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Biomedical subjects

R Kraemer

Publications and source records attributed to R Kraemer.

At least 19 recordsLinked to original sources
PubMed2006

Microcirculation of the ankle after Cryo/Cuff application in healthy volunteers.

The aim of the study was to assess the combination of compression and cryotherapy (Cryo/Cuff ankle device) on parameters of ankle microcirculation in healthy volunteers over 30 min. In 21 volunteers (12 males, 29 +/- 10 years [incl. females], BMI 24 +/- 3) the Cryo/Cuff ankle device (AIRCAST, Summit, NJ, USA) was applied with continuous assessment of parameters of ankle microcirculation, such as tissue oxygen saturation (SO2), relative postcapillary venous filling pressures (rHb), and microcirculatory blood flow at 2- and 8-mm tissue depths during 30 min with the Oxygen-to-see System, a laser-Doppler-spectrophotometry-system (LEA Medizintechnik, Giessen, Germany). Superficial tissue oxygen saturation (SO2, 48 +/- 19 %) immediately dropped to 23 +/- 15 % (-52 %, p < 0.05) within the first 2 min after Cryo/Cuff activation with a consecutive slow decrease to 32 +/- 23 % (- 32 %, p < 0.05 vs. baseline) after 30 min. Deep SO2 (8 mm, 69 +/- 5 %) did not change within 30 min of Cryo/Cuff application (70 +/- 4 %, n.s.). Superficial postcapillary venous filling pressures (61 +/- 17 relative units) showed an immediate and sustained decrease after Cryo/Cuff application within four minutes to 37 +/- 18 relative units (-39 %, p < 0.05). Deep postcapillary venous filling pressures (85 +/- 20 relative units) dropped within the first four minutes of Cryo/Cuff application to 68 +/- 19 relative units (-20 %, p < 0.05). Superficial microcirculatory blood flow (21 +/- 36 relative units) decreased significantly to 7 +/- 5 relative units after 30 min (-69 %, p < 0.05 vs. baseline). Deep microcirculatory blood flow at 8 mm tissue depth (63 +/- 43 relative units) significantly decreased over the 30 min to 39 +/- 23 relative units (-47 %, p < 0.05 vs. baseline). Using the Oxygen-to-see system we could demonstrate significant effects of the Cryo/Cuff device on the ankle level in healthy volunteers with reduced superficial tissue oxygen saturation with preserved deep tissue oxygen saturation, reduced superficial and deep postcapillary venous filling pressures, and reduced superficial and deep microcirculatory blood flow as a function of time. Further clinical studies are mandatory to elucidate the effects of the Cryo/Cuff device on the microcirculatory environment in injured ankles.

Adult↗
PubMed2001

Osmosensing and osmoregulatory compatible solute accumulation by bacteria.

Bacteria inhabit natural and artificial environments with diverse and fluctuating osmolalities, salinities and temperatures. Many maintain cytoplasmic hydration, growth and survival most effectively by accumulating kosmotropic organic solutes (compatible solutes) when medium osmolality is high or temperature is low (above freezing). They release these solutes into their environment when the medium osmolality drops. Solutes accumulate either by synthesis or by transport from the extracellular medium. Responses to growth in high osmolality medium, including biosynthetic accumulation of trehalose, also protect Salmonella typhimurium from heat shock. Osmotically regulated transporters and mechanosensitive channels modulate cytoplasmic solute levels in Bacillus subtilis, Corynebacterium glutamicum, Escherichia coli, Lactobacillus plantarum, Lactococcus lactis, Listeria monocytogenes and Salmonella typhimurium. Each organism harbours multiple osmoregulatory transporters with overlapping substrate specificities. Membrane proteins that can act as both osmosensors and osmoregulatory transporters have been identified (secondary transporters ProP of E. coli and BetP of C. glutamicum as well as ABC transporter OpuA of L. lactis). The molecular bases for the modulation of gene expression and transport activity by temperature and medium osmolality are under intensive investigation with emphasis on the role of the membrane as an antenna for osmo- and/or thermosensors.

Bacteria↗
PubMed2001

An isoflow-volume technique for assessing airway dynamics in children and adults.

