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Biomedical subjects

A Beck

Publications and source records attributed to A Beck.

At least 109 records · Page 6Linked to original sources
PubMed2000

Influence of live respiratory syncytial virus priming on the immune response generated by a recombinant vaccine candidate, BBG2Na.

Respiratory syncytial virus is one of the major respiratory pathogens for infants and immunocompromized children. With the exception of young children, all the population has encountered RSV and is seropositive. Recent reports have demonstrated however that the virus also affects the elderly and represents a major cause of illness associated with an excess of morbidity and mortality. We have generated a recombinant RSV vaccine, BBG2Na, which is highly protective in rodents against RSV infection. The aim of this study was to evaluate the ability of the vaccine to increase anti-RSV protection in RSV-primed mice and to characterize the induced immune responses. Immunization with BBG2Na increased the anti-RSV-A serum antibody titers of RSV-primed mice with induction of both IgG1 and IgG2a antibodies attesting for a mixed Th response. Moreover, the level of the induced anti-G2Na antibodies was greater in seropositive mice. Finally, sera from RSV-primed mice displayed a higher protective efficacy after transfer into naive mice following subsequent immunization with BBG2Na than sera of mice immunized with RSV-A only. Our results demonstrate that BBG2Na is immunogenic and increases the protective efficacy of serum antibodies in RSV-primed mice; they support the possibility of performing clinical trials in the seropositive human population.

Animals↗
PubMed2000

The DNA sequence of human chromosome 21.

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Base Sequence↗
PubMed2000

Simultaneous, quantitative analysis of UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine, UDP-glucose and UDP-galactose in human peripheral blood cells, muscle biopsies and cultured mesangial cells by capillary zone electrophoresis.

The aim of this study was to develop and evaluate a capillary zone electrophoretic (CE) procedure for the accurate quantification of the UDP-hexosamines as well as for the corresponding UDP-hexoses in samples from various biological origins. Testing different buffer conditions, voltages, capillary dimensions and temperatures, optimal results were achieved with a 90 mM borate buffer, pH 9.0, at 18 degrees C and 15.5 kV in an uncoated fused-silica capillary of 50 cm x 50 microm and a detection wavelength of lambda = 262 nm. The total procedure, i.e., including variations of the sample preparation, showed coefficients of variation for the peak areas between 4. 1% and 10.4% in mesangial cells (n = 7) and between 7.8 and 10.3% (n = 6) in leukocytes for the components of interest. To improve precision, an internal standard was used for calibration. The limit of detection for all compounds is an absolute amount of 180 fmol, sufficient for the precise analysis of UDP-sugars in a limited amount of biological samples, such as human leukocytes (obtained from a 10 mL blood sample), muscle biopsies (< or = 100 mg), and mesangial kidney cells (ca. 2.5 x 10(5) cells). This reproducible, quantitative analysis of all four UDP-sugars from various biomedically relevant origins by CZE is a definite improvement over the generally used high performance liquid chromatography (HPLC) procedures. The CZE method allows the study of the flux through the hexosamine pathway in diabetes mellitus and other diseases in a simple, quantitative and accurate way.

Blood Cells↗
PubMed2000

Spinal cord injury without radiographic abnormalities in children and adolescents: case report of a severe cervical spine lesion and review of literature.

The biomechanics of the child's and juvenile's spine is responsible for the commonly encountered closed spinal trauma with significant neurological injury but without bony or ligament injury (particularly of the cervical spine). The ligamentous laxity and hypermobility of the young bony cervical and thoracic spine predispose to spinal cord injury without radiographic abnormalities. We report a 16-year-old girl with typical features of this type of injury after a "flic-flac" sports injury. We conclude that children and adolescents who have neurological deficits without positive radiographic findings require appropriate diagnostic screening, monitoring, and often a prolonged therapy. The sometimes changing neurological deficits should never be ignored or dismissed as psychogenic affection.

Adolescent↗
PubMed2000

The treatment of anxiety disorders in a primary care HMO setting.

Anxiety disorders are common, yet under diagnosed, in primary care settings. Many patients with anxiety and other psychiatric disorders do not seek care in mental health care settings. An integrated primary care/mental health model offers one approach to improving outcomes for patients with anxiety disorders. This model has been researched for the treatment of depression with positive results but has not been well studied for the treatment of anxiety disorders. We describe the results of care for a cohort of adult patients with Generalized Anxiety Disorder (GAD) and clinically significant anxiety secondary to Major Depressive Disorder (MDD) treated in an integrated model. Compared to a matched cohort of adults treated in a primary care setting with usual care, the intervention cohort experienced significantly improved reduction in symptoms of anxiety at 6 months. The intervention cohort also was significantly more satisfied with care.

