Biomedical subjects

B M Murphy

Publications and source records attributed to B M Murphy.

7 recordsLinked to original sources

PubMed2006

Apoptosis induced by proteasome inhibition in cancer cells: predominant role of the p53/PUMA pathway.

The proteasome has emerged as a novel target for antineoplastic treatment of hematological malignancies and solid tumors, including those of the central nervous system. To identify cell death pathways activated in response to inhibition of the proteasome system in cancer cells, we treated human SH-SY5Y neuroblastoma cells with the selective proteasome inhibitor (PI) epoxomicin (Epoxo). Prolonged exposure to Epoxo was associated with increased levels of poly-ubiquitinylated proteins and p53, release of cytochrome c from the mitochondria, and activation of caspases. Analysis of global gene expression using high-density oligonucleotide microarrays revealed that Epoxo triggered transcriptional activation of the two Bcl-2-homology domain-3-only (BH3-only) genes p53 upregulated modulator of apoptosis (PUMA) and Bim. Subsequent studies in PUMA- and Bim-deficient cells indicated that Epoxo-induced caspase activation and apoptosis was predominantly PUMA-dependent. Further characterization of the transcriptional response to Epoxo in HCT116 human colon cancer cells demonstrated that PUMA induction was p53-dependent; with deficiency in either p53 or PUMA significantly protected HCT116 cells against Epoxo-induced apoptosis. Our data suggest that p53 activation and the transcriptional induction of its target gene PUMA play an important role in the sensitivity of cancer cells to apoptosis induced by proteasome inhibition, and imply that antineoplastic therapies with PIs might be especially useful in cancers with functional p53.

Apoptosis↗

PubMed2005

Phonon modes at the 2H-NbSe2 surface observed by grazing incidence inelastic x-ray scattering.

We have determined the dispersion of acoustic and optical surface phonon modes 2H-NbSe2 at the by inelastic x-ray scattering under grazing incidence conditions. Already, at room temperature, an anomaly is observed close to the charge density wave -vector position located at about one-third along the Gamma-M direction of the Brillouin zone. Our results indicate that the anomaly for the surface mode occurs at a lower energy than that measured in bulk sensitive geometry in the same experiment, showing evidence of a modified behavior in the uppermost layers. We demonstrate that inelastic x-ray scattering in grazing incidence conditions provides a unique tool to selectively study either surface or bulk lattice dynamics in a single experiment.

Journal Article↗

PubMed1996

Clinical similarities in siblings with schizophrenia.

Three symptom groups, identified by factor analysis of schizophrenic symptoms, together with other clinical variables, were compared among 80 sibships (169 individuals) containing two or more members affected with schizophrenia. The three factors, which were labelled negative symptom disorganization, and reality distortion, all showed a moderate but significant degree of correlation between siblings. Age at onset was also significantly correlated. Such a familial pattern of clinical heterogeneity suggests underlying common familial aetiologies that influence the clinical form of the disorder. Whether these are genetic or environmental requires further investigation. This finding confers some external validation on the three factor model. It may be feasible to develop familial symptom patterns as the basis for an a priori approach to linkage heterogeneity.

Adult↗

PubMed1994

An analysis of the clinical features of familial schizophrenia.

Clinical features of familial schizophrenia were examined in 169 siblings from 80 families. Factor analysis of symptoms produced a negative symptom factor (affective flattening and negative thought disorder), a disorganization factor (inappropriate affect and positive thought disorder) and a reality distortion factor (delusions and hallucinations). The negative symptom factor correlated positively with duration of illness and poor outcome. The disorganization factor correlated positively with poor outcome and early age at onset. The only clear correlation between these factors and affective symptoms was a negative one between the negative symptom factor and mania. There were no significant gender differences in age at onset, factor scores or outcome. The implication of these findings in relation to recent research in the areas of psychopathology and epidemiology are discussed.

Adolescent↗

PubMed1993

Development, implementation, and results of a successful multidisciplinary adverse drug reaction reporting program in a university teaching hospital.

The development and implementation of an active adverse drug reaction reporting program in a university teaching hospital is described. The progression from a solely voluntary system to a multidisciplinary program consisting of both voluntary and involuntary components is discussed. A total of 1,011 adverse reactions were reported between July 1, 1988 and July 22, 1992. The most common reaction reported was rash. Antibiotics were most commonly implicated in the reactions reported. As a single agent, digoxin was involved most frequently. Voluntary reporting by physicians, nurses, and pharmacists accounted for approximately 24% of the adverse reactions reported. Occurrence screening by the Quality Assurance department produced approximately 76% of the reports.

Adverse Drug Reaction Reporting Systems↗

PubMed1992

The influence of intensively managed rotational grazing, traditional continuous grazing, and confinement housing on bulk tank milk quality and udder health.

Monthly bulk tank milk samples and veterinary records were analyzed for 1 yr on 15 Vermont dairy farms. Data were evaluated using ANOVA to compare effects of grazing management systems on milk quality and udder health. Systems evaluated were intensively managed rotational grazing, traditional continuous grazing, and confinement housing. Bulk tank samples were evaluated for standard plate count, bacterial type counts on tryptose-blood-esculin agar, and SCC. Veterinary records were evaluated for incidence of clinical mastitis, udder edema, and teat injuries. Within- and between-treatment group analyses were conducted by season, herd size, and udder sanitation systems. Mean standard plate counts were lower in rotationally grazed herds than counts of confined herds during the grazing season. Similarly, rotationally grazed herds with fewer than 60 cows had lower standard plate counts than confined herds of similar size. Mean bulk tank counts of streptococci other than Streptococcus agalactiae during the grazing season differed among treatments. The lowest counts occurred in rotationally grazed herds. Among herd using predip products recognized as efficacious, fewer streptococci other than S. agalactiae were isolated from bulk tank milk of rotationally grazed herds than confined herds. Rotationally grazed herds using postdips recognized as efficacious had lower SCC than those using unrecognized postdips. No udder health differences were observed among grazing treatments.

Animal Husbandry↗

PubMedDate not supplied

Pathways to suicide prevention.

Society places a responsibility on the medical profession for the prevention of suicide. In this article, current trends in suicide, social prevention strategies and the role and limitations of medical intervention are reviewed.

Decision Trees↗