroscopy to characterize various phases of the isomers of DPPsC, to compare the structural differences between 1,2-dipalmitoyl-sn-glycero-3phosphocholine (DPPC) and isomers of DPPsC, and to identify structural factors responsible for the unique behavior of the R P isomer. The results from all three techniques support the previous proposal based on DSC studies that (&)and (RP + Sp)-DPPsC undergo a subtransition, a pretransition, and a main transition analogous to those of DPPC, while (Rp)-DPPsC is quite stable at the subgel phase and undergoes a direct subgelliquid-crystalline transition at 46 OC. Quantitative differences between DPPC and DPPsC (i.e., the effect of sulfur substitution rather than the configurational effect) in the subgel phase have also been observed in the chain spacing, the motional averaging, and the factor group splitting (revealed by X-ray diffraction, 31P N M R , and FT-IR, respectively). In particular, DPPsC isomers are motionally rigid and show enhanced factor group splitting in the subgel phase. These results suggest that DPPsC is packed in different subcells relative to DPPC in the subgel phase. Two unique structural features of (Rp)-DPPsC (relative to other isomers and DPPC) have also been observed in the subgel phase: The bilayer spacing is small, and the C=O stretching band is asymmetric. These features could be responsible for the unusual stability of the subgel phase of (Rp)-DPPsC.

American Journal of Orthodontics and Dentofacial Orthopedics, 2001

Two auxiliary methods of diagnosing nasopharyngeal airway obstruction were compared. Cephalometri... more Two auxiliary methods of diagnosing nasopharyngeal airway obstruction were compared. Cephalometric radiography and nasopharyngeal videoendoscopy were evaluated for efficacy in terms of reproducibility and validity. Thirty orthodontic patients (7 to 12 years of age) seeking otorhinolaryngologic treatment for mouth breathing, or mouth and nose breathing, had nasopharyngeal endoscopy and radiographic examinations performed on the same day. Two otorhinolaryngologists analyzed the results. Nasopharyngeal endoscopy was more reliable in identifying all the obstructive nasopharyngeal processes. Endoscopy obtained kappa index scores of almost perfect agreement for diagnosis of posterior nasal septum deviation, of substantial agreement for anterior nasal septum deviation and lower turbinate hypertrophy, and of moderate agreement for middle turbinate hypertrophy. Lateral cephalometric radiography obtained scores of perfect agreement for imaging hypertrophy of the middle turbinate, of almost perfect agreement for imaging hypertrophy of the posterior portion of the inferior turbinate, and of substantial agreement for imaging hypertrophy of the inferior turbinate. Radiographic diagnoses of hypertrophy of the middle and lower turbinates exhibited high sensitivity and low specificity when compared with diagnoses by nasopharyngeal endoscopy. (Am J Orthod Dentofacial Orthop 2001;120:348-52)

Journal of Toxicology and Environmental Health-part B-critical Reviews, 2007

The human fetus, child, and adult may experience adverse health outcomes from parental or childho... more The human fetus, child, and adult may experience adverse health outcomes from parental or childhood exposures to environmental toxicants. The fetus and infant are especially vulnerable to toxicants that disrupt developmental processes during relatively narrow time windows. This review summarizes knowledge of associations between child health and development outcomes and environmental exposures, including lead, methylmercury, polychlorinated biphenyls (PCBs), dioxins and related polyhalogenated aromatic hydrocarbons (PHAHs), certain pesticides, environmental tobacco smoke (ETS), aeroallergens, ambient air toxicants (especially particulate matter [PM] and ozone), chlorination disinfection by-products (DBPs), sunlight, power-frequency magnetic fields, radiofrequency (RF) radiation, residential proximity to hazardous waste disposal sites, and solvents. The adverse health effects linked to such exposures include fetal death, birth defects, being small for gestational age (SGA), preterm birth, clinically overt cognitive, neurologic, and behavioral abnormalities, subtle neuropsychologic deficits, childhood cancer, asthma, other respiratory diseases, and acute poisoning. Some environmental toxicants, notably lead, ionizing radiation, ETS, and certain ambient air toxicants, produce adverse health effects at relatively low exposure levels during fetal or child developmental time windows. For the many associations supported by limited or inadequate epidemiologic evidence, major sources of uncertainty include the limited number of studies conducted on specific exposure–outcome relationships and methodologic limitations. The latter include (1) crude exposure indices, (2) limited range of exposure levels, (3) small sample sizes, and (4) limited knowledge and control of potential confounders. Important knowledge gaps include the role of preconceptual paternal exposures, a topic much less studied than maternal or childhood exposures. Large longitudinal studies beginning before or during early pregnancy are urgently needed to accurately measure and assess the relative importance of parental and childhood exposures and evaluate relatively subtle health outcomes such as neuropsychologic and other functional deficits. Large case-control studies are also needed to assess the role of environmental exposures and their interactions with genetic factors in relatively uncommon outcomes such as specific types of birth defects and childhood cancers. There is also an urgent need to accelerate development and use of biomarkers of exposure and genetic susceptibility in epidemiologic studies. This review supports the priority assigned by international agencies to relationships between child health and air quality (indoor and outdoor), lead, pesticides, water contaminants, and ETS. To adequately address such priorities, governments and agencies must strengthen environmental health research capacities and adopt policies to reduce parental and childhood exposures to proven and emerging environmental threats.

