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Biomedical subjects

E Keller

Publications and source records attributed to E Keller.

At least 145 records · Page 8Linked to original sources
PubMed1997

Transcription termination factor Rho is essential for Micrococcus luteus.

The growth of Micrococcus luteus, a soil microorganism that belongs to the high-G+C gram-positive phylogenetic group, is prevented by bicyclomycin, an antibiotic that inhibits the activity of the M. luteus transcription termination factor Rho. A mutant that can grow in 0.3 mM bicyclomycin has a Rho that is insensitive to bicyclomycin and has the single amino acid residue change of Asp474 to Gly. These results indicate that the function of its Rho factor is essential for M. luteus and that growth of a gram-positive organism can be blocked by bicyclomycin.

Anti-Bacterial Agents↗
PubMed1997

Lack of association between an interleukin-1 receptor antagonist gene polymorphism and ulcerative colitis.

BACKGROUND: Recently, the association of a polymorphism in the gene coding for the anti-inflammatory cytokine interleukin-1 receptor antagonist with ulcerative colitis has been reported. This was interpreted as a possible genetic predisposition for severity of the inflammatory response. AIMS: To examine this polymorphism in a southern German population. SUBJECTS: The study included 234 healthy controls, 57 patients with ulcerative colitis, including 31 patients with pancolitis, 44 first degree healthy relatives of patients with ulcerative colitis, and 65 patients with Crohn's disease. METHODS: Genotypes were determined by a polymerase chain reaction amplification of the intron 2 fragment harbouring a variable number of tandem repeat nucleotide sequences. Amplification products were separated on a 2% agarose gel. RESULTS: The allele frequency for allele 2 was 27% in healthy controls, 28% in Crohn's disease, and 21% in patients with ulcerative colitis. The same allele frequency (21%) was found in a subgroup of patients with ulcerative colitis affecting the whole colon. Thus for allele 2 as well as for all other alleles, genotypes, or carriage rates no significant differences were found compared with controls. All allele frequencies in the control population were similar to those in earlier studies. CONCLUSIONS: No association of a polymorphism in the interleukin-1 receptor antagonist gene with ulcerative colitis could be identified in this southern German population. The findings of an earlier study reporting an increased frequency of allele 2, particularly in patients with pancolitis, could not be confirmed.

Adult↗
PubMed1997

Measurement of serum exon 3-retaining growth hormone-binding protein in children and adolescents by radioimmunoassay.

Recently described assays for the determination of growth hormone-binding protein (GHBP) show a wide variety of normal ranges. Their results depend on the assay design and in the case of ligand-immunofunctional assay (LIFA), probably also on the binding characteristics, i.e. epitope specificity and affinity of the employed antibody. These facts underline the necessity to look for more accurate and specific assays. In this report we describe an accurate and simple radioimmunoassay (RIA) which allows the specific quantitation of the exon 3-retaining GHBP isoform (E3-GHBP). Data of the E3-GHBP RIA were compared to those of a LIFA measuring undifferentiated functional forms of GHBP. Our results demonstrate significant relationships between GHBP and age, BMI and IGF-I as determined by RIA and by LIFA in normal children and adolescents (n = 115, p < 0.001). Moreover, BMI is the only regulating factor of GHBP for both methods as shown by multiple regression analysis (p < 0.001). All our data suggest a qualitatively paralleled regulation of E3-GHBP and undifferentiated functional GHBP forms. This finding was confirmed by a good correlation between RIA and LIFA data (r = 0.74, p < 0.001). Children with idiopathic short stature (ISS, n = 47) had significantly lower GHBP levels than normal controls (n = 58) measured by the E3-GHBP RIA (p < 0.0001) and by LIFA (p < 0.01). We conclude that (1) ISS children may have a structural or quantitative defect at the level of the GHR, and (2) the highly specific assay for E3-GHBP immunoreactivity provides a sensitive diagnostic tool in conditions with partial GH insensitivity.

