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Biomedical subjects

S Schneider

Publications and source records attributed to S Schneider.

At least 19 recordsLinked to original sources

Expression of resistance-related proteins in nephroblastoma after chemotherapy.

Tumor tissues of untreated and cytostatic-agent-treated patients with nephroblastomas were investigated for expression of resistance-related proteins (P-glycoprotein, glutathione S-transferase-pi, glutathione peroxidase and topoisomerase II) to ascertain whether resistance proteins are changed after treatment. Tumor tissue was analyzed by means of mRNA. Twenty-three children were treated with actinomycin D and vincristine for 4 to 8 weeks. Eight children received no preoperative chemotherapy. In untreated patients, no expression of P-glycoprotein was seen, whereas, in the patients who were treated with actinomycin D and vincristine, 12 out of 23 tumors showed increased P-glycoprotein expression (> mean value). Although we found no difference between treated and untreated tumors for glutathione S-transferase-pi, we found significant differences in the expression of glutathione peroxidase. In the 8 untreated patients, 7 tumors showed low glutathione peroxidase (< mean value) and one high (> mean value) glutathione-peroxidase-mRNA content. With treatment, 11 tumors expressed low levels and 12 tumors high levels of mRNA. A significant positive correlation between P-glycoprotein and glutathione peroxidase was found. In addition, of the 8 untreated patients, 2 had low topoisomerase-II expression, and 6 high expression. With treatment, the expression was reduced in 18 tumors, and only 5 tumors had high levels of this protein. These results were confirmed by PCR and immunohistochemistry.

ATP Binding Cassette Transporter, Subfamily B, Mem

The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter is removed by most 11p13 translocations in acute T cell leukaemia's (T-ALL).

The TTG-2 gene has been identified at the site of chromosomal translocations in acute T-cell leukemia's (T-ALL). These breakpoints map to a region between 2 and 30 kb upstream of TTG-2 in chromosome 11p13. To establish the role of these translocation breakpoints in the deregulation of TTG-2 in T-ALL we have determined the complete structure of this gene. Isolation of new TTG-2 cDNA clones from fetal liver identified an alternative transcript (TTG-2a) containing two new noncoding 5' exons. Analysis of exon/intron boundaries, identified 6 exons spread over 35 kb in 11p13. The gene encodes two alternative transcripts initiating from two promoters. TTG-2a, from promoter 1 (P1) and TTG-2b, from promoter 2 (P2) differ in the length of the 5' untranslated region, but encode the same protein. A high level of TTG-2a was present in fetal liver and spleen, whereas in adult kidney a low level of TTG-2a and a high level of TTG-2b was found. The transcription start site for TTG-2a was identified by RNase protection experiments and it displayed sequence homology to an initiator element (inr). P1 lacks a TATA box, but binding sites for SP1 and GATA-1 are present. This new genomic organisation revealed that all known chromosomal translocations map upstream of P2, removing P1 and putative upstream regulatory sequences leaving P2 intact. These results show that chromosomal translocations disrupt the TTG-2 gene itself, further confirming its role in the development of T-ALL.

Adaptor Proteins, Signal Transducing

Associations between disease and occupation: hypotheses generated from the National Mortality Followback Survey.

This study uses the National Mortality Followback Survey of 1986 to identify the top five Sentinel Health Events Occupational [SHE(O)s], the five leading causes of death, and to ascertain the primary occupations and industries associated with these. We found that, as expected, cardiovascular diseases were four of the five leading causes of death overall. In addition, the SHE(O) responsible for most deaths was cancer of the trachea, bronchus, and lung, followed by renal failure, bladder cancer, myeloid leukemia, and liver cancer. We employed proportionate mortality ratios to analyze the relationship between industry and occupation and category of mortality. In brief, we validated findings by other researchers; for example, farmers were at lower risk of cancer of the trachea, bronchus, and lung, and workers in eating/drinking places had excess risk of liver cancer. We also hypothesize other relationships, such as between motor vehicle dealers and bladder cancer.

Cardiovascular Diseases

Effects of sacral dorsal rhizotomy on bladder function in patients with spastic cerebral palsy.