Adult↗
PubMed2000

Synthesis and characterization of Respiratory Syncytial Virus protein G related peptides containing two disulfide bridges.

Respiratory Syncytial Virus (RSV) is the most important cause of bronchiolitis and viral pneumonia in infants and young children. Approximately 100000 children are hospitalized in the USA each year as a result of RSV infections. During the research and development of subunit human Respiratory Syncytial Virus vaccines (hRSV), we have produced numerous synthetic peptides and recombinant proteins containing the four cysteines of the highly conserved central region of the G attachment protein. For several of these disulfide-containing peptides, all possible oxidized isomers were synthesized using various oxidation conditions and resulting in different ratios of isomers. Each isolated isomer was fully characterized by RP-HPLC, FZCE and ES-MS after purification by preparative RP-HPLC. The different cysteine pairings were unambiguously established after enzymatic digestion, LC-MS analysis and peptide microsequencing. These synthesis and analytical methods were developed for the characterization on one hand, of recombinant fusion protein BBG2Na which is currently being investigated in advanced clinical phases as a very promising vaccine candidate, and on the other hand, for peptides which were synthesized to be evaluated as conjugate vaccines or as immunochemical tools, after covalent coupling to carrier proteins. Furthermore, these studies allowed us to determine which of the different possible isomers was the most stable and probably the preferred form in native conditions. Finally, the different oxidation and analysis conditions, should be useful for disulfide pairing studies of other peptides and proteins having the same 'xCxxCxxxxxCxxxCx' framework, such as G proteins of non-human RSV strains, developed by other groups as veterinary vaccine candidates for example.

Amino Acid Sequence↗
PubMed2000

CD4(+) T-cell-mediated antiviral protection of the upper respiratory tract in BALB/c mice following parenteral immunization with a recombinant respiratory syncytial virus G protein fragment.

We analyzed the protective mechanisms induced against respiratory syncytial virus subgroup A (RSV-A) infection in the lower and upper respiratory tracts (LRT and URT) of BALB/c mice after intraperitoneal immunization with a recombinant fusion protein incorporating residues 130 to 230 of RSV-A G protein (BBG2Na). Mother-to-offspring antibody (Ab) transfer and adoptive transfer of BBG2Na-primed B cells into SCID mice demonstrated that Abs are important for LRT protection but have no effect on URT infection. In contrast, RSV-A clearance in the URT was achieved in a dose-dependent fashion after adoptive transfer of BBG2Na-primed T cells, while it was abolished in BBG2Na-immunized mice upon in vivo depletion of CD4(+), but not CD8(+), T cells. Furthermore, the conserved RSV-A G protein cysteines and residues 193 and 194, overlapping the recently identified T helper cell epitope on the G protein (P. W. Tebbey et al., J. Exp. Med. 188:1967-1972, 1998), were found to be essential for URT but not LRT protection. Taken together, these results demonstrate for the first time that CD4(+) T cells induced upon parenteral immunization with an RSV G protein fragment play a critical role in URT protection of normal mice against RSV infection.

Adoptive Transfer↗
PubMed2000

[Frequency of cesarean sections in Austria].

OBJECTIVE: While there exist detailed reports on the frequency of cesarean sections in many European countries, there are only selective data of single centers available in Austria. Thus this study aims at evaluating the present frequency of cesarean sections in Austria. METHODS: To achieve this aim, we analyzed all births during the years 1996 (n = 89,208), 1997 (n = 84,408) and 1998 (n = 81,568). Along with the general mean rate of sections, we also describe the influences of the duration of pregnancy, of the birth weight, and of the number of paturitions. The data were statistically evaluated by chi-square test. RESULTS: During the study period, the frequence of sections rose from 13.08% (1996) to 14.0% (1997) and to 14.55% (1998). This rise proved to be statistically significant (p = 0.0001). 47% of premature births (< or = 35th week of gestation) are delivered by cesarean section. This rate drops to only 13.24% after the 35th week of gestation. Yet, more than half of pregnancies with dystrophic children (<2,000 g) are delivered by cesarean section even after the 35th week of gestation. Primigravidae have to expect section in 17% of the cases (1998); the section rate diminishes continuously, however, with increasing number of pregnancies. CONCLUSIONS: Following the general trend, the frequency of cesarean sections is continuously rising in Austria too. The present study can serve as a basis for international comparisons as well as for measures of intradepartmental quality control.

