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Biomedical subjects

C Stahl

Publications and source records attributed to C Stahl.

At least 19 recordsLinked to original sources
PubMed2001

Cloning, expression, and carbon catabolite repression of the bamM gene encoding beta-amylase of Bacillus megaterium DSM319.

The bamM gene from Bacillus megaterium DSM319 encoding an extracellular beta-amylase was isolated and completely sequenced. Chromosomal inactivation by deletion mutagenesis resulted in total loss of amylolytic activity, indicative of a single starch-degrading enzyme. Functional characterization of the expressed protein revealed a maltogenic enzyme exhibiting optimal activities at pH 7.5 and 50 degrees C. Amylase expression is subject to catabolite repression by glucose. A putative cis-acting catabolite-responsive element (CRE) was identified; it is located within the bamM coding region, matching the position of the predicted signal peptide processing site. Base substitutions introduced by site-directed mutagenesis within the bamM-CRE--retaining unchanged the amino acid sequence--provoked a remarkable relief from carbon catabolite repression (CCR), thereby proving functionality of the CRE for CCR.

Amino Acid Sequence↗
PubMed2001

MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatis.

MspA is an extremely stable, oligomeric porin from Mycobacterium smegmatis that forms water-filled channels in vitro. Immunogold electron microscopy and an enzyme-linked immunosorbent assay demonstrated that MspA is localized in the cell wall. An mspA deletion mutant did not synthesize detectable amounts of mspA mRNA, as revealed by amplification using mspA-specific primers and reverse-transcribed RNA. Detergent extracts of the DeltamspA mutant exhibited a significantly lower porin activity in lipid bilayer experiments and contained about fourfold less porin than extracts of wild-type M. smegmatis. The chromosome of M. smegmatis encodes three proteins very similar to MspA. Sequence analysis of the purified porin revealed that mspB or mspC or both genes are expressed in the DeltamspA mutant. The properties of this porin, such as single channel conductance, extreme stability against denaturation, molecular mass and composition of 20 kDa subunits, are identical to those of MspA. Deletion of mspA reduced the cell wall permeability towards cephaloridine and glucose nine- and fourfold respectively. These results show that MspA is the main general diffusion pathway for hydrophilic molecules in M. smegmatis and was only partially replaced by fewer porins in the cell wall of the DeltamspA mutant [corrected] This is the first experimental evidence that porins are the major determinants of the exceptionally low permeability of mycobacteria to hydrophilic molecules.

Amino Acid Sequence↗
PubMed2001

Removal of contrast media by different extracorporeal treatments.

BACKGROUND: Although the capability of extracorporeal treatments after administration of contrast media to prevent radiocontrast-induced nephropathy is controversial, haemodialysis is performed in many institutions after radiographic procedures. There are conflicting reports on the efficacy of different dialysers and treatment modalities to remove contrast media. METHODS: We compared the contrast medium-removing ability of different extracorporeal treatments in a randomized trial. Thirty-nine patients on chronic renal-replacement therapy or with chronic renal failure were randomized to receive low-flux haemodialysis (Low-HD, n=10), high-flux haemodialysis (High-HD, n=10), online haemodiafiltration (HDF, 10 litre substitution, n=10) and online haemofiltration (HF, 18 litre substitution, n=9) after administration of contrast medium during routine radiological procedures. Plasma concentrations of contrast medium (iopromide or iomeprol) were measured by energy-dispersive X-ray fluorescence analysis. RESULTS: The extraction ratio for contrast media was 0.64+/-0.1 for Low HD (P<0.05 vs. High-HD and vs. HDF), 0.74+/-0.1 for High-HD (P<0.05 vs. HF), 0.81+/-0.1 for HDF (P<0.05 vs HF), and 0.62+/-0.1 for HF. Mean extracorporeal plasma clearances were 82+/-2 for Low-HD (P<0.05 vs. High-HD and vs HDF), 100+/-2 for High-HD, 115+/-4 for HDF (P<0.05 vs. HF), and 86+/-5 ml/min for HF. CONCLUSIONS: We conclude that HDF and High-HD remove contrast media more effectively than Low-HD and HF during the time of each treatment session. However, whether this is also true for the overall elimination of contrast media by these different procedures needs to be addressed in future studies, by a precise assessment of the drug time course after the session.