BACKGROUND: We propose a new approach to the measurement of small airway function as an alternative to recordings of maximal expiratory flow-volume (MEFV) curves. OBJECTIVES: A newly developed technique to record isoflow-volume (IFV) curves to be tested against maximal respiratory flow curves. METHODS: An isoflow whistle (IFW; Iflopen) measures the length of a constant expiration after full inspiration. The note of the whistle enables a subject to generate an even expiration, and the isoflow maintenance times at 1 l x s(-1) (IFMT1) and 2 l x s(-1) (IFMT2) are recorded. The accuracy and reproducibility of the IFV technique were evaluated in 17 healthy adults (age 17-55 years) and in 14 asthmatic children (age 6-14 years). Comparisons with standard lung function parameters, such as forced expiratory volume in 1 s (FEV1), maximal expiratory flow at 50% (MEF50) and 25% (MEF25) vital capacity and peak expiratory flow (PEF), obtained with a Wright Peakflow Meter were undertaken in 102 healthy (aged 8-14 years) and 101 asthmatic children (aged 6-17 years). A bronchial challenge test was performed in 13 asthmatic children. RESULTS: The expired volume measured by the IFW showed an acceptable agreement with that of a pneumotachograph (mean error of 4.32% for IFMT1 and 5.93% for IFMT2). In healthy and in asthmatic children, the correlations between FEV1 and IFMT1 or IFMT2 (r = 0.92 and 0.94, respectively) were found to be greater than that between FEV1 and PEF (r = 0.68). During bronchial challenge tests in 13 asthmatic children, the FEV1 decreased to 69% of baseline and IFMT1 to 58% of baseline. CONCLUSIONS: The IFV technique accurately measured airway obstruction and closely followed changes in standard parameters of the MEFV curve.

Adolescent↗
PubMed2001

High morbidity and mortality in cystic fibrosis patients compound heterozygous for 3905insT and deltaF508.

Genotype-phenotype association in cystic fibrosis (CF) is difficult because of heterogeneous disease expression. The genotype-phenotype correlation for the 3905insT mutation in comparison to deltaF508 was studied here. Thirty CF patients compound heterozygous for 3905insT were compared to clinical presentation of matched patients homozygous for deltaF508 (1960-1997). Sweat tests, age at diagnosis, at death and at onset of Pseudomonas aeruginosa colonization were analysed. Chrispin-Norman scores and pulmonary function forced expiratory volume in one second (FEV1) determined severity of lung disease. Twenty-five of the patients with 3905insT had deltaF508 as a second mutation and five had another rare mutation. At the age of 15 yrs, 60% of patients with 3905insT had an FEV1 < 60% predicted in comparison to 25% of patients with deltaF508 (p<0.05). Age at death and cumulative survival rate was significantly lower (p<0.05) in the 3905insT than in the deltaF508 group (20.3 and 24.0 yrs, respectively). Age at onset of P. aeruginosa colonization was not different in the study groups. Sweat chloride concentrations were lower in patients homozygous for deltaF508 (105.63+/-15.3 mmol L(-1)) than in patients with 3905insT (119.9+/-22.1 mmol x L(-1)) (p<0.05). Patients compound heterozygous for 3905insT have similar high morbidity and mortality to patients homozygous for deltaF508.

Adolescent↗
PubMed2001

Tracheal-innominate artery fistula caused by the endotracheal tube tip: case report and investigation of a fatal complication of prolonged intubation.

CASE REPORT: A patient with extensive burns was intubated with an 8.0 mm internal diameter endotracheal tube (ETT) equipped with a subglottic suction port (Mallinckrodt HiLo Evac). The ETT was secured to a left upper molar with wire sutures throughout the hospitalization course to ensure airway stability. On the 40th day of intubation, the patient exsanguinated and died from a tracheo-innominate artery fistula. Postmortem examination revealed a 1 cm lesion of the left anterior tracheal wall at the position of the ETT tip. The prolonged stationary position of the ETT was considered the primary factor responsible for the fistula. Yet tracheo-innominate artery fistula normally is associated with high cuff pressures rather than with the tube tip. The special ETT construction required for the subglottic suction feature was suspected to have increased tube rigidity and may have played a contributory role. METHODS: The rigidity of the Mallinckrodt HiLo Evac was measured with a mechanical model and compared to 5 other commercially-available ETTs. Rigidity was expressed as the force generated by the ETT tip when the tube curvature was altered by 5 cm and 10 cm of flexion from its resting position. RESULTS: The mean force exerted by the Mallinckrodt HiLo Evac was 10.1 +/- 2.8 g at 5 cm of flexion and 17.7 +/- 5.1 g at 10 cm of flexion. This was significantly greater than all other ETT brands tested (by one-way analysis of variance and Student-Newman-Kuels test, p < 0.05). CONCLUSION: This case of fatal tracheo-innominate artery fistula formation associated with an ETT tip was unusual because of the extended duration of endotracheal intubation and the complexity of the patient's airway management problems. Our data suggest that the higher rigidity of the HiLo Evac ETT may have contributed to fistula development at the tube tip. However, we do not believe that the higher rigidity of the HiLo Evac ETT necessarily poses any greater risk than other ETTs under normal circumstances, in which the tube tip is not fixed in a stationary position for an extended period.