Austria↗
PubMed2000

Factors that contribute to positive perceived health in an older population.

This study explored the extent to which factors commonly associated with negative outcomes of aging also predicted positive perceived health in a group of community-dwelling older people. Questionnaires originally administered during a randomized trial of HMO's outpatient group visit program supplied data from approximately 700 participants. Stepwise modeling identified significant factors within categories of predictors of perceived health. Hierarchical multiple linear regression then modeled the incremental importance of theoretically-derived categories of factors. Many but not all of the factors previously associated with negative outcomes of aging also predicted positive perceived health, accounting for 38% of the variation. The most important predictors were fewer chronic conditions and no worsening of those conditions, mobility and better physical performance status, and the absence of depression. Gender, limitations in daily living activities, dementia, and utilization of services had little effect. The categories of f factors associated with positive perceived health had cumulative, interdependent effects.

Activities of Daily Living↗
PubMed2000

Psychiatric patients at greatest risk and in greatest need. Impact of the Supervision Register Policy.

BACKGROUND: Mental health provider trusts in England were required in 1994 to establish local Supervision Registers of patients at risk. AIMS: To identify the factors associated with registration, and obtain clinicians' views on its effectiveness. METHOD: At a random sample of 14 trusts data were collected from case notes, key workers and responsible medical officers. RESULTS: A sample of 133 registered patients were more disabled and had more extensive histories of violence and self-harm than 126 comparison patients on the upper tier of the Care Programme Approach (CPA). Those registered were a heterogeneous group. For some there was little evidence of risk. In most cases clinicians did not believe registration had improved care. CONCLUSIONS: The Supervision Register policy has not resulted in the identification of a well-defined group. Its effectiveness is limited by the lack of operationalized measures of risk.

Adult↗
PubMed2000

Serine residues 1177/78/82 of the insulin receptor are required for substrate phosphorylation but not autophosphorylation.

Serine residues of the human insulin receptor (HIR) may be phosphorylated and negatively regulate the insulin signal. We studied the impact of 16 serine residues in HIR by mutation to alanine and co-overexpression in human embryonic kidney (HEK) 293 cells together with the docking proteins insulin receptor substrate (IRS)-1, IRS-2, or (SHC) Src homologous and collagen-like. As a control, IRS-1 was also cotransfected with an HIR with a juxtamembrane deletion (HIR delta JM) and therefore not containing the domain required for interaction with IRS-1. Coexpression of HIR with IRS-1, IRS-2, and SHC strongly enhanced tyrosine phosphorylation of these proteins. A similar increase in tyrosine phosphorylation was observed in cells overexpressing IRS-1, IRS-2, or SHC together with all HIR mutants except HIR delta JM and a mutant carrying exchanges of serines 1177, 1178, and 1182 to alanine (HIR1177/78/82), although this mutant showed normal autophosphorylation. Analysis of total cell lysates with anti-phosphotyrosine antibodies showed that in addition to the overexpressed substrates, other cellular proteins displayed reduced levels of tyrosine phosphorylation in these cells. To study consequences for phosphatidylinositol 3-kinase (PI 3-kinase) activation, we established stable NIH3T3 fibroblast cell lines overexpressing wild-type HIR, HIR1177/78/82, and other HIR mutants as the control. Again, HIR1177/78/82 showed normal autophosphorylation but showed a clear decrease in tyrosine phosphorylation of endogenous IRS-1 and activation of PI 3-kinase. This decrease in kinase activity also occurred in an in vitro kinase assay towards recombinant IRS-1. Finally, we performed a separation of the phosphopeptides by high-performance liquid chromatography and could not detect any differences in the profiles of HIR and HIR1177/78/82. In conclusion, we have defined a region in HIR that is important for substrate phosphorylation but not autophosphorylation. Therefore, this mutant may provide new insights into the mechanism of kinase activation and substrate phosphorylation.

3T3 Cells↗
PubMed2000

Practical mental health assessment in primary care. Validity and utility of the Quick PsychoDiagnostics Panel.

