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Biomedical subjects

L Brooks

Publications and source records attributed to L Brooks.

At least 19 recordsLinked to original sources
PubMed1996

Ganciclovir treatment of hepatitis B virus infection in liver transplant recipients.

To determine the safety and efficacy of ganciclovir treatment of hepatitis B virus (HBV) infection after liver transplantation, nine patients (seven males, two females; mean age, 38 years) with posttransplant HBV infection were treated with ganciclovir for 3 to 10 months. Ganciclovir was administered intravenously at an initial dose of 5 mg/kg/d and then increased to 10 mg/kg/d. Immunosuppressive drug therapy was maintained at low levels. There were no major side effects of ganciclovir therapy. Serum HBV DNA levels decreased by a mean of 90% (range, 42% to 100%), and four of nine patients had no measurable HBV DNA at the completion of therapy. Mean serum alanine aminotransferase levels decreased by 83%. Hepatic expression of HBV antigens and HBV DNA was assessed before and after therapy in six patients and found to be reduced in three patients. The histology activity index was also stabilized or improved in all patients. After discontinuation of therapy, four of nine patients underwent retreatment for 4- to 12-fold elevation of serum HBV DNA and/or biochemical and clinical relapse, that was severe in one patient. This pilot study shows the safety and efficacy of ganciclovir therapy for reducing HBV replication in patients with HBV infection after liver transplantation.

Adult↗
PubMed1996

A test of Martens, Vealey and Burton's theory of competitive anxiety.

The purpose of this study was to test Martens, Vealey, and Burton's (1990) theoretical model of competitive anxiety. In order to assess the variables corresponding to the model, a sample of 199 (N = 126, male and N = 73, female) individual sport athletes completed the following inventories: the Sport Anxiety Scale (SAS; Smith, Smoll, & Schutz, 1990), items related to the uncertainty of outcome, items related to the importance of outcome, and the Competitive State Anxiety Inventory-2 (CSAI-2; Martens, Burton, Vealey, Bump, & Smith, 1990). In addition, the short-form of the Marlowe-Crowne Social Desirability Scale (M-C SDS; Reynolds, 1982) was completed by all subjects. The variables corresponding to the model underwent psychometric evaluation as well as a check for social desirability effects before they were used in a LISREL causal path model procedure. Results showed no concrete support for the basic propositions advanced through the model. Trait-anxiety did not significantly affect perception of threat and perception of threat had minimal effect on state-anxiety. Recommendations for future research are discussed.

Adolescent↗
PubMed1995

The expression of variant CD44 in nasopharyngeal carcinoma is unrelated to expression of LMP-1.

CD44 expression in undifferentiated nasopharyngeal carcinoma has been analyzed by sequencing cDNA clones and by immunohistochemical staining using monoclonal antibodies specific for defined variant exons. Both sequencing and antibody staining revealed expression of CD44 variants containing exon v6, which has been linked to tumor metastasis. Although nasopharyngeal carcinoma typically contains a mixture of epithelial tumor cells and infiltrating lymphocytes, the CD44 v6 variant expression could be assigned to the tumor cells in biopsies and in a mouse xenograft system. Consistent with earlier studies, biopsies from about 60% of Chinese nasopharyngeal carcinoma cases expressed the Epstein-Barr virus LMP-1 protein, although all contained EBV DNA and expressed the EBER genes. The antibody specific for CD44 exon v6 generally gave a focal pattern of staining in epithelial tumor cells, but the expression of this variant did not appear to be related to the expression of the LMP-1 protein in the tumor.

Base Sequence↗
PubMed1994

Epstein-Barr virus (EBV) latent membrane protein 1 increases HLA class II expression in an EBV-negative B cell line.

Transformation of normal resting B cells by the Epstein-Barr virus (EBV) leads to the establishment of permanent lymphoblastoid cell lines (LCL) which express high levels of HLA antigens and which are highly efficient in antigen presentation. Certain features of the LCL phenotype can be reproduced by transfecting EBV-negative B lymphoma (BL) cell lines with individual EBV latent genes under heterologous promoters. In this work we have analyzed a series of subclones derived from the EBV-negative cell line Louckes, stably transfected with constructs encoding EBV latent genes for their expression of HLA class II molecules. Louckes parental cells and control transfectants expressed detectable levels of HLA-DR, DQ and DP antigens on the cellular surface by cytofluorometry, but these levels were significantly increased in transfectants expressing the virus-coded latent membrane protein 1 (LMP-1). Northern blotting for the individual alpha and beta chain mRNA at each of the three HLA class II loci indicated correspondingly increased levels of HLA class II transcripts in the LMP-1 transfectants. Transfectants expressing the virus-coded nuclear antigens EBNA-1, EBNA-2 or EBNA-LP showed no significant changes in these parameters. These observations indicate that up-regulation of HLA-class II molecules can be a part of the changes induced by LMP-1 in B cells.

Antigens, Viral↗
PubMed1994

Reduced signal transduction through glucocorticoid receptor in Burkitt's lymphoma cell lines.

