Biotinylation sites of tumor necrosis factor-alpha determined by liquid chromatography-mass spectrometry.

Tumor pretargeting with biotinylated antibody/avidin complexes improves the therapeutic index of systemically administered biotin-tumor necrosis factor (TNF) conjugates. Since the number of biotins in this conjugate is known to be critical for activity, we have characterized the structure of different biotin-TNF conjugates, prepared by reaction with d-biotinyl-6-aminocaproic acid N-hydroxysuccinimide ester and identified the biotinylation sites by trypsin digestion, reverse-phase chromatography, and electrospray mass spectrometry analyses. The results have shown that N-terminal valine is a preferential biotinylation site at pH 5.

Identification of sulfonylureas in serum by electrospray mass spectrometry.

Identification of sulfonylureas in serum is important in the diagnosis of hypoglycemic crisis of unknown origin. Methods based on HPLC with UV or fluorescence detection may give false positive results. Mass spectrometry may successfully avoid this problem.

[Forced expiration. Various current concepts, 50 years after Robert Tiffeneau].

One hundred and fifty years after the original description of spirometry by Hutchinson and 50 years after the definition of his famous ratio by Tiffeneau, a certain number of physiological advances have enabled a better understanding of the determinants of the forced expired manoeuvre and to mitigate some of its inconveniences. This review focuses on three of these advances. The first is the influence of an inspiratory manoeuvre which precedes a forced expiration, on the expiratory flow.

Bronchial responsiveness and airway inflammation in patients with nonallergic rhinitis with eosinophilia syndrome.

Background: Nonallergic rhinitis with eosinophilia syndrome (NARES) is characterized by persistent nasal symptoms without allergy and by a marked eosinophil recruitment in the nasal cavities.

Objective: We studied whether patients with NARES had bronchial responsiveness to methacholine and airway inflammation and examined the relationship between these factors.

Methods: We selected a group of 39 patients referred to our allergy clinic for symptoms of perennial rhinitis.

Eosinophils, mast cells, and basophils in induced sputum from patients with seasonal allergic rhinitis and perennial asthma: relationship to methacholine responsiveness.

Objectives: We attempted to determine whether inflammation is present in induced sputum of patients with seasonal allergic rhinitis (AR) as compared with those with perennial asthma (AS) and examined its relationship with bronchial responsiveness to methacholine.

Methods: Sputum was induced in 30 patients with seasonal rhinitis in response to grass pollens only and in 15 patients with stable, asymptomatic asthma. The AR group was divided according to methacholine PD20 value: the AR- group (n = 15) had a methacholine PD20 greater than 24 micromol; the AR+ group (n = 15) had a methacholine PD20 ranging between 2.

Effect of inhaled furosemide and cromolyn on bronchoconstriction induced by ultrasonically nebulized distilled water in asthmatic subjects.

Background: Inhaled furosemide has been shown recently to produce a protective effect against bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Since there is a close parallel between its experimental effects and those reported for cromolyn,/it has been suggested that they may share some common mechanisms of action. Their protective effect, however, has never been compared directly.

Effects of bronchomotor tone and gas density on time dependence of forced expiratory vital capacity maneuver.

It has been shown that in normal subjects and chronic obstructive pulmonary disease (COPD) patients the maximal expiratory flows and FEV1 are significantly higher if the FVC maneuver is preceded by a rapid inspiration without an end-inspiratory pause (maneuver 1) compared with a slow inspiration with an end-inspiratory pause of approximately 5 s (maneuver 2). This time dependency of FVC was attributed primarily to loss of lung recoil (stress relaxation) during breath-holding at TLC, in association with time constant inequality within the lungs, and changes in bronchomotor tone. To examine the role of bronchomotor tone on time dependency of FVC, 11 COPD and 10 asthmatic patients performed FVC maneuvers 1 and 2 before and after administration of a bronchodilator drug (salbutamol).

Effect of acetazolamide on cough induced by low-chloride-ion solutions in normal subjects: comparison with furosemide.

Background: The antitussive activity of inhaled furosemide has been attributed to its blocking effect on the Na(+)-2Cl(-)-K+ cotransporter. It is likely that the antitussive activity of inhaled diuretics is more complex because amiloride, a diuretic that has no effect on the Na(+)-2Cl(-)-K+ cotransporter, also shows a significant effect against cough induced by low-chloride-ion solutions. Apart from pharmacokinetics of inhaled diuretics, this activity could also depend on the inhibition of carbonic anhydrase.