BACKGROUND: Many case-finding instruments are available to help primary care physicians (PCPs) diagnose depression, but they are not widely used. Physicians often consider these instruments too time consuming or feel they do not provide sufficient diagnostic information. Our study examined the validity and utility of the Quick PsychoDiagnostics (QPD) Panel, an automated mental health test designed to meet the special needs of PCPs. The test screens for 9 common psychiatric disorders and requires no physician time to administer or score. METHODS: We evaluated criterion validity relative to the Structured Clinical Interview for DSM-IV (SCID), and evaluated convergent validity by correlating QPD Panel scores with established mental health measures. Sensitivity to change was examined by readministering the test to patients pretreatment and posttreatment. Utility was evaluated through physician and patient satisfaction surveys. RESULTS: For major depression, sensitivity and specificity were 81% and 96%, respectively. For other disorders, sensitivities ranged from 69% to 98%, and specificities ranged from 90% to 97%. The depression severity score correlated highly with the Beck, Hamilton, Zung, and CES-D depression scales, and the anxiety score correlated highly with the Spielberger State-Trait Anxiety Inventory and the anxiety subscale of the Symptom Checklist 90 (Ps <.001). The test was sensitive to change. All PCPs agreed or strongly agreed that the QPD Panel "is convenient and easy to use," "can be used immediately by any physician," and "helps provide better patient care." Patients also rated the test favorably. CONCLUSIONS: The QPD Panel is a valid mental health assessment tool that can diagnose a range of common psychiatric disorders and is practical for routine use in primary care.

Adult↗
PubMed2000

Synthesis and characterization of respiratory syncytial virus protein G related peptides containing two disulphide bridges.

Respiratory Syncytial Virus (RSV) is the most important cause of bronchiolitis and viral pneumoniae in infants and young children. Approximately 100,000 children are hospitalized in the USA each year as a result of RSV infections. During the research and development of subunit human RSV vaccines, we have produced numerous synthetic peptides and recombinant proteins containing the four cysteines of the highly conserved central region of the G attachment protein. For several of these disulphide bridges containing peptides, all possible oxidizing isomers were synthesized using various oxidising conditions, resulting in different ratios of isomers. Each isolated isomer was fully characterized by RP-HPLC, FZCE and ES-MS after purification by preparative RP-HPLC. The different cysteine pairings were unambiguously established after enzymatic digestion, LC-MS analysis and peptide microsequencing. These synthetic and analytical methods were developed for the characterization of recombinant fusion protein BBG2Na which is currently investigated in clinical phase II and seems to be as a very promising vaccine candidate, and for peptides which were synthesized to be evaluated as conjugate vaccines or as immunochemical tools, after covalent coupling to carrier proteins. Furthermore, these studies allowed us to determine which of the different possible isomers was the most stable and probably the preferred form in native conditions. Finally, the different oxidising and analysis conditions, should be useful for disulphide pairing studies of other peptides and proteins having the same "xCxxCxxxxxCxxxCx" framework, such as G proteins of non-human RSV strains, developed for example as veterinary vaccine candidates.

Chromatography, Liquid↗
PubMed1999

Absence of lung immunopathology following respiratory syncytial virus (RSV) challenge in mice immunized with a recombinant RSV G protein fragment.

The relative immunopathogenic potential of a recombinant fusion protein incorporating residues 130-230 of respiratory syncytial virus (RSV-A) G protein (BBG2Na), formalin-inactivated RSV-A (FI-RSV), and phosphate-buffered saline (PBS) was investigated in mice after immunization and RSV challenge. FI-RSV priming resulted in massive infiltration of B cells and activated CD4(+) and CD8(+) T lymphocytes in mediastinal lymph nodes (MLN) and lungs, where eosinophilia and elevated IFN-gamma, IL-2, -4, -5, -10, and -13 mRNA transcripts were also detected. PBS-primed mice showed only elevated pulmonary IL-2 and IFN-gamma mRNAs, while an activated CD8(+) T cell peak was detected in MLN and lungs. Cell infiltration also occurred in MLN of BBG2Na-immunized mice. However, there was no evidence of T cell, B cell, or granulocyte infiltration or activation in lungs, while transient transcription of Th1-type cytokine genes was evident. The absence of pulmonary infiltration is unlikely due to insufficient viral antigen. Thus, this recombinant fusion RSV G fragment does not prime for adverse pulmonary immunopathologic responses.

Animals↗