Adult↗
PubMed2000

Regulation of cell migration in atherosclerosis.

In response to vascular injury, monocytes and smooth muscle cells migrate to the intimal space, resulting in the formation of atherosclerotic and restenotic lesions. Several different growth factors and cytokines have been identified as mediators of cellular migration in the development of neointimal lesions. The principle mediator of monocyte adhesion and recruitment to the injured vascular wall is monocyte chemotactic protein-1. Moreover, recent studies have demonstrated that the atherogenic properties of angiotensin II are due to its ability to induce monocyte chemotactic protein-1 and promote monocyte migration to the vascular wall. Ligand-induced activation of receptor tyrosine kinases are the principle mechanism for smooth muscle cell migration following vascular injury. The signaling pathways mediating receptor-tyrosine kinase-induced migration of smooth muscle cells are also discussed.

Animals↗
PubMed2000

p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells.

The development of atherosclerotic lesions results from aberrant cell migration, proliferation, and extracellular matrix production. In advanced lesions, however, cellular apoptosis, leading to lesion remodeling, predominates. During lesion formation, the neurotrophins and the neurotrophin receptor tyrosine kinases, trks B and C, are induced and mediate smooth muscle cell migration. Here we demonstrate that a second neurotrophin receptor, p75(NTR), is expressed by established human atherosclerotic lesions and late lesions that develop after balloon injury of the rat thoracic aorta. The p75(NTR), a member of the tumor necrosis factor/FAS receptor family, can modulate trk receptor function as well as initiate cell death when expressed in cells of the nervous system that lack kinase-active trk receptors. p75(NTR) expression colocalizes to neointimal cells, which express smooth muscle cell alpha-actin and are expressed by cultured human endarterectomy-derived cells (HEDC). Areas of the plaque expressing p75(NTR) demonstrate increased TUNEL positivity, and HEDC undergo apoptosis in response to the neurotrophins. Finally, neurotrophins also induced apoptosis of a smooth muscle cell line genetically manipulated to express p75(NTR), but lacking trk receptor expression. These studies identify the regulated expression of neurotrophins and p75(NTR) as an inducer of smooth muscle cell apoptosis in atherosclerotic lesions.

Animals↗
PubMed2000

Moment ratio analysis of multiple breath nitrogen washout in infants with lung disease.

Measurement of lung volumes at end expiratory level and assessment of ventilation inhomogeneity is important for respiratory management in infants with lung disease. This study compared multiple breath nitrogen washout was compared with body plethysmography to measure functional residual capacity in infants and assessed ventilation inhomogeneity using mean dilution numbers and alveolar based gas dilution numbers. Measurements were performed in 23 infants with lung disorders, eleven had wheezing bronchitis, four bronchopulmonary disease, and eight cystic fibrosis. Mean age was 11.2+/-5.8 months. Functional residual capacity of nitrogen washout (29.8+/-11.4 mL x kg(-1)) was significantly (p<0.05) lower than the plethysmographically measured functional residual capacity (40.3+/-11.4 mL x kg(-1)). Tidal volumes before nitrogen washout (90.4+/-35.1 mL) were significantly larger than at the end of the washout (72.2+/-26.9 mL). Alveolar based gas dilution numbers (6.7+/-2.3) were significantly lower (p<0.001) than mean dilution numbers (10+/-5.7). Functional residual capacity determination by nitrogen washout and plethysmography in infants with lung disease showed evidence of air trapping and ventilation inhomogeneity. Ventilation inhomogeneities are best described by alveolar based dilution numbers, since rebreathing of 100% oxygen changes ventilation pattern.

Breath Tests↗
PubMed2000

Early detection of lung disease and its association with the nutritional status, genetic background and life events in patients with cystic fibrosis.

