A novel glycoprotein 120 sequence from an HIV type 1 isolate of the A clade identified in North Uganda.
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Amino Acid Sequence↗
Biomedical subjects
R Wagner
Publications and source records attributed to R Wagner.
Prosaptide prevents hyperalgesia and reduces peripheral TNFR1 expression following TNF-alpha nerve injection.
This study demonstrated that hyperalgesia resulting from an intraneural injection of the cytokine tumor necrosis factor-alpha (TNF) was prevented by preemptive administration of a single dose of the prosaptide TX14(A) (200 microg/kg). TX14(A) is a synthetic 14-mer peptide with neurotrophic and cytoprotective activities. Efforts to elucidate TX14(A) antagonism of hyperalgesia concentrated on determining the effect of TX14(A) on the up-regulation of the 55 kDa TNF receptor (TNFR1) at the nerve injury site. It has been previously shown that TNFR1 expression is upregulated following nerve injury and parallels the display of nociceptive behavior. In our experiments, TNFR1 was decreased at the TNF nerve injection site in TX14(A)-treated rats when compared to vehicle-treated or control peptide-treated rats. Light microscopic evaluation of nerve injury site tissue displayed qualitatively similar neuropathology in both treatment groups during the time of peak hyperalgesia (day 3), but appeared more normal than untreated nerves at day 7 (histological scoring, mean +/-s.d., 3.7+/-0.57 for TX14(A)-treated and 5.67+/-0.5 for control peptide-treated). These results suggest that TX14(A) decreased nociceptive behavior by attenuating both TNFR1 upregulation and Schwann cell activation in response to TNF injection. This prosaptide neurotrophin may also moderate nerve degeneration or promote regeneration. It is not known whether TX14(A) also acts rostral to the lesion site.
Animals↗
A role for helix 3 of the TRbeta ligand-binding domain in coactivator recruitment identified by characterization of a third cluster of mutations in resistance to thyroid hormone.
Resistance to thyroid hormone (RTH) has hitherto been associated with thyroid hormone beta receptor (TRbeta) mutations which cluster in two regions (alphaalpha 310-353 and alphaalpha 429-461) of the hormone-binding domain and closely approximate the ligand-binding cavity. Here, we describe a third cluster of RTH mutations extending from alphaalpha 234-282 which constitute a third boundary of the ligand pocket. One mutant, T277A, exhibits impaired transactivation which is disproportionate to its mildly reduced ligand affinity (Ka). T3-dependent recruitment of coactivators (SRC-1, ACTR) by mutant receptor-RXR heterodimers was reduced in comparison with wild-type. Cotransfection of SRC-1 restored transactivation by T277A. In the TRbeta crystal structure this helix 3 residue is surface-exposed and is in close proximity to residues L454 and E457 in helix 12 which are known to be critical for coactivator interaction, suggesting that they all constitute part of a receptor-coactivator interface. The transcriptional function of other mutants (A234T, R243W/Q, A268D, Delta276I, A279V, R282S) in this cluster correlated with their reduced Ka and they inhibited wild-type TRbeta action in a dominant negative manner. DNA binding, heterodimerization and corepressor recruitment were preserved in all mutants, signifying the importance of these attributes for dominant negative activity and correlating with the absence of natural mutations in regions bordering the third cluster which mediate these functions.
Amino Acid Sequence↗
Cytotoxic T cells and neutralizing antibodies induced in rhesus monkeys by virus-like particle HIV vaccines in the absence of protection from SHIV infection.
