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Biomedical subjects

A Dent

Publications and source records attributed to A Dent.

15 recordsLinked to original sources
PubMed2000

Screening for memory problems in multiple sclerosis.

OBJECTIVES: To assess the Brief, Repeatable Battery of Neuropsychological Tests (BRB-N) as a screening measure for memory problems in people with multiple sclerosis (MS). DESIGN: Sensitivity and specificity values were calculated and Receiver Operating Characteristic (ROC) curves plotted. METHODS: Patients were recruited from the regional MS Management Clinic. The BRB-N and WMS-R were administered. RESULTS: Using the Symbol Digit Modalities Test (SDMT) and 10/36 Spatial Recall Test (10/36 SRT) Total Immediate recall, the BRB-N had a sensitivity of 93% and specificity of 48%. CONCLUSION: The BRB-N is sensitive at detecting memory impairments, although its specificity is low.

Adult↗
PubMed1996

A dominant negative mutant of an IFN regulatory factor family protein inhibits both type I and type II IFN-stimulated gene expression and antiproliferative activity of IFNs.

Type I (alpha,beta) and type II (gamma) IFNs elicit antiproliferative and antiviral activities through two distinct transcription pathways involving 1) IRF family proteins and ISGF3, and 2) STAT1. We have employed a dominant negative strategy to study the role of IRF family proteins in eliciting the biologic activities of IFN. A truncated IRF protein retaining the DNA-binding domain (DBD) of ICSBP (a member of the IRF family) was stably transfected into U937 monocytic cells. Clones expressing DBD had markedly reduced ISRE-binding activity and were defective in expressing several type I IFN-inducible genes. STAT1 was one such type I IFN-inducible gene whose expression was also inhibited in DBD clones. As a result, the expression of several IFN-gamma-inducible genes was also inhibited in these clones, indicating functional coupling of the type I and type II IFN transcription pathways. Furthermore, DBD clones grew more slowly than control clones and were refractory to antiproliferative effects of both types of IFNs. We found that IFN treatment of U937 cells leads to a G1 arrest and an increase in underphosphorylated retinoblastoma gene product. However, IFN treatment did not change the cell cycle profile, nor retinoblastoma gene product phosphorylation state in DBD clones. These data indicate that expression of DBD disrupts cell cycle regulatory mechanisms. Combined with the previously noted failure of DBD clones to elicit antiviral activity, the present work shows that IRF family proteins play an integral part in growth control activities of IFNs.

Animals↗
PubMed1996

BCL-6 expression during B-cell activation.

Translocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma. Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner. The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA. Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12-myristate 13-acetate plus ionomycin, or CD40 ligand led to a five-fold to 35-fold decrease in BCL-6 mRNA levels. Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 MRNA expression, activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms. These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression.

Amino Acid Sequence↗
PubMed1996

A study of bereavement care after a sudden and unexpected death.

Bereaved parents' perceptions of care after the sudden, unexpected death of their child (from 1 week to 12 years), and the care that was or could be offered by statutory and voluntary agencies, was assessed in 11 health districts in seven regions of England and Wales. In these 11 districts, 185 families were identified who met the criteria of the study. Permission to contact these families was given by only 72 general practitioners. Of these, 42 families responded (58%). Sudden infant death syndrome accounted for 43% of the deaths. The results from postal questionnaires sent to both parents showed that hospital care was perceived as good on the whole, although parents would like more choices. Most parents felt that community care was inadequate, leaving many feeling isolated. In contrast, questionnaires from health visitors and general practitioners in the same health districts showed that they believed that they were the most appropriate professionals to give follow up care, but as there were few policies to guide them and little training provided, felt unable to offer support.

Attitude of Health Personnel↗
PubMed1994

The location of the third cleavage plane of Xenopus embryos partitions morphogenetic information in animal quartets.

Analysis of the developmental potential of animal quartets (the set of four animal blastomeres isolated from the 8-cell stage Xenopus embryo) provided insight into the manner in which morphogenetic information is distributed along the animal-vegetal axis. Gravity treatments were employed to alter the partitioning plane. Animal quartets isolated from embryos exposed to simulated weightlessness had larger animal blastomeres, and they formed structures such as a groove and a protrusion more often than 1g-control animal quartets. Animal quartets with an unusual non-horizontal third cleavage plane were also found to have a higher frequency of protrusion formation than animal quartets with a typical horizontal cleavage plane. The increase in the frequency seen in simulated weightlessness animal quartets was not due to their increased size. Fusing two animal quartets isolated from hypergravity (3g) exposed embryos (small blastomeres and low incidence of protrusions) did not affect the frequency of protrusion formation. Molecular analyses revealed that a partial induction was associated with the protrusion formation. Transcripts of the dorsal lip specific homeobox gene, goosecoid, and alpha-cardiac actin were detectable by PCR amplification in the animal quartet with a protrusion, and alpha-cardiac actin mRNA was found by whole-mount in situ hybridization to be localized in the protrusion. Taken together, all these results are consistent with the notion that both animal and vegetal information is necessary for normal development and the partitioning of morphogenetic information into animal quartets results in gravity-dependent differential morphogenesis and gene regulation.

Actins↗
PubMed1991

Requirement for positive selection of gamma delta receptor-bearing T cells.