Progression of lung disease is the most prominent cause of morbidity and death in patients with cystic fibrosis (CF), but the severity of lung disease and the rate of lung function decline are highly variable. An attempt was made to define accurate estimates of disease progression in these patients early diagnosed and prospectively evaluated until 10 years of age. The primary question to ask was whether functional abnormalities detected already in infancy are associated with functional derangements later on in life, and may be useful as parameters of prognostic value. Early diagnosis of CF can best be achieved by screening of mutation by new techniques (buccal cell brushing) in infants, even when the sweat test or accurate blood sampling is not available. Moreover, in infants lung function can be assessed by infant whole-body plethysmography enabling the study of the interrelationship with delayed weight gain and growth retardation, as well as the associations with the most common disease-causing mutations. Out of a cohort of 80 infants (39 males, 41 females) with CF a follow-up study was started with 50 CF infants diagnosed during infancy (mean age 4.6 +/- 4.0 months; range 0.1-12.7 months) and prospectively evaluated at 6-month intervals during the first 2 years of life. Moreover, in 32 CF children out of this cohort, follow-up was continued until 10 years of age. Differences were encountered with respect to the different events occurring during the first years of life, especially the onset of chronic colonization with Pseudomonas aeruginosa. The association between infant lung function and specific mutations (DeltaF508 homozygotes, frameshift DeltaF508/3905insT compound heterozygotes and nonsense DeltaF508/R553X compound heterozygotes) furthermore revealed that differences in lung function within the genetic groups are mainly related to the degree of pulmonary hyperinflation. Pulmonary hyperinflation was also associated with the degree of impaired nutritional status. An association between impaired gas exchange characteristics at 10 years of age and the degree of pulmonary hyperinflation during infancy finally demonstrates that by early mutation screening, lung function testing and assessment of the nutritional status predictors of disease progression later on in life can be defined. Therefore, preventive therapeutic measures should primarily be based on such prognostic factors.

Age Factors↗
PubMed2000

Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization.

Brain derived neurotrophic factor, BDNF, is a neurotrophin best characterized for its survival and differentiative effects on neurons expressing the trk B receptor tyrosine kinase. Although many of these neurons are lost in the BDNF(-)(/)(- )mouse, the early postnatal lethality of these animals suggests a wider function for this growth factor. Here, we demonstrate that deficient expression of BDNF impairs the survival of endothelial cells in intramyocardial arteries and capillaries in the early postnatal period, although the embryonic vasculature can remodel into arteries, capillaries and veins. BDNF deficiency results in a reduction in endothelial cell-cell contacts and in endothelial cell apoptosis, leading to intraventricular wall hemorrhage, depressed cardiac contractility and early postnatal death. Vascular hemorrhage is restricted to cardiac vessels, reflecting the localized expression of BDNF and trk B by capillaries and arterioles in this vascular bed. Conversely, ectopic BDNF overexpression in midgestational mouse hearts results in an increase in capillary density. Moreover, BDNF activation of endogenous trk B receptors supports the survival of cardiac microvascular endothelial cells cultured from neonatal mice. These results establish an essential role for BDNF in maintaining vessel stability in the heart through direct angiogenic actions on endothelial cells.

Animals↗
PubMed2000

The rise and fall of i-STAT point-of-care blood gas testing in an acute care hospital.

In response to a $350,000 laboratory budget cut and closure of an intensive care unit-based laboratory and a desire to maintain turnaround times of 10 minutes or less, a multidisciplinary group developed and implemented point-of-care (POC) testing. Only blood gases (pH, PO2, and PCO2) and ionized calcium values were deemed essential stat tests. Three commercially available POC blood gas devices were evaluated; all yielded results comparable to in-house reference methods. The 1 device with a US Food and Drug Administration-approved method for ionized calcium testing and with an existing interface for laboratory information systems was selected. Fiscal analysis predicted annual savings of approximately $225,000. POC blood gas analysis was implemented in April 1996 coincident with closure of the intensive care unit-based laboratory. Clinical laboratories and POC blood gas test volumes remained constant through August 1998; in contrast, the number of ionized calcium tests decreased dramatically after April 1996. In August 1998, clinically significant (i.e., artificial ventilation parameters would have been altered based on test results) discrepant PCO2 values were observed sporadically and noted only with patient specimens, not with commercial controls or electronic simulators. Because investigation failed to identify the cause, use of the POC device was discontinued in September 1998.

Blood Gas Analysis↗
PubMed1999

GGF/neuregulin induces a phenotypic reversion of oligodendrocytes.

