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Biomedical subjects

C Lange

Publications and source records attributed to C Lange.

At least 19 recordsLinked to original sources

Univariate and multivariate family-based association analysis of the IL-13 ARG130GLN polymorphism in the Childhood Asthma Management Program.

Interleukin 13 (IL-13) has been demonstrated to have a crucial role in animal models of allergy and asthma. In human case-control genetic-association studies, the Arg130Gln polymorphism has been associated with elevated total serum IgE and an asthma diagnosis in atopic and nonatopic individuals (Graves et al. [2000] J. Allergy Clin. Immunol. 105:506-513; Heinzmann et al. [2000] Hum. Mol. Genet. 9:549-559). To apply family-based association methods, we obtained DNA samples from 685 asthmatic children from 640 sibships and their parents in the Childhood Asthma Management Program (CAMP). Six hundred and sixty-six asthmatic children had complete phenotypic information and were used for this analysis. We performed quantitative association analysis using the transmission disequilibrium test (TDT) on 22 individual phenotypes and 5 grouped phenotypes relating to allergy, airway responsiveness, pulmonary function, bronchodilator responsiveness, and asthma severity, using genotypes at the Arg130Gln polymorphism of the IL-13 gene. A positive association was obtained between Arg130Gln and a grouped phenotype of allergy (consisting of the individual phenotypes of eosinophils, IgE, and positive skin tests), using FBAT-GEE, a multivariate extension of the family-based association test (Lange et al. [2002] Biostatistics 1:1-15). The three phenotypes were then evaluated individually and revealed a significant association between total eosinophil count and the Arg130Gln locus; there was a trend for association between total IgE and the Arg130Gln polymorphism. The Arg130Gln polymorphism is associated with an elevated eosinophil count as well as with a grouped allergy phenotype, in children with mild to moderate asthma. No evidence for association was found between Arg130Gln and airway responsiveness, asthma diagnosis, or asthma severity.

Allergens↗

[Differentiation between vital heart muscle tissue and infarct scar using magnetocardiography].

Magnetocardiography provides touchless information about myocardial excitation propagation and repolarization. This evolving diagnostic technique has been used so far to risk-stratify patients in terms of sudden cardiac death and to detect myocardial ischemia. We evaluated its potential to assess myocardial viability in patients with coronary artery disease. Magnetocardiography was performed using a shielded prototype 49-channel LTS SQUID system. A specific algorithm was developed to calculate automatically a set of magnetocardiographic parameters. Regional myocardial viability was determined using 18F-labeled fluoro-2-deoxyglucose positron emission tomography. We found that magnetocardiography may contribute essentially to discriminate between viable myocardium and infarct scar.

Adult↗

Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure.

Biochemical data have shown that specific, tightly bound phospholipids are essential for activity of the cytochrome bc1 complex (QCR), an integral membrane protein of the respiratory chain. However, the structure and function of such phospholipids are not yet known. Here we describe five phospholipid molecules and one detergent molecule in the X-ray structure of yeast QCR at 2.3 A resolution. Their individual binding sites suggest specific roles in facilitating structural and functional integrity of the enzyme. Interestingly, a phosphatidylinositol molecule is bound in an unusual interhelical position near the flexible linker region of the Rieske iron-sulfur protein. Two possible proton uptake pathways at the ubiquinone reduction site have been identified: the E/R and the CL/K pathway. Remarkably, cardiolipin is positioned at the entrance to the latter. We propose that cardiolipin ensures structural integrity of the proton-conducting protein environment and takes part directly in proton uptake. Site-directed mutagenesis of ligating residues confirmed the importance of the phosphatidylinositol- and cardiolipin-binding sites.

Binding Sites↗

CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection.

