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Biomedical subjects

G Parisi

Publications and source records attributed to G Parisi.

At least 19 recordsLinked to original sources

Evolutionary analysis of gamma-carbonic anhydrase and structurally related proteins.

We studied the evolutionary relationships between gamma-carbonic anhydrase (gamma-CA) and a very diverse group of proteins that share the sequence motif characteristic of the left-handed parallel beta-helix (LbetaH) fold. This sequence motif is characterized by the imperfect tandem repetition of short hexapeptide units, which makes it difficult to obtain a reliable alignment based on sequence information alone. To solve this problem, we used a structural alignment of three members of the group with known crystallographic structures as a seed to obtain a reliable sequence alignment. Then, we applied protein maximum-parsimony and maximum-likelihood phylogenetic inference methods to this alignment. We found that gamma-CA belongs to a diverse superfamily of proteins that share the LbetaH domain. This superfamily is composed mainly of acyltransferases. The most remarkable feature of the phylogenetic tree obtained is that its main branches group together functionally related proteins, so that the coarse topology can be rather easily explained in terms of functional diversification. Regarding the main branch of the tree containing gamma-CA, we found that, in addition to the group of its closest relatives that had already been studied, gamma-CA is closely related to the tetrahydrodipicolinate N-succinyltransferases.

Acyltransferases↗

Interferon plus ribavirin in chronic hepatitis C non-responders to recombinant alpha-interferon.

The aim of this study was to evaluate the most appropriate therapeutic protocol for patients with chronic hepatitis C not responding to a previous course of recombinant interferon alpha-2b (rIFN). Sixty patients were randomly assigned to two groups of 30 subjects each: group A was treated with double dose of the same type of rIFN (6 MU t.i.w.) plus ribavirin for 6 months; group B was treated with the same rIFN dose and duration as group A, but without ribavirin. An end of treatment complete response (ETCR) was defined as alanine transaminase (ALT) normalization with undetectable serum HCV-RNA at the end of the treatment, while an end of treatment biochemical response (ETBR) as ALT normalization with still detectable viraemia. The two groups were homogeneous. The patients with ETCR or ETBR were than followed-up for at least 1 year. A sustained biochemical response (SBR) was defined as the persistence of normal ALT with still detectable viraemia after a 12-month follow-up, and a sustained complete response (SCR) as the persistence of normal ALT with undetectable viraemia. Side-effects were only observed in patients treated with rIFN plus ribavirin: four cases (13%) discontinued the therapy owing to haemolytic anaemia. Combination therapy induced an ETCR in 11 patients (37%) and an ETBR in six (20%), while a SCR was observed in two subjects (7%) and a SBR in four (13%). The use of a double dose of rIFN alone obtained an ETCR in four cases (13%) and an ETBR in five (17%), with a SCR in two (7%) and a SBR in three (10%). Hence, both combination therapy and single treatment with higher rIFN doses were unable to show statistically significant long-term benefits in patients with chronic hepatitis C resistant to a previous course of rIFN treatment.

Adult↗

Age-related decline of bone mass and intestinal calcium absorption in normal males.

Although about 25% of all hip fractures occur in men, little is known about the pattern of their age-related bone loss and its main determinants. The aim of this cross-sectional study was to evaluate the age-related changes of intestinal calcium absorption, bone mass, and bone turnover in normal men. In 70 normal males (age 17-91 years), we measured spinal and forearm bone density (FBD) (by DXA), fractional intestinal calcium absorption (by oral test), serum immunoreactive parathyroid hormone (PTH), dietary calcium intake (diet records), biochemical markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin, urine calcium, creatinine, and hydroxyproline), and 1,25(OH)2D3 serum levels. Vertebral bone density (VBD) showed a modest decline before age 50 and a greater decline after age 50, whereas FBD presented a significant decrease with advancing age starting at age 40, suggesting a predominant age-related cortical bone loss. Intestinal calcium absorption (47CaFA) and serum 1,25(OH)2D3 also presented an age-related decline similar to FBD. Simple correlation analysis revealed that age was significantly related to 47CaFA (r = 0.60), calcium intake (r = 0.32), VBD and FBD (r = 0.79 and 0.63, respectively), serum 1,25(OH)2D3 (r = 0.69), and serum iPTH (r = 0.72). No significant correlation was found between age and biochemical markers of bone remodeling. Partial correlation and stepwise variable selection analyses, using 47CaFA and bone mass as dependent variables, showed that in normal males, serum 1,25(OH)2D3 and dietary calcium intake were the main contributors (64%) to 47CaFA variability, whereas only age accounted for 63% of VBD and age and dietary calcium accounted for 45% of FBD variability. These results indicate that bone loss in men accelerates after age 50 years and that among other factors, intestinal calcium malabsorption and 1,25(OH)2D3 serum levels play a role.

