Drug resistance mutations as predictors of phenotypic zidovudine resistance in HIV-1 infection.
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Anti-HIV Agents↗
Biomedical subjects
F Schneider
Publications and source records attributed to F Schneider.
Secondary immune responses in parents of children with recent measles.
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Child↗
A natural IgA-anti-F(ab')2gamma autoantibody occurring in healthy individuals and kidney graft recipients recognizes an IgG1 hinge region epitope.
Natural anti-IgG autoantibodies are found both in healthy individuals and in patients with certain diseases. One group of these Abs recognizes epitopes located in the F(ab')2 region of the IgG molecule. The immunoregulatory role of these Abs in healthy individuals, graft rejection, and disease was previously studied, usually with a focus on the characterization of anti-idiotypic Abs. In the present study, we characterize the epitope recognized by an anti-F(ab')2gamma autoantibody of the IgA isotype, which occurs in the serum of healthy individuals and kidney transplant recipients. The autoantibody described herein reacts strongly with F(ab')2gamma but only poorly with Fab(gamma) fragments, a binding pattern pointing to an epitope located in the hinge region. Using synthetic peptides, we identified a conformational epitope that overlaps the middle and part of the lower hinge region. Structural analyses of peptide constructs showed that a defined conformation of the first three residues of the lower hinge is required for a full expression of the epitope. Binding of IgA to the hinge region of IgG1 covers part of the physiologically active Fc domain, immobilizes the Fab arms, and thereby can be expected to exert immunoregulatory functions.
Amino Acid Sequence↗
Isolation, cloning, sequence analysis and localization of the operon encoding dimethyl sulfoxide/trimethylamine N-oxide reductase from Rhodobacter capsulatus.
The operon encoding the periplasmic enzymes dimethyl sulfoxide reductase (DMSOR) and trimethylamine N-oxide reductase (TMAOR) from the purple, non-sulfur, photosynthetic bacterium Rhodobacter capsulatus was isolated, cloned and sequenced, and its chromosomal location determined. It was shown by analytical and crystallographic data that DMSOR and TMAOR are identical enzymes. Degenerate primers were derived from short peptide sequences generated by automated Edman degradation and a 700 bp fragment was amplified by nested PCR, subsequently cloned and radioactively labeled to screen a prepared lambda DASH library. Positive lambda clones were subcloned into pBluescript and subsequently transformed into Escherichia coli to sequence the DMSOR/ TMAOR operon. The promoter consisted of an A + T-rich region followed by a -35 region, a putative ribosome binding site, and a leader sequence of 13 amino acid residues. The transcription terminator was a G + C-rich dyad sequence capable of forming a hairpin structure, which may act rho-independently. An optimized protein purification of the wild-type enzyme is also described, giving high yields (5 mg protein per liter of culture) and a specific activity of 30 units/mg. The molecular mass was determined by electrospray mass spectrometry to be 85,034 Da; from the deduced amino acid sequence the molecular mass of the apoenzyme was 85,033 Da.
Amino Acid Sequence↗
Crystal structure of dimethyl sulfoxide reductase from Rhodobacter capsulatus at 1.88 A resolution.
The periplasmic dimethyl sulfoxide reductase (DMSOR) from the photosynthetic purple bacterium Rhodobacter capsulatus functions as the terminal electron acceptor in its respiratory chain. The enzyme catalyzes the reduction of highly oxidized substrates like dimethyl sulfoxide to dimethyl sulfide. At a molybdenum redox center, two single electrons are transferred from cytochrome C556 to the substrate dimethyl sulfoxide, generating dimethyl sulfide and (with two protons) water. The enzyme was purified and crystallized in space group P4(1)2(1)2 with unit cell dimensions of a = b = 80.7 A and c = 229.2 A. The crystals diffract beyond 1.8 A with synchrotron radiation. The three-dimensional structure was solved by a combination of multiple isomorphous replacement and molecular replacement techniques. The atomic model was refined to an R-factor of 0.169 for 57,394 independent reflections. The spherical protein consists of four domains with a funnel-like cavity that leads to the freely accessible metal-ion redox center. The bis(molybdopterin guanine dinucleotide) molybdenum cofactor (1541 Da) of the single chain protein (85,033 Da) has the molybdenum ion bound to the cis-dithiolene group of only one molybdopterin guanine dinucleotide molecule. Three additional ligands, two oxo groups and the oxygen of a serine side-chain, are bound to the molybdenum ion. The second molybdopterin system is not part of the ligand sphere of the metal center with its sulfur atoms at distances of 3.5 A and 3.8 A away. It might be involved in electron shuttling from the protein surface to the molybdenum center.
Amino Acid Sequence↗
Confirmation of reduced temporal limbic structure volume on magnetic resonance imaging in male patients with schizophrenia.
