PubMed Health⌕ Search

Biomedical subjects

A Scherer

Publications and source records attributed to A Scherer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Calmodulin differentially modulates Smad1 and Smad2 signaling.

The members of the Smad protein family are intracellular mediators of transforming growth factor beta (TGF-beta) signaling. Smad1 transduces bone morphogenetic protein signals, inducing formation of ventral mesoderm in Xenopus embryos, whereas Smad2 transduces activin/TGF-beta signals, generating dorsal mesoderm. Calmodulin directly binds to many Smads and was shown to down-regulate Smad2 activity in a cell culture system (Zimmerman, C. M., Kariapper, M. S. T., and Mathews, L. S. (1997) J. Biol. Chem. 273, 677-680). Here, we extend those data and demonstrate that calmodulin alters Smad signaling in living embryos, increasing Smad1 activity while inhibiting Smad2 function. To characterize this regulation, we undertook a structure-function analysis and found that calmodulin binds to two distinct and conserved regions in both Smad1 and Smad2. Receptor tyrosine kinase signaling also modifies Smad activity (Kretzschmar, M., Doody, J., and Massagué, J. (1997) Nature 389, 618-622; Kretzschmar, M., Doody, J., Timokhina, I., and Massagué, J. (1999) Genes Dev. 13, 804-816; de Caestecker, M. P., Parks, W. T., Frank, C. J., Castagnino, P., Bottaro, D. P., Roberts, A. B., and Lechleider, R. J. (1998) Genes Dev. 12, 1587-1592). We show that calmodulin binding to Smads inhibits subsequent Erk2-dependent phosphorylation of Smads and vice versa. These observations suggest the presence of a cross-talk between three major signaling cascades as follows: Ca(2+)/calmodulin, receptor tyrosine kinase, and TGF-beta pathways.

Amino Acid Sequence↗
PubMed2000

From micro- to nanofabrication with soft materials.

Soft materials are finding applications in areas ranging from microfluidic device technology to nanofabrication. We review recent work in these areas, discuss the motivation for device fabrication with soft materials, and describe applications of soft materials. In particular, we discuss active microfluidic devices for cell sorting and biochemical assays, replication-molded optics with subdiffraction limit features, and nanometer-scale resonators and wires formed from single-molecule DNA templates as examples of how the special properties of soft materials address outstanding problems in device fabrication.

Biomedical Engineering↗
PubMed2000

Monolithic microfabricated valves and pumps by multilayer soft lithography.

Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.

Adhesiveness↗
PubMed2000

The impact of epilepsy from the patient's perspective I. Descriptions and subjective perceptions.

This study surveyed the perceptions about and subjective experience of 1023 people with epilepsy in two community-based samples: one from a national postal survey; the other callers to the Epilepsy Foundation. Response to a mail survey was 49%. In comparison with US Census Bureau norms, respondents had received less education, were less likely to be employed or married, and came from lower income households. Complex partial seizures were the most prevalent seizure type, but a convulsion had occurred in 61%. Fifty percent of respondents reported incomplete control of their seizure disorder, although 25% of these had a seizure in the prior year. Thirteen percent had a longest inter-seizure interval of a year or greater, 37% of 3 months, 22% of 1 month, 10% of 1 week and 4% of 1 day. Respondents listed uncertainty and fear of having a seizure as the worst thing about having epilepsy. Lifestyle, school, driving, and employment limits were also listed as major problems. When asked to rank a list of potential problems, cognitive impairment was ranked highest. These data indicate that ongoing medical and psychosocial problems continue for those with epilepsy in the view of those questioned and their families, even in a sample where the majority report good control of their epilepsy.

Adolescent↗
PubMed2000

The impact of epilepsy from the patient's perspective II: views about therapy and health care.