Adolescent↗

Colonic disease in cirrhotic patients with portal hypertension: an endoscopic and clinical evaluation.

Fifty cirrhotic patients with portal hypertension but without colonic or systemic disease underwent lower gastrointestinal endoscopy in order to investigate the effects, if any, of portal hypertension on the colon. Fifty patients without liver or systemic disease, examined by colonoscopy because of irritable bowel syndrome in the same period served as controls. Rectosigmoid varices were observed in 34% of the cirrhotic patients and 2% of the controls. Hemorrhoids were observed in 70% of the cirrhotic patients and 48% of the controls. Multiple vascular-appearing lesions were found in 16% of the cirrhotic patients and 6% of the controls. Nonspecific inflammatory changes were noted in 10% of the cirrhotic patients and 4% of the controls. Simultaneous presence, in the same patient, of rectosigmoid varices, hemorrhoids, multiple vascular-appearing lesions, and nonspecific inflammatory changes, was observed in only five (10%) of the cirrhotic patients. We found polyps in 12% of the cirrhotic patients and 14% of the controls, and a malignant tumor in 4% of the cirrhotic patients. The patients with normal colonoscopic findings were 8% of the cirrhotic patients and 36% of the controls. All patients and controls were followed up for 1 year; there was no gastrointestinal hemorrhage among controls, whereas 34% of the cirrhotic patients had an upper gastrointestinal hemorrhage (88% from esophageal varices, 12% from the stomach) and 4% had a lower gastrointestinal hemorrhage (one from rectosigmoid varices and one from nonspecific inflammatory lesions). Colonic lesions were significantly more frequent in the cirrhotic patients (92%) than in the control group (64%); however, such lesions did not seem specific to the disease and were not statistically correlated with the degree of esophageal varices by Child's grading, the etiology of cirrhosis, or the bleeding risk from the lower gastrointestinal tract.

Adult↗

A numerical study of the critical line of Kauffman networks.

Kauffman networks were introduced in 1969 as a model of genetic regulatory systems. One of the most striking successes of this model is its ability to reproduce, for a critical value of its parameters, the observed scaling laws of the average cell replication time and of the average number of cell types in a given organism vs. the number of genes. Yet, the numerical evidence for such scaling laws in the model is still unsatisfactory, and restricted to a particular critical point, while we expect that the scaling behaviour is universal along the critical line. In this paper we try to sharpen the evidence for the scaling behaviour of critical systems, carrying on a detailed numerical investigation of their properties. We measure the length of the cycles (which in the model represents the period of cell cycles) and their number (which represents the number of cell types) for a point of the critical line different from the only one previously studied. Our results seem to confirm that such quantities scale as radicalN for all critical systems, at least for lengths and numbers small enough. On the other hand, we found that their probability distributions are very broad (power-law like) and become broader with system size. This means that there is an effective scale of the length and of the number of cycles that increases much faster than radicalN, and in the infinite size limit the biological analogy found by Kauffman may be lost. A numerical study of the modular structure of critical networks supports this conclusion. The implications of this fact for the biological interpretation of the model are briefly discussed. Finally, we found that the typical weight of the attraction basins tends to zero as a power law in the infinite size limit, with an exponent which seems to be universal along the whole critical line.

Animals↗

[Giant fibrovascular polyp of the esophagus].

Fibrovascular polyps of the oesophagus are rare tumor-like lesions characterized by development of the peduncolated intraluminal masses that can reach gigantic size and may have spectacular clinical presentation including regurgitation of a fleshy mass into the mouth and can lead to sudden death for occlusion of the larynx. Starting from a case observed and successfully treated by transoral resection we review the clinical radiographic and pathological findings of benign oesophageal tumor that requires surgical removal because of the progressive nature of the symptoms and the small, just known, risk of sudden death. The approach depends on the pedicule site.

Aged↗

Evaluation of clinical patterns in ulcerative colitis: a long-term follow-up.

