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Biomedical subjects

J C Yernault

Publications and source records attributed to J C Yernault.

At least 73 records · Page 4Linked to original sources

A different profile of epitopic dominance in the immunoglobulin G response to bovine betalactoglobulin in lung cancer.

BACKGROUND: The authors previously documented a quantitative defect in the immunoglobulin G (IgG) response toward bovine betalactoglobulin (BLG), the major cow's milk antigen, and antigen p1 of the house dust mite, Dermatophagoides pteronyssinus (Der p1), in patients with lung cancer. In the Der p1 model, the authors documented at the IgG level an epitope specificity that differed between patients with lung cancer (preferential specificity for cryptic epitopes) and healthy control subjects and patients with mite allergy. The current study investigated whether this varying specificity might be extended to the IgG response toward BLG. METHODS: The authors compared the IgG binding to native BLG (nBLG) and its products of pepsin hydrolysis (dBLG) in a solid-phase enzyme-linked immunosorbent assay (ELISA) using peroxidase-conjugated protein A in 120 patients with lung cancer, 52 patients with chronic obstructive pulmonary disease (COPD) who were closely matched for age, sex, and smoking habits with the patients with cancer, and 120 healthy control subjects (blood donors). RESULTS: Expressing the ratio between optical densities observed for dBLG and nBLG, respectively, the authors documented two groups: patient with lung cancer with higher levels of binding on dBLG (mean ratio +/- SD, 1.66 +/- 0.26) and healthy control subjects and patients with COPD with similar levels of retention for dBLG and nBLG (mean ratios +/- SD, 1.00 +/- 0.10 and 1.01 +/- 0.07, respectively). Influence of population characteristics could be excluded. The histologic type of cancer and its extent had no influence on the defined ratio. CONCLUSION: These results suggest a preferential recognition of epitopes unmasked by pepsin hydrolysis (cryptic epitopes?) by lung cancer IgG, contrasting with the preferential specificity of IgG from healthy control subjects and patients with COPD for structural epitopes unaffected by the proteolysis. These findings are similar to those observed previously with Der p1 and indicate a varying, and possibly specific, profile of epitopic dominance in the IgG response to antigens naturally presented at the mucosal level in patients with lung carcinoma, a model of mucosal cancer.

Adult↗

Antibody affinity disturbance in the immunoglobulin immune response to mucosal antigenic stimulation in lung cancer. The Betalactoglobulin Model.

BACKGROUND: This study is a continuation of a recent study, in which a defect in the immunoglobulin G (IgG) response to some natural antigens (bovine betalactoglobulin [BLG] from cow's milk and antigen p1 from the house dust mite Dermatophagoïdes pteronyssinus), usually presented at the mucosal level, was documented in lung cancer patients. The present study further characterizes this difference in terms of antibody relative functional affinity in the BLG model. METHODS: Relative functional affinity was evaluated by solid-phase enzyme-linked immunosorbent assay in terms of the relationship between specific IgG retention, assessed with peroxidase-labeled protein A, and serial dilutions of IgG fractions isolated from 24 sera from lung cancer patients and 24 sera from healthy control subjects matched for their anti-BLG IgG antibody titers. The procedure was performed in the presence and absence of low concentrations of diethylamine, which was expected to prevent low-affinity antigen-antibody binding without affecting the binding of high-affinity antibodies. Anti-BLG IgG antibody affinity also was evaluated in 25 patients with early-stage lung cancer, before and after (5 +/- 1 week) complete surgical excision of the tumor. RESULTS: Results, expressed as the slope of the binding curves and their leftward shift induced by diethylamine, showed different antibody populations between the two groups. Control sera showed a heterogeneous population of anti-BLG IgG antibodies, including antibodies of higher (steeper slope) and lower (more gradual slope) functional affinity. Cancer sera exhibited a less heterogeneous population of anti-BLG IgG antibodies, mostly with lower functional affinity. No change was observed in anti-BLG IgG antibody affinity in the 25 lung cancer patients tested 5 +/- 1 week after complete surgical excision of the tumor. CONCLUSIONS: These results document a persistent qualitative immunologic disturbance in patients with lung cancer, regardless of the type and extent of tumor. The potential relationship between this observation and the development of lung cancer, however, is presently unknown.

Adult↗

Whole lung sections for computed tomographic-pathologic correlations. Modified Gough-Wentworth technique.

