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Biomedical subjects

Paul Carmichael

Publications and source records attributed to Paul Carmichael.

10 recordsLinked to original sources
PubMed2004

Gene expression profiling of p53(+/-) knockout and wild-type mice following diethylstilbestrol administration.

Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/- knockout mice and wild-type mice on the kidney and uterus of female mice. p53+/- knockout mice and wild-type mice were treated with DES (500 micromole kg(-1)) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkappab1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53+/- knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53+/- knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53+/- knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and 16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/- knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.

Analysis of Variance↗
PubMed2003

Acute renal failure in the surgical setting.

Acute renal failure (ARF) is an unwelcome complication of major surgical procedures that contributes to surgical morbidity and mortality. Acute renal failure associated with surgery may account for 18-47% of all cases of hospital-acquired ARF. The overall incidence of ARF in surgical patients has been estimated at 1.2%, although is higher in at-risk groups. Mortality of patients with ARF remains disturbingly high, ranging from 25% to 90%, despite advances in dialysis and intensive care support. Appreciation of at-risk surgical populations coupled with intensive perioperative care has the capacity to reduce the incidence of ARF and by implication mortality. Developments in understanding the pathophysiology of ARF may eventually result in newer therapeutic strategies to either prevent or accelerate recovery from ARF. At present the best form of treatment is prevention. In this review the epidemiology, pathophysiology, diagnosis, treatment and possible prevention of ARF will be discussed.

Acute Kidney Injury↗
PubMed2002

Metabonomics and medicine: the Biochemical Oracle.

Occasionally, a new idea emerges that has the potential to revolutionize an entire field of scientific endeavour. It is now within our grasp to be able to detect subtle perturbations within the phenomenally complex biochemical matrix of living organisms. The discipline of metabonomics promises an all-encompassing approach to understanding total, yet fundamental, changes occurring in disease processes, drug toxicity and cell function.

Animals↗
PubMedDate not supplied

Identification of transcriptional biomarkers induced by SERMS in human endometrial cells using multivariate analysis of DNA microarrays.

Functional genomic tools such as DNA microarrays are having a major impact on the drug-discovery process. Potentially, compounds with toxic responses can be identified and removed at a relatively early stage in the drug-development process before tests on animals or humans, solely on the gene expression profiles produced in cell culture. The study examined the expression profiles of primary cultured human endometrial cells treated with 17beta-oestradiol and the SERMs (selective oestrogen receptor modulators) tamoxifen and raloxifene. Primary cultures from three individuals were split into glandular epithelial cells and stromal cell types. Principal components and partial least-squares-discriminate analyses were employed to examine the transcript profile as a whole, identifying genes responsible for patient separation and those that might have an important role in tamoxifen-associated carcinogenesis. Using multivariate data analysis, transcriptional responses were identified in epithelial cells but not in stromal cells for the three SERMs examined. However, it was demonstrated that a major problem associated with using primary cultures derived from human patients is the large transcriptional differences that might exist between the different cultures.

Analysis of Variance↗
PubMedDate not supplied

Wegener's granulomatosis of the breast.

A 60-year-old woman presented with a painless self-detected breast lump. After wide local excision, the histology of this radiologically suspicious lump turned out to be an inflammatory lesion with granulomatous foci, suggesting a diagnosis of granulomatous mastitis. Prior to the excision biopsy, this woman had suffered from and been treated for anterior uveitis, secretory otitis media, and proximal myopathy. Four weeks later, a skin biopsy of a rapidly developing widespread petechial rash, mainly affecting the lower limbs, confirmed the diagnosis as Wegener's granulomatosis. Treatment with intravenous steroids and later cyclophosphamide produced rapid remission.

Breast↗
PubMedDate not supplied

The protean face of renal sarcoid.

Sarcoidosis is a multisystem disorder of unknown etiology, which may occur in all tissues and organs of the body. Clinical presentation may be quite variable and affected by race. The most commonly affected system is the lungs with >95% of patients displaying such involvement. Renal involvement is uncommon (<2%) and may occur in the absence of pulmonary involvement resulting in diagnostic difficulties. Here we describe a sequential cohort of patients with differing presentations of renal sarcoid with and without additional organ involvement. The clinical course and treatment are described.

Adult↗