A national survey of 1023 people with epilepsy in the US assessed their attitudes about their therapies. Subjects were drawn from responders to a previous national survey of US households or from those who phoned the Epilepsy Foundation. Overall response rate was 49%. Approximately 90% of the respondents were taking medications for their epilepsy. Only 56% were on monotherapy, while 26% were taking two, 6% three, and 2% four medications. Only 68% of respondents were very satisfied with their current seizure medications. When asked to rank five areas of importance regarding their seizure medication, the rank order (highest to lowest) was seizure control, fewer side effects, convenient dosing regimens and cost. Adverse medication events were listed in descending rank order as problems with cognition, energy level, school performance, childbearing, coordination, and sexual function. Inter-individual differences in side effects of concern were listed, suggesting medication choices should be individualized according to potential side effects. Twenty percent of 920 respondents adjusted their medications on their own, by adjusting amount (62%), dosing schedule (31%), or both (3%). Eighty percent of respondents were satisfied with their medical care systems. In this group, 82% had health insurance that covered epilepsy. The large majority (94%) of respondents had seen a neurologist. Subjects expressed dissatisfaction about time limits and lack of accessible information about epilepsy. People with epilepsy are generally satisfied with efforts to treat their disorder, but adverse events are of concern. Many patients requested more information about epilepsy.

Adolescent↗
PubMed2000

[MRI of aseptic osteonecrosis in children and adolescents with acute lymphoblastic leukemia].

PURPOSE: To evaluate the incidence, localisation, and course of symptomatic aseptic osteonecrosis (AON) in children undergoing treatment for acute lymphoblastic leukemia (ALL). METHODS: 72 MRI examinations obtained from 26 children with bone pain selected from a group of 121 children with ALL were evaluated retrospectively. The area of the AON was determined by computer assisted planimetry. Follow-up examinations after 2-5 years were considered. RESULTS: 10/121 (8.3%) of the children had symptomatic AON, the number of lesions varied between 1 and 24 per child. 62/66 lesions were localized within the lower extremities. 58% of the AON were positioned in the epiphysis and 42% in the meta- and diaphysis. The mean area of AON was 7.6 cm2 with a range of 0.5 to 50 cm2. Follow-up examinations revealed a regression in 19 AON, no change in 43 and a progression in 4 lesions. AON within the epiphysis with joint involvement or lesions greater than 9 cm2 more frequently showed a progression of AON with final joint destruction. An elevated risk for AON was seen in children older than 10 years and in children with intensified chemotherapy due to high-risk ALL. CONCLUSION: AON is a common complication in ALL-children under chemotherapy. Most frequently, the course is benign but large AON with joint involvement have an elevated risk for progression of AON with final joint destruction.

Adolescent↗
PubMed2000

[Ganglioneuromas in childhood: CT and MRI characteristics].

PURPOSE: The aim of this study was to demonstrate the typical appearance of ganglioneuromas in computer-assisted tomography (CT), and magnetic resonance imaging (MRI). MATERIAL AND METHODS: Retrospective analysis of diagnostic imaging (9 CT, 6 MRI) in 9 children aged 3 to 15 years with the histological diagnosis of ganglioneuroma. RESULTS: The tomographies showed large (max. 13.4 cm in diameter) round or oval tumors with sharp delineation. The sites of the tumors were the retroperitoneum (5), the mediastinum (3), and the adrenal gland (1). Intraspinal tumor involvement occurred in 4 cases. On comparing CT with MRI, MRI was more accurate in defining the intraspinal involvement. The ganglioneuromas were of hypodense appearance in the native CT scan and showed moderate enhancement upon administration of contrast media. In five patients tumor calcifications with a disseminated sprinkled pattern were seen in CT. In MRI T1-weighted scans the tumors were homogeneous and hypointense, after gadolinium application a marked enhancement was evident. In T2-weighted scans the tumors were hyperintense. CONCLUSION: At the time of diagnosis ganglioneuromas are generally large tumors which can be well detected by CT and MRI. Information towards the diagnosis is given by the appearance of the ganglioneuromas in CT and MRI. However, MRI is the modality of choice due to its superiority in documenting intraspinal tumor expansion.