Adolescent↗
PubMed1997

Routine molecular genotyping of HLA-B27 in spondyloarthropathies overcomes the obstacles of serological typing and reveals an increased B *2702 frequency in ankylosing spondylitis.

OBJECTIVE: To evaluate the reproducibility and reliability of polymerase chain reaction (PCR) in HLA-B27 typing compared to the conventionally used microlymphocytotoxicity test (MLCT). To determine the HLA-B27 subtype frequencies (B*2701-B*2709) in patients with HLA-B27 associated disease and healthy persons using sequence specific oligonucleotides (SSO). METHODS: 398 consecutive patients were HLA-B27 typed by MLCT and PCR. Subtyping by SSO was performed in 142 patients with HLA-B27 associated disease [ankylosing spondylitis (AS) n = 38, reactive arthritis 44, undifferentiated spondyloarthropathy (uSpA) 45, psoriatic arthritis 15] and 125 healthy HLA-B27 controls. RESULTS: MLCT identified 61 HLA-B27 positive patients (15.3%); PCR identified 78 positive patients (19.6%). MLCT gave false negative results for 8 patients (2.0%) and false positives for a further 7 (1.8%). Only subtypes B*2702 and B*2705 were present in patients and controls. Overall frequencies of B*2702 in patients and controls were 14.1 and 9.6%, respectively. The B*2702 frequency was significantly (pcorr. < 0.04) higher in AS (23.7%) and lower in uSpA (6.7%) patients. CONCLUSION: HLA-B27 typing by PCR is reliable and reproducible and therefore recommended for routine typing. It overcomes the obstacles of serological typing, i.e., equivocal results and cross-reactivity. In addition, subtype frequencies (B*2702 and B*2705) are equally distributed among patients and controls, although subtype B*2702 seems to be more frequent in AS and less so in uSpA.

Amino Acid Sequence↗
PubMed1996

Strong association of dermatomyositis-specific Mi-2 autoantibodies with a tryptophan at position 9 of the HLA-DR beta chain.

OBJECTIVE: To characterize the clinical and immunogenetic features of patients with Mi-2 autoantibodies. METHODS: Eighteen adult white patients with Mi-2 antibodies were clinically characterized and compared with 41 Mi-2-negative dermatomyositis (DM) patients. HLA class I and class II typing for DRB alleles was done by microcytotoxicity assay and for DQA and DQB alleles by polymerase chain reaction-based oligotyping. RESULTS: Seventeen of the 18 Mi-2-positive patients had DM. Symptoms of scleroderma, lung involvement, and arthritis were less common in this group than in the Mi-2-negative DM patients; the V-sign rash and nailfold involvement were found more frequently. Mi-2 antibodies were strongly associated with HLA-DR7 (88% versus 24% in healthy controls), HLA-DQA1*0201 (86% versus 23%), and DR7 "homozygosity" (31% versus 0%). A tryptophan residue at position 9 of the HLA-DR beta chain was present in all Mi-2-positive patients (100% versus 62%; homozygous in 81% versus 15%). CONCLUSION: Our results reemphasize the specificity of Mi-2 antibodies for DM, and extend previous reports that Mi-2 antibody production is associated with certain HLA class II antigens. We propose beta 9-Trp as a candidate epitope on the HLA-DR beta chain as a prerequisite for this type of autoimmune response.

Adenosine Triphosphatases↗
PubMed1996

18F-fluorodeoxyglucose-PET and 99mTc-bicisate-SPECT in Creutzfeldt-Jakob disease.

In a patient with the occipitoparietal form of Creutzfeldt-Jakob disease (CJD) (Heidenhain type) positron emission tomography (PET) demonstrated decreased glucose utilization in the occipital lobes and adjacent cortical regions. Single photon emission computed tomography (SPECT) with 99mTc-bicisate showed a "coupled" decrease in blood flow in identical cortical areas in this patient. In contrast, magnetic resonance imaging (MRI) was normal. In the early stage of CJD, when still no major morphological abnormalities can be observed, functional imaging is useful for differential diagnosis, particularly to exclude other causes of dementia or pathological EEG patterns.