Angiography↗
PubMed2000

Trichostatin A modulates expression of p21waf1/cip1, Bcl-xL, ID1, ID2, ID3, CRAB2, GATA-2, hsp86 and TFIID/TAFII31 mRNA in human lung adenocarcinoma cells.

Lung adenocarcinoma cells treated for 16 h with trichostatin A (TSA), an inhibitor of histone deacetylases, and untreated cells were analyzed with respect to differential gene expression. Complex hybridization of cDNA arrays revealed repression of Bcl-xL, CRAB2 and TFIID/TAFII31 as well as induction of p21waf1/cip1, GATA-2, hsp86, ID1, ID2 and ID3 mRNA expression, which could be verified by Northern blotting. ID2 induction was further confirmed by Taqman realtime quantitative RT-PCR. The described alterations of gene expression due to TSA renders the lung adenocarcinoma cells susceptible to induction of apoptosis.

Adenocarcinoma↗
PubMed2000

Trichostatin A-mediated regulation of gene expression and protein kinase activities: reprogramming tumor cells for ribotoxic stress-induced apoptosis.

Recently we described a new signal transduction-based tumor therapeutic strategy involving first sensitization of tumor cells by trichostatin A (TSA), an inhibitor of histone deacetylation, and thereafter efficient apoptotic triggering by ribotoxic agents, which activate stress-activated protein kinases. In the present work we investigate the molecular basis of the sensitization step in this therapeutic model system and describe TSA-induced changes in mRNA and protein expression of several candidate genes identified previously by complex hybridization. Furthermore, activities of 15 different protein kinases were followed after TSA application, using a new filter-based technique (PhosphoSpots-Assay). The obtained data suggest that TSA induces pro-apoptotic genes like ID1, ID2, ID3, and down-regulates anti-apoptotic genes like Hsp27 and Bcl-xL, thereby shifting the cellular equilibrium from life to death. Furthermore, activities of calcium/calmodulin-dependent kinase II and protein kinase C, which have been assigned pro-apoptotic function in other systems, are induced.

Apoptosis↗
PubMed2000

NCCN Practice Guidelines for Cancer-Related Fatigue.

These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue, using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for the five primary factors known to be associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism. If any of these conditions are present, it should be treated according to practice guidelines, and the patient's fatigue should be reevaluated regularly. If none of the primary factors is present or the fatigue is unresolved, a more comprehensive assessment is indicated--with referral to other care providers as appropriate. The comprehensive assessment should include a thorough review of systems, review of medications, assessment of comorbidities, nutritional/metabolic evaluation, and assessment of activity level. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, restorative therapies to decrease cognitive alterations and improve mood state, and nutritional and sleep interventions for patients with disturbances in eating or sleeping. Pharmacologic therapy may include drugs such as antidepressants for depression or erythropoietin for anemia. A few clinical reports of the use of corticosteroids and psychostimulants suggest the need for further research on these agents as a potential treatment modalities in managing fatigue. Basic to these interventions, the effective management of cancer-related fatigue involves an informed and supportive oncology care team that assesses patients' fatigue levels regularly and systematically and incorporates education and counseling regarding strategies for coping with fatigue (Johnson, 1999), as well as using institutional fatigue management experts for referral of patients with unresolved fatigue.

Exercise↗
PubMed1999

[Effect of oxygen (FI02: 0.35) on the aerobic capacity in patients with COPD].