A newly revised operation for controlling spasticity in cerebral palsy patients, selective dorsal rhizotomy (SDR), has the potential to affect bladder function. The goal of this multidisciplinary study is to investigate the potential change in bladder function by characterizing and comparing pre- and post-operative symptoms and bladder function, both qualitatively and quantitatively, in 34 pediatric patients over the age of three with spastic cerebral palsy as the indication for selective dorsal rhizotomy. Video urodynamics were performed in a subset of patients. Almost all patients with quadriplegia were incontinent (8/9) and none were significantly helped with bladder control. Almost half (5/11) of patients with diplegia who failed prior bladder control training were able to gain continence post-operatively. No patient experienced permanent damage to the function of their bladder. In conclusion, selective dorsal rhizotomy using the revised technique of Peacock [Peacock et al. (1987): Pediatr Neurosci 13:61-66.] appears to be safe for spastic cerebral palsy patients' bladder function. It can help decrease symptoms and improve bladder capacity and control in almost half of those symptomatic cerebral palsy patients with diplegia.

Cerebral Palsy

Immunolocalization of lamins and nuclear pore complex proteins by atomic force microscopy.

The nuclear envelope functions as a selective barrier separating the nuclear from the cytosolic compartment. Nuclear pore complexes (NPCs) mediate nuclear import and export of macromolecules and, therefore, are potential regulators of gene expression. In this study we applied atomic force microscopy (AFM) to visualize the three dimensional (3D) structure of individual NPCs in the absence and presence of two different antibodies, one directed against a pore protein (gp62) and another directed against Xenopus lamin LIII, a component of the nuclear lamina, a filament meshwork localized on the nucleoplasmic side of the nuclear envelope (NE) adjacent to and interacting with NPCs. Using 12-nm gold-labelled secondary antibodies and transmission electron microscopy we could clearly localize the primary single anti-gp62 antibody on NPCs and the primary single anti-LIII antibody between NPCs. Using AFM, the secondary antibodies against anti-gp62 could be detected as particles 7 nm in height on the nucleoplasmic face of NPCs. The secondary antibodies against anti-LIII could be clearly identified between NPCs. The secondary antibodies, attached to a 12-nm colloidal gold particle and visualized on glass, revealed similar shapes and heights as found on NEs. According to the 3D images, the volume of a single gold particle conjugated with secondary antibodies was 10203 nm3. This volume is equivalent to the volume of 38 IgG molecules associated with one individual gold particle. A similar volume of 11987 nm3 was calculated from a model assuming that the 150-kDa IgG molecules perfectly cover the spherical gold particle. We conclude that AFM can be used for identifying antibodies or other macromolecules associated with biomembranes.

Animals

The separation of overlapping neuromagnetic sources in first and second somatosensory cortices.

In response to a somatosensory stimulus, two cortical centers in each hemisphere produce neural mass activity large enough to be detected with electric (EEG) or magnetic (MEG) measurements. Both the primary somatosensory cortex (S-I), located in the postcentral sulcus and in the depths of the central sulcus, as well as the secondary somatic sensory cortex (S-II), lying in the upper bank of the Sylvian fissure, respond within the first 100 ms such that the two activities overlap in time. We demonstrate that this overlap can be disentangled using a MUSIC-type approach, as suggested by Oppelt and Scholz. It needs no a priori information about the sources. As the results show, there are several instances in time in which only one of the two centers (SI, SII) is active. It is only for these time segments that a single moving dipole yields meaningful results. Such time intervals occur during the upstroke of the late component around 60 ms (only SI activity) and during the down-stroke around 120 ms (only SII activity). In these time intervals the activity of one of the somatosensory areas is still large enough, while the other center is not yet or is no longer active.

Adult

[A prospective study of early diagnosis of lunate necrosis by means of MRI].

AIM: Early recognition of lunate necrosis by means of MRI. METHODS: 49 patients with typical symptoms and normal radiographs were examined. Coronary T1 and T2 weighted images were obtained. In addition, an attempt was made to quantify fluid shift and measure of bone marrow oedema by means of extreme T2 weighting (TR 5950 ms, TE 150 ms). RESULTS: Three instances of necrosis were found; in two cases it was possible to demonstrate marrow oedema. Oedema preceding necrosis could not be demonstrated by quantifying a grey scale. CONCLUSIONS: The pattern of pain in the region of the lunate is not typical and is usually not of bone origin. Early MRT will show lunate necrosis only rarely; nevertheless, the therapeutic consequences justify the examination if pain persists for several weeks. Extreme T2 weighting for quantifying a grey scale to demonstrate early marrow oedema has not proved useful. Our experience suggests that T2 weighting is adequate and is the method of choice for the early recognition of necrosis of the lunate.