Aged↗
PubMed1996

[Endovascular balloon occlusion test of the internal carotid artery with increased hemodynamic monitoring for determination of circulatory reserve before planned carotid occlusion].

PURPOSE: To evaluate stroke risk assessment of balloon test occlusion of the internal carotid artery (ICA) with enlarged haemodynamic monitoring prior to permanent ICA occlusion. MATERIAL AND METHODS: 24 patients with cervical metastasis (n = 18), cavernous meningiomas (n = 3) or inoperable cavernous aneurysms (n = 3) were examined. The test occlusion was monitored by EEG, neurological examinations and transcranial Doppler sonography of the ipsilateral middle cerebral artery with evaluation of the cerebrovascular reserve capacity. Additionally 99mTc-HMPAO-SPECT imaging was added showing the perfusion during test occlusion. RESULTS: In one (4%) patient the test occlusion had to be interrupted previously due to an acute neurological deficit. This patient and two (8%) patients with highly pathological test results in SPECT and TCD were excluded from permanent carotid occlusion. In 6 (25%) patients quantitative TCD monitoring could improve the stroke risk assessment by differentiating the patients in a low and high risk group. 6 (25%) patients were definitely occluded without haemodynamic complications, but two patients suffered from embolic infarctions which cannot be predicted by this procedure. CONCLUSIONS: The multimodal balloon test occlusion with enlarged haemodynamic monitoring allows haemodynamic stroke risk assessment prior to permanent occlusion of the ICA.

Adult↗
PubMed1996

[A new application of MR tomography of the lung using ultra-short turbo spin echo sequences].

PURPOSE: Development of an improved MR sequence for examining the lung. METHOD: T2 weighted ultra-short turbo spin echo sequences were used in five individuals with variations in echo times, delayed triggering and echo intervals. To reduce movement artifacts all examinations were carried out with ECG and respiratory triggering. The sequences giving optimal image quality were then employed in 19 patients having various pulmonary abnormalities. Image resolutions, artifacts, image contrasts and diagnostic value were then judged by two observers and compared with CT. RESULTS: In the first study, a diastole-triggered UTSE sequence with the shortest echo proved optimal (TE = 90 ms, TR = 2-4 s, echo = 9 ms, turbo factor = 19). In the patient series studied, MRT was inferior to CT with regard to resolution and number of artifacts, but better in respect of contrast and diagnostic value. CONCLUSION: Using UTSE of the lung, MRT can produce images of good quality. Compared with CT, contrast is better with MRT, offering diagnostic advantages for MRT.

Diagnosis, Differential↗
PubMed1996

[Standardization and acceleration of quantitative analysis of dynamic MR mammographies via parametric images and automatized ROI definition].

PURPOSE: To evaluate quantitative analysis of dynamic breast MRI studies using a dedicated PC based diagnosis system (DS) providing parametric images and automatic ROI definition as compared to the standard subtraction image, manual-ROI based procedure. METHODS: We compared the diagnostic usefulness of parametric versus subtraction images in terms of visualisation of enhancement inhomogeneities and enhancement velocities. Quantitative analysis of enhancing lesions of 15 breast MRI studies was performed using both the DS and the system's console software (SC). We assessed the time needed for complete quantitative analysis and number of lesions evaluated. This was followed by assessment of within-reader and between-reader variability or within-case reproducibility of results of quantitative analysis. RESULTS: Parametric images are superior to subtraction images in visualizing enhancement inhomogeneities or ring enhancement in breast cancers. Mean time needed for analysis at DS and SC was 4 (3-5) min. and 23 (8-39) min., respectively. During this time period, significantly more lesions were evaluated per case using the DS as compared to the SC (2-14 vs. 1-6). Mean within-reader variability of enhancement velocities of the same lesions was 0% and 25% (DS and SC); between-reader variability of enhancement values obtained in the same lesions was 11% (DS) versus 41% (SC). CONCLUSION: The DS significantly cuts down the time needed for quantitative analysis. It significantly improves reproducibility of quantitative enhancement values due to standardization of ROI analysis.