BACKGROUND: Disability in patients with chronic obstructive pulmonary disease has led to the development of rehabilitation programs to increase exercise tolerance. OBJECTIVE: To determine, if the effect of training can be improved by giving supplemental oxygen during exercise. MEASUREMENTS: Ten male patients with COPD (mean FEV1 = 43.2 +/- 17.1% pred) underwent a five day per week cycle ergometer training program for four weeks at least 45 minutes per day at a constant workload of 80% of their highest achieved workrate--measured in an incremental exercise test before training. At this workrate all patients performed exercise above their anaerobic threshold. Five patients were breathing 35% oxygen during exercise, five were breathing roomair (randomised, single blind). To evaluate and compare the results of training before and after the program all patients performed an incremental exercise test (continuously increasing workrate) with roomair. RESULTS: In the group breathing 35% O2 during training the maximally achieved power in the incremental exercise test after training was 15.9% higher. In the group breathing roomair during training the maximally achieved power after training was 36.3% higher than before (p < 0.05). This group also showed significant reductions in lactate levels (p < 0.05) after training at the maximum workload achieved in the pre-training test. CONCLUSIONS: Training in the roomair-group resulted in a significant increase in the maximum power and total amount of work. In this group training could induce a physiologic response (increase of aerobic capacity), which was shown by significantly lower lactate levels at a comparable workload.

Exercise↗
PubMed1999

Sensitization of tumor cells to ribotoxic stress-induced apoptotic cell death: a new therapeutic strategy.

We describe a procedure that sensitizes chemotherapy-and tumor necrosis factor-resistant human tumor cell populations in vitro and in nude mouse transplants to the immediate triggering of high rates of cell death by anisomycin, an agent causing activation of stress-activated protein kinases [SAPKs, as defined by P. Cohen (Trends Cell Biol., 7: 353-361, 1997)] including p38/RK and c-jun NH2-terminal kinase homologues, following its binding to ribosomal 28S RNA (M. S. Iordanov et al, Mol. Cell. Biol., 17: 3373-3381, 1997). Sensitization is effected by successive application of an inhibitor of histone deacetylation (trichostatin A, butyrate) and of flavopiridol, known as an inhibitor of cyclin dependent kinases and evaluated presently in clinical trials. Effective concentrations of anisomycin, flavopiridol, and trichostatin A are in the submicromolar range. Tumor cell death can be prevented by epidermal growth factor (EGF), if added before flavopiridol or after anisomycin but not if applied between the additions of these agents, suggesting that flavopiridol interrupts an EGF-activated survival pathway and that anisomycin, besides triggering cell death, guards this pathway against the interference by flavopiridol. In contrast to EGF, dibutyryl-cAMP exerts protection that is flavopiridol-insensitive. For triggering cell death, anisomycin cannot be replaced by DNA- or mitotic spindle-targeted drugs in this system. The present findings, that a combination of transcriptional and signal transduction-targeted modulators sensitizes tumor cells synergetically to stress-mediated triggering of cell death and that ribotoxic stress is more efficient in this respect than genotoxic or spindle-targeted stress, bear important implications for the therapeutic exploitation of cellular stress responses. The stepwise sensitization and triggering of cell death in the present system allow separate analysis and manipulation of processes contributing to cellular death susceptibility and of the mechanism responsible for triggering cell death, thus providing the operational basis for further development of this therapeutic approach.

Animals↗
PubMed1997

Is heparin contraindicated in pelvic lymphadenectomy and radical prostatectomy?

PURPOSE: We initiated a prospective study to verify or refute the complications of lymphocele formation and excessive blood loss associated with heparin prophylaxis in pelvic lymphadenectomy and radical prostatectomy. MATERIALS AND METHODS: A prospective study was completed on 579 men undergoing pelvic lymphadenectomy usually in association with radical prostatectomy. Patients were assigned to group 1 (given preoperative and postoperative subcutaneous heparin) and group 2 (no heparin). All patients were evaluated 2 to 3 weeks after surgery with ultrasound for pelvic lymphocele. RESULTS: There was no statistically significant difference in the number or size of pelvic lymphoceles or blood loss in group 1 versus group 2. CONCLUSIONS: The use of heparin prophylaxis to prevent thromboembolic complications in conjunction with pelvic lymphadenectomy and radical prostatectomy is not associated with increased blood loss or increased rate of lymphocele formation.

Blood Loss, Surgical↗
PubMed1997

Recombinant, B-domain deleted factor VIII (r-VIII SQ): pharmacokinetics and initial safety aspects in hemophilia A patients.