We have previously shown that glial growth factor (GGF), a member of the neuregulin (NRG) family of growth factors, is a mitogen and survival factor for oligodendrocyte progenitors in cell culture and blocks their differentiation at the pro-oligodendrocyte stage (P. D. Canoll et al., 1996, Neuron 17, 229-243). We now show that GGF is able to induce differentiated oligodendrocytes to undergo a phenotypic reversion characterized by loss of MBP expression, reexpression of the intermediate filament protein nestin, reorganization of the actin cytoskeleton, and a dramatic reduction in the number of processes per cell. TUNEL analysis demonstrates that GGF is not cytotoxic for mature oligodendrocytes, but rather enhances their survival. GGF also induces the rapid activation of the PI 3-kinase and MAP kinase signaling pathways. These results further support a role for the NRGs in promoting the proliferation and survival of and inhibiting the differentiation of cells in the oligodendrocyte lineage and demonstrate that oligodendrocytes that differentiate in culture retain a substantial degree of phenotypic plasticity.

Actins↗
PubMed1999

Two buffer PAGE system-based SSCP/HD analysis: a general protocol for rapid and sensitive mutation screening in cystic fibrosis and any other human genetic disease.

The large size of many disease genes and the multiplicity of mutations complicate the design of an adequate assay for the identification of disease-causing variants. One of the most successful methods for mutation detection is the single strand conformation polymorphism (SSCP) technique. By varying temperature, gel composition, ionic strength and additives, we optimised the sensitivity of SSCP for all 27 exons of the CFTR gene. Using simultaneously SSCP and heteroduplex (HD) analysis, a total of 80 known CF mutations (28 missense, 22 frameshift, 17 nonsense, 13 splicesite) and 20 polymorphisms was analysed resulting in a detection rate of 97.5% including the 24 most common mutations worldwide. The ability of this technique to detect mutations independent of their nature, frequency, and population specificity was confirmed by the identification of five novel mutations (420del9, 1199delG, R560S, A613T, T1299I) in Swiss CF patients, as well as by the detection of 41 different mutations in 198 patients experimentally analysed. We present a three-stage screening strategy allowing analysis of seven exons within 5 hours and analysis of the entire coding region within 1 week, including sequence analysis of the variants. Additionally, our protocol represents a general model for point mutation analysis in other genetic disorders and has already been successfully established for OTC deficiency, collagene deficiency, X-linked myotubular myopathy (XLMTM), Duchenne and Becker muscular dystrophy (DMD, BMD), Wilson disease (WD), Neurofibromatosis I and II, Charcot-Marie-Tooth disease, hereditary neuropathy with liability to pressure palsies, and defects in mitochondrial DNA. No other protocol published so far presents standard SSCP/HD conditions for mutation screening in different disease genes.

Base Sequence↗
PubMed1999

NGF activates similar intracellular signaling pathways in vascular smooth muscle cells as PDGF-BB but elicits different biological responses.

The signaling pathways that regulate smooth muscle cell migration and proliferation are incompletely understood. Smooth muscle cells express at least 3 families of receptor tyrosine kinases that mediate cell migration: platelet-derived growth factor (PDGF) receptors, the trk family of neurotrophin receptors, and insulin-like growth factor 1 receptor. The neurotrophin, nerve growth factor (NGF), and insulin-like growth factor 1 induce the migration but not the proliferation of smooth muscle cells, whereas PDGF-BB stimulates both responses. To determine whether distinct signaling pathways downstream of receptor tyrosine kinases specifically mediate smooth muscle cell migration or proliferation, the ligand-induced activation of different signaling pathways in smooth muscle cells was examined. NGF induces prolonged activation of the Shc/MAP kinase pathway and phospholipase Cgamma compared with PDGF-BB. The activation of phosphatidylinositol-3 kinase, however, was 10-fold greater in response to PDGF-BB compared with NGF. Insulin-like growth factor 1 activates only phosphatidylinositol-3 kinase. Pharmacological inhibitors of phosphatidylinositol-3 kinase, Wortmannin and LY294002, inhibit PDGF-BB and NGF-induced migration, whereas an inhibitor of MAP kinase kinase, PD98059, has no effect. Our results suggest that (1) different receptor tyrosine kinases use similar patterns of activation of signaling pathways to mediate distinct biological outcomes of cell migration and proliferation, (2) NGF activates signaling proteins in smooth muscle cells similar to those activated during NGF-induced neuronal differentiation, and (3) the combinatorial effects of different signaling pathways are important for the regulation of smooth muscle cell migration and proliferation. Further studies using mutant trk receptors will help to define the signal transduction pathways mediating NGF-induced smooth muscle cell migration.