Signal transduction through the glucocorticoid receptor (GR) was shown to be significantly reduced in Epstein-Barr virus (EBV)-positive group I Burkitt's lymphoma (BL) cell lines compared to human B-lymphocytes immortalized by EBV (LCLs). On the basis of hormone binding assays, nuclear DNA binding activity, and transactivation assays the response was reduced 5- to 10-fold. Direct sequence analysis of the expressed glucocorticoid receptor mRNA in two BL cell lines indicated that the phenotype did not result from mutation of the GR gene. By preparing a high-titer polyclonal antiserum against the t-1 region of the human GR, we further showed that the deficient GR response in BLs is largely reflected in reduced GR steady-state protein levels in BL cells compared to LCLs. However, the level of GR mRNA varies less between the BL cell lines and the LCLs. The Cp promoter of EBV which normally drives expression of the EBNA gene family in EBV-immortalized LCLs contains a functional glucocorticoid response element. Transfection of GR expression constructs to group I BL cells converted the GR response to approximately LCL levels both with respect to hormone binding and glucocorticoid-dependent transcription of a glucocorticoid-dependent promoter. A modest activation of EBNA-2 expression was seen in some such cell lines, suggesting that the lower GR response contributes to the down-regulation of EBNA expression observed in BL.

Antigens, Viral↗
PubMed1994

A comprehensive reproductive health program in the workplace.

This paper summarizes the reproductive health component of the AT&T Bell Laboratories occupational health program. The comprehensive R&D Reproductive Health Program is a collaborative effort between the Health Services Group and the Environmental Health & Safety Center. It provides a tailored curriculum to occupational health nurses and physicians so that they may respond to employee questions and concerns with detailed information and with referrals to appropriate subject-matter experts. Expanding on the typical regulatory approaches of hazard communication and right-to-know, the program encourages employees of both sexes to learn about workplace, environmental, and lifestyle aspects of reproductive and developmental health.

Chemical Industry↗
PubMed1994

Balancing workloads under GP attachment.

Alignment with a GP practice resulted in fluctuating workloads for health visitors Lynda Brooks, Caro Fickling and Caroline Walker. Here they describe how the introduction of a corporate caseload helped to restore balance.

Community Health Nursing↗
PubMed1993

Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells.

Epstein-Barr virus (EBV) is associated with a number of different human tumors and appears to play different pathogenetic roles in each case. Thus, immunoblastic B cell lymphomas of the immunosuppressed display the full pattern of EBV latent gene expression (expressing Epstein-Barr nuclear antigen [EBNA]1, 2, 3A, 3B, 3C, and -LP, and latent membrane protein [LMP]1, 2A, and 2B), just as do B lymphoblastoid cell lines transformed by the virus in vitro. In contrast, those EBV-associated tumors with a more complex, multistep pathogenesis show more restricted patterns of viral gene expression, limited in Burkitt's lymphoma to EBNA1 only and in nasopharyngeal carcinoma (NPC) to EBNA1 and LMP1, 2A, and 2B. Recent evidence has implicated EBV in the pathogenesis of another lymphoid tumor, Hodgkin's disease (HD), where the malignant Hodgkin's and Reed-Sternberg (HRS) cells are EBV genome positive in up to 50% of cases. Here we extend preliminary results on viral gene expression in HRS cells by adopting polymerase chain reaction-based and in situ hybridization assays capable of detecting specific EBV latent transcripts diagnostic of the different possible forms of EBV latency. We show that the transcriptional program of the virus in HRS cells is similar to that seen in NPC in several respects: (a) selective expression of EBNA1 mRNA from the BamHI F promoter; (b) downregulation of the BamHI C and W promoters and their associated EBNA mRNAs; (c) expression of LMP1 and, in most cases, LMP2A and 2B transcripts; and (d) expression of the "rightward-running" BamHI A transcripts once thought to be unique to NPC. This form of latency, consistently detected in EBV-positive HD irrespective of histological subtype, implies an active role for the virus in the pathogenesis of HD and also suggests that the tumor may remain sensitive to at least certain facets of the EBV-induced cytotoxic T cell response.

Antigens, Viral↗
PubMed1993

Group child health assessments.

'Health for all children' emphasises health promotion and parental involvement in child health surveillance checks. Heavy caseloads and the need to incorporate these principles in their practice prompted an Oxfordshire team of health visitors to introduce group health assessments. Here they describe the new approach and the response from parents.

Child Health Services↗
PubMed1992

Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin's disease.