Adult

[The magnetic resonance tomographic optimization of hip joint cartilage visualization by the selection of a T1-volume gradient-echo sequence and the use of hip-joint traction].

PURPOSE: The purpose of this study was to examine the accuracy of MR imaging of the healthy and the arthrotically altered articular hip cartilage with in vivo and in vitro separation of femoral head cartilage and acetabular cartilage. MATERIAL AND METHODS: Images of three animal cadaver hips, 8 dissected patient femoral heads and 18 hip joints of human corpses, all either with arthrosis stage I-III or artificial cartilage defects, were compared with their corresponding anatomic sections. Additional histomorphologic examinations of the arthrotic cartilages were conducted, and MR-Imaging of 20 healthy and 21 arthrotic patient hips was performed using a specific traction method. RESULTS: Using a T1-weighted 3-dimensional gradient-echo sequence and a traction of the hip joint, it was possible due to the low-signal imaging of the joint space to separate in vivo the high-signal femoral head cartilage from the high-signal acetabular cartilage. In horizontal position of the phase-encoding parameter, minimisation of the chemical-shift artifact, mainly in the ventro-lateral areas, was accomplished. MRI measurements of the articular cartilage widths showed significant correlations (p < 0.001) with the corresponding anatomic sections. At the same time the T1 3-dimensional gradient-echo sequence of the lateral femoral head with r = 0.94 showed the lowest deviations of the measurements. It was possible with MR imaging to distinguish four cartilage qualities. CONCLUSIONS: Using these MR-examinations, an improved imaging of early stage arthrotic cartilage defects is possible, and the status of the arthrotic hip cartilage with regard to intertrochanteric osteotomy can also be assessed.

Animals

Preventing post-treatment bacteremia: comparing topical povidone-iodine and chlorhexidine.

It is well known that the occurrence of bacteremia after dental procedures can place certain patients at risk for bacterial endocarditis. The authors compared the efficacy of two antiseptic agents in the prevention of post-treatment bacteremia in 120 dental patients. Before treatment, dentists irrigated the gingival sulcus of each patient with 10 percent povidone-iodine, 0.2 percent chlorhexidine or sterile water. The authors report lower levels of bacteremia among patients treated with the povidone-iodine solution.

Adult

Mutations of p53 in Wilms' tumors.

Mutations of p53 frequently occur in a wide variety of cancers including lung, breast, gastrointestinal, brain, and hematologic malignancies. These alterations apparently contributed to development of the malignant phenotype. Wilms' tumor is one of the most common solid tumors in childhood. The frequency of p53 alterations in this tumor is unknown. We analyzed 66 Wilms' tumor samples for p53 mutations by single-stand conformational polymorphism (SSCP) following polymerase chain reaction (PCR). Samples with an abnormal SSCP pattern were reamplified and analyzed by direct sequencing method. Mutations of p53 were found in three (5%) of 66 Wilms' tumors within the coding region (exons 2-11), showing that the frequency of p53 mutations was low. Two mutations substituted amino acids residues and one encoded a stop codon. Two of the mutations were located in the mutational hotspots (exons 5 and 6); the other was in exon 10. These data suggest that p53 mutations are infrequent in the development of Wilms' tumors.

Base Sequence

Synthesis and degradation of hyaluronate by synovia from patients with rheumatoid arthritis.

OBJECTIVE: Hyaluronate degradation was analyzed in cultures of healthy tissue and tissue obtained from patients with rheumatoid arthritis. METHODS: Arthritic and healthy synovial tissues were incubated in culture with [3H]glucosamine. Labelled hyaluronate was extracted and its size determined by gel filtration. The production of low molecular weight hyaluronate was analyzed by pulse-chase experiments. Radical production was measured by a cytochrome C reduction assay. RESULTS: Healthy tissues and some arthritic tissues that did not contain significant amounts of granulocytes produced high molecular weight hyaluronate. In contrast, arthritic tissue infiltrated with granulocytes released low molecular weight hyaluronate. Pulse-chase experiments suggested that hyaluronate was degraded in these arthritic tissues. Exogenous hyaluronate was degraded only by intact tissue, but not by cells in culture obtained from synovial membranes of synovial fluids. Hyaluronate degradation was accompanied by massive oxygen radical production. Radical scavengers protected hyaluronate from degradation in synovial tissue. Some protection was achieved by superoxide and catalase or by methionine and complete protection by the iron chelators diethyltriaminepentacetic acid or deferoxamine mesylate. CONCLUSION: Degradation of hyaluronate in arthritic synovial tissue may be inhibited in tissue culture by radical scavengers.