Psychoneuroendocrinology, 2004

The ovarian hormone estrogen is presumed to modulate processes of learning and memory in adulthoo... more The ovarian hormone estrogen is presumed to modulate processes of learning and memory in adulthood. In this study, we examined the effects of shortterm estrogen replacement on associative memory formation. Adult ovariectomized female rats received two injections of estradiol (10, 20 or 40 lg) 24 h apart and were trained for 4 h following each injection on the hippocampal-dependent task of trace eyeblink conditioning. Only the highest dose of estrogen, which produced plasma estradiol levels >250 pg/ml, enhanced conditioned responding. One day after the last injection, estrogen treated rats continued to exhibit elevated levels of conditioning and extinguished responding when the conditioned stimulus was no longer presented. Exposure to estrogen did not alter pain sensitivity or activity levels, but did greatly increase uterine weight. These results provide additional support to the view that that ovarian steroids are beneficial to the performance of certain forms of learning and memory tasks, albeit at supraphysiological doses. They are discussed with reference to hormone replacement and its effects on cognitive processes. #

Journal of Toxicology and Environmental Health-part B-critical Reviews, 2008

This review summarizes the level of epidemiologic evidence for relationships between prenatal and... more This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory and other childhood diseases, neuropsychological deficits, premature or delayed sexual maturation, and certain adult cancers linked to fetal or childhood exposures. Environmental exposures considered here include chemical toxicants in air, water, soil/house dust and foods (including human breast milk), and consumer products. Reports reviewed here included original epidemiologic studies (with at least basic descriptions of methods and results), literature reviews, expert group reports, meta-analyses, and pooled analyses. Levels of evidence for causal relationships were categorized as sufficient, limited, or inadequate according to predefined criteria. There was sufficient epidemiological evidence for causal relationships between several adverse pregnancy or child health outcomes and prenatal or childhood exposure to environmental chemical contaminants. These included prenatal high-level methylmercury (CH3Hg) exposure (delayed developmental milestones and cognitive, motor, auditory, and visual deficits), high-level prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related toxicants (neonatal tooth abnormalities, cognitive and motor deficits), maternal active smoking (delayed conception, preterm birth, fetal growth deficit [FGD] and sudden infant death syndrome [SIDS]) and prenatal environmental tobacco smoke (ETS) exposure (preterm birth), low-level childhood lead exposure (cognitive deficits and renal tubular damage), high-level childhood CH3Hg exposure (visual deficits), high-level childhood exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (chloracne), childhood ETS exposure (SIDS, new-onset asthma, increased asthma severity, lung and middle ear infections, and adult breast and lung cancer), childhood exposure to biomass smoke (lung infections), and childhood exposure to outdoor air pollutants (increased asthma severity). Evidence for some proven relationships came from investigation of relatively small numbers of children with high-dose prenatal or early childhood exposures, e.g., CH3Hg poisoning episodes in Japan and Iraq. In contrast, consensus on a causal relationship between incident asthma and ETS exposure came only recently after many studies and prolonged debate. There were many relationships supported by limited epidemiologic evidence, ranging from several studies with fairly consistent findings and evidence of dose-response relationships to those where 20 or more studies provided inconsistent or otherwise less than convincing evidence of an association. The latter included childhood cancer and parental or childhood exposures to pesticides. In most cases, relationships supported by inadequate epidemiologic evidence reflect scarcity of evidence as opposed to strong evidence of no effect. This summary points to three main needs: (1) Where relationships between child health and environmental exposures are supported by sufficient evidence of causal relationships, there is a need for (a) policies and programs to minimize population exposures and (b) population-based biomonitoring to track exposure levels, i.e., through ongoing or periodic surveys with measurements of contaminant levels in blood, urine and other samples. (2) For relationships supported by limited evidence, there is a need for targeted research and policy options ranging from ongoing evaluation of evidence to proactive actions. (3) There is a great need for population-based, multidisciplinary and collaborative research on the many relationships supported by inadequate evidence, as these represent major knowledge gaps. Expert groups faced with evaluating epidemiologic evidence of potential causal relationships repeatedly encounter problems in summarizing the available data. A major driver for undertaking such summaries is the need to compensate for the limited sample sizes of individual epidemiologic studies. Sample size limitations are major obstacles to exploration of prenatal, paternal, and childhood exposures during specific time windows, exposure intensity, exposure–exposure or exposure–gene interactions, and relatively rare health outcomes such as childhood cancer. Such research needs call for investments in research infrastructure, including human resources and methods development (standardized protocols, biomarker research, validated exposure metrics, reference analytic laboratories). These are needed to generate research findings that can be compared and subjected to pooled analyses aimed at knowledge synthesis.

