Search PubMed⌕ Search

Biomedical subjects

B Murphy

Publications and source records attributed to B Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Aspergillus infection limited to renal allograft: case report and review of literature.

We report a case of a 28-year-old recipient of a cadaveric renal transplant who developed Aspergillus infection in the allograft without having disseminated disease. We review the previously reported cases of isolated Aspergillus in kidney transplant recipients and discuss the possible route of transmission in our patient. We also discuss the alternate but successful treatment that our patient received.

Adult↗
PubMed2006

The proteolysis-inducing factor: in search of its clinical relevance in patients with metastatic gastric/esophageal cancer.

The proteolysis-inducing factor is a putative mediator of cancer-associated weight loss. The goal of this study was to examine for the first time: (i) its prevalence in patients with metastatic gastric/esophageal cancer; and (ii) whether it possibly correlated with weight loss and anorexia and whether it predicted tumor response and patient survival. This study recruited 41 patients as part of a phase II therapeutic, chemotherapy protocol for patients with metastatic gastric/esophageal cancer. Patient eligibility criteria were designed to select a group of patients who would tolerate treatment with the drugs capecitabine and oxaliplatin. Urine for assaying the proteolysis-inducing factor was obtained at registration and then 6 weeks later. Patients completed the FACT-E questionnaire every 6 weeks and had their weights checked at the same interval. Patients were followed prospectively for tumor response and patient survival. Twenty-three (56%) patients had the proteolysis-inducing factor in their urine at registration, and 18 (64%) had it at 6 weeks. There was no statistically significant correlation between the presence of the proteolysis-inducing factor and weight loss or between its presence and anorexia. Moreover, there was no evidence that the presence of the proteolysis-inducing factor in urine was able to predict tumor response or patient survival. The proteolysis-inducing factor in urine does not appear to be tied to weight loss, anorexia, tumor response, or patient survival in the clinical setting of metastatic gastric/esophageal cancer.

Adenocarcinoma↗
PubMed2004

Incidental neurodevelopmental episodes in the etiology of schizophrenia: an expanded model involving epigenetics and development.

Epidemiological data favors genetic predisposition for schizophrenia, a common and complex mental disorder in most populations. Search for the genes involved using candidate genes, positional cloning, and chromosomal aberrations including triplet repeat expansions have established a number of susceptibility loci and genomic sites but no causal gene(s) with a proven mechanism of action. Recent genome-wide gene expression studies on brains from schizophrenia patients and their matched controls have identified a number of genes that show an alteration in expression in the diseased brains. Although it is not possible to offer a cause and effect association between altered gene expression and disease, such observations support a neurodevelopmental model in schizophrenia. Here, we offer a mechanism of this disease, which takes into account the role of developmental noise and diversions of the neural system. It suggests that the final outcome of a neural developmental process is not fixed and exact. Rather it develops with a variation around the mean. More important, the phenotypic consequence may cross the norm as a result of fortuitous and/or epigenetic events. As a result, a normal genotype may develop as abnormal with a disease phenotype. More important, susceptible genotypes may have reduced penetrance and develop as a normal phenocopy. The incidental episodes in neurodevelopment will explain the frequency of schizophrenia in most populations and high discordance of monozygotic twins.

Brain↗
PubMed2004

Successful treatment of vancomycin-resistant Enterococcus faecium endocarditis with linezolid in a renal transplant recipient with human immunodeficiency virus infection.

Infections with vancomycin-resistant Enterococci cause significant morbidity and mortality in hospitalized patients, including transplant recipients. We report the successful use of oral linezolid to treat a case of vancomycin-resistant Enterococcus faecium endocarditis in a renal transplant recipient with human immunodeficiency virus infection.

Acetamides↗
PubMed2003

Study of the impact of penetrant characteristics upon diffusion into Teflon membranes to further assess the performance of an ATR/FTIR sensor.

In order to critically assess the performance and measuring dynamics of an attenuated total reflectance (ATR)/Fourier transform infrared (FTIR) sensor based on polymer preconcentration the impact of penetrant properties upon diffusion into the enrichment membrane must be characterised. Teflon AF2400, a highly amorphous and robust polymer not previously used in this role, was chosen as the enrichment membrane and various environmentally significant chlorinated hydrocarbon and alcohol species selected as analytes. Analyses were performed on aqueous solutions running in continuous flow configuration. Diffusion coefficients, calculated through regression of experimental data with simulated Fickian diffusion curves, were employed as the primary indicator of diffusion behaviour. Penetrant size and shape were both demonstrated to exhibit a substantial impact upon diffusion behaviour. Significant multi-component effects were observed for the simultaneous detection of two analytes. The results presented highlight the necessity for full characterisation of the observed effects prior to the development of a sensing technology for real applications.

Journal Article↗
PubMed2003

The validity and reliability of surface EMG to assess the neuromuscular response of the abdominal muscles to rapid limb movement.