Adolescent↗
PubMed2000

MRI evaluation of aseptic osteonecrosis in children over the course of hyperbaric oxygen therapy.

PURPOSE: The study aimed at MRI evaluation of aseptic osteonecrosis (AON) in children over the course of hyperbaric oxygen (HBO) therapy. MATERIAL AND METHODS: Retrospective analysis of 72 MRI studies in 20 children presenting with AON during chemotherapy. Two groups were differentiated: Gr. I (n = 8) was treated exclusively with relief of weightbearing structures, Gr. II (n = 12) was additionally treated with HBO therapy. The MRI examinations were evaluated by a point-score system (1-6 points) by two radiologists. RESULTS: Gr. II initially showed more severe findings (average score: 3.4) in comparison to Gr. I (average score: 2.65). During the follow-up time period the average scores rose to 3.2 score-points in Gr. I and 4.1 points in Gr. II. No statistically significant difference was evident between the two groups in the course of AON. CONCLUSION: The majority of chemotherapy associated AON which initially present with advanced findings show a progression in MRI over their further course. HBO therapy in addition to the relief of affected weightbearing structures statistically shows no significant improvement in MRI morphology during the course of the treatment.

Antineoplastic Agents↗
PubMed1999

Two-dimensional photonic band-Gap defect mode laser

A laser cavity formed from a single defect in a two-dimensional photonic crystal is demonstrated. The optical microcavity consists of a half wavelength-thick waveguide for vertical confinement and a two-dimensional photonic crystal mirror for lateral localization. A defect in the photonic crystal is introduced to trap photons inside a volume of 2.5 cubic half-wavelengths, approximately 0.03 cubic micrometers. The laser is fabricated in the indium gallium arsenic phosphide material system, and optical gain is provided by strained quantum wells designed for a peak emission wavelength of 1.55 micrometers at room temperature. Pulsed lasing action has been observed at a wavelength of 1.5 micrometers from optically pumped devices with a substrate temperature of 143 kelvin.

Journal Article↗
PubMed1999

A microfabricated device for sizing and sorting DNA molecules.

We have demonstrated a microfabricated single-molecule DNA sizing device. This device does not depend on mobility to measure molecule size, is 100 times faster than pulsed-field gel electrophoresis, and has a resolution that improves with increasing DNA length. It also requires a million times less sample than pulsed-field gel electrophoresis and has comparable resolution for large molecules. Here we describe the fabrication and use of the single-molecule DNA sizing device for sizing and sorting DNA restriction digests and ladders spanning 2-200 kbp.

Bacteriophage lambda↗
PubMed1999

A microfabricated fluorescence-activated cell sorter.

We have demonstrated a disposable microfabricated fluorescence-activated cell sorter (microFACS) for sorting various biological entities. Compared with conventional FACS machines, the microFACS provides higher sensitivity, no cross-contamination, and lower cost. We have used microFACS chips to obtain substantial enrichment of micron-sized fluorescent bead populations of differing colors. Furthermore, we have separated Escherichia coli cells expressing green fluorescent protein from a background of nonfluorescent E. coli cells and shown that the bacteria are viable after extraction from the sorting device. These sorters can function as stand-alone devices or as components of an integrated microanalytical chip.

Escherichia coli↗
PubMed1997

Crystallization and preliminary X-ray crystallographic study of the Ras-GTPase-activating domain of human p120GAP.

Ras-GTPase-activating proteins (Ras-GAPs) are important regulators of the biological activity of Ras within the framework of intracellular communication where GTP-bound Ras (Ras:GTP) is a key signal transducing molecule (Trahey and McCormick, Science 238:542-545, 1987; Boguski and McCormick, Nature 366:643-654, 1993). By accelerating Ras-mediated GTP hydrolysis, Ras-GAPs provide an efficient means to reset the Ras-GTPase cycle to the GDP-bound 'OFF'-state and terminate the Ras-mediated signal. Here we report the crystallization of the GTPase-activating domain of the human p120GAP. The crystals-belong to the orthorhombic space group symmetry P2(1)2(1)2(1) with unit cell dimensions of a = 42.2 A, b = 55.6 A, c = 142.2 A, alpha = beta = gamma = 90 degrees. Assuming a Matthews parameter of 2.2 A3/Da, there is one molecule per asymmetric unit. Applying micro-seeding techniques, we grew large single crystals that could not be obtained by other routine methods for crystal improvement. They diffracted to a resolution of approximately 3 A using X-rays from a rotating anode generator and to better than 1.8 A in a synchrotron beam. Chemical cross-linking led to reduction of the maximum resolution but to significantly increased stability against mechanical and heavy atom stress.