The aim of this prospective research was to compare, in a seven-year follow-up, the clinical outcome of ulcerative pancolitis with that of non-progressive ulcerative colitis. The activity of the disease was evaluated by a Clinical Activity Index and an Endoscopic Index. Of 112 cases of ulcerative colitis observed, 95 showed no change in extent and were studied as examples of non-progressive UC, and in this group the extension of the disease was: pancolitis in 19%, left-sided colitis in 39%, proctosigmoiditis in 17% and proctitis in 25%. A colectomy had to be performed in 5%. None of the enrolled cases developed a cancer during the follow-up. The patients with ulcerative pancolitis or left-sided colitis were treated with 5-ASA 1.6 g/day in a delayed-release formulation, while the cases with proctosigmoiditis or proctitis were treated with 5-ASA enemas 4 g/day. The cases with more than one relapse/year were 39%. The proportion of patients with only one relapse/year was 53%. The patients with steady remission for all the seven years of the trial were only 8%, but with a statistically significant difference between the groups with initial diagnosis of proctosigmoiditis or proctitis and the group with initial diagnosis of pancolitis or left-sided colitis (12% versus 5%). Among the cases with continuous remission, 37% showed colonic alterations, with an endoscopic score higher than 4 but a clinical score less than 6. Side-effects were observed in 6% patients but without treatment withdrawal. Non-progressive ulcerative colitis throughout the colon has a relatively good prognosis which seems to be independent of the location of the disease, even if we have found a statistically significant higher percentage of cases with steady remission among the patients with more distal disease.

Administration, Oral↗

[A case report of reversible biliary pseudolithiasis caused by ceftriaxone in childhood: does the problem deserve greater attention?].

The authors report the case of a nine-year-old girl admitted to hospital with signs of meningeal irritation during the course of hyperpyretic phlogosis of the upper airways who presented, after 6 days' treatment with CFTX, at a dose of 50 mg/kg/day (1.5 g/day), therefore at the maximum recommended dose for the antibiotic in question, symptomatic cholecystic "pseudolithiasis" which resolved two weeks after the suspension of the drug. This case appears to concord with recent reports of "pseudolithiasis" in childhood that appeared with doses not regarded as being at risk, and it draws attention to the etiopathogenetic importance of other factors, including familial recurrence. The authors recommend a reasonable use of CFTX and the need to be "vigilant" both in relation to the onset and evolution of the clinical condition described above.

Ceftriaxone↗

Computational characterisation of potential RNA-binding sites in arenavirus nucleocapsid proteins.

A nucleocapsid protein of an RNA virus was characterised using computational methods. Similarity searches using standard algorithms and more sensitive methods based on profiles were performed. Also, secondary structure prediction and statistical methods were used. The results show that the protein belongs to a unique well-characterised family, with three regions with potential RNA binding capacity. The amino-terminal region is found to contain a mixed-charge segment similar to proteins that bear nucleic acid-protein interaction capacity. The middle-region has a slight homology to the nucleolar protein Fibrillarin containing an atypical RNP-1 conserved octamer. Finally, the carboxyl-terminal region has a putative zinc-finger.

Algorithms↗

Re-treatment of interferon-resistant patients with chronic hepatitis C with interferon-alpha.

Non-responders to 6-months treatment with recombinant interferon (rIFN)-alpha, 3 MU thrice weekly (primary non-responders) were treated for 6 further months with the same therapy or with a double dose of rIFN-alpha or with a different type of IFN (L-IFN). 112 primary non-responders were randomly enrolled into four groups of 28 patients each over a period of 4 years and were followed up for 6 months: group A continued the same dose of rIFN-alpha, group B was treated with the same rIFN-alpha but received a double dose (6 MU thrice weekly), group C received L-IFN, 3 MU thrice weekly, and group D stopped IFN therapy and did not receive any treatment. Patients were examined at monthly intervals and response was defined as a complete normalization of alanine amino transferase (ALT). The four groups were homogeneous as to age, sex, duration of the disease, probable source of infection, histological diagnosis. ALT and gamma glutamyl transferase (gamma GT) levels. No patient discontinued therapy for side-effects. Further treatment with rIFN-alpha 3 MU thrice weekly (group A) induced normalization of ALT levels in four patients (14%); treatment with double-dosed rIFN-alpha (group B) induced normalization of liver enzymes in six cases (21%); a different type of interferon (L-IFN) (group C) achieved normalization of serum ALT in five patients (18%). None of 28 primary non-responders who did not receive any treatment (group D) showed normalization of ALT levels. None of the patients was anti-HCV negative at the end of the study and no statistically significant difference was noted between responders and non-responders to the second course of IFN therapy as to age, sex, duration of the disease. ALT and gamma GT levels at the end of the trial. Overall at the end of the study the primary non-responders with normal levels of ALT were 15/112 (13%), with a therapeutic advantage of 7%. No statistically significant difference in the response rate was found among patients who continued IFN therapy, but prolongation of rIFN-alpha treatment at double dosage seems to be the best therapeutic regimen.