The transversus abdominus muscle (TrA) has been demonstrated to be active prior to rapid movements of the upper and lower limbs. This activity is termed feed forward motivation. The lack of feed-forward activation for TrA has been demonstrated in subjects with low back pain. The measures used for investigation of TrA function have been fine-wire needle EMG. This limits the practical application of TrA study due to the cost and level of specialisation required for this technique. The objective of the current study was to investigate the validity and reliability of using a surface EMG site to replicate the findings for the feed-forward activation of TrA prior to rapid limb movement. A population of healthy, young males (n = 20) were studied and it was found that four of the subjects did not meet feed-forward criteria. These results were shown to be highly reliable after a 2-week period for the TrA/IO site only. The validity of the signal was further investigated using several functional tasks to specifically target muscles of the abdominal region. Using a cross-correlation analysis to evaluate crosstalk from adjacent muscles, it was concluded that the signal representing TrA/IO accurately demonstrates the functional activity of the muscle. This study has demonstrated a viable surface EMG method to evaluate the feed-forward activation of TrA/IO prior to rapid limb movement. This may lead to opportunities for the clinical application of this method. It was also a finding of this study that four asymptomatic subjects did not pre-activate, therefore providing a rationale for future prospective investigations on whether the lack of TrA/IO feed-forward activation is a cause or an effect of low back pain.

Abdominal Muscles↗
PubMed2003

Glomerular infiltration by CXCR3+ ICOS+ activated T cells in chronic allograft nephropathy with transplant glomerulopathy.

The pathogeneses of chronic allograft nephropathy (CAN), a leading cause of allograft failure, and one of its complications, transplant glomerulopathy (TGP), are unknown. Immunohistologic analysis of human renal transplant biopsies showed expression of inducible costimulator (ICOS), the chemokine receptor CXCR3, and its ligands, Mig and IP-10, by intraglomerular and periglomerular leukocytes in biopsies with CAN and TGP but not CAN alone. ICOS and CXCR3 are both characteristics of activated, effector T cells, suggesting different pathogenetic mechanisms underlying TGP vs. CAN. We conclude that targeting of specific chemokine and chemokine receptor pathways and/or ICOS may have clinical application in the prevention and treatment of TGP.

Adult↗
PubMed2003

Occult tumor cells detected in autologous blood stem cell harvests have no impact on 5 year outcomes for breast cancer patients with 4-9 positive nodes treated with adjuvant high-dose therapy and stem cell transplantation.

Breast cancer cells have been detected in autologous blood stem cell collections of early stage breast cancer patients, but their clinical significance is undefined. From October 1993 to August 1998, 32 consecutive Stage II breast cancer patients with 4-9-positive nodes underwent stem cell apheresis. The patients were treated with cyclophosphamide 1.75 gm/m(2), etoposide 400 mg/m(2) and cisplatin 50 mg/m(2) daily for 3 days, followed by infusion of the autologous cells. Cytospins of cells from each apheresis collections and from an aliquot of three pooled collections were examined for cytokeratin expression using an immunocytochemical assay. The cells were considered positive for tumor if at least one cell with tumor morphology stained positively for cytokeratin. Negative aliquots were confirmed with RT-PCR. Six patients (19%) had positive collections. In total, 24 patients (75%) were disease free a median of 61 (30-86) months after transplant. Eight patients relapsed at a median of 17 (8-27) months after transplant. Four of the disease-free patients and two of the relapsed patients had positive apheresis collections. There was no significant correlation between the presence of detectable tumor cells in the graft product and outcome.

Adult↗
PubMed2003

Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease.

The cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene on 2q33 is associated with autoimmune thyroid diseases (AITDs). Our earlier study in 56 families showed linkage of 2q33 to the presence of thyroid antibodies (TAbs). The goals of this study were to confirm the linkage of the 2q33 region to TAbs, to fine map this region, and study the ICOS gene. We performed a linkage study in an expanded data set of 99 multiplex AITD-TAb families (529 individuals). The highest two-point LOD score of 2.9 was obtained for marker D2S325 on 2q33. To fine map this locus, we genotyped 238 Caucasian AITD patients and 137 controls for five additional markers in the linked locus, which contained the CTLA-4, CD28, and ICOS genes. The A/G single-nucleotide polymorphism at position 49 of CTLA-4 was associated with AITD (P=0.01, OR=1.5), while markers inside CD28 and ICOS were not. Functional studies have shown that the G allele was associated with reduced inhibition of T-cell proliferation by CTLA-4. We concluded that: (1) the AITD gene in the 2q33 locus is the CTLA-4 gene and not the CD28 or ICOS genes; and (2) the G allele is associated with decreased function of CTLA-4.

Alleles↗
PubMed2003

Involvement of gene-diet/drug interaction in DNA methylation and its contribution to complex diseases: from cancer to schizophrenia.