HIV Pr55gag has in the absence of other viral components the capacity to self assemble in budding noninfectious virus-like particles (VLP). The immunological spectrum of the HIV-1IIIB gag-derived VLP was expanded either by stable anchoring of chimeric modified gp 120 on the surface of the VLP (type 1) or by replacing sequences of the Pr55gag precursor by the V3 loop and a linear portion of the CD4 binding domain (type 2). This noninfectious antigen delivery system was evaluated for immunogenicity and efficacy in rhesus macaques without adjuvants. Intramuscular immunization with both types of VLP induced high titers of gag-specific antibodies ranging from 1/8000 to 1/510,000 for type 1 VLP and from 1/4000 to 1/16,000 for type 2 VLP. Only animals immunized with type 1 VLP developed substantial endpoint titers of env-specific antibodies (1/2000-1/32,000) with a neutralizing capacity at serum dilutions of 1/32-1/128. Gag- and env-specific cytotoxic T lymphocyte (CTL) activity was induced by both types of VLP at similar levels. Four weeks after the last immunization animals were challenged intravenously with 20 MID50 of the cell free homologous envelope simian/HIV-1IIIB chimeric challenge stock Despite HIV-1-specific neutralizing and CTL responses, all vaccinated animals became infected.
AIDS Vaccines↗
32-Ascomycinyloxyacetic acid derived immunosuppressants. Independence of immunophilin binding and immunosuppressive potency.
The potent immunosuppressant ascomycin (1b) was selectively alkylated at the C-32 carbinol, thus providing esters and amides of 32-ascomycinyloxyacetic acid (4, AOAA). These compounds present structural variation at the FKBP/calcineurin interface. While the native carboxylic acid 4 shows no activity in vitro, esters and simple amides of 4 exhibit potent immunosuppression in the human MLR assay. Moreover, amides show inhibitory activity in the rat popliteal lymph node hyperplasia assay. Surprisingly, FKBP binding was weakened by several orders of magnitude when secondary hydrophobic aryl amides of 4 were tested, while maintaining potent immunosuppressive efficacy in vitro.
Animals↗
Thylakoid membranes contain a high-conductance channel.
Ion channels in the thylakoid membrane were investigated by direct patch clamping on swollen thylakoids. A preparation method has been developed in order to release osmotically swollen intact thylakoids from pea protoplasts derived from cotyledons of young Pisum sativum plants. The swollen thylakoids with typical diameters between 10 microm and 20 microm formed reproducibly high-resistance seals with patch pipettes. We observed a potassium channel with a main conductant state of lambda approximately 40 pS and a conductance of lambda approximately 90 pS (in asymmetric 20/100 mM KCl) for the fully open channel. Surprisingly, the thylakoid membranes also contained a high-conductance channel with a main conductant state of lambda approximately 620 pS (in asymmetric 20/100 mM KCl), revealing also higher and lower conductant states. With a different experimental approach we showed that thylakoids are able to accumulate transiently the membrane impermeant fluorescent dye Lucifer Yellow which likewise suggests the presence of a pore-like channel with a diameter large enough to allow permeation of Lucifer Yellow.
Fluorescent Dyes↗
Ammonium ion and glucosamine dependent increases of oligosaccharide complexity in recombinant glycoproteins secreted from cultivated BHK-21 cells.
The effect of different ammonium concentrations and glucosamine on baby hamster kidney (BHK)-21 cell cultures grown in continuously perfused double membrane bioreactors was investigated with respect to the final carbohydrate structures of a secretory recombinant glycoprotein. The human interleukin-2 (IL-2) mutant glycoprotein variant IL-Mu6, which bears a novel N-glycosylation site (created by a single amino acid exchange of Gln100 to Asn), was produced under different defined protein-free culture conditions in the presence or absence of either glutamine, NH4Cl, or glucosamine. Recombinant glycoprotein products were purified and characterized by amino acid sequencing and carbohydrate structural analysis using matrix-assisted laser desorption ionization time of flight mass spectrometry, high-pH anion-exchange chromatography with pulsed amperometric detection, and methylation analysis. In the absence of glutamine, cells secreted glycoprotein forms with preponderantly biantennary, proximal fucosylated carbohydrate chains (85%) with a higher NeuAc content (58%). Under standard conditions in the presence of 7.5 mM glutamine, complex-type N-glycans were found to be mainly biantennary (68%) and triantennary structures (33%) with about 50% containing proximal alpha1-6-linked fucose; 37% of the antenna were found to be substituted with terminal alpha2-3-linked N-acetylneuraminic acid. In the presence of 15 mM exogenously added NH4Cl, a significant and reproducible increase in tri- and tetraantennary oligosaccharides (45% of total) was detected in the secretion product. In glutamin-free cultures supplemented with glucosamine, an intermediate amount of high antennary glycans was detected. The increase in complexity of N-linked oligosaccharides is considered to be brought about by the increased levels of intracellular uridine diphosphate-GlcNAc/GalNAc. These nucleotide sugar pools were found to be significantly elevated in the presence of high NH3/NH4+ and glucosamine concentrations.