A structural deficit in the temporal lobes has been implicated in the pathogenesis of schizophrenia. A prospective magnetic resonance imaging (MRI) study was carried out in 20 young male patients with schizophrenia and 20 age-matched healthy male volunteers. Volumetric measurements were performed in all slices with temporal lobe cross-sections from the temporal pole to the tip of the Sylvian fissure. Volumetric assessment included the temporal lobe as a whole, hippocampal formation and amygdala complex, temporal horn and cella media of the lateral ventricle, the third ventricle, and hemispheric volume in all slices that showed temporolimbic structures. Brain structural deficit in the patients was most conspicuous in the posterior portion of the hippocampal formation. Significant effects of diagnosis were also found for the total temporal lobe and the third ventricle. Multiple regression analysis revealed posterior hippocampal volume to be significantly determined by diagnosis, but not by age or by temporal lobe or hemispheric volume. Significant correlations of morphologic and clinical parameters were restricted to negative correlations of temporal lobe volume with the global rating and sum score of the Scale for the Assessment of Negative Symptoms. The study confirms subtle temporolimbic deficit reported in previous MRI studies in patients with schizophrenia.
Adult↗
Influence of organochlorine pesticides on physiological potency of cultured granulosa cells from bovine preovulatory follicles.
In the present study the direct effect of Dichlorodiphenyltrichloroethane (DDT), Methoxychlor (MXC) and Hexachlorocyclohexane (gammaHCH) was investigated on the DNA synthesis (measured by [3H]thymidine incorporation); proliferation (determined by colorimetric MTT[3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide] assay); and steroidogenesis (estradiol 17beta, progesterone determination) of granulosa cells during in vitro culture. The cells were aspirated from preovulatory follicles in PMSG-treated heifers. They were cultivated in phenol red and serum (0.1% FCS) RPMI 1640 medium without or with the 3 pesticides in different concentrations. In summary, the results showed differential inhibition of parameters named above by these pesticides (gammaHCH < MXC < DDT) in comparison with vehicle-treated control. Progesterone synthesis was more inhibited than estradiol 17beta production by 3 chemicals, which resulted from the loss of viability of cells indicated by estimation of cell-shape-factor and viability of cells. Besides the inhibitory effect, there was a stimulatory effect of low concentrations of DDT and MXC on [3H]thymidine incorporation and proliferation.
Journal Article↗
Estrogen receptor immunocytochemistry in paraffin embedded tissues with ER1D5 predicts breast cancer endocrine response more accurately than H222Sp gamma in frozen sections or cytosol-based ligand-binding assays.
BACKGROUND: Historically, estrogen receptor (ER) determinations have been made by the ligand-binding assay of tumor homogenates, primarily by the dextran-coated charcoal method (DCC). Immunocytochemical assays (ICA) for ER are more recent and have been executed mostly on frozen sections with the monoclonal antibody H222Sp gamma (H222). Lately, new monoclonal antibodies derived by recombinant ER technology have been developed that work well on paraffin embedded, formalin fixed tissue sections. However, there is little information as to whether such assays prognosticate endocrine response. METHODS: Using antigen retrieval, the immunoglobulin G1 monoclonal antibody ER1D5, and the streptavidin-biotin detection system, 74 patients with breast cancer in whom endocrine response was known were assayed and the results compared with ER by DCC and ER by ICA in frozen section with H222. RESULTS: ER1D5 in paraffin provided the highest correlation with endocrine response (Kendall's tau [r] = 0.57; P<0.001) whereas ER by DCC failed to correlate (r= -0.002; P<0.99). ER1D5 in paraffin correlated weakly though significantly with DCC (Kappa Statistic [K] = 0.204; P<0.02). H222 in frozen sections also correlated moderately with endocrine response (r = 0.34; P<0.001). CONCLUSIONS: ER can be detected in routine tissue sections processed with antigen retrieval and ER1D5, and can be relied upon to provide accurate prognostic information regarding response to endocrine therapies in breast cancer patients.
Adult↗
Increased activation of indirect semantic associations under psilocybin.
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Adult↗
[Effect of interferon-alpha2b therapy in chronic hepatitis C].
In chronic hepatitis C the interferon treatment given three times a week in a dosage of 3 million units (MU) normalizes the values of alanin-amino-transferase in a part of cases (25-40%), and produces bettering in the subjective complains of patients. In the short term therapy (3-6 months) the activity of ALT increases again after leaving the therapy, and the disease becomes active. The aim of this multicenter study in Hungary was to give newer data in the case of longterm efficacy with alpha-interferon. Ninety-one patients with chronic hepatitis C were selected into the open prospective clinical study in university and hospital departments. Treatment protocol was the following: Patients with chronic hepatitis C diagnosed by clinical and histological methods were treated with interferon-alpha 2B given 3 times a week in a dosage of 3 MU. Treatment period had lasted for one year and afterwards the patient had been on control for an other half a year. In non responder cases after 3 month treatment with interferon the dose of therapy was increased for 3 x 5 MU. In 37 cases (40.6%) out of 91 patients the authors found longterm sustained remission and in other 22 cases (24.2%) they observed a partial remission (among them 5 cases with late relapse). The rate of longterm sustained remission under 40 years was higher, than above 40. Higher rate was found when the treatment was started with a shorter chronicity of the disease. On te basis of the results the authors conclude: Interferon-alpha 2B is a good therapeutic modality for the treatment of patients with chronic hepatitis C. Efficacy of therapy is higher in younger patients and also in earlier application.