CD8 T cells are classified as naïve, effector, or memory cells on the basis of CD45RA, CD62L, and CCR7 expression. Sequential engagement of cell-surface CD62L and CCR7 receptors is required for efficient trafficking to lymphoid tissue by means of high endothelial venules. Naïve CD8 T cells are CCR7(+)CD62L(+) CD45RA(+), whereas long-term memory cells are CCR7(+)CD62L(+)CD45RA(-). Effector cytotoxic T cells are thought to be CCR7(-)CD45RA(+). The distribution of CD8 subsets and cytolytic protein expression in healthy donors and donors seropositive for human immunodeficiency virus (HIV) were compared. In HIV-infected subjects, CCR7(-) CD8 T cells expanded at the expense of naïve and long-term memory cells. In both healthy donors and HIV-infected donors, CCR7(+) CD8 T cells were uniformly negative for perforin. In all subsets, perforin and granzyme A were not coordinately expressed, with perforin expression being more tightly regulated. The properties of CD8 T cells specific for cytomegalovirus, Epstein-Barr virus (EBV), and HIV were studied by staining with major histocompatibility complex peptide tetramers. Antigen-specific cells for chronic infections with these viruses were uniformly CCR7(-) and predominantly CD62L(-). In 2 HIV-seropositive donors, 3- to 4-fold fewer EBV-tetramer-positive cells were present in lymph nodes compared with blood. Antigen-specific CD8 T cells are therefore preferentially excluded from lymphoid sites, even when infection is primarily in lymphoid tissue. This may protect lymphoid tissues from immunopathological changes but compromise immune defense against viruses, such as HIV and EBV, that target lymphocytes. HIV-specific CD8 T cells do not express CD45RA, whereas EBV- and CMV-specific CD8 T cells are heterogeneous in CD45RA(+) expression. Lack of CD45RA expression may indicate incomplete differentiation of HIV-specific CD8 T cells to cytotoxic T cells.

CD8-Positive T-Lymphocytes↗

Substituting Coomassie Brilliant Blue for bromophenol blue in two-dimensional electrophoresis buffers improves the resolution of focusing patterns.

In a new area of postgenomics challenges, the optimization of protein identification has become a central goal in microbiochemistry. In this work, we demonstrate that the substitution of Coomassie Brilliant Blue for bromophenol blue in two-dimensional electrophoresis (2-DE) buffers improves the focusing of whole proteins from Pseudomonas aeruginosa. This improvement of focusing concerns more particularly basic proteins. This enhancement may be attributed to a better transfer from the first to the second dimension, which probably highlights an increase in the solubility of proteins in the IPG strips. Hence, the use of an efficient tracking dye in the 2-DE buffers may enlarge protein recovery on proteome maps.

Bacterial Proteins↗

Conformational study of a new SGTx1 neurotoxin from the spider Scodra griseipes using mass spectrometry.

SGTx1 is a new neurotoxin from the venom of Scodra griseipes. Because of the small quantity of this natural peptide available, mass spectrometry was used to obtain information on its higher-order structure. The kinetics of reduction by 1,4-dithiothreitol (DTT) was monitored by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), and showed that one of the three disulfide bridges was appreciably more accessible to the DTT. Studies based on the charge state distribution (CSD) and H/D exchange of the non-reduced peptide, under neutral and acidic conditions, were performed using electrospray mass spectrometry (ES-MS). In neutral solution, SGTx1 showed a maximum charge state of four compared with seven potentially protonated basic residues, and all labile hydrogens were exchanged. However, under acidic conditions, a maximum charge state of only five was observed, and four of the labile hydrogens could not be deuterated. These observations are interpreted in terms of a rigid structure maintained by the disulfide bridges, which can be temporarily relaxed by disulfide bridge scrambling only at higher pH values.

Amino Acid Sequence↗

[Coping with illness and psychotherapy for patients after amputation].

Psychology is often neglected or glossed over in most works dealing with the rehabilitation of the amputee. Treating the psychological and social problems faced by the amputee often has more significance for his-satisfaction with life than the quality of the surgery or the nature of his prosthetic device. In the following paper, a complex model for the biopsychosocial adaptation after amputation is presented. In this model, the important diagnostic criteria in interaction with specific individual coping strategies are formulated, which explain the difficult psychosocial adaptation. Professional diagnosis and further indication are necessary on an individual basis. The main goal of every intervention is the psychic stabilization of the patient by taking into account his personal resources. Because of the complex somatic, social, and psychic problems which arise after an amputation, thorough cooperation between specialists is recommended.

