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Biomedical subjects

V Di Francesco

Publications and source records attributed to V Di Francesco.

At least 19 recordsLinked to original sources

Effect of vegetarian diet on homocysteine levels.

OBJECTIVE: To compare fasting total plasma homocysteine (tHcy) levels in vegans, lacto-ovovegetarians and control subjects, and to evaluate the relationships between tHcy levels and nutritional variables in vegetarians. METHODS: The study was conducted on 45 vegetarian subjects: 31 vegans (19 males, 12 females, mean age 45.8 +/- 15.8 years); 14 lacto-ovovegetarians (6 males, 8 females, mean age 48.5 +/- 14.5 years), and 29 control subjects (19 males, 10 females, mean age 43.4 +/- 16.7 years). tHcy was evaluated by high-performance liquid chromatography. Serum vitamin B(12) and folate were analyzed by automated chemiluminescence systems. Clinical records, nutritional and anthropometric variables were collected for all vegetarian subjects. RESULTS: tHcy was significantly higher in vegetarian subjects than in controls (23.9 +/- 21.3 vs. 11.6 +/- 4.9 micromol/l, p < 0.001). The prevalence of hyperhomocysteinemia was higher in vegetarians than in controls (53.3 vs. 10.3%, p < 0.001). Serum vitamin B(12) levels were lower in vegetarians than in control subjects (171.2 +/- 73.6 vs. 265.0 +/- 52.2 pmol/l, p < 0.01; normal range 220-740 pmol/l). In vegetarian subjects, significant inverse correlations were found between tHcy and serum vitamin B(12) levels (r = -0.776, p < 0.001) and between tHcy and serum folate levels (r = -0.340, p < 0.05). Positive correlations were found between tHcy and mean red cell volume (r = 0.44, p < 0.01) and between tHcy and fat-free mass (r = 0.36, p < 0.05). CONCLUSION: Vegetarian subjects presented significantly higher tHcy levels, higher prevalence of hyperhomocysteinemia, and lower serum vitamin B(12) levels than controls.

Adult↗

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗

Homocysteine and life-style in the elderly.

Elevated homocysteine increases the risk of vascular diseases but little information is available about this issue in the elderly. The aim of this cross-sectional study was to evaluate the relationships between homocysteinemia and gender, anthropometric, and life-style characteristics in a community-dwelling elderly population (65 men and 120 women; 67-78 years). Basal plasma homocysteine levels were determined by High Performance Liquid Chromatography (HPLC). Clinical records, and nutritional and anthropometric variables were collected in all subjects. Body composition was evaluated in all subjects by Dual energy X-ray Absorptiometry (DXA). Thirty-three percent of women and 66% of men had hyper-homocysteinemia. In women, a positive correlation was present between homocysteinemia, age, diastolic blood pressure and plasmatic creatinine, and a negative correlation between homocysteine, fiber intake and folates. In males, there was a positive correlation between plasma homocysteine, age, and body mass index. Multiple regression analysis showed that fat-free mass, cigarette smoking, fiber intake, vitamin B6 and total kcal intake accounted for 18% of homocysteine variance in males (R2 = 0.18, p<0.05). Significantly higher homocysteine values were found in women with a history of cardiovascular disease than in those without (16.6 +/- 9.4 vs 13.8 +/- 4.4 micromol/L, p<0.05). Homocysteinemia was significantly higher in elderly men compared to women (16.7 +/- 4.7 vs 15.3 +/- 7.6; p<0.05). Gender differences in homocysteine disappeared after adjusting for fat-free mass. This study confirms the age-related increase in plasma homocysteine. Life-style characteristics seem to influence significantly homocysteine levels in the elderly. Our study shows that gender effects on homocysteine may be attributed to differences in body composition.

Aged↗

High serum levels of secretory immunoglobullin A in chronic pancreatitis.