Adult↗

Ultrasonographic assessment of bone in normal Italian males and females.

Recently ultrasound techniques have been proposed to evaluate skeletal status. Speed of sound and attenuation through the bone are the ultrasound properties currently used to assess bone strength and fragility. The speed of sound in m s-1 (SOS), broadband ultrasound attenuation in dB MHz-1 (BUA) and stiffness (S) in 134 healthy females (age range 10-90 years) and in 100 healthy males (age range 10-93 years) was measured using the Achilles scanner (Lunar Corp., Madison, WI, USA). A polynomial function was applied to the observed data to evaluate a pattern of age-related BUA, SOS and S changes. Peak values of SOS, BUA and S were reached in both sexes at the age of 30 years. Average decreases of 12.9% in BUA, 4.9% in SOS and 28.9% in S were found in men aged between 30 and 90 years. In women average decreases of 17.2% in BUA, 4.2% in SOS and 31.9% in S were discovered in those aged between 30 and 90 years. The analysis of SOS, BUA and S changes between pre- and post-menopausal women revealed a significant decrease of these parameters with years since menopause. These data indicate an age-related decrease of ultrasound signals in both sexes. Furthermore, this technique is able to detect, in females, menopause related changes due to oestrogen failure. In contrast, in males, the age-related loss of ultrasound signals appears to be more linear.

Adolescent↗

[Natural history of prostatic adenocarcinoma. Recent advances in prognostic parameters and biological behavior].

For many years diagnosis and management of prostatic adenocarcinoma were straightforward. However, with the advent of medical and less invasive therapies for the treatment of prostatic cancer, it has become necessary to know more about the etiology and pathophysiology of the disease. For example, hormonal factors, growth factors, stromal-epithelial interactions and aging have all been implicated in the etiology of the disease. The pathology of the disease demonstrates heterogeneity in the ratio of the stroma to the epithelium in any given patient, and the pathophysiology varies. Recognizing this heterogeneity in the disease, it is clear that no one form of medical or interventional therapy should be expected to result in a complete response.

Adenocarcinoma↗

Sustained remission and viraemia in chronic hepatitis C treated with recombinant alpha-interferon (rIFN-alpha).

In this retrospective trial we report the immediate and long-term effects of rIFN-alpha therapy on serum aminotransferases, especially on their behaviour in relation to the disappearance of serum HCV-RNA at the end of the treatment and one year later. Eighty-eight subjects were eligible in our study. The diagnosis of hepatitis was based on clinical, serological and histological data in all patients. They showed ALT and AST levels at least twice the upper maximum normal value and detectable serum HCV-RNA before the study. These patients were treated with rIFN-alpha 3MU, 3 times a week, in 54 cases for 6 months and in 34 for 1 year. Patients were examined at monthly intervals. Serum HCV-RNA was assessed before and at the end of the treatment and every six months during the follow-up. A complete response was defined exclusively as a normalization of aminotransferases and disappearance of serum HCV-RNA. The two groups were homogeneous. During the treatment drop-outs were 5 (5.7%), and 7 patients (7.9%) stopped the therapy for side-effects. The treatment induced a complete response in 13 (25.4%) of 51 patients treated for 6 months, and in 8 (32%) of 25 cases treated for 12 months. The patients with normalization of aminotransferase levels but with still detectable HCV-RNA in serum were 20 (39.2%) of 51 treated for 6 months and 13 (41.9%) of 31 treated for 12 months. The cases with normalization of aminotransferases were followed up for one year after IFN withdrawal. Serum liver function tests and HCV-RNA were performed every 6 months in these patients. One year after IFN withdrawal the numbers with persistent normalization of liver enzymes and absence of serum HCV/RNA were 9 (69.2%) of 13 cases with complete response after a 6-month course, and 5 (62.5%) of 8 subjects with complete response after a 12-month course. The subjects with continuous normalization or liver enzymes but persistence of serum HCV-RNA at the end of the trial were 3 (15.7%) of 19 patients with normalization of liver enzymes and still detectable HCV-RNA after a 6-month course, and 2 (15.3%) of 13 cases with normalization of liver enzymes and still detectable HCV-RNA after a 12-month course. Overall at the end of our study the patients with normal aminotransferases were 19 (21.5%) of 88 cases studied. 14 of them (73.6%) being from the subjects with disappearance of serum HCV-RNA just after IFN treatment.

Adult↗