Adaptation, Psychological↗

[Diagnostic control. Psychiatric comorbidity in patients of technical orthopedic units].

Because of the new hospital finance law a DRG (Diagnosis Related Groups) controlled discount liquidation under consideration of the medical impairment becomes necessary. In this paper the importance of a correct and complete description of the psychic comorbidity for the development of German-Refined-DRGs (GR-DRGs) in the orthopedic field is described. Therefore we analysed data of orthopedic in-patients, who are diagnosed by consultation of the clinic for psychosomatics and psychotherapy. A psychic comorbidity (ICD-10 Chapter F (V)) was diagnosed by 95% of the consulted patient. 30% of the patients showed difficulties in coping with their disease. 40% suffered from chronical psychoneurotic patterns and conflicts, which can be explained (a) as consequence of a difficult psychosocial adaptation by chronic disease or after an amputation (b) as basic mental disorders (c) as cause of the orthopaedic complications. Therefore the number of indications for a psychotherapeutic or psychiatric treatment is very high. The knowledge about a psychic comorbidity can--beside financial aspects--help the team on the orthopaedic station in the treatment of difficult patient.

Adaptation, Psychological↗

[Treatment outcome of inpatient psychosomatic rehabilitation of elderly patients].

Empirical data about the different effects of a specific inpatient psychotherapeutic intervention for elderly patients (over 55 years) are presented in this study. An analysis of sub-units presented four different groups of elderly patients with different psychotherapy effects. Three of four groups showed significant reduced stress in self-rated well-being and depression, only one group had no significant effects one year after the inpatient psychotherapy. Because the patients of this group describes themselves at the beginning of the treatment as "quite normal", significant effects in outcome are hardly to be expected. For a better understanding of this group, other-rated information is necessary. Implications for changing the treatment are discussed.

Aged↗

Spontaneous pregnancy-induced hypertension and intrauterine growth restriction in rats.

The SHHF/Mcc-fa(cp) (spontaneous hypertension and heart failure) rat is advanced as a novel and suitable non-primate model of pregnancy-associated hypertension and fetal growth restriction because it simultaneously has spontaneous pregnancy-associated hypertension, small for gestational age (SGA) offsprings, and altered placental gene expression. Pregnancy-associated hypertension is a major contributor to maternal and fetal morbidity and mortality with the potential to result in maternal death and the need for iatrogenic preterm delivery. It has been reported to develop spontaneously in humans, but not in animals; consequently, progress in identifying the cause and pathogenesis of this disorder has been hampered. Spontaneous hypertension and heart failure rats develop hypertension spontaneously as they age, therefore we sought to determine whether these rats developed hypertension and SGA offsprings during pregnancy. Our results show that systolic blood pressure (BP) increased >40 mm Hg by the end of the first trimester and remained at this elevated level for the remainder of pregnancy, but decreased after parturition. Placenta weights of SHHF rats (0.60 +/- 0.02 g, n = 36) were significantly higher than Wistar-Kyoto (WKY) rats (0.42 +/- 0.01 g, n = 22, P < .05), but pup weights were significantly lower (2.68 +/- 0.06 g for SHHF rats compared to 3.24 +/- 0.06 g for WKY controls, P < .05). Histologic examination revealed pathologic lesions in neither heart, liver, placenta, nor kidney. L-Arginine administered in drinking water prevented the elevation of BP, particularly during the third trimester. Placentas from SHHF rats displayed altered expression of several genes whose protein products have been implicated in preeclampsia, including serotonin receptor, sodium channel, carbonic anhydrase, estrogen receptor regulator, major histocompatibility complex proteins, superoxide dismutase, and angiotensiogen. In addition, gene expression profiling showed alteration of a number of subcellular putative myristoylproteins not previously associated with preeclampsia, particularly those engaged in post-translational modifications in the placenta. Thus, SHHF rats may be a valuable tool, because it simultaneously has spontaneous pregnancy-associated hypertension, SGA offsprings, and altered placental gene expression.

