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Biomedical subjects

D Stanescu

Publications and source records attributed to D Stanescu.

At least 19 recordsLinked to original sources
PubMed2000

Lung function study and diffusion capacity in anorexia nervosa.

STUDY OBJECTIVES: In humans, malnutrition alters the respiratory system in different ways. It impairs the ventilatory drive, decreases respiratory muscle strength and reduces immune competence. In addition, typical emphysema-like changes were demonstrated in starved animals. The presence of emphysema has never been demonstrated in starved humans. Our objective was to investigate whether pulmonary emphysema occurs in anorexia nervosa by means of a pulmonary function study. POPULATION AND METHOD: We examined 24 women aged between 14 and 38 years (nine smokers). We studied the lung function including lung volumes, ventilatory capacity, maximal respiratory pressures and transfer factor, as well as PaO2. RESULTS: All respiratory tests were within normal limits with the exception of decreased maximal inspiratory (59% of predicted values) and expiratory pressures (35%), and increased residual volume (162%). Diffusion capacity (98.1 +/- 16.2%) and transfer coefficient (98.4 +/- 16.2%) were also normal. The diffusion coefficient was lower in current smokers than in those who had never smoked (P < 0.01), a difference similar to that calculated from existing reference values for transfer factor for smokers and nonsmokers. CONCLUSION: In anorexia nervosa, pulmonary function tests are within normal limits with the exception of maximal pressures and residual volume. Diffusion capacity is not decreased. The present results within the limitations of the used method are not compatible with the hypothesis of starvation-induced pulmonary emphysema.

Adolescent↗
PubMed2000

The CD44-initiated pathway of T-cell extravasation uses VLA-4 but not LFA-1 for firm adhesion.

Leukocytes extravasate from the blood in response to physiologic or pathologic demands by means of complementary ligand interactions between leukocytes and endothelial cells. The multistep model of leukocyte extravasation involves an initial transient interaction ("rolling" adhesion), followed by secondary (firm) adhesion. We recently showed that binding of CD44 on activated T lymphocytes to endothelial hyaluronan (HA) mediates a primary adhesive interaction under shear stress, permitting extravasation at sites of inflammation. The mechanism for subsequent firm adhesion has not been elucidated. Here we demonstrate that the integrin VLA-4 is used in secondary adhesion after CD44-mediated primary adhesion of human and mouse T cells in vitro, and by mouse T cells in an in vivo model. We show that clonal cell lines and polyclonally activated normal T cells roll under physiologic shear forces on hyaluronate and require VCAM-1, but not ICAM-1, as ligand for subsequent firm adhesion. This firm adhesion is also VLA-4 dependent, as shown by antibody inhibition. Moreover, in vivo short-term homing experiments in a model dependent on CD44 and HA demonstrate that superantigen-activated T cells require VLA-4, but not LFA-1, for entry into an inflamed peritoneal site. Thus, extravasation of activated T cells initiated by CD44 binding to HA depends upon VLA-4-mediated firm adhesion, which may explain the frequent association of these adhesion receptors with diverse chronic inflammatory processes.

Animals↗
PubMed1999

Expiratory flow limitation in awake sleep-disordered breathing subjects.

Increased upper airways (UA) collapsibility has been implicated in the pathogeny of sleep-disordered breathing (SDB). An increased UA instability during expiration has recently been shown in healthy subjects. The present study assessed UA collapsibility in SDB patients by applying negative pressure during expiration. Full-night polysomnography was performed in 16 subjects (all snorers) with a wide range of SDB, and in six healthy control subjects. Physical examination, spirometry, and maximal inspiratory and expiratory flow rates were within normal limits for all 22 subjects. Negative expiratory pressure (NEP) (-5 cmH2O) was applied during quiet breathing in seated and supine position. Flow limitation (FL) during NEP was expressed as the percentage of tidal volume during which expiratory flow was less than or equal to the flow recorded during quiet breathing (%FL). The mean desaturation index (DI) of the 16 subjects was 27.3+/-26.4 (+/-sD) and the average FL in supine position was 38.4+/-37.9%. A close correlation between %FL supine during wakefulness and DI during sleep (r=0.84, p<0.001) was found. All obstructive sleep apnoea subjects had >30%FL supine. There was no FL in the six control subjects. In conclusion, negative expiratory pressure application during expiration appears to be a useful, noninvasive method for the evaluation of subjects with sleep-disordered breathing. Present results suggest that upper airway collapsibility can be detected in these subjects during wakefulness.

Adult↗
PubMed1999

Influence of gas density on simulated snoring.