Adult↗
[Psychological research on pain in Western Europe].
Utilizing MEDLINE and PSYCLIT, a search for articles covering psychological research on pain in the Western European countries was undertaken for the period from 1 January 1990 to 31 December 1994. A total of 398 publications were identified, of which 44 were classified as experimental research in the laboratory, 33 as psychodiagnostic and 225 as clinical studies. The most frequent diagnosis was back pain, followed by musculoskeletal pain and headache. With regard to the total number of publications, Germany was first, followed by The Netherlands and Great Britain. In an analysis of the subcategories, the leading position of Germany could only be confirmed with respect to laboratory studies; in psychodiagnostic publications, Germany fell back behind Great Britain and The Netherlands. In clinical studies, Germany was second to Sweden. Relating the number of publications to the number of personnel estimated to be engaged in research, The Netherlands and the Scandinavian countries demonstrate very high efficiency. Compared with Germany, these countries facilitate the integration of psychological procedures into an interdisciplinary management of pain.
English Abstract↗
Hapten resistant dextran induced ARDS reaction following intracoronary stent deployment.
A case of dextran induced adult respiratory distress syndrome is used to illustrate the most serious complication of dextran usage during intracoronary stent placement. This reaction occurred despite premedication with the hapten dextran 1. Mechanisms of dextran induced complications are discussed. A mechanism for hapten resistant dextran reactions is postulated. Suggestions to prevent such reactions are made.
Anticoagulants↗
[Examination of psychological functions by functional imaging with positron emission tomography and magnetic resonance imaging].
Changes in regional cerebral blood flow (rCBF) during experimentally modified psychological activation can be measured using radioactive ligands with positron emission tomography (PET) and using magnetic resonance principles with functional magnetic resonance imaging (fMRI). With PET it is possible to determine not only rCBF, but also metabolic changes, as well as the density and binding of several neuroreceptors. This can be done in conjunction with psychological and pharmacological challenge. fMRI is an imaging technique for perfusion-based signal intensities of the brain which does not involve radioactivity and gives better anatomical and temporal resolution than PET. Under appropriate experimental conditions, subjects' behavior and experience can be modified while they are lying in a tomograph. These experiments can be used for the scientific investigation of cognitive constructs such as memory and attention, or emotional processes. In this review, both functional neuroimaging techniques are assessed.
Arousal↗
Effects of organochlorine pesticides on DNA synthesis of cultured oviductal and uterine cells and on estrogen receptor of uterine tissue from heifers.
The pesticides DDT, MXC and gamma HCH at concentrations between 41 and 200 microM inhibited DNA synthesis (measured by [3H]thymidine incorporation) of cultured bovine oviductal endosalpingeal and uterine cells in the order DDT > MXC > gamma HCH, in comparison ton nonexposed controls. Sensitivity to the toxicants was greater in uterine epithelial and stromal cells than in uterine smooth muscle or oviductal endosalpingeal cells. Besides the inhibitory effect, there was a stimulatory effect on DNA synthesis in epithelial cells in the range of 28 nM to 2.8 microM DDT and in stromal cells at 2.8 and 28 nM for MXC. An explanation for this reaction could be that both toxicants have an estrogen-like effect. In the present study, it is shown that the o,p' isomer of DDT can bind to the cytoplasmatic estrogen receptor and DDT or MXC were able to inhibit the binding of radiolabelled estradiol to the uterine endometrial explants in bovine, whereas gamma HCH did not change the binding. These findings represent an estrogenic effect of DDT and MXC in two complete in vitro systems.
Animals↗
Bifidobacteria strain behavior toward cholesterol: coprecipitation with bile salts and assimilation.
Resting cells and growing cells of bifidobacteria strains exhibited an ability to remove cholesterol in the presence of bile salts. In resting cell assays, the removed cholesterol was precipitated in the presence of cholic acid at pH values lower than 5.4. However, this precipitated cholesterol was redissolved when the pellets were washed with phosphate buffer, pH 7, and no cholesterol was found in the cells. It appears that this precipitation is a transient phenomenon. In the case of growing cells, the removed cholesterol was partially recovered when cells were washed with phosphate buffer, pH 7, while the remaining cholesterol was extracted from the cells. Cultured in the presence of radiolabeled free or esterified cholesterol, bifidobacteria strains were able to assimilate esterified cholesterol. It is concluded that the removal of cholesterol from the growth medium by bifidobacteria strains is due to both bacterial assimilation and precipitation of cholesterol.