$Research paper thumbnail of Enrichment of low molecular weight fraction of serum for MS analysis of peptides associated with hepatocellular carcinoma$

Proteomics, 2006

A challenging aspect of biomarker discovery in serum is the interference of abundant proteins wit... more A challenging aspect of biomarker discovery in serum is the interference of abundant proteins with identification of disease-related proteins and peptides. This study describes enrichment of serum by denaturing ultrafiltration, which enables an efficient profiling and identification of peptides up to 5 kDa. We consistently detect several hundred peptide-peaks in MALDI-TOF and SELDI-TOF spectra of enriched serum. The sample preparation is fast and reproducible with an average CV for all 276 peaks in the MALDI-TOF spectrum of 11%. Compared to unenriched serum, the number of peaks in enriched spectra is 4 times higher at an S/N ratio of 5 and 20 times higher at an S/N ratio of 10. To demonstrate utility of the methods, we compared 20 enriched sera of patients with hepatocellular carcinoma (HCC) and 20 age-matched controls using MALDI-TOF. The comparison of 332 peaks at p < 0.001 identified 45 differentially abundant peaks that classified HCC with 90% accuracy in this small pilot study. Direct TOF/TOF sequencing of the most abundant peptide matches with high probability des-Ala-fibrinopeptide A. This study shows that enrichment of the low molecular weight fraction of serum facilitates an efficient discovery of peptides that could serve as biomarkers for detection of HCC as well as other diseases.

Immunogenetics, 2008

Rhesus macaques (Macaca mulatta) provide well-established models for studying human disease patho... more Rhesus macaques (Macaca mulatta) provide well-established models for studying human disease pathogenesis and vaccine development. When challenged with infectious agents, macaques exhibit individual differences in susceptibility. An important determinant of these differences is the complement of major histocompatability complex (MHC) class I sequences expressed by each animal. Although previous studies have reported strong associations between MHC expression and disease outcome, a rapid, cost-effective method for high-resolution MHC genotyping in macaques is lacking. In this study, we adapted a modified heteroduplex assay, reference strand-mediated conformational analysis (RSCA) to an ABI 3130xl capillary electrophoresis genetic analyzer for macaque MHC class I genotyping. For validation, we investigated the concordance of RSCA genotyping for 14 MHC class I sequences in 12 Chinese rhesus macaques whose genotypes were established through complementary DNA cloning and sequencing of MHC class I sequences. We observed a concordance greater than 98% between RSCA and the cloning and sequencing data. Furthermore, RSCA confirmed the presence of MHC haplotype sharing between three macaques as predicted previously by microsatellite analysis. RSCA genotyping of an additional 25 Chinese rhesus macaques demonstrated that the frequency of these 14 MHC class I sequences ranged from 5% to 32%, with the Mamu-A1*2601 sequence being most common in this cohort. Capillary RSCA genotyping has the potential to enable researchers to rapidly evaluate MHC class I genotypes in rhesus macaques and associate specific MHC sequences with disease susceptibility.

Toxicologic Pathology, 2004

Bioinformatics/computer Applications in The Biosciences, 2005

Motivation: Mass spectrometric profiles of peptides and proteins obtained by current technologies... more Motivation: Mass spectrometric profiles of peptides and proteins obtained by current technologies are characterized by complex spectra, high dimensionality and substantial noise. These characteristics generate challenges in the discovery of proteins and protein-profiles that distinguish disease states, e.g. cancer patients from healthy individuals. We present low-level methods for the processing of mass spectral data and a machine learning method that combines support vector machines, with particle swarm optimization for biomarker selection. Results: The proposed method identified mass points that achieved high prediction accuracy in distinguishing liver cancer patients from healthy individuals in SELDI-QqTOF profiles of serum.

Blood, 2011

Until recently, thrombocytopenia 2 (THC2) was considered an exceedingly rare form of autosomal do... more Until recently, thrombocytopenia 2 (THC2) was considered an exceedingly rare form of autosomal dominant thrombocytopenia and only 2 families were known. However, we recently identified mutations in the 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-untranslated region of the ANKRD26 gene in 9 THC2 families. Here we report on 12 additional pedigrees with ANKRD26 mutations, 6 of which are new. Because THC2 affected 21 of the 210 families in our database, it has to be considered one of the less rare forms of inherited thrombocytopenia. Analysis of all 21 families with ANKRD26 mutations identified to date revealed that thrombocytopenia and bleeding tendency were usually mild. Nearly all patients had no platelet macrocytosis, and this characteristic distinguishes THC2 from most other forms of inherited thrombocytopenia. In the majority of cases, platelets were deficient in glycoprotein Ia and α-granules, whereas in vitro platelet aggregation was normal. Bone marrow examination and serum thrombopoietin levels suggested that thrombocytopenia was derived from dysmegakaryopoiesis. Unexplained high values of hemoglobin and leukocytes were observed in a few cases. An unexpected finding that warrants further investigation was a high incidence of acute leukemia. Given the scarcity of distinctive characteristics, the ANKRD26-related thrombocytopenia has to be taken into consideration in the differential diagnosis of isolated thrombocytopenias.