According to a recent theoretical model, snoring is related to instability of the upper airway (UA). Factors promoting UA instability include increased gas density. The aim of this study was to test the influence of gas density on simulated snoring production and supraglottic resistance. Supraglottic pressure and flow rate (V') were measured in 10 healthy seated subjects during simulated snoring. Subjects breathed three different gas mixtures: Helium-oxygen, He 79%-O2 21% (He-O2); air; and sulphur hexafluoride-oxygen, F6S 79%-O2 21% (F6S-O2) administered in a random order. Supraglottic resistance (Rsg) was measured on its linear range during quiet breathing and V' was measured at the onset and middle of snoring. Linear Rsg increased and V' conversely decreased with gas density. These data are in agreement with predictions of a mathematical model of the upper airway showing that snoring occurs at lower flow rates when gas density is increased.

Adult↗
PubMed1999

Effect of CPAP on breathlessness perception in healthy subjects during methacholine induced bronchoconstriction.

Application of continuous positive airway pressure (CPAP) in asthmatic patients decreases breathlessness (B). The effect of CPAP on induced bronchoconstriction was studied in healthy subjects. The changes in B were related to changes in lung function indices. In nine healthy volunteers, males aged 20-27 years, acute bronchoconstriction was induced by inhalation of 1 to 128 mg/ml methacholine (M). CPAP (0.5 kPa) was then applied for 1 min. It was followed by inhalation of albuterol. Forced expiratory volume in 1 s (FEV1) and vital capacity (VC) were measured by spirometry and end expiratory lung level (EELL), to derive inspiratory capacity (IC), by inductive plethysmography. B was assessed by Borg scale. After the maximal concentration of M, FEV1 decreased by 14% (p < 0.01) as compared to the control values and Borg score (BS) increased to 2.4 (p < 0.01). In 7 out of 9 subjects we found a significant (p < 0.05) correlation between the changes in FEV1 and BS. BS decreased during CPAP (p < 0.01) and it further decreased significantly after albuterol. There was no correlation between the changes in IC and FEV1 during bronchoconstriction, or between IC and BS during CPAP. In conclusion, in healthy subjects with induced bronchoconstriction CPAP decreased significantly BS, which was further improved by inhalation of albuterol. B was related to changes in FEV1 but not in IC.

Adult↗
PubMed1998

Lung granulomatosis in a dental technician.

BACKGROUND: Dental technicians are potentially exposed to various occupational dusts and chemicals. Not surprisingly, occupational related lung diseases have been documented in this population. METHODS: We describe the case of a dental laboratory technician presenting progressive exertional dyspnea and cough. We used lung function tests, computed tomography, histological examination, mineralogical and immunological studies to characterize his condition. RESULTS: Lung function studies disclosed a restrictive pattern with a low diffusion capacity. A high-resolution CT scan revealed the presence of micronodules in both lungs corresponding to non-caseating foreign body granulomas at histological examination. Mineralogic studies showed the presence of silica, silicates, and aluminum. The lymphocytic transformation test was positive with the bronchoalveolar lavage for beryllium. CONCLUSIONS: This dental technician developed pulmonary granulomatosis. Combined histological, mineralogical, and immunological studies led us to consider the diagnosis of pneumoconiosis most likely related to occupational exposure to beryllium and aluminum.

Adult↗
PubMed1998

Comparative studies of rat IgG to further delineate the Fc:FcRn interaction site.

Recent data have indicated that the MHC class I-related receptor, FcRn, regulates the half-lives of serum IgG in addition to its known role in transferring IgG from mother to young. In the current study, the activity of rat IgG (rIgG) isotypes in FcRn-mediated functions has been analyzed. The serum half-life and maternofetal transfer in mice decreased in the order rIgG2a > rIgG1 > rIgG2c > rIgG2b. This decrease in activity correlates well with reduced binding affinity for soluble mouse FcRn, and site-directed mutagenesis of a recombinant Fc-hinge fragment has been used to investigate the molecular basis for the differences in activities of the rIgG. Analysis of the serum half-lives of the mutated Fc-hinge fragments demonstrated that, in addition to Ile253, His310, His435 and His436 that were identified in earlier studies, amino acids at positions 257, 307 and 309 play a role in building the FcRn interaction site of IgG. The study also excludes the involvement of amino acids in a fourth loop located at the CH2-CH3 domain interface that encompasses residues 386-387 in FcRn binding. Sequence differences at positions 257, 307 and 309 between rIgG most likely account for the reduced affinity of rIgG2b and IgG2c relative to rIgG1 and rIgG2a for binding to FcRn.

Animals↗
PubMed1997

The antigen-binding domain of a human IgG-anti-F(ab')2 autoantibody.