Distribution and phenotype of Epstein-Barr virus (EBV)-harboring cells were determined in Hodgkin's disease (HD) biopsies by in situ hybridization with [35S]-labeled RNA probes specific for the small EBV-encoded nuclear RNAs, EBER1 and EBER2, in some instances preceded by immunohistology for CD20, CD30, CD45RO, and CD68 antigens, the T-cell receptor beta-chain, and latent membrane antigen (LMP) of EBV. Twenty-three of 46 HD cases displayed EBER transcripts in all Hodgkin and Reed-Sternberg (H-RS) cells, and 18 of these cases showed LMP expression exclusively in neoplastic cells. EBER+ small reactive cells were present in 39 cases in low numbers, and in three cases in abundance. Thus, presence of H-RS cells with or without LMP expression was not accompanied by an unrestricted proliferation of reactive EBER+/LMP- lymphoid cells in the majority of HD patients. Simultaneous in situ hybridization with [35S]-labeled immunoglobulin light chain (IgLC) gene probes and nonisotopically labeled EBER probe showed a phenotype of mature B lymphocytes and a polyclonal composition for a large proportion of the EBER+ small cells. However, in contrast to noninfected cells, CD20 expression was not detectable in many of these cells, which may indicate downregulation of certain differentiation antigens in latently EBV-infected small lymphoid cells in vivo.

Antigens, CD↗
PubMed1992

Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue.

Taking advantage of the abundant expression of the small Epstein-Barr virus (EBV)-encoded RNAs (EBERs) in latently infected cells, we have analyzed 72 normal and hyperplastic lymph nodes and three tonsils of acute infectious mononucleosis (IM) for the presence and distribution of EBV+ cells using EBER-specific in situ hybridization, in some cases combined with immunohistologic demonstration of cell type-characteristic antigens. In IM, large numbers of EBV+ lymphoid B blasts were detectable in extrafollicular areas, whereas germinal centers were generally free of EBV+ cells. In reactive lymph nodes, the frequency of EBV+ cells varied with the degree of lymphoid hyperplasia and underlying immune status. The lowest numbers of EBV+ cells were detected in nonactivated lymph nodes and highest in human immunodeficiency virus-associated lymphadenopathy. If present in these lymph nodes, EBV+ cells were almost exclusively localized to extrafollicular areas, as also observed in IM. However, in contrast to IM, these cells were mainly small lymphocytes. Furthermore, in some instances, occasional scattered EBV+ cells were seen within germinal centers, and in two cases diffuse expansions of EBV+ cells occurred within a single germinal center each, indicating that under certain circumstances EBV+ B lymphocytes may participate in physiologic germinal center reactions. These findings reflect the interference of EBV with physiologic lymphoid differentiation pathways and provide a link to EBV-associated malignant lymphomas with a postulated origin from germinal center cells.

B-Lymphocytes↗
PubMed1992

Gold labelling of RNA in virus-induced mitochondrial vesicles in the sheep blowfly Lucilia cuprina.

Membranous vesicles are thought to be the replication site for viral RNA of many plant and animal viruses. A relatively rare site of virus-associated vesiculation is that of the mitochondrial outer membrane. In this study, virus-induced mitochondrial vesicles of the blowfly, Lucilia cuprina, were labelled with ribonuclease/gold and an antibody against double stranded RNA (anti-polyinosinic:polycytidylic acid). Both methods showed the presence of RNA in the vesicles thus indicating they may be a site for viral RNA replication in Lucilia.

Animals↗
PubMed1992

Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts.

Epstein-Barr virus (EBV) genome-positive nasopharyngeal carcinomas (NPCs) regularly express the virus-coded nuclear antigen EBNA1, but not other EBNAs, and a subset of tumors also appear to be latent membrane protein LMP1 positive; the status of NPCs with respect to a second virus-coded latent membrane protein LMP2 is unknown. In the present work the EBV-NPC cell interaction has been analyzed at the RNA level with reverse transcription and polymerase chain reaction-based amplification to detect specific latent viral mRNAs. All four transplantable NPC cell lines studied and 17 of 18 fresh snap-frozen NPC biopsy specimens expressed an EBNA1 mRNA with a BamHI Q/U/K splice structure exactly like that recently identified in group I Burkitt's lymphoma (BL) cell lines and shown to be driven from a novel viral promoter, Fp. The BamHI Y3/U/K-spliced EBNA1 mRNA characteristic of virus-transformed B-lymphoblastoid cell lines (LCLs) was never found in NPCs. These same NPC biopsy specimens were then analyzed for evidence of the various LMP transcripts which are constitutively expressed in LCLs but down-regulated in BL cells. While only 3 of 18 tumors gave a clear LMP1 mRNA-specific signal after first-round amplification with either of two sets of polymerase chain reaction primers, the majority proved to be LMP1 mRNA positive after second-round amplification with nested primers. A rather similar pattern of results was obtained with respect to LMP2B mRNA expression, such transcripts being detectable only in a subset of tumors, and then at apparently low levels. In contrast, clear evidence of LMP2A mRNA expression was obtained in 17 of 17 fresh biopsies. The predominant form of EBV infection in NPCs, with coexpression of EBNA1 and LMP mRNAs, is therefore quite distinct from that seen in BL cells (in which EBNA1 is the only expressed mRNA) and in LCL cells (in which all six EBNA and three LMP transcripts are present). This third form of EBV latency may not be restricted to NPC but may have more general relevance in the context of EBV infection in vivo.

Antigens, Viral↗