The alpha beta and gamma delta T cell receptors for antigen (TCR) delineate distinct T cell populations. TCR alpha beta-bearing thymocytes must be positively selected by binding of the TCR to major histocompatibility complex (MHC) molecules on thymic epithelium. To examine the requirement for positive selection of TCR gamma delta T cells, mice bearing a class I MHC-specific gamma delta transgene (Tg) were crossed to mice with disrupted beta 2 microglobulin (beta 2M) genes. The Tg+beta 2M- (class I MHC-) offspring had Tg+ thymocytes that did not proliferate to antigen or Tg-specific monoclonal antibody and few peripheral Tg+ cells. This is evidence for positive selection within the gamma delta T cell subset.

Animals↗
PubMed1991

Repertoire development and ligand specificity of murine TCR gamma delta cells.

During the past several years, we have been studying the circulating TCR gamma delta cells expressed in peripheral lymphoid tissues. Biochemical and molecular characterization of the TCR gamma delta heterodimers present on these TCR gamma delta cells identified 3 TCR gamma proteins, V gamma 2-C gamma 1, V gamma 1.2-C gamma 2, and V gamma 1.1-C gamma 4. In addition, at least 6 different V delta gene products (V delta 2,4,5,6,V alpha 10, V alpha 11) are expressed in peripheral lymphoid tissue. Nucleotide sequence analysis has revealed a great deal of junctional diversity present among the different V gamma and V delta proteins. Thus, compared to other nonlymphoid tissues (e.g., skin), this population of TCR gamma delta cells appears quite extensive. The development and specificity of TCR gamma delta cells has been pursued by two approaches. First, different TCR gamma delta cells clones were generated which recognize MHC-encoded gene products. One clone recognizes an unconventional TL-encoded antigen, whereas others have been shown to recognize either classical MHC class I or class II antigens. The TCR gamma delta receptor genes have been cloned from the TL-specific TCR gamma delta cell and used to construct transgenic mice to examine the development of TCR gamma delta cells. Although the Tg+ TCR gamma delta cells are tolerized by thymic clonal tolerance similar to TCR alpha beta cells, the epithelial Tg+ TCR gamma delta cells are subjected to non-deletional tolerance (anergy). A second approach towards examining the development of TCR gamma delta cells has been to compare the repertoire of TCR gamma delta splenocytes in a variety of inbred and MHC-congenic strains of mice using subset-specific anti-murine TCR gamma delta mAb. The percentage of individual subsets of splenic TCR gamma delta cells differ widely between different inbred strains of mice due to both MHC- and TCR-encoded genetic differences. In summary, these studies provides a basis for understanding and determining the ligand(s) of the TCR gamma delta heterodimer and the factors which shape the peripheral TCR gamma delta repertoire.

Animals↗
PubMed1987

Suppressor T cell growth and differentiation: production of suppressor T cell differentiation factor by the murine thymoma BW5147.

Previous studies have identified a lymphokine, termed Ts differentiation factor (TsDF), in primary MLR supernatants that induces effector function of alloantigen-primed MLR-Ts. The present report describes constitutive production of TsDF by the murine thymoma BW5147, and its use to analyze alloantigen and TsDF requirements for MLR-Ts activation to TsF production. Serum-free supernatants of BW5147 restored the capacity of MLR-TsF production to alloantigen-primed MLR-Ts cultured with glutaraldehyde-fixed allogeneic stimulator cells, and were not themselves directly suppressive in the MLR assay. BW5147 supernatant induced MLR-TsF production from primed L3T4-Ly2+ MLR-Ts in the absence of concomitant proliferation, suggesting that the function of BW5147 supernatant, like that of MLR-derived TsDF, is a differentiative rather than a proliferative one, and is required for the synthesis or release of TsF. The differentiative activity of BW5147 supernatant was associated with a molecular species of approximately 14,500 m.w. by HPLC fractionation and was expressed independently of detectable IL 2, IL 3, IFN-gamma, and IL 1. The functional activity of BW5147 supernatant has therefore been provisionally designated BW5147-derived Ts differentiative factor, or BW-TsDF. By using BW-TsDF, it was demonstrated that MLR-Ts fail to respond to TsDF in the absence of, or preceding, reexposure to priming alloantigen. Instead, alloantigen binding by primed MLR-Ts appears to create a transient state of TsDF responsiveness. Primed MLR-Ts were fully sensitive to delayed addition of TsDF for approximately 12 hr after reexposure to alloantigen, but became TsDF-unresponsive within 24 to 36 hr. MLR-Ts cultured alone for 36 hr were fully responsive to the combined addition of TsDF and alloantigen. Thus, MLR-Ts activation to TsF release requires the sequential events of specific alloantigen binding, which induces a TsDF-responsive state, followed by interaction with TsDF. The transience of induced TsDF responsiveness suggests a precise mechanism for control of antigen-initiated Ts activation to effector function.

Animals↗
PubMed1986

The effect of inspiratory resistive training on exercise capacity in optimally treated patients with severe chronic airflow limitation.

This study was designed to determine whether inspiratory resistive training could improve the exercise performance of patients with severe chronic airflow limitation who had already received optimum conventional therapy with bronchodilators and physiotherapy. Eighteen patients were studied. Ten patients were trained with an inspiratory resistance device for six weeks and eight patients used a placebo device. Psychological factors, likely to influence exercise capacity, were taken into account. Although there was no significant increase in maximum inspiratory pressure in the ten trained subjects, inspiratory muscle endurance was improved. Exercise performance, as assessed by progressive cycle exercise, stair climbing, 12 minute walking distance and treadmill walking did not change significantly in either group. It was concluded that inspiratory muscle training, using a currently available technique, produced no additional improvement in exercise capacity beyond that achieved by conventional bronchodilator and rehabilitation therapy.

Aged↗
PubMed1965

OE "Hors-ome".

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History of Medicine↗