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Biomedical subjects

M Kraft

Publications and source records attributed to M Kraft.

At least 19 recordsLinked to original sources
PubMed1999

Nocturnal asthma is associated with reduced glucocorticoid receptor binding affinity and decreased steroid responsiveness at night.

BACKGROUND: The mechanisms for heightened nocturnal inflammation in patients with nocturnal asthma (NA) are not well understood. OBJECTIVE: We sought to determine the glucocorticoid receptor (GR) characteristics and steroid responsiveness in subjects with NA. METHODS: Eleven subjects with NA, 12 subjects with nonnocturnal asthma (NNA), and 16 nonasthmatic control subjects underwent blood sampling at 4 pm and 4 am in a random order separated by 1 week. GR binding affinity was measured in PBMCs by using a [3H]-dexamethasone (DX) radioligand binding assay and Scatchard analysis. The capacity of hydrocortisone (HC) and DX to suppress proliferation of PBMCs stimulated with PHA was also determined. RESULTS: The subjects with NA exhibited a significantly lower GR binding affinity at 4 am, detected by an elevated dissociation constant (Kd) of 22.2 +/- 1.6 nmol/L compared with Kd at 4 pm (10.9 +/- 0.7 nmol/L; P =.0001). The GR Kd of the NNA and control groups did not change significantly from 4 pm to 4 am. Within the NA group, there was also a significant inverse correlation between the absolute FEV1 at 4 am and the Kd at 4 am (r = -0.65, P =.04). PBMCs from subjects with NA exhibited less suppression of PBMC proliferation with HC and DX at 4 am compared with that at 4 pm (P =.0004 and.03 for HC and DX, respectively). There were no circadian changes in suppression of PBMC proliferation in either the NNA or control groups. CONCLUSION: GR binding affinity and steroid responsiveness exhibit a circadian variation in subjects with NA, with a reduced GR binding affinity and suppression of PBMC proliferation at 4 am that is not observed in normal subjects or asthmatic subjects without nocturnal exacerbation. These observations may contribute to nocturnal airway inflammation by inhibiting the antiinflammatory effects of glucocorticoids.

Adult↗
PubMed1999

Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma.

We have shown in nocturnal asthma that alveolar tissue eosinophils are increased at night as compared with the proximal airway, and that they correlate with the overnight decrement in lung function. As the CD4+ cell is thought to be the principal orchestrating cell in eosinophil recruitment, we evaluated its presence in the proximal and distal airways in nocturnal asthma. Eleven patients with nocturnal asthma (NA) and 10 patients with non-nocturnal asthma (NNA) underwent two bronchoscopies with proximal airway endobronchial and distal alveolar tissue transbronchial biopsy in a random order at 4:00 P.M. and at 4:00 A.M. separated by 1 wk. Immunohistochemical staining and morphometric analysis were used to determine the number of CD3+, CD4+, and CD8+ cells and EG2+ eosinophils per mm2 in the epithelium, lamina propria, and alveolar tissue. At 4:00 A.M., the NA group had a significantly greater number of CD4+ cells in the alveolar tissue than the NNA group (9.8 cells/ mm2 [5.6-30.8, interquartile (IQ)] versus 1.5 cells/mm2 [0-6. 3, IQ], p = 0.04). Within the NA group, there were significantly greater numbers of CD3+, CD4+, CD8+, and EG2+ cells in the proximal airway lamina propria than in the distal airway at both 4:00 P.M. and 4:00 A.M. There were no differences within the epithelium between the groups at either time point. Only alveolar tissue, not airway tissue, CD4+ cells correlated inversely with the percentage predicted FEV1 at 4:00 A.M. (r = -0.68, p = 0.0018) and positively with the number of alveolar tissue EG2+ cells (r = 0.66, p = 0.01). These findings suggest that the CD4+ lymphocyte is increased in the alveolar tissue at night in nocturnal asthma as compared with non-nocturnal asthma.

Adult↗
PubMed1998

Influence of different trocar tips on abdominal wall penetration during laparoscopy.