Crystallization↗
PubMed1997

Production, crystallization, and preliminary X-ray analysis of rabbit skeletal muscle troponin complex consisting of troponin C and fragment (1-47) of troponin I.

Troponin is a ternary protein complex consisting of subunits TnC. TnI, and TnT, and plays a key role in calcium regulation of the skeletal and cardiac muscle contraction. In the present study, a partial complex (CI47) was prepared from Escherichia coli-expressed rabbit skeletal muscle TnC and fragment 1-47 of TnI, which is obtained by chemical cleavage of an E. coli-expressed mutant of rabbit skeletal muscle TnI. Within the ternary troponin complex, CI47 is thought to form a core that is resistant to proteolytic digestion, and the interaction within CI47 likely maintains the integrity of the troponin complex. Complex CI47 was crystallized in the presence of sodium citrate. The addition of trehalose improved the diffraction pattern of the crystals substantially. The crystal lattice belongs to the space group P3(1)(2)21, with unit cell dimensions a = b = 48.2 A, c = 162 A. The asymmetric unit presumably contains one CI47 complex. Soaking with p-chloromercuribenzenesulfonate (PCMBS) resulted in loss of isomorphism, but enhanced the quality of the crystals. The crystals diffracted up to 2.3 A resolution, with completeness of 91% and R(merge) = 6.4%. The crystals of PCMBS-derivative should be suitable for X-ray studies using the multiple-wavelength anomalous diffraction technique. This is the first step for elucidating the structure of the full troponin complex.

Animals↗
PubMed1995

The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue.

The X-ray crystal structure of the complex between the Ras-related protein Rap1A in the GTP-analogue (GppNHp) form and the Ras-binding domain (RBD) of the Ras effector molecule c-Raf1, a Ser/Thr-specific protein kinase, has been solved to a resolution of 2.2 A. It shows that RBD has the ubiquitin superfold and that the structure of Rap1A is very similar to that of Ras. The interaction between the two proteins is mediated by an apparent central antiparallel beta-sheet formed by strands B1-B2 from RBD and strands beta 2-beta 3 from Rap1A. Complex formation is mediated by main-chain and side-chain interactions of the so-called effector residues in the switch I region of Rap1A.

Amino Acid Sequence↗
PubMed1995

The ribose 5-phosphate isomerase-encoding gene is located immediately downstream from that encoding murine immunoglobulin kappa.

The immunoglobulin kappa locus (Ig kappa) is active only in the B-lymphocyte cell lineage. By exon-trapping we found a gene situated downstream from the murine Ig kappa locus. This gene encodes a protein with 53% sequence identity to the ribose 5-phosphate isomerase A (RPI-A) of Escherichia coli and is therefore likely to be the murine homologue (mRPI) of this enzyme. We confirmed this assumption by showing that a glutathione S-transferase (GST)::mRPI fusion protein has enzymatic activity and that an anti-mRPI antibody detects a protein of the predicted mass of RPI (33 kDa). Cloning and sequencing of the human counterpart show that the RPI gene is evolutionarily conserved. The expression of mRPI is not influenced by the rearrangement status of the Ig kappa locus in B cells and mRPI is expressed in all tissues. We thus show that two genes with very different expression patterns, a housekeeping gene and a gene expressed in a tissue-specific manner, can be located on a chromosome in close proximity to each other.

Aldose-Ketose Isomerases↗