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Biomedical subjects

B Krauss

Publications and source records attributed to B Krauss.

At least 37 records · Page 2Linked to original sources
PubMed1998

Gene structures and properties of enzymes of the plasmid-encoded nicotine catabolism of Arthrobacter nicotinovorans.

Arthrobacter nicotinovorans is a Gram-positive aerobic soil bacterium able to grow on nicotine as its sole source of carbon and nitrogen. The initial steps of nicotine catabolism are catalyzed by nicotine dehydrogenase, the l- and d-specific 6-hydroxynicotine oxidases, and ketone dehydrogenase. The genes encoding these enzymes reside on a 160 kb plasmid, pAO1. The cccDNA of this plasmid was isolated in high purity and reasonable yield. It served as template material for the construction of a lambda-phage DNA library of the plasmid. The genes coding for 6-hydroxy-l-nicotine oxidase and for the subunits of the heterotrimeric ketone dehydrogenase were identified, subcloned and sequenced. The 6-hlno gene was identified as a 1278 bp open reading frame; its regulatory elements were also recognized. The derived primary structure of the monomer of apo-6-hydroxy-l-nicotine oxidase (46,264.5 Da) agrees with the data obtained by partial amino acid sequencing. 6-Hydroxy-l-nicotine oxidase and 6-hydroxy-d-nicotine oxidase were expressed in Escherichia coli and obtained in a state of high purity and crystallized. Ketone dehydrogenase (KDH) was found to be a heterotrimer with subunits of molecular mass 89,021.71, 26,778.65 and 17,638.88. The genes of KDH-A and KDH-B are juxtaposed; the A of the stop codon of KDH-A is used in the start codon of KDH-B, eliciting a frame shift. KDH-C is separated from KDH-A by 281 bp.

Arthrobacter↗
PubMed1998

Sedation patterns in pediatric and general community hospital emergency departments.

BACKGROUND AND OBJECTIVES: Although pediatric sedation (PS) is widely used in emergency departments (ED), the practice of PS in general community hospital (GH) ED has not been described. We surveyed PS practice patterns in pediatric hospitals (CH) and GH and compared frequency and usage between the two groups. METHODS: All CH (n = 115) and 400 randomly selected GH were surveyed. Alcohol and drug detoxification, psychiatric, chronic care, rehabilitation, and specialty facilities were excluded. Data were collected on hospital type (pediatric or community), location (urban, suburban, rural), annual visits, academic affiliation (presence of an emergency medicine residency or pediatric emergency medicine fellowship in the hospital), and sedation agents used. RESULTS: Of 515 hospitals surveyed, 238 responded [84/115 CH (73%), 154/400 GH (39%)] yielding an overall response rate of 46%. Of the responding CH the majority were urban [57 (68%) were urban, 15 (18%) suburban, and 12 (14%) rural]. GH were more evenly distributed by location [44/153 (29%) were urban, 49/153 (32%) suburban, and 60/153 (39%) rural]. Eight (5%) GH had emergency medicine residencies, while 39 (46%) CH had pediatric emergency medicine fellowships. The mean annual pediatric volume was 38,000 for CH and 6500 for GH. For the four specified clinical scenarios, representing the most common ED procedures using sedation (laceration repair, fracture reduction, radiologic imaging), GH performed significantly fewer sedations than CH when matched for pediatric volume. PS was less frequently used among rural GH compared to suburban (P < 0.01) and urban GH (P < 0.01). Midazolam was listed as the most frequently used drug in all three geographic locations for both CH and GH. CH listed fentanyl as a second agent, while GH preferred meperidine. Fentanyl and ketamine were listed as preferred agents only in CH. For cranial computerized tomography, chloral hydrate was listed as the drug of choice by both CH and GH. Both CH and GH listed "relief of pain and anxiety" as the first and "agitation control" as the second most common reason for using sedation. CH and GH listed "the risks outweigh the benefits" as the primary reason and "ED too busy/takes too much time" as the secondary reason for not using sedation. CONCLUSIONS: GH performed fewer sedations than did CH when matched for pediatric volume in all geographic locations and for the most common ED procedures using sedation. Since 1989, sedation patterns have shifted in CH to include the short-acting agents, while GH (with the exception of midazolam) continue to prefer the long-acting agents. Midazolam is now the most frequently used sedation agent for ED procedures in both CH and GH.

