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R Steffens

Publications and source records attributed to R Steffens.

12 recordsLinked to original sources
PubMed1999

Ca(2+)-dependent inactivation of high-threshold Ca(2+) currents in hippocampal granule cells of patients with chronic temporal lobe epilepsy.

Intracellular Ca(2+) represents an important trigger for various second-messenger mediated effects. Therefore a stringent control of the intracellular Ca(2+) concentration is necessary to avoid excessive activation of Ca(2+)-dependent processes. Ca(2+)-dependent inactivation of voltage-dependent calcium currents (VCCs) represents an important negative feedback mechanism to limit the influx of Ca(2+) that has been shown to be altered in the kindling model of epilepsy. We therefore investigated the Ca(2+)-dependent inactivation of high-threshold VCCs in dentate granule cells (DGCs) isolated from the hippocampus of patients with drug-refractory temporal lobe epilepsy (TLE) using the patch-clamp method. Ca(2+) currents showed pronounced time-dependent inactivation when no extrinsic Ca(2+) buffer was present in the patch pipette. In addition, in double-pulse experiments, Ca(2+) entry during conditioning prepulses caused a reduction of VCC amplitudes elicited during a subsequent test pulse. Recovery from Ca(2+)-dependent inactivation was slow and only complete after 1 s. Ca(2+)-dependent inactivation could be blocked either by using Ba(2+) as a charge carrier or by including bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) or EGTA in the intracellular solution. The influence of the cytoskeleton on Ca(2+)-dependent inactivation was investigated with agents that stabilize and destabilize microfilaments or microtubules, respectively. From these experiments, we conclude that Ca(2+)-dependent inactivation in human DGCs involves Ca(2+)-dependent destabilization of both microfilaments and microtubules. In addition, the microtubule-dependent pathway is modulated by the intracellular concentration of GTP, with lower concentrations of guanosine triphosphate (GTP) causing increased Ca(2+)-dependent inactivation. Under low-GTP conditions, the amount of Ca(2+)-dependent inactivation was similar to that observed in the kindling model. In summary, Ca(2+)-dependent inactivation was present in patients with TLE and Ammon's horn sclerosis (AHS) and is mediated by the cytoskeleton similar to rat pyramidal neurons. The similarity to the kindling model of epilepsy may suggest the possibility of altered Ca(2+)-dependent inactivation in patients with AHS.

Adult↗
PubMed1998

Voltage-dependent Ca2+ currents in epilepsy.

Voltage-dependent Ca2+ channels (VCCs) represent one of the main routes of Ca2+ entry into neuronal cells. Changes in intracellular Ca2+ dynamics and homeostasis can cause long-lasting cellular changes via activation of different Ca2+ dependent signalling pathways. We have investigated the properties of VCCs in human hippocampal dentate granule cells (DGCs) using the whole-cell configuration of the patch-clamp method. Classical high-threshold Ca2+ currents were composed mainly of omega-CgTx-sensitive N-type and nifedipine-sensitive L-type currents that were present in similar proportions. In addition, a Ca2+ current component that was sensitive to low concentrations of Ni2+, but not to nifedipine or omega-conotoxin GVIA (omega-CgTx GVIA) was present. This latter component showed a half-maximal inactivation at more hyperpolarized potentials than high-threshold currents and a more rapid time-dependent inactivation. This current was termed T-type Ca2+ current. Current components with similar pharmacological and kinetic characteristics could be elicited in acutely isolated control rat DGCs. The current density of high threshold and T-type Ca2+ components was significantly larger in human DGCs and in the kainate model compared to DGCs isolated from adult control rats. These differences in current density were not accompanied by parallel differences in the voltage-dependence of VCCs. Taken together, these data suggest that an up-regulation of Ca2+ current density may occur in hippocampal epileptogenesis without consistent changes in Ca2+ current properties.

Adult↗
PubMed1997

Properties of voltage-activated Ca2+ currents in acutely isolated human hippocampal granule cells.

Properties of Ba2+ currents through voltage-dependent Ca2+ channels (IBa) were investigated in 61 dentate granule cells acutely isolated from the resected hippocampus of nine patients with therapy-refractory temporal lobe epilepsy (TLE). Currents with a high threshold of activation (HVA) peaked at 0 mV, and showed some time-dependent inactivation and a voltage of half-maximal steady-state inactivation (V1/2inact) of -16.4 mV. Application of saturating doses of omega-conotoxin (omega-CgTx) GVIA or nifedipine distinguished characteristic N-type (38%) and L-type (62% of HVA currents) Ca2+ currents. Combined application of both agents blocked HVA currents by > 95%. In a 10-mo-old child but not in adult patients, an omega-agatoxin IVA (omega-AgaTxIVA)-sensitive but omega-CgTx MVIIC-insensitive, noninactivating component of HVA currents (approximately 24%) was present that most probably corresponds to a P-type current. A T-type Ca2+ current could be separated from HVA components on the basis of its steady-state voltage-dependent inactivation (V1/2inact = -71.0 mV). The T-type Ca2+ current isolated by subtraction peaked at more negative potentials (-10 mV), showed a significantly more rapid time-dependent inactivation, and could be selectively blocked by low concentrations of Ni2+. It was insensitive to nifedipine and omega-CgTx GVIA. We conclude that L-, N-, and T-type currents are present in adult human dentate granule cells and an additional P-type current is present in neurons from a 10-mo-old patient. These data may provide a basis for comparison with animal models of epilepsy and for the elucidation of mechanisms of action of drugs intended for use in human disease.