Recent studies revealed an immunoregulatory role of natural IgG-anti-F(ab')2 antibodies in both healthy individuals and patients with certain diseases. The implication of anti-F(ab')2 antibodies in the pathogenesis of diseases prompted us to study the gene segment structure of their antigen-binding domains and their binding characteristics. cDNA was prepared from the lymphocytes of a patient with a high IgG-anti-F(ab')2 serum titer. Variable heavy and light gene segments were amplified by PCR and inserted into a phagemid surface expression vector. Single-chain antibodies displayed on the phage surface were screened for binding to F(ab')2 fragments. The subsequent analysis of 95 single clones demonstrated that they all bound specifically to F(ab')2. Sequence analyses of 12 clones showed that 11 were identical and 1 contained a silent point mutation in the heavy chain and three amino acid exchanges in the light chain. The heavy chains belonged to the V(H)3 and the light chains to the V(kappa)2 gene family. The 11 identical light-chain genes were completely homologous to a germ-line sequence (DPK-15). Binding assays showed that the single-chain antibodies bind to F(ab')2, but not to Fab, Fc, or intact IgG. This binding pattern was confirmed by surface plasmon resonance studies, which revealed a relatively high affinity (Ka = 2.8 x 10(7) M(-1)). The strong binding capacity was further demonstrated by competitive inhibition of the serum anti-IgG antibody's interaction with antigen. The present study defines for the first time to our knowledge the gene segment structure of the antigen-binding domain of two human IgG-anti-F(ab')2 autoantibody clones and describes the binding kinetics of the purified monomeric fragments.

Amino Acid Sequence↗
PubMed1996

Integrin upregulation on sputum neutrophils in smokers with chronic airway obstruction.

To determine the relationship between the expression of leukocyte-specific integrins in the airways and the airway obstruction in smokers, we analyzed hypertonic saline-induced sputum in 33 male subjects, age 64.7 +/- 0.5 yr (mean +/- SEM), with a smoking history of 12 to 94 pack-years, at the end of a 15-yr follow-up study. Average FEV1/VC ratio was 69 +/- 1% at the beginning of the study and 66 +/- 2% at the end of the follow-up period, and annual decline of FEV1 was 20 +/- 3 ml/yr. Fourteen individuals exhibited airway obstruction as assessed by a FEV1/VC ratio lower than 63.3%. Differential leukocyte count was performed on cytospin preparations and the expression of integrin alpha (CD11a, CD11b, CD11c) and beta (CD18) chains was assessed on granulocytes and mononuclear cells by immunocytology. The numbers of neutrophils expressing CD11b and CD18, but not CD11c or CD11a, were increased in the subjects with airway obstruction compared with those without airway obstruction. CD11b- and CD18-positive neutrophils were negatively correlated with FEV1/VC ratio (p < 0.01). No significant correlations were found between CD11a-, CD11b-, CD11c-, CD18-positive mononuclear cells and lung function measurements. In conclusion, our results suggest that leukocyte-specific integrin CD11b/CD18 expressed on sputum polymorphonuclear leukocytes represents a marker for the smokers who develop chronic airway obstruction.

Aged↗
PubMed1987

Epidemiological survey among workers exposed to manganese: effects on lung, central nervous system, and some biological indices.

A cross-sectional epidemiological study was carried out among 141 male subjects exposed to inorganic manganese (Mn) in a Mn oxide and salt producing plant (mean age 34.3 years; duration of exposure, mean 7.1 years, range 1-19 years). The results were compared with those of a matched control group of 104 subjects. The intensity of Mn exposure was moderate as reflected by the airborne Mn levels and the concentrations of Mn in blood (Mn-B) and in urine (Mn-U). A significantly higher prevalence of cough in cold season, dyspnea during exercise, and recent episodes of acute bronchitis was found in the Mn group. Lung ventilatory parameters (forced vital capacity, FVC; forced expiratory volume in one second, FEV1; peak expiratory flow rate, PEFR) were only mildly altered in the Mn group (smokers) and the intensity and the prevalence of these changes were not related to Mn-B, Mn-U, or duration of exposure. There was no synergistic effect between Mn exposure and smoking on the spirometric parameters. Except for a few nonspecific symptoms (fatigue, tinnitus, trembling of fingers, increased irritability), the prevalence of the other subjective complaints did not differ significantly between the control and Mn groups. Psychomotor tests were more sensitive than the standardized neurological examination for the early detection of adverse effects of Mn on the central nervous system (CNS). Significant alterations were found in simple reaction time (visual), audioverbal short-term memory capacity, and hand tremor (eye-hand coordination, hand steadiness). A slight increase in the number of circulating neutrophils and in the values of several serum parameters (ie, calcium, ceruloplasmin, copper, and ferritin) was also found in the Mn group. There were no clear-cut dose-response relationships between Mn-U or duration of Mn exposure and the prevalence of abnormal CNS or biological findings. The prevalences of disturbances in hand tremor and that of increased levels of serum calcium were related to Mn-B. The response to the eye-hand coordination test suggests the existence of a Mn-B threshold at about 1 microgram Mn/100 ml of whole blood. This study demonstrates that a time-weighted average exposure to airborne Mn dust (total dust) of about 1 mg/m3 for less than 20 years may present preclinical signs of intoxication.

