Biomedical subjects

D Merry

Publications and source records attributed to D Merry.

5 recordsLinked to original sources

PubMed2000

CREB-binding protein sequestration by expanded polyglutamine.

Spinal and bulbar muscular atrophy (SBMA) is one of eight inherited neurodegenerative diseases known to be caused by CAG repeat expansion. The expansion results in an expanded polyglutamine tract, which likely confers a novel, toxic function to the affected protein. Cell culture and transgenic mouse studies have implicated the nucleus as a site for pathogenesis, suggesting that a critical nuclear factor or process is disrupted by the polyglutamine expansion. In this report we present evidence that CREB-binding protein (CBP), a transcriptional co-activator that orchestrates nuclear response to a variety of cell signaling cascades, is incorporated into nuclear inclusions formed by polyglutamine-containing proteins in cultured cells, transgenic mice and tissue from patients with SBMA. We also show CBP incorporation into nuclear inclusions formed in a cell culture model of another polyglutamine disease, spinocerebellar ataxia type 3. We present evidence that soluble levels of CBP are reduced in cells expressing expanded polyglutamine despite increased levels of CBP mRNA. Finally, we demonstrate that over-expression of CBP rescues cells from polyglutamine-mediated toxicity in neuronal cell culture. These data support a CBP-sequestration model of polyglutamine expansion disease.

Animals↗

PubMed1998

Endoscopic stapling treatment of pharyngeal pouch.

BACKGROUND: We describe our experience of a recently reported endoscopic stapling technique for the treatment of pharyngeal pouch. METHODS: In contrast to other endoscopic procedures, which only divide the common wall between oesophagus and diverticulum, the linear cutting stapler also tightly seals the divided edges of mucosa and muscle. RESULTS: The procedure was performed without complications in three patients with complete resolution of pre-treatment symptoms. CONCLUSIONS: To our knowledge this is the first report of the use of this procedure in Australia. This endoscopic stapling operation appears to be safe, simple and cost-effective and offers advantages over previously used techniques.

Endoscopy↗

PubMed1996

Induction of apoptosis by La Crosse virus infection and role of neuronal differentiation and human bcl-2 expression in its prevention.

La Crosse virus causes a highly cytopathic infection in cultured cells and in the murine central nervous system (CNS), with widespread neuronal destruction. In some viral infections of the CNS, apoptosis, or programmed cell death, has been proposed as a mechanism for cytopathology (Y. Shen and T. E. Shenk, Curr. Opin. Genet. Dev. 5:105-111, 1995). To determine whether apoptosis plays a role in La Crosse virus-induced cell death, we performed experiments with newborn mice and two neural tissue culture models. Newborn mice infected with La Crosse virus showed evidence of apoptosis with the terminal deoxynucleotidyl transferase-mediated nicked-end labeling (TUNEL) assay and, concomitantly, histopathological suggestion of neuronal dropout. Infection of tissue culture cells also resulted in DNA fragmentation, TUNEL reactivity, and morphological changes in the nuclei characteristic of apoptotic cells. As in one other system (S. Ubol, P. C. Tucker, D. E. Griffin, and J. M. Hardwick, Proc. Natl. Acad. Sci. USA 91:5202-5206, 1994), expression of the human proto-oncogene bcl-2 was able to protect one neuronal cell line, N18-RE-105, from undergoing apoptosis after La Crosse virus infection and prolonged the survival of infected cells. Nevertheless, expression of bcl-2 did not prevent eventual cytopathicity. However, a human neuronal cell line, NT2N, was resistant to both apoptosis and other types of cytopathicity after infection with La Crosse virus, reaffirming the complexity of cell death. Our results show that apoptosis is an important consequence of La Crosse virus infection in vivo and in vitro.

Animals↗

PubMed1986

The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13).

A clone that cross-hybridizes with a mouse p53 probe has been isolated from a cDNA library of simian virus 40-transformed human fibroblasts. This cloned human p53 cDNA was used as a probe to examine DNAs obtained from human-rodent somatic cell hybrids that have segregated human chromosomes. The results show that the human p53 gene is located on chromosome 17. In addition, Southern analysis of hybrids prepared from human cells containing a chromosome 17 translocation allowed regional localization of the human p53 gene to the most distal band on the short arm of this chromosome (17p13). Localization of the p53 gene to 17p13 was confirmed by in situ hybridization of metaphase spreads with the human p53 probe.

Animals↗

PubMedDate not supplied

A preliminary evaluation of a prototype western blot confirmatory test kit for syphilis.

A prototype Western blot kit was evaluated as a confirmatory test for syphilis using 131 sera characterized by other serological tests for syphilis. There were 114 treponemal sera (including 94 cases of early syphilis, 83 of which were untreated) and 17 non-treponemal problem sera (11 gave false positive reactions on screening with the TmpA recombinant antigen enzyme immunoassay (EIA), 3 gave false positive fluorescent treponemal antibody absorbed (FTA-abs) tests, and 3 false positive Captia Syphilis G EIA results). Based on the manufacturer's criteria of reactivity in multiple bands for designating a positive result the Western blot test gave a sensitivity of 99.1% (113/114) and a specificity of 88.2% (15/17) when indeterminate reactions were scored positive and 98.2% (112/114) and 100% (17/17) when indeterminate reactions were scored negative. Sensitivity was high in both treated and untreated infection. Corresponding sensitivities for the TPHA and FTA-abs when equivocal reactions were scored negative were 97.5% (111/114) and 99.1% (113/114). The high sensitivity of the FTA-abs in this study is probably due to the large number of untreated primary infections. Our results with the Western blot, confirm earlier studies using 'in-house' test systems and, support a role for a commercial Western blot test in the confirmatory diagnosis of syphilis. Further studies are required to confirm the high specificity and sensitivity of the kit in a larger series including a wider variety of non-treponemal cases as well as patients with untreated and treated infection.

Blotting, Western↗