Angiotensinogen↗

Mapping quantitative trait Loci using generalized estimating equations.

A number of statistical methods are now available to map quantitative trait loci (QTL) relative to markers. However, no existing methodology can simultaneously map QTL for multiple nonnormal traits. In this article we rectify this deficiency by developing a QTL-mapping approach based on generalized estimating equations (GEE). Simulation experiments are used to illustrate the application of the GEE-based approach.

Algorithms↗

On prediction of genetic values in marker-assisted selection.

We suggest a new approximation for the prediction of genetic values in marker-assisted selection. The new approximation is compared to the standard approach. It is shown that the new approach will often provide substantially better prediction of genetic values; furthermore the new approximation avoids some of the known statistical problems of the standard approach. The advantages of the new approach are illustrated by a simulation study in which the new approximation outperforms both the standard approach and phenotypic selection.

Computer Simulation↗

Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study.

In order to determine if age and comorbidity influence the tolerability of the cytoprotective agent amifostine, we compared side effects related to amifostine in patients > or = 70 years (group I) with patients < 70 years (group II). We evaluated 268 consecutive administrations of amifostine (119 in group I and 149 in group II, respectively), given i.v. at a dose of 740 mg/m(2) just before platinum-, taxol- or cyclophosphamide-based chemotherapy. Transient hypotension was the most common side effect occurring in association with amifostine. Decreases in systolic blood pressure > 20 mmHg were of similar frequency in both groups (27.1 versus 28.8% of amifostine infusions in group I and II, respectively). Hypotension did not result in medical sequelae in any of the patients. The amifostine infusion was interrupted 16 times in group I and 8 times in group II, respectively, mainly due to hypotension, but could be restarted after a few minutes in all patients except for three cases in group I. Patients in group II more often suffered from nausea/vomiting than in group II (20.8 versus 10.0% in group I). Other subjective symptoms (e.g. warmed, flushed sensation, sneezing, metallic taste, mouth dryness, dizziness and sleepiness) and hypocalcemia occurred with a similar frequency in both groups. Adverse effects associated with amifostine were not observed more frequently in elderly patients than in younger ones, although more elderly patients had a comorbidity than the younger ones.

Adult↗

[Nursing knowledge production in Argentina, Chile, Paraguay and Uruguay].

Research is being pointed out as a path to nursing recognition. The knowledge production concerning the tendencies of research lines in nursing during the 90's, in Argentina, Chile, Paraguay and Uruguay, took part of a study that had the purpose to know the impact of the nursing profession practice on health in Latin America and in the Caribbean Islands. The methodology used was the exploratory quantitative research, and the database used were Lilacs and Medline. The most frequent investigation themes refer to nursing profession (up to 13.2%). Regarding the lines of investigation in nursing, we found out that the nursing professional stood out with 41%, being technique and methodology the main approaches. Chile was the country that produced the largest amount of research, 86.8% of the summaries. Referring to the financing source, no reference is made in 86.8% of the summaries. With reference to the number of authors involved with the published literature, 50.7% of the literature have only one author. The nurses should be aware to invest in the enlargement of this production.

Argentina↗

Cloning and initial analysis of the human multidrug resistance-related MVP/LRP gene promoter.

The lung resistance-related protein (LRP) was identified as the human major vault protein (MVP), and is overexpressed in various multidrug-resistant cancer cell lines and clinical samples. We characterized DNA sequences upstream to the transcription initiation site of the MVP gene in the human non-small cell lung cancer cell line SW-1573. A 1.9-kb and a shortened 0.7-kb fragment of the 5'-upstream genomic region show strong promoter activity in chloramphenicol acetyltransferase (CAT) reporter assays. The promoter is TATA-less and contains an inverted CCAAT-box and a Sp1 site located near to a p53 binding motif. An alternative 3'-splice site of intron 1 results in a splicing variant within the 5'-untranslated region of MVP mRNA.

5' Untranslated Regions↗