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Biomedical subjects

G Fillola

Publications and source records attributed to G Fillola.

29 records · Page 2Linked to original sources

Human neutrophils are not severely injured in conditions mimicking social drinking.

In an attempt to assess the effect of alcohol per se on human polymorphonuclear neutrophils (PMN), irrespective of other physiopathological parameters, we examined neutrophil function in healthy volunteers who had taken a single large dose of whisky. Before and at different times after ingestion, several PMN properties were simultaneously tested including random migration, in vitro chemotaxis, adherence, aggregation, cytochrome C reduction, phagocytosis, bacterial killing, intracellular cAMP and cGMP contents, myeloperoxidase, and neutrophil alkaline phosphatase scores. Only phagocytosis of Staphylococcus aureus was significantly depressed after alcohol ingestion. Adherence was inhibited only in some individuals when their respective blood alcohol levels were the highest. Both alterations were moderate and reversible. These data point out the limited effect of occasional alcohol consumption on the different facets of neutrophil behavior. These findings suggest that factors other than alcohol itself could be concerned in the marked PMN dysfunction well established in chronic alcoholism.

Alcohol Drinking↗

Blood cell parameters do not change during physiological human ageing.

Despite the considerable amount of data published during the last 30 years concerning the hematological status of the aged, practitioners are still confronted with the problem of 'normal' or 'physiological' values in these subjects. Indeed, significantly different values are presented in the literature as normal for the aged, apparently depending on the various types of populations studied. Criteria used to define the subjects as 'normal' could be the main factor responsible for this discrepancy. Based on this hypothesis, we determined the values of usual blood cell parameters in two groups of apparently healthy subjects of over 75 years of age. Subjects of group A (16 men and 13 women) were selected according to the stringent criteria of the Senieur protocol and subjects of group B (15 men and 20 women) were recruited using 'conventional' admission criteria. For both groups, sex-matched young controls aged 20-29 years were tested in parallel. No clinically significant alteration was observed in group A, whereas more pronounced differences were found in group B. Our results confirm the necessity for stringent selection criteria in biological investigations in gerontology. Moreover, they demonstrate that blood cell parameters are not altered in the aged, provided that the latter are really 'healthy'.

Aged↗

Neutrophils of healthy aged humans are normal.

Polymorphonuclear functions are reported to be altered in aged humans. We have previously shown that chemotactic response, adherence, oxidative metabolism and Candida killing activity were abnormal in subjects over 70 years. These results lead us to investigate further the basic mechanisms of these alterations in a complementary series of elderly people over 75 years. However, we used in the present study the admission criteria of the SENIEUR protocol specially designed for immunogerontological investigations in humans. Neither the tests exploring the functions as a whole (migration and bacterial killing) nor those investigating the elementary components of these functions exhibited significant difference when compared to the sex-matched young controls. The discrepancy with our prior results is probably explained by the fact that the presently tested subjects had been selected according to more strict criteria. These data clearly demonstrate that neutrophils are intrinsically normal in the aged. Thus, it appears that the frequently observed neutrophil dysfunction in the elderly is due to the action of abnormal humoral components related to the aging process on otherwise normal neutrophils.

Aged↗

A rapid isolation procedure of plasma membranes from human neutrophils using self-generating Percoll gradients. Importance of pH in avoiding contamination by intracellular membranes.

In this study we report an overall procedure for the isolation of both human polymorphonuclear neutrophils and their plasma membrane, by means of self-generating Percoll gradients. After efficient purification (40% yield), neutrophils were lysed by nitrogen cavitation and cellular structures quickly isolated in a one-step procedure. Plasma membrane recovery was monitored by [3H]concanavalin A and 5'-nucleotidase (EC 3.1.3.5) activity. We showed the latter activity is indeed present in human neutrophils. The procedure resulted in a good yield of plasma membrane, since 45% and 55% of total 5'-nucleotidase and [3H]concanavalin A activity, respectively, were recovered within two gradient fractions. Depending on the final pH of the Percoll gradient medium, endoplasmic reticulum markers contaminated either the plasma membrane or the granule fractions. At pH 9.05, NADH-ferricyanide reductase activity clearly separated from plasma membrane markers and displayed the same profile as CDPcholine:diacylglycerolcholine phosphotransferase (EC 2.7.8.2), a typical enzyme of endoplasmic reticulum. These results emphasize the need for strict monitoring of the pH of the gradient medium in subcellular fractionation of neutrophils.

