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Biomedical subjects

A Pastore

Publications and source records attributed to A Pastore.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

A structural approach to trinucleotide expansion diseases.

Fourteen neurological diseases are known to be caused by anomalous expansion of unstable trinucleotide repeats. The mechanism that links such expansions to the corresponding pathologies is still unknown. It is thought to cover a variety of mechanisms ranging from interference with nucleic acid structure and transcription to alterations in protein structure and functions. Understanding the cellular role of the proteins involved in these diseases is of primary importance to design possible therapeutical approaches. Structural biology is a powerful tool for providing a detailed description at atomic resolution of protein functions and suggesting working hypotheses which can then be tested experimentally. In this review we discuss the available structural knowledge about proteins involved in trinucleotide expansion diseases and how this may influence our current means of investigation.

Fragile X Messenger Ribonucleoprotein 1↗
PubMedDate not supplied

The solution structure of human epidermal growth factor.

The epidermal growth factors (EGFs) are powerful mitogens for a wide variety of cells in culture; human EGF (hEGF), known as urogastrone, also inhibits gastric acid secretion in vivo. The transforming growth factors (TGF-alpha) are related to the EGF family both in sequence and activity and EGF-like sequences are often observed in a wide range of functionally unrelated proteins. Attempts to examine the structure of EGF by diffraction methods have not yet succeeded because of difficulties with crystallization. We report here a three-dimensional structure of a biologically active derivative (residues 1-48) of the 53-residue human EGF. An analysis of high resolution 1H nuclear magnetic resonance (NMR) spectra was used together with a combination of distance geometry, restrained energy minimization and restrained molecular dynamics methods. The three-dimensional structure provides a basis for understanding the properties of EGFs and for predicting the structures of homologous sequences in other proteins.

Chemical Phenomena↗
PubMedDate not supplied

Variation of chromogranin A serum levels after radical retropubic prostatectomy for prostate adenocarcinoma.

This study evaluated perioperative and postoperative variations in serum CgA levels induced by radical retropubic prostatectomy (RRP) and their relationship with serum PSA levels in prostate cancer patients. Thirty consecutive patients with clinically localized adenocarcinoma of the prostate undergoing RRP were prospectively analyzed. Serum levels of CgA and total PSA were analyzed in each case preoperatively (time 0), at removal of the prostate (time 1), 1 h after the end of RRP (time 2) and then at regular postoperative intervals till 12 weeks (time 14). During the postoperative period no adjuvant therapies were performed and none of the 30 cases showed biochemical (PSA > 0.2 ng/mL) and/or clinical progression. Mean preoperative serum levels of CgA were 57 +/- 14 ng/mL. Immediately after the surgical removal of the prostate gland (time 1), in all 30 cases there was a significant (time 0-time 1: p = .001) increase in serum PSA, but a nonsignificant modification in serum CgA levels (60 +/- 15 ng/mL). After time 1, serum PSA levels progressively decreased to below the detection limit of 0.2 ng/mL. On the contrary, at time 2, serum CgA levels were postoperatively increased (time 2 = 145 +/- 47) and they remained significantly higher than preoperative values (time 0) till the 21-day postoperative interval (time 11). Moreover, at the last control (time 14) mean and median CgA levels were very similar to those shown preoperatively (time 14: 58 +/- 18 ng/mL). In patients with untreated clinically localized adenocarcinoma of the prostate submitted to RRP, surgical and postoperative stress, more than surgical manipulation of the prostate gland, could produce a significant increase in serum CgA levels maintained for a longer period when compared to the increase in serum PSA levels.

Adenocarcinoma↗
PubMedDate not supplied

Daily use of the physio dialysis system: long-term experience.