Adult↗
PubMed1981

[Study of lung symptomatology and lung function in steelworkers].

We have examined 272 steelworkers, aged 45 to 55 years, by means of the ECSC-questionnaire and the following lung function tests: vital capacity (VC) and forced expiratory volume in one second (FEV1), residual volume (RV) and total lung capacity (TLC); maximal expiratory flow rates (Vmax, Vmax 50, Vmax 75); specific airways conductance (SGaw); slope of the N2 alveolar plateau after oxygen inhalation (delta N2) and the bolus closing volume (CV). The influence of smoking on respiratory symptoms and lung function was confirmed. In order to assess the influence of occupational pollution a sample of 163 workers was classified according to smoking habits and workplace (either LD-steelplant and continuous casting department, or sheet rolling mill). In the nonsmokers group we found that the workers from the steelplant and continuous casting department (n = 12) had a significantly lower SGaw value (delta = 0.065 cm H2O-1 . s-1, p less than 0.01) and a significantly higher CV value (delta = 4.5% VC, p less than 0.05) than the workers from the sheet rolling mill (n = 11). Differences in FEV1/VC, Vmax 50 and Vmax 75 were not significant, but were also consistent with a slight airflow obstruction in the steelplant workers. In the smokers (n = 99) and exsmokers (n = 41) groups no differences existed between both working categories. Our results suggest that nonsmoking workers from the steelplant and the continuous casting department have undergone moderate, but detectable effects from industrial pollution. These effects are probably masked by those of tobacco in smokers and exsmokers.

Air Pollutants, Occupational↗
PubMed1979

Investigations on the lung and kidney function in workers exposed to cadmium.

The kidney seems more sensitive to the chronic effect of cadmium than the lung. Only minor impairments of lung function (mild form of obstructive lung disease) were found after long-term occupational exposure (less than 20 yr) to moderate concentration of cadmium oxide dust and fume. This conclusion, cannot, however be extrapolated to acute or subacute inhalational exposure. The nephrotoxicity of cadmium consists in a tubular dysfunction characterized by an increased excretion of beta 2-microglobulin and giving rise to the classical tubular proteinuria and in a glomerular dysfunction evidenced by an increased excretion of high molecular weight proteins and increased levels of beta 2-microglobulin and creatinine in plasma and giving rise to a glomerular type proteinuria. These renal changes were mainly found in workers whose cadmium concentration at time of the survey exceeded 1 microgram Cd/100 ml in blood and 10 microgram Cd/g creatinine in urine. It should, however, be stressed that higher levels of Cd in blood and in urine are not necessarily associated with the presence of excessive proteinuria. In newly exposed workers, the Cd level in blood increases progressively to a plateau after several weeks. Cadmium level in urine fluctuates more. In workers exposed for several months to an airborne concentration exceeding 200 microgram/m3, Cd concentration in urine seems mainly influenced by recent exposure.

Adult↗
PubMed1979

Constancy of effort and variability of maximal expiratory flow rates.

In 14 normal subjects and in 13 patients with obstructive pulmonary diseases, we studied the variability within an individual of values for the maximal expiratory flow rate (Vmax) recorded simultaneously vs expired pulmonary volume (at the mouth) and vs thoracic volume (measured with a body plethysmograph). We found that the variance of Vmax within an individual at 25, 50, and 75 percent of the expired vital capacity did not differ statistically whether pulmonary volume was the expired or the thoracic gas volume. In ten healthy subjects on two occasions (at an interval of 12 days, on the average), we measured the peak expiratory flow rate and Vmax at different levels of inflation, with respect to either expired or thoracic volume. There was no statistical differences in Vmax between the first and the last day. A larger variability of Vmax measured vs expired volume implies a change in the expiratory effort from one forced expiration to another and a different degree of compression of intrathoracic air. Since this was not the case, we conclude that muscular effort during repeated forced expirations is similar. The good reproducibility of effort explains in great measure the good reproducibility of Vmax.

Adult↗