Adult↗
PubMed1996

Assessment of cellular telephone and other radio frequency exposure for epidemiologic research.

Epidemiologists are now embarking on the evaluation of the hypothesis that exposure to radio frequency energy from low-power wireless communication devices, such as portable cellular telephones, causes brain cancer and other adverse health outcomes. Even in the laboratory, exposures from radio frequency sources are difficult to quantify; their measurement in large populations for epidemiologic study is challenging. In this paper, we outline the nature and magnitude of these exposures and discuss the prospects for obtaining useful measures of exposure for epidemiologic research.

Brain Neoplasms↗
PubMed1996

[Hospital drug supply around the turn of the century--the founding of the pharmacy at the city hospital of Worms].

Around the turn of the century drug supply of the civil hospital in Worms was carried out by local pharmacists, drug distribution and preparation of simple solutions by a nurse. The municipal authorities which were responsible for the hospital were sure that the establishment of a pharmacy in the hospital itself could improve drug supply. The study shows how the authorities went through with the opening of a hospital pharmacy despite the expected opposition of the local pharmacists and that such an establishment and the employment of a pharmacist were profitable even for a hospital with only 200 beds.

Germany↗
PubMed1980

Immunocytochemical localization of myosin in the brush border region of the intestinal epithelium.

Myosin was localized in rat intestinal epithelium by means of indirect immunofluorescence and immunoelectron microscopy (unlabeled antibody peroxidase method), using a specific antibody to myosin from chicken gizzard. Immunoreactivity was localized in the apical cytoplasm, where it was concentrated along the rootlets of the microvillar filament bundles and in the terminal web. A model of microvillar contraction is proposed.

Animals↗
PubMed1979

On the activation of the canine pepsinogens.

Acidification induces a conversion of canine pepsinogens by a sequential mechanism to the active pepsins. Activation in the presence of pepstatin, which strongly inhibits the pepsins but does not prevent the first step of activation, allows the isolation of the peptide released in this first step. This peptide inhibits the milk clotting activity of canine and also porcine pepsin. Canine pepsins obtained in the absence of pepstatin were characterized by amino acid composition, molecular weight, and activity against hemoglobin and milk and compared with those of other mammalian pepsins.

Amino Acids↗
PubMedDate not supplied

Differences in verotoxin neutralizing activity of therapeutic immunoglobulins and sera from healthy controls.

Intestinal infection by Escherichia coli O157 and other verotoxin (VT) producing E. coli has been increasingly recognized as an important factor for the causation of classic (enteropathic) hemolytic uremic syndrome (HUS) and hemorrhagic colitis (HC). Toxins most frequently involved are VT1 and VT2. As with other toxin-mediated diseases, administration of immunoglobulin (Ig) may be beneficial. However, little is known about the immune response elicited by the toxin(s), and the prevalence of VT neutralizing antibodies in the healthy population. We studied the capacity of seven Igs and a commercial plasma preparation to neutralize four different VTs (VT1, VT2, VT2c and VT2e). The results were compared with the neutralization titers (NT50%) of normal human serum samples from various age groups. Plasma products and normal sera were separated by protein G affinity chromatography to investigate the factor(s) responsible for VT neutralization. All Igs neutralized VT1 (8 to 96 NT50%). None of them inhibited VT2, VT2c or VT2e effectively. In contrast, none of 40 pediatric, and only one of 20 adult control sera (starting dilution 1:4) neutralized VT1 (25 NT50%). All 60 samples as well as the plasma preparation blocked VT2 (22 to 446 NT50%, median 137), but not VT2c and VT2e. The VT1 neutralizing activity was eluted with the IgG fraction. The VT2 neutralizing activity was not bound by protein G, but was recovered in the IgG-free effluent. In conclusion, therapeutic Igs significantly neutralize VT1, but are largely ineffective against other VTs. In contrast, all control sera inhibited VT2, but rarely VT1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Awareness of heightened breast cancer risk among first-degree relatives of recently diagnosed breast cancer patients. The High Risk Breast Cancer Consortium.

This investigation had two goals: (a) to determine the proportion of first-degree relatives of recently diagnosed breast cancer patients who are unaware of their elevated risk for breast cancer; and (b) to identify demographic medical, and lifestyle factors that characterize these women. The ultimate objective was to identify women at increased risk who could benefit from breast cancer risk education. Three hundred ninety-five female first-degree relatives, ages 30-75 years, completed a structured telephone interview. Twenty-five % of these women believed that their risk for breast cancer was the "same as or lower than" women who do not have a family history of breast cancer, despite the fact that they had an objectively increased risk. Bivariate analyses revealed that women who were unmarried (chi2 = 14.8; P = 0.001) and had less than or equal to a high school education (chi2 = 9.2; P = 0.002) were significantly less likely to perceive themselves as being at increased risk for breast cancer. In addition, almost one-half of African-American women were unaware of their increased risk compared to only 19% of white women (chi2 = 29.9; P < 0.001). More smokers were unaware of their elevated risk compared to nonsmokers (43 versus 21%; chi2 = 15.1; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