Acetylgalactosamine↗
Mutations in the leader region of ribosomal RNA operons cause structurally defective 30 S ribosomes as revealed by in vivo structural probing.
The biogenesis of functional ribosomes is regulated in a very complex manner, involving different proteins and RNA molecules. RNAs are not only essential components of both ribosomal subunits but also transiently interacting factors during particle formation. In eukaryotes snoRNAs act as molecular chaperones to assist maturation, modification and assembly. In a very similar way highly conserved leader sequences of bacterial rRNA operons are involved in the correct formation of 30 S ribosomal subunits. Certain mutations in the rRNA leader region cause severe growth defects due to malfunction of ribosomes which are assembled from such transcription units. To understand how the leader sequences act to facilitate the formation of the correct 30 S subunits we performed in vivo chemical probing to assess structural differences between ribosomes assembled either from rRNA transcribed from wild-type operons or from operons which contain mutations in the rRNA leader region. Cells transformed with plasmids containing the respective rRNA operons were reacted with dimethylsulphate (DMS). Ribosomes were isolated by sucrose gradient centrifugation and modified nucleotides within the 16 S rRNA were identified by primer extension reaction. Structural differences between ribosomes from wild-type and mutant rRNA operons occur in several clusters within the 16 S rRNA secondary structure. The most prominent differences are located in the central domain including the universally conserved pseudoknot structure which connects the 5', the central and the 3' domain of 16 S rRNA. Two other clusters with structural differences fall in the 5' domain where the leader had been shown to interact with mature 16 S rRNA and within the ribosomal protein S4 binding site. The other differences in structure are located in sites which are also known as sites for the action of several antibiotics. The data explain the functional defects of ribosomes from rRNA operons with leader mutations and help to understand the altered biogenesis pathway from mutations in an rRNA leader region to the formation of functionally defective ribosomes.
Base Sequence↗
A chemical modification method for the structural analysis of RNA and RNA-protein complexes within living cells.
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Aldehydes↗
Cloning and characterization of a virtually full-length HIV type 1 genome from a subtype B'-Thai strain representing the most prevalent B-clade isolate in China.
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Amino Acid Sequence↗
The ORF YBL042 of Saccharomyces cerevisiae encodes a uridine permease.
The purpose of this work was to identify the function of an open reading frame called YBL042, found during the systematic sequencing of Saccharomyces cerevisiae's chromosome II. The YBL042 gene product shows 70% similarity with the uracil permease and the allantoin permease encoded by FUR4 and DAL4, respectively. The mutation constructed by disruption of this ORF is allelic to the FUI1 gene previously described as encoding the uridine permease but not cloned yet. A strain carrying the disrupted allele and a fui1 mutant exhibit the same phenotype as they do not grow on a medium containing uridine as the sole source of pyrimidines and as they are resistant to 10(-3) M 5-fluorouridine (5FUI), a toxic analog of uridine. Even though the FUI1 gene has a multicopy suppressor effect on uracil transport, its product does not seem to be involved in this transport, in contrast to the FUR4 gene product which is involved in uridine transport. Moreover, the FUI1 gene product does not play any role in allantoin transport.
Allantoin↗
IXDB, an X chromosome integrated database.
