Biomedical subjects

Tobias Lange

Publications and source records attributed to Tobias Lange.

5 recordsLinked to original sources

PubMed2006

Physiological concept for a blood based CFTR test.

We tested the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) could be involved in the volume regulation of human red blood cells (RBC). Experiments were based on two gadolinium (Gd(3+)) sensitive mechanisms, i.e. inhibition of ATP release (thetaATP(i)) and membrane destabilization. RBC of either cystic fibrosis (CF) patients or healthy donors (non-CF) were exposed to KCl buffer containing Gd(3+). A significantly larger quantity of non-CF RBC (2.55 %) hemolyzed as compared to CF RBC (0.89 %). It was found that both of the Gd(3+) mechanisms simultaneously are needed to achieve hemolysis, since either overriding thetaATP(i) by exogenous ATP addition prevented Gd(3+) induced hemolysis, or mimicking thetaATP(i) by apyrase in absence of Gd(3+) could not trigger hemolysis. Additionally, ion driven volume uptake was found to be a prerequisite for Gd3+ induced hemolysis as chloride and potassium channel blockers reduced the Gd(3+) response. The results show that in non-CF RBC Gd(3+) exerts its dual effect leading to hemolysis. On the contrary, in CF RBC, lacking CFTR dependent ATP release, the sole Gd(3+) effect of membrane destabilization is not sufficient to induce hemolysis similar to non-CF. This concept could form the basis of a novel method suitable for testing CFTR function in a blood sample.

Adenosine Triphosphate↗

PubMed2005

First-line systemic treatment with gefitinib in stage IV non-small cell lung cancer.

Lung cancer has a high mortality rate and is often diagnosed in locally advanced or metastatic stages. A new therapeutic option for patients with non-small cell lung cancer (NSCLC) in these stages with progress or relapse after platinum-based chemotherapy exists in the inhibitors of the epidermal growth factor receptor (EGFR) tyrosine-kinase. EGFR tyrosine-kinase inhibitor treatment might also be an option for patients ineligible for surgery and conventional chemotherapy. We present a case of a 53-year-old woman who was diagnosed due to pain from multiple bone metastases of a lung adenocarcinoma. She refused cytotoxic chemotherapy, and we administered first-line systemic treatment with gefitinib subsequent to radiotherapy of metastatic bone disease. The patient responded well to gefitinib treatment and achieved a partial response after 3 weeks. No relevant side effects occurred, and the patient experienced an 8-month remission of disease. With a follow-up of 10 months, the patient is still alive. Retrospectively, we found a mutation of the EGF receptor in tumor cells of the patient, which is associated with sensitivity to gefitinib. EGFR tyrosine-kinase inhibitors (TKI) can be an alternative first-line systemic treatment option for selected patients with metastatic NSCLC.

Adenocarcinoma↗

PubMed2004

Non-small-cell lung cancer: multimodality approach in stage-III resectable disease.

The long-term results of surgery +/- radiotherapy in patients with operable disease of locally advanced non-small-cell lung cancer are discouraging. In the vast majority, disseminated microscopic disease, resulting in the later occurrence of distant metastases, contributes substantially to this poor long-term outcome. The further development of multimodality treatment approaches in randomised trials, including effective systemic therapy, is necessary. These approaches and the current status of multimodality treatment strategies of resectable locally advanced non-small-cell lung cancer are discussed.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Exhaled breath condensate nitrite and its relation to tidal volume in acute lung injury.

STUDY OBJECTIVE: Mechanical ventilation may damage the lung. Low tidal volume (VT) is protective, but VT is scaled to body weight (BW) and may be high in functionally small ARDS lungs. We hypothesized that exhaled breath condensate (EBC) nitrite (NO(2)(-)) concentration may increase with lung distension. DESIGN: Prospective, noncontrolled study. SETTING: University hospital and medical ICU. PATIENTS: Thirty-five ICU patients requiring mechanical ventilation (severe pneumonia, n = 31; exacerbated COPD, n = 4). Patients were scored according to American and European Consensus Conference on ARDS criteria (AECC) [no lung injury, n = 7; acute lung injury, n = 13; ARDS, n = 15], as well as the Murray lung injury severity score (LISS) [score 0, n = 3; score 0.1 to 2.5, n = 19; score > 2.5, n = 13]. INTERVENTIONS: EBC was collected and analyzed for NO(2)(-), interleukin (IL)-6, and IL-8. Serum was analyzed for IL-6, IL-8, and procalcitonin. RESULTS: and measurements: EBC NO(2)(-) correlated well with VT (milliliters per kilogram of BW; r = 0.79, p < 0.0001) and expiratory minute volume (r = 0.60, p < 0.0001) but not with other ventilatory parameters or parameters of pulmonary (EBC IL-6, EBC IL-8) or systemic (serum IL-6, IL-8, and procalcitonin) inflammation. The ratio of EBC NO(2)(-) and the size of the VT correlated directly with lung injury (AECC, r = 0.66, p < 0.0001; LISS, r = 0.84, p < 0.0001). CONCLUSION: EBC NO(2)(-) increased linearly with VT. The ratio of EBC NO(2)(-) to VT is assumed to reflect NO(2)(-) release at a given VT. An increase in this ratio indicates an inappropriate increase of NO(2)(-) production most likely due to mechanical stress of the remaining open lung units in injured lungs. We conclude that the EBC NO(2)(-)/VT ratio may help to identify situations of critical mechanical stress.

Acute Disease↗

PubMedDate not supplied

Reduced number of CFTR molecules in erythrocyte plasma membrane of cystic fibrosis patients.

Cystic fibrosis (CF), the most common genetic disease among Caucasians, is caused by mutations in the gene encoding CFTR (cystic fibrosis transmembrane conductance regulator). The most frequent mutation, DeltaF508, results in protein misfolding and, as a consequence, prevents CFTR from reaching its final location at the cell surface. CFTR is expressed in various cell types including red blood cells. The functional role of CFTR in erythrocytes is still unclear. Since the number of CFTR copies in a single erythrocyte of healthy donors and CF patients with a homozygous DeltaF508 mutation is unknown, we counted CFTR, localized in erythrocyte plasma membrane, at the single molecule level. A novel experimental approach combining atomic force microscopy with quantum-dot-labeled anti-CFTR antibodies, used as topographic surface markers, was employed to detect individual CFTR molecules. Analysis of erythrocyte plasma membranes taken from healthy donors and CF patients with a homozygous DeltaF508 mutation reveals mean (SEM) values of 698 (12.8) (n=542) and 172 (3.8) (n=538) CFTR molecules per red blood cell, respectively. We conclude that erythrocytes reflect the CFTR status of the organism and that quantification of CFTR in a blood sample could be useful in the diagnosis of CFTR related diseases.

Antibodies↗