BACKGROUND AND AIM: Elevated levels of secretory immunoglobulin A have been reported in patients with cholestatic hepatitis. Secretory immunoglobulin A is present in the biliary and pancreatic tract. Chronic pancreatitis is a disease characterized by dilatation of Wirsung's duct. The aim of the study was to evaluate secretory immunoglobulin A levels in patients suffering from chronic pancreatitis. PATIENTS AND METHODS: The study population consisted of 66 consecutive chronic pancreatitis patients (55 male, 11 female; mean age 49.6+/-10 years), 26 patients suffering from acute recurrent pancreatitis (9 males, 17 females; mean age 39.6+/-10.6 years) and 90 healthy controls, pair-matched for sex and age with the chronic pancreatitis patients. Secretory immunoglobulin A was determined by enzyme-linked immunosorbent assay, as were serum alanine transaminase and GGT. RESULTS: Secretory immunoglobulin A levels were significantly higher in chronic pancreatitis patients (35+/-23.7 mg/l) than in those acute recurrent pancreatitis group (16.1+/- 7.9) and in healthy controls (11.8+/-4.9 mg/l) (p<0.0001). Secretory immunoglobulin A was significantly higher in chronic pancreatitis patients with steatorrhoea, diabetes and calcifications and in those undergoing pancreatic surgery. Of 61 chronic pancreatitis patients, 14 (23%) had pathological GGT. When only chronic pancreatitis patients with normal GGT levels were analysed, the differences in secretory immunoglobulin A levels between groups of patients and between chronic pancreatitis subgroups remained statistically significant. CONCLUSIONS: This study demonstrates that secretory immunoglobulin A is elevated in chronic pancreatitis. Its value in the staging of patients needs to be further evaluated.

Adult↗

Waist circumference and abdominal sagittal diameter as surrogates of body fat distribution in the elderly: their relation with cardiovascular risk factors.

OBJECTIVE: To evaluate the relationship between supine sagittal abdominal diameter (SAD) and other indicators of body fat distribution with cardiovascular (CVD) risk factors in the elderly. SUBJECTS: One-hundred and forty-six women aged from 67 to 78 y with a body mass index (BMI) ranging from 18.7 to 50.6 kg/m2 and 83 men aged between 67 and 78 y with BMI ranging from 19.8 to 37.1 kg/m2. MEASUREMENT: Body fat distribution was assessed using anthropometric indicators: waist circumference, SAD, waist-to-hip ratio (WHR), waist-to-height ratio and SAD-to-thigh ratio. RESULTS: In women, there was a negative correlation between HDL-cholesterol and body weight, BMI, waist, SAD, WHR, waist-to-height ratio and SAD-to-thigh ratio. A significant association was found between triglycerides, basal glucose, 2 h glucose during oral glucose tolerance test (OGTT), systolic blood pressure (SBP), diastolic blood pressure (DBP) and anthropometric variables. In men a negative correlation was found between HDL-cholesterol and all the anthropometric variables. A significant association was found between triglycerides, DBP and body weight, BMI, waist, SAD and waist-to-height ratio. In women, after adjusting for age and BMI, a significant correlation was observed between waist and HDL-cholesterol, triglycerides and basal glucose. This was also seen with SAD and SAD-to-thigh ratio and triglycerides, basal and 2 h glucose. In men, after adjusting for age and BMI a significant correlation was found between SAD and HDL-cholesterol and triglycerides. When adjustments were made for age and waist, the correlations between BMI and metabolic variables as well between BMI and SBP and DBP were no longer significant. CONCLUSIONS: Our study shows that indicators of body fat distribution are associated with CVD risk factors in the elderly independently of BMI. Our data also show that waist and SAD are the anthropometric indicators of fat distribution which are most closely related to CVD risk factors in old age.

Abdomen↗

Elevated serum levels of antibodies to carbonic anhydrase I and II in patients with chronic pancreatitis.

An immune-mediated reaction to pancreatic structures has been postulated for the pathogenesis of chronic pancreatitis (CP). Several reports demonstrate the presence of antibodies to the pancreatic ductal epithelium in some patients suffering from CP. Serum antibodies to carbonic anhydrase I (anti-CA I) and II (anti-CA II) are present in patients affected by idiopathic CP. The aim of this study was to evaluate the presence of anti-CA I and anti-CA II in a series of patients with CP. We studied 78 consecutive CP patients (62 male, 16 female; mean age 48.6 +/- 10.2 years) referred to the Verona University Center for the Study of the Pancreas. As a control group, we studied 26 healthy subjects recruited from among the medical and nursing staff of the center. Serum anti-CA I and anti-CA II levels were quantified by enzyme-linked immunosorbent assay using a standard method with minor modifications. The mean absorbance of antibodies was higher in CP patients than in control subjects (anti-CA I: 0.064 +/- 0.042 vs. 0.047 +/- 0.015, p = 0.051; and anti-CA II: 0.038 +/- 0.02 vs. 0.029 +/- 0.014, p = 0.033). Positive results were arbitrarily defined as absorbance values >0.067 for anti-CA I and 0.047 for anti-CA II. We found anti-CA I and anti-CA II positivity in 21 of 78 (27%) and 20 of 78 (26%) of CP patients, respectively, and in only two of 26 control subjects (7.7%) (p = 0.032 and 0.039). Twenty-two of 26 subjects in the control group (84.6%) and 48 of 78 patients (61.5%) in the CP group tested negative for both antibodies (p = 0.03). None of the control subjects and 12 of 78 (16.6%) of the CP patients tested positive for both anti-CA I and anti-CA II. We observed a significant correlation between anti-CA I and anti-CA II serum levels in control subjects (R = 0.423; p = 0.016) and in CP patients (R = 0.584; p < 0.0001). No correlation was found between serum antibody levels and any of the following variables: length of disease, alcohol consumption, smoking habits, pancreatic surgery, pancreatic calcifications, diabetes, and steatorrhea. Serum levels of anti-CA I and anti-CA II are elevated in some patients suffering from CP.