The integrated X chromosome database (IXDB) is a repository for physical mapping data of the human X chromosome. Its current content is the result of a strict integration of data stemming from many different sources. The main features of IXDB include a flexible and extendible schema, a comfortable and fully cross-referenced WWW interface (http://ixdb.mpimg-berlin-dahlem.mpg.de ) and a graphical map viewer implemented in JAVA. The database stores objects used in physical mapping as well as the maps resulting from this work, but a strong emphasis is placed on recording experiments that connect objects together. This should greatly contribute to fulfilling one of the major goals of the database: to support the construction of an integrated physical, genetic, transcript and sequence map of the human X chromosome.
Chromosome Mapping↗
The uracil permease of Schizosaccharomyces pombe: a representative of a family of 10 transmembrane helix transporter proteins of yeasts.
The uracil permease gene of Schizosaccharomyces pombe was cloned and sequenced. The deduced protein sequence shares strong similarities with five open reading frames from Saccharomyces cerevisiae, namely the uracil permease encoded by the FUR4 gene, the allantoin permease encoded by DAL4, a putative uridine permease (YBL042C) and two unknown ORFs YOR071c and YLR237w. A topological model retaining ten transmembrane helices, based on predictions and on experimental data established for the uracil permease of S. cerevisiae by Galan and coworkers (1996), is discussed for the four closest proteins of this family of transporters. The sequence of the uracil permease gene of S. pombe has been deposited in the EMBL data bank under Accession Number X98696.
Amino Acid Sequence↗
Plasma concentrations of leptin in a bulimic patient.
Recently, the obese gene in the ob/ob mouse was cloned, along with its human homologue. The gene product leptin is important in the regulation of body weight. Excessive food intake during a binge might affect leptin synthesis. Alternatively, fluctuations in leptin synthesis might induce binge eating. Therefore, plasma leptin levels of a patient with bulimia nervosa were determined over a period of 48 hr in a natural setting. Amount, type, time of food intake, and binging and purging episodes were concomitantly assessed. Although binging and purging episodes were quite frequent, leptin levels remained stable and were neither related to food intake nor to binge episodes.
Adult↗
[Solution to the problem of extra-articular, femoral hip fracture by the "sliding screw-nail principle". Results of 2 different systems (classical nail and gamma nail)].
Between January 1993 and December 1995 we treated 109 patients (median age: 75 years) with 112 extraarticular hip fractures including combined trochanteric and shaft fractures using two different "sliding-screw-nail implants" (intramedullary hip screw = classic nail: n = 61; gamma nail: n = 51). Comparing the two systems in detail certain advantages and disadvantages were seen, with both being equivalent. We encountered the following complications: secondary varus malalignment of the collum femoris with "cut out" of the sliding-screw (1.8%) and without "cut out" (1.8%), fissure of the femoral shaft occurring intraoperatively and being treated conservatively (1.8%), femoral perforation by the nail (0.9%), infection (2.7%). Thus, 5 reoperations (4.5%) were necessary. None of these complications were attributable to the principle itself or to the different implants used. Each patient was followed-up for a minimum of 12 months postoperatively. In 59% of all patients the pre-trauma range of mobility could be fully restored. Intramedullary hip screw and gamma nail are excellent and equivalent systems, which fully satisfy the biomechanical needs of above mentioned fractures.
Adolescent↗
Taking the wrong drugs: the role of substance abuse and medication noncompliance in violence among severely mentally ill individuals.