Acute Disease↗
PubMed1998

Sensing lead insulation defect resulting in a damage of the ICD pulse generator case.

Eight months after ICD implantation with an electrically active case the patient presented with ICD system sensing failure. Upon reoperation, we found an insulation defect of the proximal sensing lead and the generator case showed arc marks suggesting a short circuit between the sensing lead and case. The generator was replaced, the original sensing lead insulated, and a new sensing lead inserted. Bench testing of the explanted generator showed a damaged internal circuitry. Proximal lead insulation defects combined with electrically active cases may result in damage of the case. The potential damage of internal circuitry warrants generator replacement.

Defibrillators, Implantable↗
PubMed1997

Hypoxia induces c-fos transcription via a mitogen-activated protein kinase-dependent pathway.

Hypoxia is a pathophysiological condition that occurs during injury, ischemia, and stroke. It is characterized by a decrease of reactive oxygen intermediates and a change of the intracellular redox level. In tumors hypoxia is regarded as a trigger for enhanced growth and metastasis. Here we report that in HeLa cells, hypoxic conditions induce the transcriptional activation of c-fos transcription via the serum response element. Mutations in the binding site for the ternary complex factor Elk-1 and the serum response factor abolished this induction, indicating that a ternary complex at the serum response element is necessary for the induction of the c-fos gene under hypoxia. The transcription factor Elk-1 was covalently modified by phosphorylation in response to hypoxia. Furthermore this hyperphosphorylation of Elk-1, the activation of mitogen-activated protein kinase (MAPK), and the induction of c-fos transcripts were blocked by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase kinase 1. An in vitro kinase assay with Elk-1 as substrate showed that MAPK is activated under hypoxia. The activation of MAPK corresponds temporally with the phosphorylation and activation of Elk-1. Thus, a decrease of the intracellular reactive oxygen intermediate level by hypoxia induces c-fos via the MAPK pathway. These results suggest that the intracellular redox levels may be directly coupled to tumor growth, invasion, and metastasis via Elk-1-dependent induction of c-Fos controlled genes.

Anaerobiosis↗
PubMed1996

The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB.

Opportunistic infections, such as aspergillosis, are among the most serious complications suffered by immunocompromised patients. Aspergillus fumigatus and other pathogenic fungi synthesize a toxic epipolythiodioxopiperazine metabolite called gliotoxin. Gliotoxin exhibits profound immunosuppressive activity in vivo. It induces apoptosis in thymocytes, splenocytes, and mesenteric lymph node cells and can selectively deplete bone marrow of mature lymphocytes. The molecular mechanism by which gliotoxin exerts these effects remains unknown. Here, we report that nanomolar concentrations of gliotoxin inhibited the activation of transcription factor NF-kappaB in response to a variety of stimuli in T and B cells. The effect of gliotoxin was specific because, at the same concentrations, the toxin did not affect activation of the transcription factor NF-AT or of interferon-responsive signal transducers and activators of transcription. Likewise, the activity of the constitutively DNA-binding transcription factors Oct-1 and cyclic AMP response element binding protein (CREB), as well as the activation of protein tyrosine kinases p56lck and p59fyn, was not altered by gliotoxin. Very high concentrations of gliotoxin prevented NF-kappaB DNA binding in vitro. However, in intact cells, inhibition of NF-kappaB did not occur at the level of DNA binding; rather, the toxin appeared to prevent degradation of IkappaB-alpha, NF-kappaB's inhibitory subunit. Our data raise the possibility that the immunosuppression observed during aspergillosis results in part from gliotoxin-mediated NF-kappaB inhibition.

Cells, Cultured↗
PubMed1994

Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes.