The pharmacokinetics of a second-generation recombinant B-domain deleted factor VIII (FVIII) preparation (r-VIII SQ) were studied in 36 patients with severe hemophilia A. In contrast to full-length recombinant FVIII, no albumin needs to be added to stabilize the final formulation of this B-domain deleted FVIII preparation. The in vivo recovery and half-life of r-VIII SQ were similar to those of plasma-derived (pd) FVIII (mean half-life of r-VIII SQ, 11.7 h). The volume of distribution and clearance were slightly, but significantly, higher for r-VIII SQ than for pdFVIII (p < 0.05). Peak plasma levels of FVIII were consistently related to the administered dose of r-VIII SQ (r = 0.94, p < 0.0001). The pharmacokinetic profile of r-VIII SQ remained essentially unchanged in a dose range of 25-100 IU/kg body weight and could be reproduced after repeated doses. r-VIII SQ was well tolerated. In conclusion, deletion of the B-domain of FVIII does not influence its in vivo pharmacokinetics.

Adolescent↗
PubMed1996

Methodologic considerations in the interpretation of postmortem carboxyhemoglobin concentrations.

The interpretation of postmortem carboxyhemoglobin (COHb) concentrations can have major implications even when COHb is not the direct cause of death. Much litigation may hinge on the length of time an individual was alive during the fire. Therefore, the reliability of an analytical method to measure COHb, ranging from low to sub-lethal levels, is critical to the proper interpretation of results. This study used 40 blood specimens from fire deaths and 15 blood specimens from non-fire deaths to compare COHb levels obtained from a spectrophotometric method (IL 482 CO-Oximeter; CO-Ox) with a reference gas chromatographic method (GC). Since spectrophotometric methods are influenced by the amount of total hemoglobin (Hb) present in the blood, multiple saline dilutions of specimens were performed to yield Hb as low as 1g/dl. For GC COHb concentrations < 5% and Hb > or = 4g/dl, the average and median ratios of CO-Ox COHb to GC COHb concentrations were 2.8 and 2.6 respectively. These ratios were 8.0 and 6.8 respectively when Hb < 4g/dl. At GC COHb levels ranging from 5 to 40% and Hb > or = 4g/dl, the average and median ratios were 1.6 and 1.0 respectively. These ratios were correspondingly 2.1 and 1.9 when Hb < 4 g/dl. These data clearly indicate COHb can be influenced by the analytical methods used.

Carbon Monoxide↗
PubMed1996

[Proportional assisted ventilation--clinical use of a new ventilation mode].

BACKGROUND: Proportional assist ventilation (PAV), a new mode for assist ventilation, allows the patient not only to trigger the ventilator but enables him to keep his breathing pattern. The basis of PAV is a positive feed back between patient and ventilator. PATIENTS AND METHOD: PAV was applied in 6 patients, who were under long-term ventilation and who were stable. The ventilator was adjusted to compensate for the endotracheal tube, different parts between 90 and 40% of resistance and elastance were assisted. Airway pressure, flow and tidal volume were measured. PAV was compared with pressure support ventilation (PSV). RESULT: No difference in blood gases were found in PAV as compared to PSV. Airway pressure were lower in PAV than in PSV (10.4 +/- 3.3 cm H2O vs. 18.8 +/- 5.9 cm H2O in PSV). Breathing frequency was higher (22.4 +/- 8.1 vs. 15.8 +/- 5.9 in PSV). CONCLUSION: The higher breathing frequencies in PAV were associated with the underlying diseases and resulted in a better synchronisation with the respiratory center output.

Humans↗
PubMed1995

Mupirocin ointment with and without chlorhexidine baths in the eradication of Staphylococcus aureus nasal carriage in nursing home residents.