Increasing numbers of severely mentally ill individuals are being treated in nonhospital, community-based settings and public concern about potential violence by these individuals has increased, often as a result of tragic, albeit uncommon events. The present study examines potential predictors of serious violence among persons with severe mental illness (SMI), with a specific focus on the joint effect of substance abuse and medication noncompliance. Subjects in the study are involuntarily admitted inpatients with SMI awaiting a period of court-ordered outpatient treatment, termed "involuntary outpatient commitment". During enrollment in a longitudinal outcome study of the effectiveness of OPC, 331 subjects and, whenever feasible, family members or other informants were interviewed. In addition, complementary data were gathered by review of involuntary commitment records and hospital records. Data collection included sociodemographic characteristics, illness history, clinical status, medication adherence, substance abuse and violent behavior during the 4 months preceding hospitalization. Descriptive and multivariable logistic regression procedures were used to examine the association between serious violent acts and a number of personal, social, and clinical characteristics. The combination of medication noncompliance and substance abuse was a significant predictor of serious violent acts in the community. Individuals who had problems with both alcohol and illicit drug abuse appear to be at greatest risk for violence. These results suggest that reducing violence risk among persons with SMI requires an aggressive approach to improving medication adherence in the context of integrated mental health and substance abuse treatment.
Adolescent↗
Psychiatric impairment, social contact, and violent behavior: evidence from a study of outpatient-committed persons with severe mental disorder.
The need to better understand and manage risk of violent behavior among people with severe mental illness in community care settings is increasingly being recognized, as public-sector mental health systems face mandates to provide more cost-effective services in less restrictive environments. The potential for serious violence in a small proportion of severely mentally ill (SMI) individuals has emerged as a key factor that increases cost and limits continuity and normalization of community-based services for populations with psychiatric disabilities. A major challenge to developing better strategies for risk assessment and management in community care settings involves specifying complex interactions between psychiatric impairment and the conditions of social life--including the quality and frequency of contact with others at close quarters. This is a study of the determinants of violent behavior in a sample of 331 adults with severe mental disorders in community-based treatment. An interaction between severity of functional impairment and frequency of social contact was found to be significantly associated with risk of violence. Among respondents with Global Assessment of Functioning (GAF) scores in the lowest 20%, more frequent contact with family and friends was linked to a higher probability of violent events. However, among better functioning respondents, frequent social contact was associated with lower risk of violence and greater satisfaction with relationships. These findings suggest that, where violence risk is concerned, the most salient feature of psychiatric impairment is the impairment of social relationships--the ways in which disorders of thought and mood not only distort one's subjective appraisal of experience and threat, but impair the ability to relate meaningfully to others, to resolve conflict and derive necessary support from family and friends. Thus, social contact may be a mixed blessing for SMI individuals. For some, it signals a positive quality of life, but for others--particularly those with extreme psychiatric impairment--frequent contact may add to conflict, stress, and increased potential and opportunity for physical violence. The impact of psychiatric impairment on violent behavior cannot be known in isolation, but must be considered in a social context. Effective community-based strategies to anticipate and prevent violence in the lives of persons with severe mental illness must take into account such interactions between social and clinical variables.
Adolescent↗
[Twilight vision and glare sensitivity in monofocal and multifocal pseudophakia].
UNLABELLED: Reduced contrast sensitivity and an increase in glare sensitivity may be observed in patients with cataract and in pseudophakic persons. By means of Mesoptometer II we examined night driving ability according to the recommendations of the German Ophthalmological Society (DOG) in patients with cataract, monofocal or multifocal pseudophakia. METHODS: A total of 176 patients were included in the study: 85 patients (68.8 years) with a monofocal standard IOL, 50 patients (66.1 years) with a multifocal IOL type AMO Array SSM-26NB/SA-40NB and 41 patients with beginning cataract (66.4 years). The corrected visual acuity of all patients was at least 0.7. Contrast acuity was examined at a luminance setting of 0.32 cd/m2; glare sensitivity was measured at a luminance of 0.1 cd/m2 with additional glare source. RESULTS: Night driving ability (both criteria accomplished) was found in 41% of patients with binocular monofocal IOL and in 38% of patients with binocular multifocal IOL. CONCLUSION: Elderly pseudophakic patients and patients with beginning cataract cannot sufficiently fulfill the criteria for night driving ability because of contrast and glare sensitivity. It seems to be indispensable, for the parameters mentioned to be carefully examined and for patients to be informed that night driving ability may be impaired, even if visual acuity is sufficient.
Aged↗