Tight junctions between endothelial cells of brain capillaries are the most important structural elements of the blood-brain barrier. Cultured brain endothelial cells are known to loose tight junction-dependent blood-brain barrier characteristics such as macromolecular impermeability and high electrical resistance. We have directly analyzed the structure and function of tight junctions in primary cultures of bovine brain endothelial cells using quantitative freeze-fracture electron microscopy, and ion and inulin permeability. The complexity of tight junctions, defined as the number of branch points per unit length of tight junctional strands, decreased 5 hours after culture but thereafter remained almost constant. In contrast, the association of tight junction particles with the cytoplasmic leaflet of the endothelial membrane bilayer (P-face) decreased continuously with a major drop between 16 hours and 24 hours. The complexity of tight junctions could be increased by elevation of intracellular cAMP levels while phorbol esters had the opposite effect. On the other hand, the P-face association of tight junction particles was enhanced by elevation of cAMP levels and by coculture of endothelial cells with astrocytes or exposure to astrocyte-conditioned medium. The latter effect on P-face association was induced by astrocytes but not fibroblasts. Elevation of cAMP levels together with astrocyte-conditioned medium synergistically increased transendothelial electrical resistance and decreased inulin permeability of primary cultures, thus confirming the effects on tight junction structure and barrier function. P-face association of tight junction particles in brain endothelial cells may therefore be a critical feature of blood-brain barrier function that can be specifically modulated by astrocytes and cAMP levels. Our results suggest an important functional role for the cytoplasmic anchorage of tight junction particles for brain endothelial barrier function in particular and probably paracellular permeability in general.

Animals↗
PubMed1991

The relation between pharmacokinetics and endocrine effects of buserelin implants in patients with mastalgia.

Six patients with mastalgia were treated with polylactide/glycolide 50:50 implants containing 6.6 mg buserelin once every 4 weeks, to study the relationship between buserelin pharmacokinetics and suppression of pituitary-ovarian function. On the first treatment day there was an initial rise in plasma and urinary buserelin levels followed by a rapid fall during the next 2 days. After a plateau phase (60-80 micrograms/g creatinine) urinary buserelin/creatinine ratios decreased slowly to a mean value of 25 micrograms/g creatinine 4 weeks after implantation. Plasma oestradiol concentrations dropped to castrate values within 2 weeks of treatment reaching a mean concentration of 17 pmol/l compared to 27 pmol/l (P less than 0.01) determined in 680 postmenopausal control women. After the last implant injection urinary buserelin/creatinine ratios remained relatively high (greater than 5 micrograms/g creatinine) during more than 8 weeks followed by an exponential decrease (half-life of buserelin release: 15 days) to undetectable buserelin levels at 16-22 weeks after the last implantation. A rise of suppressed plasma oestradiol concentrations to above castrate levels was found 15-20 weeks after the last buserelin implantation, at a time when urinary buserelin excretion had decreased below 0.2 micrograms/g creatinine. It is concluded that after initial suppression of pituitary-ovarian function only very low concentrations of buserelin are needed to maintain suppression of ovarian activity by using slow release preparations.

Adult↗
PubMed1990

Destructive changes of the spine in magnetic resonance imaging.

Twenty-nine patients were examined by magnetic resonance imaging for various lesions of the spine. The results of these scans were compared with those of plain radiographs, computertomographs, and radionuclide bone scans. The findings were substantiated by intraoperative or histological findings in 18 cases. The MRI scans proved to be very sensitive in the detection of a wide spectrum of morphological changes of the bone marrow of vertebral bodies. Characteristic changes of the signal patterns for inflammatory and tumorous lesions were not observed. The differentiation of these lesions will presently continue to have to be based on morphological criteria.

Adolescent↗
PubMed1989

Binding of FAD to 6-hydroxy-D-nicotine oxidase apoenzyme prevents degradation of the holoenzyme.