Prevalence and repeatability of the cough response induced by inhalation of low chloride ion solutions in normal subjects.

Although the inhalation of low Cl- ion solutions has often been used to induce cough, the prevalence and repeatability of the challenge has never been studied in detail. We, therefore, examined cough response in a group of 59 volunteers (aged 15-57 yrs; 34 females and 25 males; 20 smokers) to ascertain prevalence and repeatability. Each subject performed, 2 weeks apart, two identical cough challenges by inhaling four isosmolar solutions with decreasing Cl- ion concentrations (150, 75, 37.

Effect of intranasal azelastine and beclomethasone dipropionate on nasal symptoms, nasal cytology, and bronchial responsiveness to methacholine in allergic rhinitis in response to grass pollens.

Background: We compared the effect of nasal azelastine (0.56 mg/day), nasal beclomethasone dipropionate (BDP, 200 micrograms/day) and matched placebo on seasonal symptoms, nasal cytology, and the increase in bronchial responsiveness occurring during pollen season in a group of subjects with history of allergic rhinitis to grass pollens only.

Methods: The study was completed by nine subjects in the azelastine group, 13 subjects in the BDP group, and 13 subjects in the placebo group.

Dependence of maximal flow-volume curves on time course of preceding inspiration in patients with chronic obstruction pulmonary disease.

Thirteen patients with chronic obstructive pulmonary disease (COPD) performed forced vital capacity (FVC) maneuvers either immediately after a rapid inspiration (maneuver 1) or after a slow inspiration with a 4- to 6-s end-inspiratory pause (maneuver 2). Seated in a body plethysmograph, they breathed through a pneumotachograph. Inspirations were initiated from resting end-expiratory lung volume.

Lung function and diffusing capacity for carbon monoxide in patients with juvenile chronic arthritis: effect of disease activity and low dose methotrexate therapy.

Objective: We measured lung function, in terms of lung volumes, forced expiratory flow-volume curves and diffusing capacity of carbon monoxide (DLCO), in a group of 61 patients with juvenile chronic arthritis (42 female; age range 5 to 33 years) to ascertain whether disease activity and treatment with low dose methotrexate (MTX) influenced these parameters. The whole population was divided into subgroups based on onset type (systemic, n = 27; pauciarticular, n = 12; polyarticular, n = 22), disease activity (active, n = 42; inactive, n = 19), and MTX treatment (treated, n = 27; not treated, n = 34).

Results: We found that maximal-mid expiratory flow (MMEF) was significantly reduced in patients with active disease (p < 0.

Reproducibility of allergen-induced asthma and associated increase in bronchial responsiveness to methacholine in asthmatic children.

We studied the reproducibility of early (EAR) and late (LAR) asthmatic response to allergen challenge in 13 asthmatic children (four girls, age range: 10 to 17 years) sensitized only to Dermatophagoides pteronyssinus (Dp). Further, changes in bronchial responsiveness to inhaled methacholine following LAR were examined by measuring PC20FEV1 methacholine after 24, 48, and 72 hours. We carried out two carefully controlled allergen challenges with the same allergen dose within 4 to 6 weeks, at least 3 weeks apart, in each subject.

Calcium channel autoantibodies in myasthenic syndrome and small cell lung cancer.

Lambert-Eaton myasthenic syndrome (LEMS) is one of the neurologic paraneoplastic syndromes often found in patients with lung cancer. It is characterized by a generalized deficit of neurotransmitter release. Patients with small cell lung cancer (SCLC) in particular may develop LEMS, and SCLC is very often detected in patients affected by LEMS.

Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.

Evaluation of a new method for assessing arterial oxygen pressure, avoiding arterial blood collection.

Arterial computed PO2 (PO2 com) was computed from SaO2 ear and finger capillary pH using equations of Severinghaus and Ellis, and compared with measured arterial PaO2 in 100 patients with chronic obstructive pulmonary disease (76 men, aged 42 to 82 yr). SaO2 ear ranged from 73 to 98%. There was no significant difference between SaO2 ear and SaO2 com (calculated from PaO2 and arterial pH), nor between arterial pH and pHc (capillary blood).

Cutaneous response to intradermal histamine in lung cancer.