BACKGROUND: Mupirocin ointment has been shown to be effective in eradicating Staphylococcus aureus nasal carriage in residents of a long-term care facility. Antiseptic soaps have been used as adjunct to this therapy. We compared the efficacy of short-term intranasal mupirocin ointment with and without chlorhexidine baths in the eradication of S. aureus nasal carriage with follow-up for 12 weeks. METHODS: Residents in four nursing homes known to have endemic methicillin-resistant S. aureus were screened for nasal carriage of S. aureus. Residents who had anterior nares cultures positive for S. aureus on two separate occasions were divided into two groups. Both groups received intranasal mupirocin ointment twice daily for 5 days and one group also received chlorhexidine baths for the first 3 days. Cultures of anterior nares, axilla, and groins were performed before treatment and 1 day and 1, 4, 8, and 12 weeks after treatment. RESULTS: After treatment, S. aureus nasal carriage was eradicated in all residents. Recolonization with S. aureus had occurred at 12 weeks in 24% of residents receiving mupirocin ointment alone (6/25) and in 15% of residents receiving mupirocin ointment plus chlorhexidine baths (4/27). CONCLUSIONS: A short course of mupirocin ointment was effective in eradicating nasal carriage of S. aureus in nursing home residents. There were no statistical differences in efficacy between the two regimens with respect to the eradication of nasal carriage and prevention of recolonization with S. aureus.

Administration, Intranasal↗
PubMed1995

[The significance of citrate, uromucoid and GAG for diagnosis of renal tubular acidosis in patients with urinary calculi].

Renal tubular acidosis (type I) is characterized by alterations that lead to disturbed acidification in the tubule. As a result of these alterations, the excretion of uromucoid (formed in the distal tubule), citrate and glycosaminoglycan (GAG) is considerably reduced. There have been numerous investigations on changes in urine pH, citrate and calcium, but few, if any studies on the excretion of uromucoid and GAG. Apart from calcium, phosphate, pH and urease, the present study investigated the excretion of uromucoid, citrate and GAG in a collective of 41 stone patients with renal tubular acidosis (type I). We found that uromucoid excretion was reduced on 90.5%, GAG in 72.2% and citrate in 96% of cases. The reduction of uromucoid excretion in particular is characteristic of RTA I, and it has the function of a marker.

Acidosis, Renal Tubular↗
PubMed1994

Mefloquine distribution in postmortem cases.

Mefloquine is currently the drug-of-choice for malaria prophylaxis among military personnel. Four active duty military personnel receiving 250 mg mefloquine per week were killed in the line of duty under combat conditions. Samples of blood, bile, liver, kidney, muscle, brain, spleen and lung were submitted to the Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, for routine toxicologic analysis. Qualitative screening revealed only the presence of ethanol (< 25 mg/dl, probably attributable to postmortem formation) and mefloquine. Quantitation of mefloquine was performed using an HP 5880 gas chromatograph equipped with a nitrogen/phosphorus detector. The column was an HP-5 cross-linked 5% phenyl methyl silicone fused silica capillary column (15 m x 0.25 mm i.d. x 0.25 microns film thickness). The temperature program began at 110 degrees C, was held for 1 min and ramped at 20 degrees C/min to 200 degrees C, held for 1 min and then ramped at 10 degrees C/min to 280 degrees C and held for 10 min. Mefloquine elutes with a relative retention time similar to that of the tricyclic antidepressants. No postmortem data concerning mefloquine concentrations or tissue distribution was available. Quantitated blood concentrations in the presented cases were greater than the expected therapeutic values indicating the possibility of postmortem redistribution of this drug. No mefloquine overdoses were identified in the literature making comparison to the postmortem therapeutic concentrations impossible at this time.

Adult↗
PubMed1990

[Systemic lysotherapy using recombinant tissue plasminogen activator for fulminant pulmonary embolism].

A 44-year-old woman sustained massive pulmonary embolization from a deep leg-vein thrombosis. She was given 70 mg recombinant tissue plasminogen activator (rt-PA) by continuous intravenous drip over two hours. Before this treatment perfusion scintigraphy had demonstrated complete absence of flow in the right lung due to embolic occlusion of the central hilar vessels. In addition there were several segmental filling defects in the left lung. Even during the two-hour infusion the circulatory state began to improve, as did echo- and electrocardiographic signs of acute right heart strain. Correspondingly there was a rapid raise in arterial pO2. Another scintigraphy after 48 hours revealed almost complete reperfusion of the right lung and the left lung segments. This case demonstrates that infusion of rt-PA can be an effective and relatively risk-free method of treating haemodynamically significant massive lung embolism, even in comparison with selective or systemic thrombolysis with urokinase or streptase or with surgical embolectomy.

Adult↗