BACKGROUND: Hypovolaemia has been implicated as a major causal factor of morbidity during haemodialysis (HD). In order to avoid the appearance of destabilising hypovolaemia a biofeedback control system for intra-HD blood volume (BV) change modelling has been developed (Hemocontrol, Hospal Italy). It is based on an adaptive controller incorporated into a HD machine (Integra, Hospal Italy). The Hemocontrol biofeedback system (HBS) monitors BV contraction during HD with an optical device; furthermore, HBS modulates BV contraction rates (by adjusting the ultrafiltration rate--UFR) and the refilling rate (by adjusting dialysate conductivity--DC) in order to obtain the desired pre-determined BV trajectories. METHODS: Nineteen patients prone to hypotension (7 males, 12 females, mean age 64.5 +/- 3.0 SEM years, on maintenance HD for 80.5 +/- 13.2 months) volunteered for the prospective study which aimed to compare the efficacy and safety of bicarbonate HD treatmentequipped with HBS, as a whole (HBS),with the gold standard, bicarbonate treatment, equipped with a constant UFR and DC (BD). The study included one period of 6 months of BD always preceding a follow-up period of HBS treatment ranging from 14 to 30 months (mean 24.0 +/- 1.6). RESULTS: The overall occurrence of symptomatic hypotension and muscle cramps was significantly less in HBS treatment. Self-evaluation of intra- and inter-HD symptoms (the worst score was o and the best one 10) did reveal a statistically significant difference, as far as post-HD fatigue is concerned (6.2 +/- 0.2 in HBS vs. 4.3 +/- 0.1 in BD treatment, p < 0.0001). No difference between the two treatments was observed when comparing pre- and post-HD lying blood pressure, heart rate, body weights and body weight changes. CONCLUSIONS: HBS is an effective treatment. Hypovolaemia-associated morbidity occurs less in BD treatment than HBS. Furthermore, HBS is a safe treatment in the medium-term because these results are achieved without potentially harmful changes in blood pressure, body weight and serum sodium concentration.

Bicarbonates↗
PubMedDate not supplied

Division of the major birch pollen allergen, Bet v 1, into two non-anaphylactic fragments.

We have expressed in Escherichia coli two halves of the major birch pollen allergen, Bet v 1. Both fragments representing the complete 17-kD allergen were purified to homogeneity. In contrast to the complete recombinant, Bet v 1, the fragments had almost completely lost their IgE-binding capacity and exhibited a random coil structure as analyzed by circular dichroism. The ability of the recombinant fragments to trigger histamine release from allergic patients' basophils as well as their capacity to elicit skin reactions were also largely abolished. Both non-anaphylactic Bet v 1 fragments carried the majority of T cell epitopes and may therefore be considered as safe tools for immunotherapy of tree pollen and associated food allergy.

Allergens↗
PubMedDate not supplied

Sentinel lymph node analysis in squamous carcinoma of the oral cavity and oropharynx.

AIMS: The aim of our study was to evaluate the usefulness and applicability of sentinel lymph node (SLN) identification in N0 carcinomas of the oral cavity and oropharynx. STUDY DESIGN: We carried out a prospective evaluation of SLN identification in 20 patients with oral cavity or oropharynx carcinomas with no clinical evidence of lymph node metastases. METHODS: Peritumoral infiltration with technetium-99-labeled nanocolloid followed by lymphoscintigraphy was carried out approximately 18 hours prior to surgery. A vital dye was injected intraoperatively and the SLN was identified with the aid of a gamma probe. All patients underwent routine neck dissection. RESULTS: While multiple radioactive nodes were generally identified on lymphoscintigraphy, the number of nodes ranging from one to five with variable degrees of uptake, intraoperative gamma probe scanning allowed the identification of a single more radioactive lymph node in 19 of the 20 patients. In only one patient did this method lead to the identification of two equally highly radioactive SLNs, with no uptake in the remaining nodes. All SLNs were ipsilateral to the neoplastic lesion. In 15 cases the SLN was tumor negative and so were the remaining nodes obtained by comprehensive neck dissection. In five cases the SLN was the only lymph node containing micrometastasis among those obtained by dissection. There were no instances of node positivity not involving the SLN. CONCLUSIONS: Sentinel lymph node identification in ENT surgery may indicate intraoperatively if node metastasis are present, thereby avoiding overtreatment in a substantial proportion of patients with N0 carcinomas of the oral cavity or oropharynx.