Most biological processes, including diseases, involve genetic and non-genetic factors. Also, the realization of a genetic potential may depend on environmental factors by directly affecting the expression of gene(s). Exactly how different environmental factors affect gene expression is not well understood. One of the mechanisms may involve DNA methylation and thereby gene expression. Diet, chemicals, and metals are known to affect DNA methylation and other epigenetic processes but are just beginning to be elucidated. For example, methylation of cytosine(s) in the promoter region could prevent the binding of transcription factors or create binding sites for complexes that deacetylate neighboring histones that in turn compact the chromatin, encouraging a gene to become silent. This article will discuss DNA methylation as an epigenetic mechanism of gene regulation and examine how factors like diet, chemicals, and metals may affect DNA methylation. The effect of alterations in DNA methylation may include aberrant expression of genes or genomes and chromosomal instability, which in turn may contribute to the etiology of complex multifactorial diseases. A similar mechanism is now recognized in a number of cancers. There is also indirect evidence to suggest that methylation could apply to a number of complex diseases, including schizophrenia.

DNA Methylation↗
PubMed2002

Comparisons of estradiol, LH and FSH patterns in pregnant and nonpregnant beagle bitches.

To characterize plasma estradiol, LH and FSH patterns of secretion during the bitch estrous cycle, blood samples were obtained daily from 15 days before until 135 days after the LH surge in 10 pregnant and 10 nonpregnant beagle bitches. After an initial increase between days 15 and 10 and an expected proestrous peak, estradiol concentrations increased again from days 9-12 (corresponding to cytological metestrus) from basal values observed around day 9 after the LH surge, and remained significantly elevated throughout the luteal phase both in pregnant and nonpregnant animals. Concomitantly with the end of the luteal phase, plasma concentrations of estradiol returned to basal values in both groups. During the mid- to late-luteal phase, mean basal LH secretion was significantly elevated throughout in the pregnant relative to the nonpregnant animals. However, in nonpregnant animals, pulsatility was increased and peaks of higher amplitude were observed. The plasma FSH profiles, determined by a specific homologous RIA, differed significantly between pregnant and nonpregnant bitches during the last two-thirds of the luteal phase with a mean FSH level more elevated during pregnancy. The FSH level then decreased around parturition and low concentrations during lactation period were observed. The FSH concentrations remained steady in nonpregnant luteal phases from early luteal phase through mid-anestrus. The differences in pregnant and nonpregnant LH and FSH concentrations suggest pregnancy differences in regulation of the corpus luteum. Finally, the elevated estradiol concentrations observed during the luteal phase of both pregnant and nonpregnant animals suggest that an ovarian production of estrogens may be involved in overall corpus luteum regulation in dogs as in other species.

Animals↗
PubMed2002

Epigenetic contributors to the discordance of monozygotic twins.

Human monozygotic (MZ) twins estimated to occur once in 250 live births, result from an errant decision by embryonic cell(s) to develop as separate embryos. They are considered genetically identical and any phenotypic discordance between them has been used to implicate the role of environment. More recent literature, however, has questioned these assumptions but the frequency and the nature of any genetic discordance between MZ twins remains poorly understood. We will review published cases of phenotypic and genetic discordance between monozygotic twins to argue that not all discordance between such twins is due to differences in environment. The causes of reduced concordance between MZ twins remains poorly understood. They represent among the challenging aspects of the genetics of complex multi-factorial traits and diseases. A number of questions regarding the published results on MZ twins merit a re-assessment in the light of modern molecular insight of the human genome. Such an assessment is needed in directing future studies on MZ twins. In particular, we will deal with the origin, development, genetic and epigenetic factors that may have implications in discordance of the MZ twin pairs.

DNA Methylation↗
PubMed2002

Plasma from poorly mobilizing human subjects inhibits cytokine-induced murine blood stem-cell mobilization.

BACKGROUND: Cytokine-induced mobilization of hematopoietic stem/progenitor cells to the circulation facilitates efficient harvest of blood stem cells by leukapheresis. Up to 30% of autologous, and 10-20% of allogeneic blood stem-cell donors respond poorly to mobilizing cytokines and preliminary studies implicated a circulating inhibitor of mobilization. METHODS: In this study, plasma from 11 allogeneic and 23 autologous stem cell donors was assayed for inhibition of mobilization in mice. RESULTS: There were significant correlations between CD34(+) cells collected/kg human donor weight and spleen weight, CD34(+) CD45(+) cells, GMCFC and HPP-CFC per spleen in murine recipients of these plasma samples. Overall, there was a positive association between transforming growth factor beta (TGF-beta) levels and CD34(+) cells per liter of blood processed (LBP). However, when arbitrarily segregated into good versus poor mobilizers, based on less or greater than 15 million CD34(+) cells collected per LBP, the majority (64%) of normal donors were good mobilizers. The majority of the poor mobilizers (83%) were patients. For a subset of 12 individuals whose plasma strongly inhibited mobilization in the mouse, a significant positive correlation of the extent of inhibition with TGF-beta levels was found. For 11 individuals whose plasma, based on colony assays, enhanced mobilization when injected into mice, no correlation with TGF-beta levels was evident. DISCUSSION: Elevated plasma TGF-beta levels in some stem-cell donors may be associated with poor stem-cell mobilization. It remains to be determined whether elevation of TGF-beta levels is a cause of, or a compensatory response to, poor mobilization.

Animals↗