Expression of the 6-hydroxy-D-nicotine oxidase (6-HDNO) gene from Arthrobacter oxidans cloned into Escherichia coli showed a marked temperature-dependence. Transformed E. coli cells grown at 30 degrees C exhibited a several-fold higher 6-HDNO activity than did cells grown at 37 degrees C. This effect did not depend on the promoter used for expression of the cloned gene in E. coli, nor was it an effect of 6-HDNO mRNA instability at 37 degrees C. Studies performed in vivo and in vitro revealed that an increased susceptibility of apo-6-HDNO to proteolytic attack at 37 degrees C was responsible for the observed phenomenon. Extracts from cells grown at 37 degrees C showed on Western blots a decrease in immunologically detectable 6-HDNO polypeptide when compared with extracts from cells grown at 30 degrees C. The 6-HDNO polypeptide is covalently modified by attachment of the cofactor FAD to a histidine residue. It could be shown that covalent flavinylation of the apoenzyme in vitro, i.e. formation of holoenzyme, by incubation of cell extracts with FAD and phosphoenolpyruvate protected the 6-HDNO polypeptide from degradation at 37 degrees C. Of a variety of proteinase inhibitors tested only the cysteine-proteinase inhibitor L-3-trans-carboxyoxiran-2-carbonyl-L-leucylagmatine (E64) prevented degradation, by up to 70%, of the apoenzyme.

Apoenzymes↗
PubMed1989

Pharmacokinetics and endocrine effects of the LHR analogue buserelin after subcutaneous implantation of a slow release preparation in prostatic cancer patients.

The pharmacokinetics and endocrine effects of the LHRH analogue buserelin [D-Ser(TBU)6-LHRH], released from biodegradable implants, were studied in 14 patients with stage C and D prostate cancer. Six patients received a subcutaneous implant of 3.3 mg buserelin monthly, and 8 patients received a subcutaneous implant of 6.6 mg buserelin every two months. Serum levels of buserelin decreased rapidly immediately after implantation. After 1-2 weeks a more gradual decline occurred, while in the two-monthly treated group a third phase of the elimination curve started after 5 weeks. Mean serum buserelin levels just before the next implantation in the two groups were not different. Urinary excretion of buserelin followed the same pattern. Serum LH levels in both groups became non-detectable 2 weeks after the first implant. This decrease of LH levels was accompanied by a suppression of serum testosterone to concentrations below 1 nmol/l (castration level). Side effects were not different from those observed with the intranasal application of buserelin. It is concluded that the subcutaneous application of buserelin is an easily administered form of treatment which has more profound and more reliable endocrine effects when compared with the intranasal administration of the drug. The greatest advantage of the new preparation is that the intervals between applications may be prolonged to at least 2 months.

Aged↗
PubMed1988

[Clinical use of gradient echo sequences of longer repetition times].

Studies designed to optimise image contrasts of gradient echo sequences showed, that especially repetition times between 250 and 500 ms in combination with adequate echo times and flip angles provide new image contrasts. The clinical purpose of gradient echo sequences with longer TR was systematically evaluated in 450 patients. A major advantage of GE sequences was the low signal intensity of fat and bone tissue. On the other hand different pathologic changes showed a high signal intensity in comparison to T2 weighted spin echo sequences as well. With the possibility of multiple slices GE sequences were of outstanding diagnostic value especially in MR of soft tissue and of the musculoskeletal system. T2 weighted SE sequences provided no additional informations and could therefore be omitted in a great number of examinations.

Abdomen↗
PubMed1988

[Gradients of echo sequences with extended repetition time in the diagnosis of bone marrow changes in the spine].

Hitherto T1-weighted Spin-Echo-Sequences, most combined with T2-weighted sequences, were used to detect pathological bone marrow lesions. This method needs a long examination time and results in T2-images with a low morphological resolution. In the majority of examinations using Gradient-Echo-Sequences with prolonged repetition-times (FLASH: flip angle 40 degrees, TR/TE = 500/17 msec) there is no need of an additional measurement. Therefore these sequences save about 75% of the examination time and they give higher contrast between normal and pathological bone marrow.

Bone Marrow↗
PubMed1987

Action of tulobuterol and fenoterol on the mucociliary clearance.