Most trocars currently used to place a cannula through the abdominal wall have a conical or pyramidal tip. Because the risk of inadvertent injury along with removal of the cannula is probably related to (a) the force needed to traverse the abdominal wall, (b) the force needed to remove the trocar, and (c) the defect in the abdominal wall, the optimum configuration of the penetrating tip should be determined. The entry force needed to perforate the abdominal wall, the removal force necessary to remove the trocar, and the defect in the abdominal wall were measured in a porcine model under standardized conditions (general anesthesia, 12 mmHg pneumoperitoneum). Nineteen trocars (six disposable, seven reusable, six custom-made) have been tested. They were divided into six groups according to the shape of the tip (conical, pyramidal, or a combination). The entry force (F = 25.6, p < 0.0001) and the removal force (F = 5.1, p < 0.01) were related to the shape of the tip. Conical tips needed a higher force than purely pyramidal tips. The abdominal defect was also different between groups (F = 6.5, p < 0. 001). The trocar with a pyramidal shape caused a greater defect than conical tips. The defect in the abdominal wall was inversely related to the entry force (r = -0.55, p < 0.001) and to the removal force (r = -0.57, p < 0.001). There is not an optimum configuration of a simple push-through trocar with a low entry force and a high removal force. Some kind of a conical tip is recommended for insertion of trocars under direct view.

Abdominal Muscles↗
PubMed1998

Expression of epithelial markers in nocturnal asthma.

BACKGROUND: Although the airway epithelium participates in inflammation and repair, the circadian expression of epithelial cell markers involved in these processes has not been investigated. OBJECTIVE: We sought to determine whether expression of CD51 (vitronectin and fibronectin receptor), CD54 (intercellular adhesion molecule-1), HLA-DR (activation marker), CD29 (beta1 integrin), CD49b (collagen receptor), and CD11b (complement receptor) exhibit a circadian rhythm in asthma. METHODS: Eleven patients with nocturnal asthma (NA), 9 subjects with nonnocturnal asthma (NNA), and 10 control subjects underwent bronchoscopy at 4 PM and 4 AM in a random order 1 week apart, with brushing of the proximal and distal airways. The percentage of cells staining for a particular marker was determined. RESULTS: At 4 PM, HLA-DR in the proximal airways and CD54 in the distal airways was significantly greater in control subjects as compared with asthmatic subjects (HLA-DR, control subjects: 10.0% [range, 5.0% to 21.0%]; NNA: 8.0% [range, 4.0% to 14.5%] NA: 3.5% [range, 2.0% to 6.0%], P = .01; CD54, control subjects: 17.0% [range, 8.0% to 25.0%], NNA: 8.0% [range, 5.3% to 11.5%], NA: 7.0% [range, 4.0% to 15.0%], P = .O;). At 4 AM, CD51 in the distal airways was significantly greater in patients with NA as compared with patients with NNA and control subjects (control subjects, 23.0% [range, 13.8% to 30.5%]; NNA, 32.0% [range, 13.0% to 35.0%]; NA, 40.0% [range, 23.0% to 50.0%], P = .05). Expression of CD51 in the distal airways correlated with the degree of airway obstruction (r = -0.57, P = .001). Control subjects exhibited significant circadian variation in the expression of HLA-DR in the proximal airways and CD54 in the distal airways. CONCLUSION: The increased CD51 at night in patients with NA may be related to increased airway inflammation and repair processes in response to injury. The circadian changes in CD54 and HLA-DR in control subjects require further study to determine their significance. (J Allergy Clin

Adult↗
PubMed1998

Synovial fibroblasts as target cells for staphylococcal enterotoxin-induced T-cell cytotoxicity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown aetiology. Recently, superantigens have been implied in the pathogenesis of RA. Superantigens activate a large fraction of T cells leading to the production of cytokines and proliferation. In addition, superantigens direct cellular cytotoxicity towards major histocompatibility complex (MHC) class II-expressing cells. There is now increasing evidence that cytotoxic T cells may be involved in the pathogenesis of RA. In the inflamed synovia class II-positive synovial fibroblasts (SFC) are found. In the present study it was tested whether MHC class II-positive SFC serve as target cells for superantigen-induced cellular cytotoxicity. SFC were stimulated with interferon-gamma to express class II antigens, then they were cultivated in the presence of CD4-positive T cells with or without staphylococcal enterotoxins (SE). Cytotoxicity of T cells was measured as release of lactate dehydrogenase from SFC. Specific cytotoxicity was only found in the presence of class II-positive SFC depending on the dose of SE. Maximum lysis was seen after 20 hr. T-cell cytotoxicity was inhibited by antibodies to MHC class II antigens. The data suggest that class II-positive SFC not only function as accessory cells for SE-mediated T-cell proliferation and interleukin-2 production but may also be the targets of superantigen-mediated cellular cytotoxicity.