Recent evidence has suggested that human neoplastic patients show decreased blood histamine levels and cutaneous responses to intradermal histamine. In this study we evaluate the skin response to intradermal injections of histamine and IgE levels in 34 male patients with lung cancer (of which 21 had metastasis) and in 16 control subjects. Analysis of our data does not reveal any difference in the areas of wheal and flare between control subjects and lung cancer patients with or without metastasis.

Cancer and skin sensitivity to intradermal histamine: a preliminary report.

Any meaningful relationship of histamine concentrations, serum IgE concentrations, and the prevalence of cancer is unproven. Several reports indicate that tumor growth is associated with an increased synthesis of histamine. Others demonstrate decreased blood histamine levels and reduced cutaneous response to intradermal histamine in patients with solid malignant tumors.

Effect of salbutamol on potassium influx in erythrocytes of allergic subjects and investigation of beta 2 receptor autoantibodies.

Recent experimental and clinical reports have demonstrated that beta-adrenergic blockade impairs and beta-adrenergic stimulation enhances in vivo extrarenal potassium uptake in man. In some allergic patients extrarenal potassium disposal in vivo was reduced compared with normal subjects. In the present study we report that in vitro salbutamol induced potassium uptake by red blood cells may be reduced in some atopic patients.

FEV1 decline in asymptomatic young adults: relationships with some tests of small airways function.

The aim of this study is to determine whether some tests proposed as diagnostic of small airways obstruction (SAO) are useful in identifying the subjects at risk of developing chronic airflow limitation. Eighty five healthy male workers (46 nonsmokers and 39 smokers, aged 21-41 yrs), living in the same area and not exposed to occupational pollutants were re-examined after an interval of 6 yrs. At the first survey 39 had functional evidence of SAO as determined by the presence of one of: maximal mid-expiratory flow (MMEF) less than 65% of predicted value (pred); maximal expiratory flow when 25% forced vital capacity remains to be expired (Vmax25) less than 60% pred; closing capacity (CC) greater than 130% pred; 46 had all functional values in the normal range.

The effect of adrenoceptor agonists and antagonists on histamine-induced wheal response in the skin of normal subjects and atopic patients.

The role of the adrenergic mechanism in the pathogenesis of atopic diseases is controversial. Recent experimental and clinical reports have suggested that beta-2 adrenergic stimulation impairs and beta-2 adrenergic blockade enhances the histamine effect on vascular permeability. This led us to study the effect of salbutamol and of propranolol on histamine-induced cutaneous response in 13 healthy subjects and in 16 patients with allergic oculo-rhinitis.

Evaluation of the intensity and duration of the bronchodilatory action of fenoterol-ipratropium bromide in combination compared with terbutaline and placebo in patients with chronic obstructive lung disease.

The effect obtained using terbutaline and Duovent was studied in a group of 16 patients with chronic obstructive lung disease. The drugs were administered by aerosol in doses based on spirometric indices of flow and lung capacity. The results obtained confirm the efficacy of the two drugs in improving gas flow.

The effect of intravenously administered salbutamol on serum potassium in asthmatic and nonasthmatic atopic subjects.

The role of adrenergic mechanism in the pathogenesis of allergic disease is controversial. Recent experimental and clinical reports have suggested that beta-adrenergic blockade impairs and beta stimulation enhances extrarenal potassium uptake in humans. This led us to study the effect of the intravenous administration of salbutamol, a specific beta-2-adrenergic agonist, on serum potassium in 9 healthy subjects and in 23 patients with allergic asthma and/or rhinitis.

[Hemorheologic characteristics in beta-thalassemic homozygotes before and after splenectomy].

In a group of 36 homozigous beta-thalassaemic children we studied the effect of splenectomy on hemorheologic characteristics. The aim of the work was to evaluate the importance of such operation either on anemia or on erythrocyte deformability. Whole blood viscosity was measured with a Brookfield Microviscometer (LVT) and erythrocyte deformability was evaluated with the erythrocyte filtration technique using policarbonate membranes.

Potassium tolerance and bronchial reactivity in asthmatic and nonasthmatic atopic subjects.

Abnormal autonomic nervous system responsiveness may contribute to the pathogenesis of allergic diseases. Therefore, we measured the beta-adrenergic systemic (metabolic) responsiveness by means of acute potassium load in 10 normal healthy subjects and in 19 patients with allergic asthma and/or rhinitis. Ten allergic patients showed a greater potassium increment, as in normal subjects, when potassium was infused in the presence of propranolol.