Adult↗

Comparison of ultrasound-secretin test and sphincter of Oddi manometry in patients with recurrent acute pancreatitis.

Manometry is considered the gold standard for evaluating sphincter of Oddi dysfunction. It has recently been demonstrated that the ultrasound (US) secretin test proposed a few years ago as a noninvasive test for the study of sphincter of Oddi dysfunction yields a substantial percentage of pathological findings in patients with acute recurrent pancreatitis. The aim of this study was to compare the results of the US secretin test with sphincter of Oddi manometry findings in a consecutive series of patients with recurrent acute pancreatitis. Forty-seven patients admitted to our gastrointestinal unit suffering from recurrent acute pancreatitis underwent ultrasonographic measurement of the main pancreatic duct at baseline and for 60 min after maximal stimulation with secretin at 1 IU/kg. According to the US secretin test findings in 35 healthy control subjects, the test results were considered to indicate pathology when the duct was still dilated after 20 min. Within three to seven days the same patients underwent perendoscopic manometry. Thirty-six patients (17 men, 19 women; mean age 41 +/- 15 years) had a successful US secretin test and sphincter of Oddi manometry. Eleven patients (30.6%) presented normal manometric findings. Two of these had an abnormal US secretin test. Twenty-five patients had abnormal manometry findings, revealing stenosis in 19 (52.7%) (17 with abnormal US secretin test) and dyskinesia in six (five with an abnormal US secretin test). Compared to manometry findings, the US secretin test sensitivity and specificity for sphincter of Oddi dysfunction were 88% and 82%, respectively. In conclusion, most patients with recurrent acute pancreatitis have sphincter of Oddi dysfunction documented by both at the US secretin test and sphincter of Oddi manometry; results of the US secretin test are reliable compared to sphincter of Oddi manometry, and therefore the US secretin test may offer a valid alternative to the more expensive and invasive manometric procedure for assessing sphincter of Oddi dysfunction in patients with recurrent acute pancreatitis.

Acute Disease↗

Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer.

The aim of this study was to compare alcohol and smoking as risk factors in the development of chronic pancreatitis and pancreatic cancer. We considered only male subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47 extrapancreatic cancers; (2) 69 patients with histologically well documented pancreatic cancer and no clinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona polling list and submitted to a complete medical check-up. Chronic pancreatitis subjects drink more than control subjects and more than subjects with pancreatic cancer without chronic pancreatitis (P<0.001). The percentage of smokers in the group with chronic pancreatitis is significantly higher than that in the control group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; P<0.001] and in the group with pancreatic carcinomas but with no history of chronic pancreatitis (OR 5.3; 95% CI 3.0-9.4; P<0.001). In conclusion, our study shows that: (1) the risk of chronic pancreatitis correlates both with alcohol intake and with cigarette smoking with a trend indicating that the risk increases with increased alcohol intake and cigarette consumption; (2) alcohol and smoking are statistically independent risk factors for chronic pancreatitis; and (3) the risk of pancreatic cancer correlates positively with cigarette smoking but not with drinking.

Adenocarcinoma↗

FORESST: fold recognition from secondary structure predictions of proteins.

