Are sputum eosinophil cationic protein and eosinophils differently associated with clinical and functional findings of asthma?

BACKGROUND: Sputum eosinophil counts and eosinophil cationic protein (ECP) levels are usually increased in asthmatic patients. The correlation between sputum eosinophils or ECP and clinical findings of asthma has been previously investigated but many of these studies have been performed on small samples of asthmatic patients, considering only few clinical indices and often including patients on oral or inhaled corticosteroids, which might be confounding when interpreting the relationship between disease activity and airway inflammation. OBJECTIVE: To assess whether sputum eosinophils and ECP were differently related to functional and clinical parameters of asthma in a large number of steroid-naïve asthmatic patients, taking into account several potential determinants of activity and chronicity of asthma. METHODS: One hundred and twenty-nine patients with mild-moderate asthma were studied. Sputum was induced by hypertonic saline inhalation and processed using the whole sample method. RESULTS: Sputum eosinophils and ECP significantly correlated with each other (r = 0.41, P < 0.001). When patients were grouped on the basis of high/low sputum eosinophils and high/low sputum ECP levels, significant differences were observed among groups, with patients with high sputum eosinophils and ECP showing the greatest asthma severity. In the overall sample, disease duration inversely correlated with sputum eosinophils, whereas FEV1 and peak expiratory flow (PEF) inversely correlated with sputum ECP. Rescue ß2 -agonist use and total symptom score positively correlated with both eosinophil counts and sputum ECP. Stepwise regression analysis showed that symptom score and disease duration accounted for 17.6% of sputum eosinophil variance, whereas symptom score and FEV1 accounted for 14.7% of sputum ECP variance. CONCLUSIONS AND CLINICAL RELEVANCE: Both sputum eosinophils and ECP are weakly related to clinical markers of asthma severity. However, ECP was more closely related to lung function parameters than eosinophil counts.

Experimental ocular acute hypertension-induced chromatinic alterations in astrocytic cells in rat optic nerve.

The effects of ocular acute hypertension experimentally induced on the astrocyte cells of rat have been studied. Evaluation was made of the damage to the chromatin of those cells by means of cytochemical (haematoxylin-eosin) analysis and of the state of fragmentation of the DNA by means of the TUNEL technique as well as the protective effect of the peroxide scavenger, troxol, on those events.

[The mortality due to pulmonary silicosis in the Tuscany region in the last decade demonstrates that the health effects of work exposure to silica are still marked]. / La mortalità per silicosi polmonare in Regione Toscana nell'ultimo decennio dimostra che gli effetti sulla salute dovuti all'esposizione lavorativa a silice sono tuttora marcati.

An analysis of death certificates from 1987 to 1996 among residents of the Tuscany Region identified 1518 deaths from pneumoconiosis, the large majority from silicosis, a disease explained by occupational exposure to silica dust. A dozen of deaths are from asbestosis, occurred at younger ages and are concentrated in a restricted area where a cement-asbestos factory was active. Deaths from pneumoconiosis occurred mainly among males, and the rates of the disease are decreasing only in the latest years. About 10% of deaths from silicosis are among subjects dying before 65 years of age. Mortality rates are very high in several areas of the Region, approximating those from lung cancer and ischaemic heart disease. For the above reasons the disease is still of concern from the point of view of public health and actions are suggested to obtain a description of prevalence and incidence of the disease.

[Long-term survival after resection surgery for cancer of the lung in the elderly patient]. / Sopravvivenza a distanza dopo chirurgia di exeresi per cancro del polmone nel paziente anziano.

Five hundred and twenty (520) patients with lung resection for cancer and known follow-up were studied. The aim of the study was to analyse long-term results in relation to the age of the patients. Two hundred and forty (240) cases were less than 55 years old, 227 were aged between 55 and 65 years, 53 were aged over 65 years. Type of lung resection, extent of resection, histological type, Degree of Nuclear Differentiation of primary tumours (NG), Degree of Lymphocytic Infiltration of primary tumours (LI) and Post-Surgical Stage were tested to assay their influence on long-term survival. The data were statistically analysed by the Number Cruncher Statistical System (NCSS 5.5). Univariate (Logrank Test) and multivariate analyses (Cox's Proportional Hazards Model for survival data) were used to test the influence of age and the above-mentioned prognostic factors on survival. The results of the study demonstrated that age doesn't influence long-term prognosis while Post-Surgical Stage (p < 0.00001), NG (p < 0.0001) and LI (p < 0.00001) are related to survival as independent variables. Then patients should not be denied lung resection on the basis of age alone.