Animals↗
PubMed1999

Airway and tissue resistance in wheezy infants: effects of albuterol.

We partitioned total respiratory system resistance into airway (Raw) and tissue (Rti) resistance in 16 sedated infants (age 15 to 88 wk) with a history of wheezing disorders before and after inhalation of albuterol. Using systems identification methods, airway (Raw-z) and tissue resistance (Rti-z) were extracted from measurements of respiratory system transfer impedance (Ztr[omega]) over a wide frequency range (typically, 4 < f < 140 Hz). Baseline Raw-z (80.6 +/- 31.5 cm H(2)O/L/s) was significantly (p < 0.01) reduced after albuterol inhalation (60.6 +/- 22.2 cm H(2)O/L/s) but pre- and postalbuterol Rti-z were not significantly different (2.3 +/- 1.7 and 2.7 +/- 2.4 cm H(2)O/L/s, respectively). Raw-z was compared with airway resistance measured with whole-body plethysmography (Raw-p) in 10 of the 16 infants. Raw-z and Raw-p were significantly different in baseline as well as postalbuterol conditions (86.4 +/- 36.9 versus 19.0 +/- 7.0, and 60.6 +/- 22.0 versus 22.5 +/- 14.7, respectively) and they were not correlated. There was no significant difference between Raw-p under baseline and postalbuterol conditions. We conclude that airway resistance estimated from Ztr measurements comprises the major portion of total resistance (approximately 97%) in infants with wheezing disorders in baseline as well as post-beta agonist inhalation, and it is significantly reduced by albuterol inhalation.

Administration, Inhalation↗
PubMed1998

Multicenter, open-label study of recombinant human DNase in cystic fibrosis patients with moderate lung disease. DNase International Study Group.

Cystic fibrosis is characterized by the accumulation of thick viscous purulent secretions. Recombinant human deoxyribonuclease I (rhDNase) breaks down extracellular DNA, which contributes to the increased viscosity of sputum. A multinational, open-label study was conducted in 974 cystic fibrosis patients with moderate lung disease [forced vital capacity (FVC) 40-70% of predicted values] to examine the safety and efficacy of aerosolized rhDNase, 2.5 mg, once daily over a period of at least 12 weeks. Patients were assessed under conditions reflecting routine clinical practice. During rhDNase therapy, at least one respiratory tract infection (RTI) requiring intravenous antibiotics was experienced by 29.5% of patients. Forced expiratory volume in 1 second (FEV1) and FVC were significantly improved from baseline by a mean of 10.5% and 7.2%, respectively. Voice alteration and pharyngitis were the most frequent rhDNase-related adverse events, but only 2% of all patients discontinued treatment due to adverse events. The results obtained were similar to a subanalysis of data from the first 3 months of a placebo-controlled U.S. study. The patients in the present study had a similar frequency of RTIs and improvement in pulmonary function, and reported fewer rhDNase-related and cystic fibrosis-related adverse events than patients in the U.S. study. We conclude that administration of rhDNase is safe, well tolerated, and effective under conditions reflecting routine clinical practice in patients with cystic fibrosis and moderate lung disease.

Administration, Inhalation↗
PubMed1998

Screening of the Fc epsilon RI-beta-gene in a Swiss population of asthmatic children: no association with E237G and identification of new sequence variations.

BACKGROUND: The gene of the beta subunit of the high affinity receptor for IgE (Fc epsilon RI-beta) encoded on chromosome 11q13 has recently been identified as a candidate gene for asthma and atopy. Two coding variations, E237G and I181L have been described as being associated with asthma and atopy. Our aim was to investigate a Swiss population of atopic and asthmatic children for variations in this gene. METHODS: We screened all 7 exons of the Fc epsilon RI-beta-gene in 224 atopic/asthmatic, 68 relatives and 159 control subjects using exon amplification by PCR and single strand conformation polymorphism (SSCP) analysis followed by fluorescence based DNA sequencing. RESULTS: The sequence variant E237G was found in 3.7% in atopics and in 2.6% in the control population. None of the samples carried the I181L mutation. In addition, we characterised nine novel mutations (1 nonsense mutation, 2 missense mutations, mutation, 2 silent mutations, 4 intronic mutations). CONCLUSIONS: Our results suggest that the E237G does not have a primary effect on the development of atopy and asthma, and thus excludes the Fc epsilon RI-beta locus from being a candidate gene directly involved in these diseases.

Adolescent↗