RATIONALE AND OBJECTIVES: High-resolution computed tomography of the lung has been advocated in the evaluation of interstitial lung diseases and emphysema. To provide material for correlations with gross pathology and macroscopic quantitation of emphysema, the authors have shortened and simplified the Gough-Wentworth technique. METHODS: The method permits more precise correlation of cross-sectional images and pathologic specimens and is less time-consuming. RESULTS AND CONCLUSIONS: This modified method can be routinely performed in a clinical laboratory of pathology and provides paper-mounted whole lung sections within four days. The sections are protected by a transparency film.

Histological Techniques↗

Detection of mycobacterial antigens present in short-term culture media using particle counting immunoassay.

Particle counting immunoassay (PACIA) was compared with the BACTEC system for detecting mycobacterial growth after short-term culture and was used to identify M. tuberculosis. The latex particles were coated with polyclonal anti-BCG or with specific 2A1-2 monoclonal antibodies. Bottles containing nonradioactive Middlebrook 7H9 liquid medium and BACTEC 12B vials were inoculated with equal amounts of mycobacteria from four reference strains (M. tuberculosis, M. kansasii, M. avium, and M. xenopi). Using anti-BCG, PACIA detected mycobacterial antigens 3 to 6 days before the BACTEC system. M. tuberculosis was differentiated from the other mycobacteria using 2A1-2. Seventeen clinical samples were also studied. In the same 10, the two techniques detected mycobacteria, PACIA with anti-BCG after 9 days and BACTEC 1 to 5 days later. For 9 of the 10 samples, PACIA with 2A1-2 detected M. tuberculosis after 20 days, a result confirmed with the AccuProbe system. M. xenopi was biochemically identified in Specimen 10. Nonmycobacterial diseases were diagnosed in the 7 remaining unreactive specimens. We conclude that PACIA detects mycobacterial growth earlier than BACTEC and that M. tuberculosis can be distinguished from other mycobacteria in PACIA performed with specific monoclonal antibodies.

Antibodies, Monoclonal↗

Severe hemolysis due to a donor anti-D antibody after heart-lung transplantation. Association with lung and blood chimerism.

Hemolysis due to donor-derived red cell antibodies is a potential complication after minor ABO-mismatched solid organ transplantation. It has also been described in Rh-positive recipients receiving organs from previously isoimmunized Rh-negative donors. We report on a group O, Rh(D)-positive patient who received a heart-lung transplant from a group O, Rh(D)-negative donor presenting an anti-D antibody. Severe hemolytic anemia developed in the early postoperative period and lasted for 3 mo. Anti-D antibodies that were of donor origin were found in bronchoalveolar lavage fluid and serum. In addition, using the polymerase chain reaction for human leukocyte antigen class II genotyping, we were able to demonstrate the presence of a mixed population of donor and recipient cells in the lungs and the peripheral blood of the recipient. The chimeric state in the blood persisted until at least the fifty-seventh postoperative day. This first case report of hemolysis due to Rh(D) antibody after heart-lung transplantation emphasizes the need for routine red cell antibody screening of donors and for close monitoring of signs of red cell destruction in the recipient in cases of pretransplant donor isoimmunization.

Adult↗

Intrinsic PEEP in patients with chronic obstructive pulmonary disease. Role of expiratory muscles.

Many patients with severe chronic obstructive pulmonary disease (COPD) contract the transversus abdominis (TA) muscle during expiration. The mechanical correlates of this contraction, however, are uncertain. In the present study, we have measured airflow, esophageal (Pes), and gastric (Pga) pressures, the anteroposterior (AP) diameter of the abdomen, and the electromyogram of the TA during resting breathing in 25 seated patients with severe COPD (FEV1 = 28 +/- 8% of predicted). Nine patients (Group I: FEV1 = 29 +/- 8% of predicted) in general had no TA activity during breathing, and 16 patients (Group II: FEV1 = 27 +/- 8% of predicted) had invariable phasic expiratory TA activity. In all patients of Group II, the decrease in abdomen AP diameter during expiration was associated with a gradual fall in Pga. In contrast, in 13 patients of Group II, the expiratory decrease in abdomen AP diameter was associated with a rise in Pga; this rise in Pga averaged 2.8 +/- 2.2 cm H2O. Furthermore, most patients had positive alveolar pressure at end-expiration, as shown by the time lag between the fall in Pes at the beginning of the inspiratory effort and the onset of inspiratory flow. However, whereas end-expiratory alveolar pressure averaged 2.4 +/- 2.2 cm H2O in Group II, it was only 0.8 +/- 0.6 cm H2O in Group I (p < 0.05). For the patient group as a whole, there was a close relationship between the rise in Pga during expiration and end-expiratory alveolar pressure (r = 0.87; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Dextroposition of the left lower lobe after heart-lung transplantation.