[Surgical excision of lung neoplasms in the elderly. Immediate results]. / Chirurgia di exeresi per cancro del polmone negli anziani. Risultati immediati.

The authors have analyzed a series of 807 patients who underwent resection for Bronchogenic Carcinoma at the "I Istituto di Clinica Chirurgica" of the University of Rome "La Sapienza" since 1950. The aim of the search was to evaluate the immediate results of surgical treatment in relation to age of the patients. Seventy-one patients were < 65 years old, 91 patients were older. The incidence of post-operative complications and mortality rate (within the 30th day from surgery) was related to the following risk factors: concomitant pulmonary and extrapulmonary diseases, cigarette smoking, laboratory values (red blood cell count, protein electrophoresis, urea nitrogen, glucose), type of lung resection, extent of resection, histology and post-surgical stage. The rates of post-operative complications and mortality were 34.1% and 27.5% in elderly patients, while in younger patients they were respectively 26.3% and 16.2%. In the elderly, cigarette smoking, cardiovascular diseases, diabetes, renal failure, type of lung resection and extent of resection, were related to an increase of the post-operative complications and mortality rate. In the younger patients, the extent of resection to adjacent structures was the primary risk factor for immediate results. Screenings in elderly and early diagnosis represent the strategy to allow more conservative surgical treatments and reduction of complications and mortality.

[Prognosis and immunomorphological characteristics in rectal cancer: results of a multivariate analysis]. / Prognosi e caratteristiche immunomorfologiche nel cancro del retto: risultati di una analisi multivariata.

The survival advantage of a pronounced lymphocytic infiltration within and around the primary tumor and some hyperplastic reactions in the regional lymph nodes in specimens of colorectal cancer has been reported in many studies. However, none of these studies allowed the grade of these immunomorphological reactivities to compete with more traditional prognostic variables, using the proportional hazard models. In this study the survival rates of 219 patients who underwent operation for rectal cancer were analyzed statistically according to sex, age, tumor site, type of operation, histology, nuclear grade, p-TNM stage of disease and to the following immunomorphological parameters: lymphocytic infiltration (LI) within and around the primary tumor, paracortical activity (PCA), cortical activity (CA) and sinus histiocytosis (SH) of the regional lymph nodes. The presence of an evident local and regional immune reactivity was significantly related to a less advanced stage of disease and better differentiated tumor. The multivariate survival analysis (Cox model) identified LI, PCA and SH and p-TNM stage as independent prognostic factors. Survival within each stage progressively increased in presence of one or more favourable immunomorphologic features. These results indicate that an adequate prospective evaluation of LI, PCA and SH should improve our ability to assess prognosis in rectal cancer and, therefore, allow a more rational utilization of adjuvant therapy.

[The effect of the degree of lymphocytic infiltration on the long-term survival of patients undergoing surgery for the exeresis of gastric cancer]. / L'influenza del grado di infiltrazione linfocitaria sulla sopravvivenza a distanza dei pazienti sottoposti a chirurgia d'exeresi per cancro gastrico.

The predictive value of tumor lymphocytic infiltration was studied in 186 gastric cancer patients curatively resected. All patients were followed-up for over 10 years. LI was negatively correlated with p-TN stage of disease. A poorer prognosis was detected in patients with minor or no tumor lymphocytic infiltration. LI was an independent prognostic parameter according to the Cox model and logistic regression analysis. These findings suggest that LI should also have been considered in the current staging of gastric cancer.

Alpha-glucan synthesis on a protein primer. A reconstituted system for the formation of protein-bound alpha-glucan.