Adult↗
PubMedDate not supplied

Potential markers of tongue tumor progression selected by cDNA microarray.

Squamous cell carcinoma (SCC), the most frequent malignant tumor of the oral cavity, generally exhibits a poor prognosis and metastases are the main cause of death. This tumor often arises from pre-malignant lesions. To date, it is difficult to predict if and which pre-malignant lesions may progress into oral SCC using traditional methods. For these reasons, several studies are trying to identify markers useful in the progression of pre-malignant lesions and tumors. To define the genetic expression profile of tongue tumor progression we compared 9 dysplasias (DS), 8 tumors without metastasis (TWM), 11 metastasizing SCCs (MT) of the tongue, and a baseline of 11 normal tissues by using cDNA microarray containing 19.2 K clones. We initially applied hierarchical agglomerative clustering based on information from all 6026 clones. Results were obtained by performing a two steps analysis: a Significance Analysis of Microarray (SAM) and a Gene Ontology search. One hundred and five clones have statistically significant different expression levels (FDR < 0.01) between DS and TWM, whereas 570 genes have statistically significant difference expression levels between TWM and MT (FDR < 0.01) as detected by SAM. By filtering with FatiGo only 33 genes were differentially expressed in TWN, respect to DS, whereas 155 genes were differentially expressed in MT respect to TWM. We detected some genes which encode for oncogenes, transcription factors and cell cycle regulators as potential markers of DS progression. Examples are BAG4, PAX3 and CCNI, respectively. Among potential markers of metastases are some genes related to cell mobility (TSPAN-2 and SNTA1), intercellular adhesion (integrin alpha 7) or extracellular matrix components (ADAMTS2 and cathepsin O). Additionally, under-expressed genes encoded apoptosis-related proteins (PDCD4 and CASP4). In conclusion, we identified several genes differentially expressed in tumor progression which can potentially help in better classifying pre-malignant lesions and tongue SCCs.

Adult↗
PubMedDate not supplied

[Atypical presentation of lateral cervical metastasis of occult tumor].

The authors describe the case of a 58 years old man, affected by severe obesity, alcohol addict, observed because of a retromandibular mass, measuring 6 cm. Clinical and instrumental findings indicated the presence of a mass apparently due to a parotid abscess; no evident lesions appeared at the examination of the ENT regions. Ultrasonography and fine needle aspiration cytology revealed the presence of a cystic cervical metastasis of a squamous cell carcinoma arising from an occult tonsillar cancer. The authors describe diagnostic procedures, differential diagnosis, treatment and peculiar aspects related to staging and follow-up.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

[Stage grouping for head and neck cancer: a meta-analysis].

BACKGROUND: To compare the correlation of TANIS and 1997 UICC stage grouping with survival rate in head and neck carcinoma. METHODS: A series of 820 patients affected by primary carcinoma of paranasal sinuses (43 patients), oral cavity (100 patients), oropharynx (64 patients), larynx (599 patients) and parotid gland (134 patients) was considered in this retrospective study for a minimum follow-up of 5 years. The data set was classified according to 1997 UICC T-category and then grouped as recommended by the two systems. Data were analyzed by means of survival analyses (Kaplan-Meier and Cox algorithms). RESULTS: The total disease-specific survival rate at 5 years was 44% for paranasal sinuses, 54% for oral cavity, 28% for oropharynx, 86% for larynx and 65% for parotid gland. Globally, univariate analysis by means of Log Rank Test yielded significant p-values both for TANIS and 1997 UICC systems. Multivariate analysis (Cox regression adjusted for age and gender) showed a significant correlation between the two staging systems with the mortality rate. However, TANIS resulted in a higher prognostic value in oral cavity, oropharynx and larynx that are three sites affected by a homogeneous histological type of carcinoma (i.e. squamous cell carcinorna). CONCLUSIONS: TANIS stage grouping better defines the prognosis for head and neck cancer than the 1997 UICC system.