Arthritis, Rheumatoid

Xenopus cadherins: the maternal pool comprises distinguishable members of the family.

Three maternal cadherins have been reported to occur in the pregastrula Xenopus embryo. EP- and XB-cadherin are distinguished by their distinct cDNA sequences. U-cadherin has been characterized by its reaction with a specific monoclonal antibody (mAb 6D5). Thus far, lack of specific probes that discriminate between these molecules has prevented their identification as distinct cadherins. We now demonstrate by means of RNase protection assays that both EP- and XB-cadherin mRNAs are present in oocytes and mature eggs. By use of the Xenopus cadherin proteins expressed in mammalian cell lines, we find that mAb 6D5 crossreacts with XB-cadherin, but not with EP-cadherin. The major fraction of the maternal cadherins does not contain the 6D5 epitope and probably represents EP-cadherin. A minor fraction carries the 6D5 epitope indicative for the XB- and U-type of cadherins. We have termed this fraction XB/U-cadherin. The function of maternal cadherins was examined by in vitro cell adhesion assays. A newly developed antiserum with a broad specificity for various Xenopus cadherins efficiently blocks all calcium dependent cell adhesion in the early embryo. We conclude that the maternal cadherins play a central role in interblastomere adhesion in the early embryo and comprise at least two discrete cadherin forms, EP- and XB/U-cadherin.

Amino Acid Sequence

Child and adolescent psychopathology research: problems and prospects for the 1990s.

In November 1990 the National Institute of Mental Health (NIMH) convened a special conference of over 100 scientists and leaders to outline specific strategies and research initiatives that should be developed to implement the recently released National Plan for Research on Child and Adolescent Mental Disorders. Participants included journal editors, educators from psychology and psychiatry, representatives from private foundations, and leaders of research program areas in public funding agencies. Critical knowledge gaps were identified in five areas of child and adolescent psychopathology, including depression, attention deficit hyperactivity disorder, conduct disorder, the anxiety disorders, and the developmental disorders. For each of these areas, special emphasis was placed on developing new ideas and obtaining critical input from other areas of investigation. This report summarizes the identified research gaps and recommends research initiatives to implement the National Plan, as outlined by the conference participants.

Adolescent

Spatial differences of the duration of ventricular late fields in the signal-averaged magnetocardiogram in patients with ventricular late potentials.

Magnetocardiography (MCG) allows one to noninvasively localize cardiac electrical activity in three dimensions. It was the purpose of this study to obtain information about the spatial variations of signal-averaged ventricular late magnetic fields recorded by a biomagnetic multichannel system. Biomagnetic signals of 170-600 heart cycles obtained by the 37-channel system KRENIKON (Siemens Medical Engineering Group) were simultaneously averaged in all channels. The absolute values of the filtered signals (digital, bidirectional, four-pole butterworth, bandpass filter [3-dB range, 40-250 Hz]) were calculated in each channel. The noise level was determined within the TP segment. The onset of the terminal low amplitude signals (TLAS) was defined when the signals became lower than 1/23 of Rmax of the QRS complex for the channel with the largest filtered QRS complex after filtering. The TLAS ended when the signal was lower than twice the standard deviation (2 sigma) above the mean noise level. Ventricular late fields were defined as present when the TLAS had a duration of more than 39 msec. In this study, five patients with ventricular late potentials (four with sustained ventricular tachycardia) and three healthy individuals were examined. Ventricular late fields were detected in the patient group in 2-15 MCG channels with a mean length of 49.6 msec (43-60 msec). The spatial distribution of the ventricular late fields was consistently found to exhibit maximum duration in a certain area. In the normal subjects no ventricular late fields were detected. Thus, MCG is able to detect ventricular late fields and their spatial variations. In addition to the information obtained by signal averaging from the surface ECG, averaging of biomagnetic signals with a multichannel device can reveal spatial inhomogeneity of delayed myocardial excitation.

Electrocardiography