Reconstitution experiments with the DEAE-cellulose-treated enzymes, engaged in a two-step mechanism of synthesis of alpha-glucan bound to protein, are performed. Urea/sodium dodecyl sulfate/polyacrylamide gel electrophoretic analysis of the radioactive products synthesized by the reconstituted system shows highly glucosylated, labeled bands, whose apparent molecular masses change with the acrylamide concentration in the gels. The long carbohydrate chains synthesized during the second step arise from the sequential addition of glucosyl moieties to the glucoprotein formed during the first step. A deglucosylation experiment confirms that the product of the reconstituted system originates from the 38-kDa glucosylated component of the reaction 1 product by the addition of beta-amylase-sensitive glucosyl moieties. Our data suggest that specific phosphorylases and starch synthetases are found in potato tuber, which are capable of utilizing reaction 1 product as primer for the synthesis of protein-bound glucan.

alpha-Glucan synthesis on a protein primer, uridine diphosphoglucose: protein transglucosylase I. Separation from starch synthetase and phosphorylase and a study of its properties.

It was found that the DEAE-cellulose-treated UDP-Glc:protein transglucosylase I catalyzing the first step (reaction 1) in the formation of alpha-glucan bound to protein in potato tuber is not only specific for the glucosyl donor but also for the endogenous acceptor. A single radioactive 38-kDa macromolecular component appeared during denaturing polyacrylamide gel electrophoresis of reaction 1 product. The labeled component is probably the polypeptide subunit of the endogenous acceptor which is being glucosylated. The radioactivity incorporated in reaction 1 product was isolated from a protease digest as a low-molecular-mass glucopeptide fraction. A beta-elimination reaction carried out in the presence of a reducing agent demonstrated that only one glucosyl moiety is transferred from UDP-Glc to the aminoacyl residue, thus forming an O-glucosidic linkage. 3H-labeled sodium borohydride showed that serine and threonine are involved in the peptide bond to glucose. Ion-exchange chromatography on DEAE-cellulose, affinity chromatography on concanavalin-A--Sepharose, gel filtration on Sephacryl S-300 and sucrose density gradient centrifugation failed to separate the enzyme catalyzing reaction 1 from the endogenous acceptor.

A two-step enzymatic formation of a glucoprotein in potato tuber.

Evidence is presented on the occurrence of a two-step mechanism for the synthesis of protein bound glucan in a potato tuber particulate preparation. Experiments carried out with a differently labeled sugar donor for each step enabled the isolation of a double-labeled glucoprotein. Smith periodate degradation of the product confirmed this hypothesis.

A primer independent activity of rabbit muscle phosphorylase b.

Rabbit muscle phosphorylase b was found to be capable of forming protein bound alpha-1,4 glucosyl chains upon incubation of the enzyme with appropriate concentrations of glucose-1-phosphate with no primer addition (unprimed synthesis). This activity would only be present in a small fraction of the total muscle phosphorylase b activity, as judged from the high concentrations of enzyme which are required to demonstrate the occurrence of unprimed synthesis. Polyacrylamide gel electrophoresis shows the presence of a phosphorylase isoenzyme capable of accepting glucosyl moieties, giving rise to a glucosylated protein enzymatically active in the chain lengthening of its own glucan.

Biosynthesis of starch. Formation of a glucoproteic acceptor by a potato non-sedimentable preparation.

1. A non-sedimentable fraction of potato tuber has been found to catalyze [14C]glucose transfer from [14C]glucose 1-phosphate to an endogenous proteic acceptor in the absence of added primer. This transfer is activated by Mn2+. 2. The labeled glucosylated product formed is trichloroacetic acid insoluble and sensitive to proteolytic and amylolytic digestions. It appears to be a glucoprotein with glucosyl chains bound to the peptide portion of the molecule through an unknown linkage. 3. The carbohydrate portion of the glucoprotein can be released by prolonged incubations with the enzymatic preparation, and becomes in turn, trichloroacetic acid soluble and alcohol precipitable. 4. Both products, the glucoprotein as well as the alpha-1,4-glucan that seems to arise from the enzymatic cleavage of the former, can be used as primers by the transglucosylating system with ADP[14C]glucose, UDP[14C]glucose or GDP[14C]glucose as glucosyl donors. The results presented in this paper are the first demonstration of soluble glucosyl transferases with the same glucose donor specificity to that of the particulate starch synthetase. 5. This report presents further evidence in favor of the assumption of a glucoproteic intermediate in alpha-a,4-glucan synthesis initiation.