Immediately after heart-lung transplantation for cystic fibrosis, a patient had development of a right lower lobe retrocardiac density that persisted on all postoperative chest radiographs. A computed tomographic examination of the thorax performed 3 weeks after surgery showed that there was partial collapse of the left lower lobe in the right hemithorax. The patient required a posterolateral thoracotomy for cure.

Adult↗

Pneumonitis complicating low-dose methotrexate therapy for rheumatoid arthritis. Discrepancies between lung biopsy and bronchoalveolar lavage findings.

Two very similar cases of drug-induced pneumonitis complicating treatment of rheumatoid arthritis with low-dose methotrexate are presented. Diagnosis was suggested by clinical history and findings, but the bronchoalveolar lavage showed a high percentage of neutrophils, an unusual feature in methotrexate-induced pneumonitis. Transbronchial lung biopsies (TBB) confirmed the diagnosis by showing interstitial lymphocytic infiltrate with microgranulomas. Although histologic findings are not strictly pathognomonic, when a differential diagnosis has to be made with infectious and rheumatoid lung disease, TBB appears to be of great promise.

Aged↗

[Dyspnea and inspiratory effort capacity in COPD].

The aim of this work was to study the relationship between dynamic hyperinflation and dyspnoea perception on exercise in patients with chronic obstructive pulmonary disease (COPD). Seven men and three women with COPD (mean FEV1 45.9 +/- 9.8% predicted) were studied. The upper end of the visual analogue scale was anchored on a preliminary test on a cycle ergometer (day 1). On the study day (day 2) the relationship between dyspnoea and ventilatory indices during high intensity exercise was evaluated, using within-subject linear regression analysis. On a repeat study (day 3), the addition of inspiratory capacity (IC) manoeuvres allowed to monitor the end expiratory lung volume. The highest degree of within-subject correlation was observed between dyspnoea and the tidal peak inspiratory flow (PIFT), as well without (median r2 = 0.920, day 2) as with (median r2 = 0.880, day 3) IC manoeuvres. At maximal exercise, IC decreased in 8 out of 10 subjects (delta IC range -150 to -900 ml). A negative relationship was found between delta IC and the rate of increase in dyspnoea on exercise, measured as the dyspnoea/PIFT slope (r = 0.844, p < 0.01). Our results suggest that dynamic hyperinflation on exercise observed in most patients with COPD allows these subjects to minimize the rate of increase in dyspnoea on exercise.

Aged↗

Respiratory dysfunction in congestive heart failure: correction after heart transplantation.

Severe chronic congestive heart failure (CCHF) is known to induce a restrictive ventilatory defect, with a small decrease in lung transfer factor for carbon monoxide (TLCO). The aim of the present work was to assess the reversibility of this dysfunction. We studied a group of 47 patients with CCHF, before and one year after heart transplantation. The measurements included static and dynamic lung volumes, TLCO and cardiac function. On initial evaluation, vital capacity (VC), total lung capacity (TLC) and TLCO were reduced to 76, 79 and 64% of the predicted value (% pred), respectively. Forced expiratory volume in one second (FEV1) was decreased to 69% pred, with a FEV1/VC ratio below 0.70 in 13 out of 47 patients. One year after transplantation, cardiac function had markedly improved, as shown by a normalized left ventricular ejection fraction (from 18% preoperatively to 59% postoperatively), and mean pulmonary wedge pressure (from 26 to 12 mmHg). At this time, VC (94% pred) and TLC (98% pred) were within the normal range, whereas TLCO remained low (67% pred). The FEV1/VC ratio did not change, even in the subgroup with an initial low value. Smoking habits did contribute to the low TLCO and FEV1/VC ratio. In conclusion, respiratory dysfunction induced by CCHF is reversible, with the exception of the reduction in TLCO, which probably reflects permanent changes in the lung vasculature. CCHF does not induce an obstructive ventilatory pattern.

Female↗

Effects of chemotherapy on antibody levels directed against PGL-I and 85A and 85B protein antigens in lepromatous patients.