Adult↗
PubMed1996

[Intramural hematoma of the thoracic aorta: diagnostic imaging and differential diagnosis].

PURPOSE: Aortic wall thickening due to intramural hemorrhage may be the only sign of aortic dissection. The aim of this study was to evaluate the incidence, imaging features and differential diagnoses of intramural hemorrhage (IMH) of the thoracic aorta. METHODS: 98 patients with clinically suspected aortic dissection were investigated via Spiral-CT and MRT. Diagnosis of IMH based on the presence of smooth crescentic or concentric wall thickening over a longer segment of the thoracic aorta without flow visualization and without compression or distortion of the aortic lumen. RESULTS: 69 patients had classic aortic dissections and 7 patients were diagnosed to have IMH of thoracic aorta. One patient with IMH of the ascending aorta died of aortic rupture and subsequent pericardial tamponade 12 hours after onset of symptoms. In one patient with IMH of the descending aorta on initial examination, there was a progression of overt aortic dissection at follow-up after three weeks. In two patients with IMH of the descending aorta, wall thickening decreased in size at follow-up (10-15 weeks), whereas in one patient it remained unchanged. CONCLUSION: IMH of the aorta should be considered a precursor of aortic dissection. At follow-up IMH may decrease in size, rupture or progress to overt aortic dissection.

Adult↗
PubMed1996

Nonclassical adrenal hyperplasia due to 21-hydroxylase-deficiency: does genotyping predict the clinical manifestation?

8 patients of 7 families with nonclassical adrenal hyperplasia (NCAH) were analysed for defects of the 21-hydroxylase-B-gene. As the defects were small or rare, complete molecular genetic diagnostic up to sequencing of this gene was necessary to detect the genotype, which then was associated with the phenotype. However, mutations in 4 alleles from 3 families are still undetectable. Thus, correct prenatal diagnosis in NCAH-families without index patient remains difficult.

Adolescent↗
PubMed1996

Aortic dissection: a comparative study of diagnosis with spiral CT, multiplanar transesophageal echocardiography, and MR imaging.

PURPOSE: To compare the usefulness of spiral computed tomography (CT), multiplanar transesophageal echocardiography (TEE), and magnetic resonance (MR) imaging in the diagnosis of thoracic aortic dissection and arch vessel involvement. MATERIALS AND METHODS: Forty-nine symptomatic patients with clinically suspected aortic dissection were examined with contrast material-enhanced spiral CT, multiplanar TEE, and 0.5-T MR imaging (T1-weighted, cardiac-gated, spin-echo sequences). Imaging results were confirmed at autopsy (five patients), intraoperative exploration (23 patients), angiography (nine patients), and follow-up (12 patients). RESULTS: Sensitivity in the detection of thoracic aortic dissection was 100% for all techniques. Specificity was 100%, 94%, and 94% for spiral CT, multiplanar TEE, and MR imaging, respectively. In the assessment of aortic arch vessel involvement, sensitivity was 93%, 60%, and 67%, respectively, and specificity was 97%, 85%, and 88%, respectively. CONCLUSION: Spinal CT and multiplanar TEE are as valuable as MR imaging in the detection of thoracic aortic dissection. In the assessment of the supraaortic branches, spiral CT is superior (P<.05).

Adult↗
PubMed1996

Activity-dependent ultra-slow inactivation of calcium currents in rat anterior pituitary cells.