Bifidobacterium↗
Hierarchic T-cell help to non-linked B-cell epitopes.
The induction of antibodies against peptides requires the presence of a T helper cell epitope. In the absence of an added T-cell epitope only 10% of the mice, or less depending on the strain, gave an antibody response to a series of peptides of the measles virus (MV) fusion (F) protein. After coimmunization with a non-covalently coupled T-cell epitope more than 60% of the peptides became immunogenic. Considerable differences became apparent when BALB/c mice were immunized with peptides in the presence of different T-cell epitopes. An immunodominant T-cell epitope of the MV-F protein was more efficient than a subdominant or a cryptic T-cell epitope in providing help to a non-linked B-cell epitope. There is both a ranking order of the amount of help which B-cell epitopes require and a ranking order for the help T-cell epitopes are able to provide. The capability of a T-cell epitope to provide help to a B-cell epitope correlated with its own immunogenicity, i.e. the intensity of the antibody response to the peptide representing the T-cell epitope. The data suggest that for each MHC class II allele there is an optimal T-cell epitope which can provide help to a maximal number of B-cell epitopes and that such a peptide can be identified by its ability to induce antibodies against itself. By using this strategy, the authors were able to induce antibodies which cross-reacted with the MV.
Animals↗
Activation of T cells by the ragged tail of MHC class II-presented peptides of the measles virus fusion protein.
The efficient and sustained immune response of an antigen requires T cell epitopes, capable of inducing a long lasting T cell memory. To detect T cell epitopes of the measles virus fusion protein (MV-F), the proliferation of lymphocytes from late convalescent donors in response to overlapping pentadecapeptides covering the whole protein sequence was studied. Three major immunodominant regions (F51-70, F121-135 and F211-225) containing promiscuous peptides induce proliferation in peripheral blood lymphocytes in approximately 50% of the donors. Potential DR1-restricted epitopes were mapped using an MHC competition binding assay. Both the proliferation and the binding data identified a DR1-restricted T cell epitope (F51-65). Contact sites of the peptide HQSLVIKLMPNITLL with MHC were characterized using substitution analogs. Alanine substitutions at most positions did not interfere with F51-65 binding. These analogs were therefore useful for studying the residues which were recognized by the TCR of MV- and F51-induced T cells lines. In addition to amino acid residues of the core of peptide F51-65 both the C-terminal and the N-terminal amino acids were essential for T cell interaction. Since peptides presented by class II molecules vary in length, these findings suggest that residues of the ragged tail are important for T cell activation. It is speculated that in late convalescent donors the length of the flanking sequence of MHC II-restricted peptides may play a role in controlling the heterogeneity of MV-specific T cell clones recruited as T helper/memory cells.
Adult↗
Differential activation of T cells by antibody-modulated processing of the flanking sequences of class II-restricted peptides.
Despite poor presentation of measles virus (MV) nucleoprotein (NP) by MHC class II of infected cells, NP-specific antibodies are one of the hallmarks of the early immune response against this virus. To study the influence of antibodies on processing and presentation of NP to three different T cell hybridomas, mAb recognizing distinctive llnear NP epitopes were developed. Two T cell hybridomas TNP408B and TNP408 reacted with the same core epitope of NP (amino acids 383-391), but differed in their sensitivity to the flanking sequences of peptides containing this epitope. TNP408B reacted with minimal concentrations of NP when this was complexed with mAb BNP146. NP alone or saturating concentrations of other mAb did not activate this T cell. Both T cells, TNP408 and TNP408B, were similar in their sensitivity to NP in the presence of saturating concentrations of BNP146 or of appropriate peptide (NP379). TNP408 did not differ from another T cell hybridoma (TNP79) in its sensitivity to different mAb, suggesting a specificity-dependent and a specificity-independent effect of mAb. Antibody-mediated activation was attributed to FcR-mediated uptake independent of the fine specificity of the mAb. In the case of TNP408B, this effect was further enhanced by a specific effect of BNP146. While all NP-specific mAb were sufficient to enhance presentation to TNP408 and TNP79 of their respective peptides derived from processed NP, BNP146 was necessary to generate the peptides with the proper flanking sequences required by TNP408B. Since the binding site of BNP146 coincides with the T cell epitope of TNP408B (and TNP408) it is suggested that binding of this mAb modulates processing of the flanking sequences of the peptides corresponding to this epitope. This study shows that antibodies can influence the T cell response to an antigenic protein quantitatively and qualitatively by taking advantage of the sensitivity of T cells to flanking sequences of class II-restricted peptides.
Amino Acid Sequence↗