IgG antibodies against antigens 85A and 85B from Mycobacterium bovis BCG, IgM antibodies against phenolic glycolipid-I (PGL-I) and circulating PGL-I antigen were measured in the serum of 11 patients with lepromatous leprosy receiving multidrug therapy (MDT). Before treatment, 6 patients were reactive to antigen 85A, 10 patients to antigen 85B, and 11 patients to PGL-I; circulating PGL-I was detected in the sera of all of them. After 2 years of MDT PGL-I antigen could no longer be detected in all of the patients, except for two who were not compliant with treatment. IgG antibodies directed against the 85A and 85B antigens and IgM antibodies against the PGL-I antigen also decreased significantly during treatment but more slowly. The determination of circulating PGL-I antigen remains the most appropriate tool for monitoring lepromatous leprosy under MDT.

Antibodies, Bacterial↗

How do patients with either asthma or COPD perceive acute bronchodilation?

The purpose of this study was to assess the perception of bronchodilation, as a change in shortness of breath on a bipolar visual analogue scale (VAS), in 16 asthmatics and 20 subjects with COPD. Bronchodilation was gradually induced by five consecutive terbutaline inhalations (cumulated dose 800 micrograms). The subjects were categorized into high and low perceivers, on the basis of a cut-off of 25% VAS line length (after the fifth inhalation). The quality of perception was studied on a within-subject basis by linear regression analysis of VAS ratings against changes in lung function, and was characterized in terms of strength of correlation (squared correlation coefficient, r2), slope, and VAS axis intercept. Fourteen out of 16 asthmatics, and 13 out of 20 COPD subjects, were high perceivers. In the COPD group, the high perceivers had a larger objective response--particularly in inspiratory vital capacity--than the low perceivers. The strongest correlation between subjective and objective response was obtained in asthmatics when the improvement in shortness of breath was evaluated against the decrease in specific inspiratory resistance (median r2 = 0.831). In COPD low perceivers, subjective and objective response were unrelated, while COPD high perceivers differed from the asthmatics by larger intercepts. The perceptual characteristics were unrelated to the degree of baseline obstruction, whilst a modest relationship (r = 0.51) was found between the increase in forced expiratory volume in one second (FEV1) and r2 of the VAS/delta FEV1 analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗

Abnormal humoral immune response to mucosal antigenic stimulation in patients with lung cancer.

Previous studies have suggested an inverse relationship between atopy and cancer of mucosal surfaces. Atopy is classically assessed by detecting specific immunoglobulin E (IgE) antibodies against inhalant allergens. However, Platts-Mills recently proposed that atopy is the ability of an organism to recognize and to respond to limited doses of allergens presented at the mucosal level by producing not only IgE, but also immunoglobulin A and immunoglobulin G (IgG) antibodies. The authors compared the prevalence of atopy in 103 patients with lung cancer (a model of mucosal cancer), 51 patients with chronic obstructive pulmonary disease matched for age, sex, and smoking habits with patients with lung cancer, and 102 healthy control subjects. The authors investigated whether the IgG response to antigens presented at the mucosal level, exacerbated in atopic subjects, might inversely be decreased in patients with lung cancer. Serum IgE antibodies against five common inhalant allergens (Dermatophagoides pteronyssinus [Der p1], Aspergillus fumigatus, grass pollen, and cat and dog danders) were detected through a radioallergosorbent test assay. Serum IgG antibodies against allergens naturally presented at the mucosal level (respiratory mucosa with Der p1 and digestive mucosa with betalactoglobulin [BLG] and soya proteins [SP]) were measured through a solid phase enzyme-linked immunosorbent assay test. Atopic status was assessed in 19 patients (18.4%) with lung cancer, 9 patients (17.6%) with chronic obstructive pulmonary disease (COPD), and 18 healthy control subjects (17.6%). Distributions of specific IgG levels were represented on frequency histograms after natural logarithmic transformation and showed reduced levels of anti-Der p1 and anti-BLG IgG in the cancer population compared with the control populations but similar levels of anti-SP IgG. Influence of sex, age, smoking habits, histologic type of cancer, and its extent could be excluded. The authors' results show no difference in the prevalence of atopy between the three groups. They document a selective, rather than general, defect in the immune response initiated at the mucosal level in patients with lung cancer, the most frequent mucosal cancer in man.

Administration, Inhalation↗