1. The inactivation of high-voltage-activated (HVA) calcium currents during long depolarizations in holding potential (Vh) was studied with the use of whole cell patch-clamp recording from rat anterior pituitary cells. 2. An ultra-slow inactivation in the amplitude of HVA calcium currents, with an average slow time constant of 149.3 s for peak currents and 159.1 s for sustained currents (n = 9), was unveiled during 5-min step depolarizations in Vh. 3. The ultra-slow inactivation of HVA calcium currents was found to be generated by at least two processes: a voltage-dependent inactivation that increases with increasing depolarization in Vh and an activity-dependent inactivation that is initiated, but not increased, with increasing depolarization in Vh. The relative contribution of the activity-dependent component to the ultra-slow inactivation was 80% when Vh was stepped from -80 to -60 mV and only 40% when Vh was stepped from -80 to -40 mV. 4. The activity-dependent inactivation of the HVA currents was not altered significantly in experiments in which barium replaced calcium as charge carrier and 1,2-bis (1-aminophenoxy) ethane N,N,N' N'-tetraacetic acid (BAPTA) was used as an intracellular calcium buffer instead of the less potent ethylenglycol-bis-(beta-aminoethylether) N,N,N' N'-tetraacetic acid (EGTA). In addition, activity-dependent inactivation was observed with sodium as the charge carrier through the calcium channels. 5. The activity-dependent inactivation depends on divalent cation influx. The activity-dependent inactivation was abolished when the test potentials, during the depolarization in Vh, were increased from 0 to +70 mV (close to the reversal potential for calcium currents under our experimental conditions). This reduction in driving force for calcium currents eliminated divalent cation influx and abolished the activity-dependent inactivation. 6. The activity-dependent inactivation lacks several characteristic features for calcium-dependent inactivation, such as dependence on charge carrier (see above), dependence on the size of the calcium current, and increase in decay rate of the calcium current during the test pulse. These latter notions were also supported by our paired pulse experiments, in which the calcium current elicited by a constant test pulse was virtually unaffected (7%) by conditioning pulses that produced maximal calcium currents. We therefore conclude that the dependence of activity-dependent inactivation on divalent cation influx cannot be attributed to the known form of calcium-dependent inactivation. 7. In conclusion, this study shows that calcium influx through HVA channels in anterior pituitary cells can be regulated by subthreshold changes in membrane potential and that the extent of this regulation depends on low-frequency activation of HVA calcium channels during the depolarization in membrane potential. Thus the pituitary cell may regulate hormone secretion by changes in membrane potential and in a use-dependent manner via regulation of calcium influx.

Analysis of Variance↗
PubMed1996

Pharmacokinetic profile of cyclosporine A after conversion to Sandimmun Optoral: influence on ambulatory blood pressure in renal transplant patients.

The aim of the present study was to investigate whether the pharmacokinetic profile of cyclosporin A under Sandimmun Optoral compared to Sandimmun has an effect on blood pressure in patients with stable renal allograft function. Twenty-eight patients were randomized into two groups. Two pharmacokinetic profiles (I, II; time interval 7 days) were obtained in each group. One group (n = 18) was switched from Sandimmun to an equal dose (1:1) of Sandimmun Optoral after the first kinetic and the other (n = 10) received Sandimmun for both kinetics. Eight blood samples were taken during each kinetic and cyclosporine values were measured. Ambulatory blood pressure measurement was performed during each kinetic. There were no differences in the pharmacokinetic parameters between kinetics I and II in the control group but significant differences in the switched group with increased Cmax (+64%), AUC (+44%), C0 (+17%) and decreased Tmax (-39%) in kinetic II compared to kinetic I. Correlation of C0 with AUC was stronger for Sandimmun Optoral (r = 0.792) than for Sandimmun (r = 0.718). Correlation of C0 with Cmax was similar for Sandimmun Optoral (r = 0.53) and Sandimmun (r = 0.56). Mean 12 h blood pressure of kinetic II tended to be lower than that of kinetic I in the control group, but the opposite was true for the switched group. When blood pressure levels around Tmax +/- 1 h were analyzed only, RR (syst/diast) in mmHg was 135 +/- 3.7/89 +/- 2.2 (kinetic I) and 130 +/- 2.8/85 +/- 2.8 (kinetic II) for control as compared to 134 +/- 2.4/85 +/- 2.9 and 137 +/- 3.1/86 +/- 2.8 for the switched group, respectively. Sandimmun Optoral shows an improved pharmacokinetic profile. However, higher blood concentrations of cyclosporine under Sandimmun Optoral tend to increase slightly systemic blood pressure as compared to that under Sandimmun.

Adult↗