5'-Nucleotidase↗

[Effect of ethanol on human polynuclear neutrophils. In vitro and in vivo study].

Human polynuclear neutrophilic function was studied to determine the role of alcohol in the increased susceptibility to infection of chronic alcoholics: in vitro studies investigated the effects of different concentrations of ethanol; in vivo studies included comparison with healthy subjects after alcohol intake, with excessive drinkers without liver disease and with chronic alcoholics with confirmed cirrhosis. In vitro depression of polynuclear neutrophilic function was observed only with significantly higher concentrations of ethanol than encountered clinically. In social and excessive drinkers, phagocytosis was decreased but there was no change in bactericidal activity. On the other hand, in cirrhotic alcoholics chemotaxis, phagocytosis and bactericidal activity were all significantly reduced. A direct action of alcohol alone on polynuclear function would not seem to be the cause of the increased risk of bacterial infection of chronic alcoholics.

Adult↗

Polymorphonuclear dysfunction in bronchopulmonary diseases in human adults.

Polymorphonuclear (PMN) functions were assessed in 55 patients with asthma or bronchial bacterial infection to evaluate the systemic phagocyte capability of patients with bronchopulmonary diseases. Random migration, nitroblue tetrazolium dye reduction, and Candida killing activity were markedly decreased in the 2 types of patients studied. PMN dysfunction was more pronounced in the most affected and heavily treated patients. Considering both the rare occurrence of congenital polymorphonuclear defects and the age of the patients studied we concluded that the PMN abnormalities observed were secondary to the onset of respiratory disease. This impairment of circulating phagocytes may contribute to the rise of a systemic susceptibility to infection able to aggravate the underlying bronchopulmonary disease.

Adult↗

Simultaneous study of platelets and phagocytes in myeloproliferative disorders.

In order to determine the relationship between the anomalies affecting two types of blood cell in myeloproliferative disorders (MPD), a functional study was performed in individuals presenting with such diseases. Thus, platelet function was investigated by means of Ivy's method for bleeding time, platelet retention to glass beads, aggregation with epinephrine and density distribution on a discontinuous sucrose gradient. Simultaneously, three granulocyte functions, i.e. capillary tube random migration, particle ingestion activity and nitroblue tetrazolium dye reduction were studied. This investigation was carried out in 47 patients presenting with chronic myeloproliferative disorders (MPD): chronic granulocytic leukemia (18 cases), polycythemia vera (18 cases), myelofibrosis (6 cases) and essential thrombocythemia (5 cases). The results of the present study indicate that functional abnormalities are more frequent and more strongly marked in platelets than in phagocytes. The tests most affected were platelet density distribution and granulocytic random migration. Simultaneous assessment of platelet and phagocytic functions, though insufficient in itself to determine the type of MPD or to appraise the prognosis of the disease, could be useful in the diagnosis of some atypical cases of myeloproliferative disorders.

Blood Platelets↗

Impairment of polymorphonuclear functions in hospitalized geriatric patients.

Polymorphonuclear (PMN) functions were assessed in 93 non-selected hospitalized patients, 32 active, healthy, elderly controls and 29 young controls. The results confirm the impairment of PMN functions in the aged. However, PMN functions in hospitalized older persons are similar to those in non-institutionalized controls, and underlying diseases and treatment do not seem to aggravate the PMN impairment. Thus, it can be assumed that the frequent and severe infections afflicting the hospitalized aged are due to the alteration of the other host-defense mechanisms.

Aged↗