Adult↗
PubMedDate not supplied

[Selective adsorption of homocysteine using HFR-on line technique].

Homocysteine (Hcy) is grossly elevated in hemodialysis (HD) patients. Treatment with folic acid and/or vitamin B12 fails to normalize Hcy levels in the majority of patients. Treatment with various dialyzers with different flux characteristics has produced contrasting results. Hemodiafiltration reinfusion (HFR) on-line (double chamber hemodiafiltration (HDF) with regenerated ultrafiltrate reinfusion) is a novel method combining the processes of diffusion, convection and absorbance. The ultrafiltrate is regenerated through a charcoal-resin device. Our aim was to observe the effect of the HFR on-line technique on removing Hcy. We investigated the effect of this treatment on Hcy levels in 10 patients with a mean Hcy level of 57.6 micromol/L (range 24.1-119.7). We measured Hcy, folate and vitamin B12 pre- and post-dialysis and in the ultrafiltrate pre- and post-cartridge at 10, 120 and 240 min. Mean Hcy levels were 57.6 and 35.3 micromol/L (range 9.9-80.3) (p=0.005) pre- and post-dialysis, respectively, while folate and vitamin B12 were unchanged. Pre- and post-cartridge Hcy levels were 11.6 vs 2.5 (p=0.005), 9.3 vs 3.9 (p=0.005), 7.7 vs 4.6 micromol/L (p=0.012) at three time points considered, while folate and vitamin B12 were essentially undetectable. These preliminary data, which need confirmation in a long-term study, seem to indicate that HFR on-line reduces Hcy levels, not only through a possible reduction in uremic toxins, but also through the actual removal of Hcy by absorbance on the charcoal-resin cartridge.

Adult↗
PubMedDate not supplied

[Clinical and biological considerations on adenocystic carcinoma of the head].

The purpose of the present work was to define some aspects (i.e. the influence of histological grading on prognosis and the possibility of an eventual hormone dependency) of adenoidocystic carcinoma, a highly controversial form of carcinoma still open to debate. A study is thus reported of 33 cases of adenoidocystic carcinoma of the head and neck seen from 1965-1985 at the E.N.T. Clinic of Ferrara. The individual histological samples were seen over a period of time by a single histopathologist who was not informed as to the patients' clinical progression. In this manner the diagnostic criteria was kept constant. Tumoral grading was then performed on the basis of the Marsh and Allen classification. The overall actuarial survival curves are presented according to site and grading. Besides confirming the already known data regarding the decrease in survival rate well beyond the fifth year, local recurrences and the frequency of lymph node and secondary metastases, the results indicate a direct relationship between grading and prognosis. In fact, overall survival decreases for the less differentiated forms while the frequency of local recurrences increases as does that of lymph node and systemic metastases. Furthermore, in 63.3% of the female patients a genital hormone dependent pathology was noted prior to the appearance of a salivary gland tumor. These observations would suggest that hormones may play a role in the genesis of adenoidocystic carcinoma.

Actuarial Analysis↗
PubMedDate not supplied

[New therapeutic prospects in acute acoustic trauma].

A total of 50 young soldiers hospitalized for high frequency hearing loss and tinnitus following exposure to gun impulse noise was studied in order to ascertain the effects of two kinds of medical treatment. A first group (18 subjects) was treated for 10 consecutive days with cerebral gangliosides. In a second group (17 subjects) gangliosides were associated with subcutaneous infiltration of bupivacaine chlorhydrate (0.5%). A third group (15 subjects) was taken as control. An improvement in hearing threshold (= greater than 20 dB at 4-8 kHz) and a consistent relief of tinnitus was respectively found in 52% and 66% of the treated subjects, while hearing status and tinnitus persisted unchanged among the control group subjects. The amount of hearing improvement over the control group proved to be statistically significant, although no significant difference was demonstrated between the two kinds of medical treatment. Since therapy was initiated 5 to 21 days after acoustic trauma, these results indicate that a pharmacological treatment may be effective even in cases where diagnosis is forwarded relatively late in respect to the trauma.

Adult↗