MOTIVATION: A method for recognizing the three-dimensional fold from the protein amino acid sequence based on a combination of hidden Markov models (HMMs) and secondary structure prediction was recently developed for proteins in the Mainly-Alpha structural class. Here, this methodology is extended to Mainly-Beta and Alpha-Beta class proteins. Compared to other fold recognition methods based on HMMs, this approach is novel in that only secondary structure information is used. Each HMM is trained from known secondary structure sequences of proteins having a similar fold. Secondary structure prediction is performed for the amino acid sequence of a query protein. The predicted fold of a query protein is the fold described by the model fitting the predicted sequence the best. RESULTS: After model cross-validation, the success rate on 44 test proteins covering the three structural classes was found to be 59%. On seven fold predictions performed prior to the publication of experimental structure, the success rate was 71%. In conclusion, this approach manages to capture important information about the fold of a protein embedded in the length and arrangement of the predicted helices, strands and coils along the polypeptide chain. When a more extensive library of HMMs representing the universe of known structural families is available (work in progress), the program will allow rapid screening of genomic databases and sequence annotation when fold similarity is not detectable from the amino acid sequence. AVAILABILITY: FORESST web server at http://absalpha.dcrt.nih.gov:8008/ for the library of HMMs of structural families used in this paper. FORESST web server at http://www.tigr.org/ for a more extensive library of HMMs (work in progress). CONTACT: valedf@tigr.org; munson@helix.nih.gov; garnier@helix.nih.gov

Computer Simulation↗

Comparing protein sequence-based and predicted secondary structure-based methods for identification of remote homologs.

We have compared a novel sequence-structure matching technique, FORESST, for detecting remote homologs to three existing sequence based methods, including local amino acid sequence similarity by BLASTP, hidden Markov models (HMMs) of sequences of protein families using SAM, HMMs based on sequence motifs identified using meta-MEME. FORESST compares predicted secondary structures to a library of structural families of proteins, using HMMs. Altogether 45 proteins from nine structural families in the database CATH were used in a cross-validated test of the fold assignment accuracy of each method. Local sequence similarity of a query sequence to a protein family is measured by the highest segment pair (HSP) score. Each of the HMM-based approaches (FORESST, MEME, amino acid sequence-based HMM) yielded log-odds score for the query sequence. In order to make a fair comparison among these methods, the scores for each method were converted to Z-scores in a uniform way by comparing the raw scores of a query protein with the corresponding scores for a set of unrelated proteins. Z-Scores were analyzed as a function of the maximum pairwise sequence identity (MPSID) of the query sequence to sequences used in training the model. For MPSID above 20%, the Z-scores increase linearly with MPSID for the sequence-based methods but remain roughly constant for FORESST. Below 15%, average Z-scores are close to zero for the sequence-based methods, whereas the FORESST method yielded average Z-scores of 1.8 and 1.1, using observed and predicted secondary structures, respectively. This demonstrates the advantage of the sequence-structure method for detecting remote homologs.

Algorithms↗

Salivary gland involvement in patients with chronic pancreatitis.

The salivary glands are structurally similar to the exocrine pancreas and may be involved in the course of diseases of autoimmune origin (sclerosing cholangitis, ulcerative rectocolitis, primary biliary cirrhosis). For a not-yet-quantified proportion of chronic pancreatitis (CP) cases, a possible autoimmune pathogenesis has been postulated. The aim of the study was to assess the frequency of salivary ductal system abnormalities in patients with CP. Fifty-one patients with CP consecutively admitted to our center were studied (44 men, seven women; mean age, 48.2 +/- 10.8 years). The mean duration of disease was 11.7 years (range, 1-37 years); 44 (86%) of 51 patients had pancreatic calcifications, 25 (49%) of 51 diabetes, 25 (52%) of 48 steatorrhea, and 32 (63%) of 51 underwent pancreatic surgery. As a control group, we studied 10 patients of whom four with liver cirrhosis (three alcoholic and one posthepatitis; three men, one woman; mean age, 57 +/- 12.5 years), and six with temporomandibular pain (five men and one woman; mean age, 42 +/- 10.3 years). The patients were given parotid sialography, the findings being read by two independent observers. In two CP patients, parotid sialography was unsuccessful. Fifteen (31 %) of 49 patients and none of the 10 control patients exhibited abnormalities of the glandular ducts compatible with chronic inflammation of the salivary ducts (p = 0.039). None of the CP patients had salivary intraductal calcifications. Findings of parotid ductal abnormalities are frequent in the course of CP and may indicate a common pathogenetic mechanism, even of an immune type.