The influence of tulobuterol and fenoterol upon mucociliary clearance (mC) and airway obstruction was investigated in 8 patients with chronic obstructive bronchitis and two patients with chronic bronchial asthma. The lung function and mC measurements were repeated after a 1-week random oral treatment with 4 mg tulobuterol/day or 7.5 mg fenoterol/day in a double-blind cross-over design. Tulobuterol and fenoterol improved mC of the total, central and peripheral bronchial tree significantly in comparison to the pretreatment values (p less than 0.001) reaching, after beta 2-agonist therapy, values observed in normal subjects. In comparison to no treatment and pretreatment with oral fenoterol, tulobuterol protected slightly better from the inhalative provocation with 99mTc radioactive erythrocytes used to measure mC. Inhalative fenoterol was more efficient than oral fenoterol or tulobuterol to reverse the bronchospastic part of airway obstruction. No differences of mean daily peak flows, systolic and diastolic systemic blood pressure measurements and pulse rate were recorded during tulobuterol and fenoterol treatment. Both drugs were tolerated without side effects.

Adrenergic beta-Agonists↗
PubMed1986

[Lung complications in AIDS].

A short description of epidemiologic and clinical facts correlated with the acquired immunodeficiency syndrome (AIDS) is followed by a report on the manifestation of pulmonary infections mostly effected by Pneumocystis carinii. Two examples out of four cases will demonstrate the radiographic appearance of the Pneumocystis carinii pneumonia and clinical data. Only in rare cases does it seem possible to reduce the fatal outcome by early diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1983

[Comparison of mammography and automated sonography in 700 patients].

700 patients underwent routinely x-ray mammography and breast ultrasound with an automated grey-scale breast scanner. The parenchymal pattern of the ultrasound B-scan was morphological identical to the x-ray film. The echogram gave further informations about the topographic localisation of pathologic lesions to the chest wall including the pectoral muscles. The sonogram was of no value in 10 percent due to diffuse reflection of the breast. In cystic disease the diagnostic accuracy of the ultrasound was with about 100 percent superior to that of x-ray mammography. On the contrary the accuracy of the x-ray mammography was higher than that of ultrasound in the diagnosis of benign or malignant solids. Benign adenoma smaller than 1 cm could not be definetively recognised as carcinoma of this size. The diagnostic accuracy of the sonogram was 70 percent by 40 histologically proved carcinomas. The only use of the automated scanner in the diagnostics of the breast seams to be not justified, even not as a screening method, especially because small tumors with good prognosis are not recognized, however, the ultrasound gives additional important informations in the differential diagnosis of benign and malignant lesions of the female breast.

Adenofibroma↗
PubMed1983

Antibody production against an agonist analogue of luteinizing hormone-releasing hormone: evaluation of immunochemical and physiological consequences.

Because of the widespread long-term clinical use of luteinizing hormone-releasing hormone (LRH) agonists, the possibility of antibody development to one of these, (D-Ser-(Butt)6) LRH (1-9) nonapeptide-ethylamide (buserelin), has been studied by examining sera from experimental animals and humans receiving long-term agonist-treatment for ability to bind 125I-labelled buserelin. None of the sera from monkeys, rabbits, dogs or rats receiving buserelin by sc injection or via minipump or from 81 patients receiving the agonist by sc injection or nasal spray had detectable antibodies. The immunochemistry of buserelin was investigated by actively immunizing male rabbits against the agonist. This also enabled us to determine the possibility of this stimulus to the immune response resulting in the generation of antibodies which could cross-react with endogenous LRH and neutralize its biological effect. All 41 rabbits immunized against unconjugated buserelin and all 23 immunized against buserelin conjugated to a protein carrier developed antibodies, those in the latter group producing highest titres. Serum from one of the animals immunized against unconjugated buserelin and from 9 of the animals immunized against conjugated buserelin had the capacity to bind 125I-labelled LRH. These LRH antibody titres were very low and were insufficient to cause suppression of serum testosterone concentrations or affect testicular weight except in one rabbit immunized against unconjugated agonist. The LRH antibody titre in this rabbit was always less than 1:100 which our other studies have indicated to be too low to produce a biological effect. It may be that the association of low LRH antibody titre with decreased testes weight in this animal was fortuitous. We conclude that the possibility of circulating antibodies being produced to buserelin or their interfering with the action of endogenous LRH is extremely low.

Animals↗