Antibodies, Monoclonal↗
PubMed1998

Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma.

Infection with Mycoplasma pneumoniae has been shown to exacerbate asthma in humans. However, the role of M. pneumoniae in the pathogenesis of chronic asthma has not been defined. Eighteen asthmatics with chronic, stable asthma and 11 nonasthmatic control subjects underwent evaluation of the upper and lower airways and serologic analysis to determine the presence of M. pneumoniae, Chlamydia pneumoniae, and seven respiratory viruses through culture, enzyme-linked immunoassay (EIA) and polymerase chain reaction (PCR). M. pneumoniae was detected by PCR in 10 of 18 asthmatics and one of 11 control subjects (p = 0.02). In nine of the 10 patients, the organism was detected in bronchoalveolar lavage or bronchial biopsies. Seven of 18 asthmatics and one of 11 control subjects were also positive for M. fermentans and M. genitalium by PCR. All patients' cultures, EIAs, and serology were negative for M. pneumoniae. All PCR and cultures were negative for C. pneumoniae, and all EIAs for respiratory viruses were negative in all subjects. Nine asthmatics and one control subject exhibited positive serology for C. pneumoniae (p = 0.05). M. pneumoniae was present in the lower airways of chronic, stable asthmatics with greater frequency than control subjects, and may play a role in the pathogenesis of chronic asthma.

Adult↗
PubMed1998

Human corticotropin-releasing hormone improves overnight FEV1 in nocturnal asthma.

Corticotropin-releasing hormone (CRH) exhibits anti-inflammatory properties independent of its effect on adrenal function. We investigated the safety and effect of CRH in nocturnal asthma, a disease where inflammation is prominent. Five subjects underwent an overnight infusion of placebo on the first night, CRH at a 2.5 micrograms/kg/hr on the second night, and three subjects received CRH at 4.0 micrograms/kg/hr on the third night. A significant improvement occurred in overnight change in forced expiratory volume 1 sec. % (delta FEV1) with CRH (+17.4 +/- 9.1%) as opposed to placebo (-25.9 +/- 7.1%), p = 0.024, CRH was well tolerated. Further research with CRH may clarify the pathophysiology of nocturnal asthma.

Adult↗
PubMed1998

Serum cortisol in asthma: marker of nocturnal worsening of symptoms and lung function?

UNLABELLED: Changes in the hormone cortisol have been implicated in the pathogenesis of nocturnal worsening of asthma, or nocturnal asthma (NA). We studied 45 patients, 15 with NA, 15 subjects with non-nocturnal asthma (NNA), and 15 controls over a 24h period, measuring forced expiratory volume in 1 second (FEV1) and serum cortisol at 08:00, 12:00, 16:00, 20:00, 23:00, 04:00, and 08:00 the following day. Evaluation of the time response curves for cortisol revealed a significant difference in the shape of the curves (p = 0.04 by mixed-effects model). Evaluation of individual time points revealed that the cortisol levels in the NNA and control groups were significantly lower than in the NA group at 20:00 (NNA: 3.5 +/- 0.8 mg/mL; CONTROLS: 3.4 +/- 0.8 mg/mL; NA: 4.9 +/- 0.8 mg/mL; p = 0.007). The percentage (%) predicted FEV1 was significantly different among the three groups over the 24h period (p < 0.001). The percentage predicted FEV1 was significantly lower in the NA group compared to the control group at all time points and significantly lower than the NNA group at 16:00, 23:00, and 04:00. The difference among the groups was most pronounced at 04:00, when the percentage predicted FEV1 was 58.9 +/- 2.2% in the NA group, 76.8 +/- 2.9% in the NNA group, and 91.6 +/- 2.8% in the control group (p = 0.001, where each group is significantly different from the others). Although the time response curves for cortisol were significantly different among the three groups, the differences in serum levels of cortisol do not appear to be clinically significant. Therefore, serum levels of cortisol may not be the appropriate measurement to assess the role of cortisol in nocturnal asthma.

Adult↗