Adult↗

Incidence of cancer in the course of chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis patients appear to present an increased incidence of pancreatic cancer. The aim of the study was to compare the incidence of cancer, whether pancreatic or extrapancreatic, in our chronic pancreatitis cases with that in the population of our region. METHODS: We analyzed 715 cases of chronic pancreatitis with a median follow-up of 10 yr (7287 person-years); during this observation period they developed 61 neoplasms, 14 of which were pancreatic cancers. The cancer incidence rates were compared, after correction for age and gender, with those of a tumour registry. RESULTS: We documented a significant increase in incidence of both extrapancreatic (Standardized Incidence Ratio [SIR], 1.5; 95% confidence interval [CI], 1.1-2.0; p <0.003) and pancreatic cancer (SIR, 18.5; 95% CI, 10-30; p <0.0001) in chronic pancreatitis patients. Even when excluding from the analysis the four cases of pancreatic cancer that occurred within 4 yr of clinical onset of chronic pancreatitis, the SIR is 13.3 (95% CI, 6.4-24.5; p <0.0001). If we exclude these early-onset cancers, there would appear to be no increased risk of pancreatic cancer in nonsmokers, whereas in smokers this risk increases 15.6-fold. CONCLUSIONS: The risks of pancreatic and nonpancreatic cancers are increased in the course of chronic pancreatitis, the former being significantly higher than the latter. The very high incidence of pancreatic cancer in smokers probably suggests that, in addition to cigarette smoking, some other factor linked to chronic inflammation of the pancreas may be responsible for the increased risk.

Adult↗

Lithostathine messenger RNA expression in different types of chronic pancreatitis.

Lithostathine may play a physiological role in preventing the precipitation of excess calcium in the pancreatic juice. The hypothesis has been advanced that in chronic calcifying pancreatitis the abnormal biosynthesis of lithostathine might be the original defect to which genetic proneness to the disease may be ascribed. The aim of the present work was to study lithostathine messenger RNA expression in the pancreas of patients with different types of pancreatitis. Lithostathine and chymotrypsinogen mRNA were determined in surgical specimens obtained from the pancreases of the following subjects: (a) 13 patients with chronic alcoholic pancreatitis (84.6% calcified); (b) 4 patients with chronic hereditary pancreatitis (all calcified); (c) 6 patients with chronic obstructive pancreatitis (4 calcified); and (d) 27 subjects suffering from pancreatic cancer. Significantly lower concentrations of both mRNAs were found in the pancreases of chronic pancreatitis patients than in non-cancerous tissue from pancreatic cancer subjects. However, about 70% of the pancreatic cancer subjects showed lithostathine and chymotrypsinogen mRNA levels comparable to those of chronic pancreatitis patients. These results indicate that the decrease in the level of mRNA is not specific to lithostathine and it is unrelated to the presence of pancreatic stones.

Adult↗

Long-term follow-up of patients with chronic pancreatitis in Italy.

BACKGROUND: We investigated the epidemiologic, clinical, and radiologic aspects of a mixed medicosurgical series of chronic pancreatitis patients observed at the University of Verona Centre for the Study of Pancreatic Diseases over the period 1971-1995. METHODS: Even though the pathogenesis of chronic pancreatitis has yet to be clarified and the classification is still debatable, the patients were subdivided in accordance with the Marseilles-Rome classification into those with alcoholic, obstructive, familial, and idiopathic forms of the disease. A total of 715 patients were analysed with a median follow-up period of 10 years (range, 1-25 years). RESULTS AND CONCLUSIONS: At the end of follow-up the dropout rate amounted to 7.1% (51 patients), and 176 patients (24.6%) had died. Data are reported about the type of chronic pancreatitis, sex, and age distribution at the onset of the disease, drinking and smoking habits before onset and during follow-up, and incidence of calcifications, pain, diabetes, steatorrhoea, and pseudocysts. Surgical aspects, survival curves, and causes of death are also analysed, and the most frequent concomitant diseases in chronic pancreatitis sufferers are discussed.

Adolescent↗

Protein topology recognition from secondary structure sequences: application of the hidden Markov models to the alpha class proteins.

The three-dimensional fold of a protein is described by the organization of its secondary structure elements in 3D space, i.e. its "topology". We find that the protein topology can be recognized from the ID sequence of secondary structure states of the residues alone. Automated recognition is facilitated by use of hidden Markov models (HMMs) to represent topology families of proteins. Such models can be trained on the experimentally observed secondary structure sequences of family members using well established algorithms. Here, we model various topology groups in the alpha class of proteins and identify, from a large database, those proteins having the topology described by each model. The correct topology family for protein secondary structure sequences could be recognized 12 out of 14 times. When the observed secondary structure sequences are replaced with predicted sequences recognition is still achievable 8 out of 14 times. The success rate for observed sequences indicates that our approach will become increasingly useful as the accuracy of secondary prediction algorithms is improved. Our study indicates that the HMMs are useful for protein topology recognition even when no detectable primary amino acid sequence similarity is present. To illustrate the potential utility of our method, protein topology recognition is attempted on leptin, the obese gene product, and the human interleukin-6 sequence, for which fold predictions have been previously published.

Algorithms↗