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Biomedical subjects

Brian Carpenter

Publications and source records attributed to Brian Carpenter.

8 recordsLinked to original sources
PubMed2005

The roles of heterogeneous nuclear ribonucleoproteins in tumour development and progression.

The heterogeneous nuclear ribonucleoproteins (hnRNP) are a family of proteins which share common structural domains, and extensive research has shown that they have central roles in DNA repair, telomere biogenesis, cell signaling and in regulating gene expression at both transcriptional and translational levels. Through these key cellular functions, individual hnRNPs have a variety of potential roles in tumour development and progression including the inhibition of apoptosis, angiogenesis and cell invasion. The aims of this review are to provide an overview of the multi functional roles of the hnRNPs, and how such roles implicate this family as regulators of tumour development. The different stages of tumour development that are potentially regulated by the hnRNPs along with their aberrant expression profiles in tumour tissues will also be discussed.

Animals↗
PubMed2005

VEGF is crucial for the hepatic vascular development required for lipoprotein uptake.

Hepatic lipid catabolism begins with the transport of lipoprotein remnants from the sinusoidal vasculature into hepatocytes by endocytosis via microvilli. To test the hypothesis that fenestrated sinusoidal endothelial cells (SECs) are crucial for this process, we selectively disrupted SECs by downregulating vascular endothelial growth factor (VEGF) signaling, using hepatocyte-specific, tetracycline-regulatable expression of a VEGF receptor that can sequester VEGF but cannot relay its signal. Newborn mutant livers appeared grossly normal, but displayed a dark-red color that was distinguishable from normal physiological lipid-rich pink livers. Mutant sinusoidal networks were reduced and their SECs lacked fenestrae. Hepatocellular lipid levels were profoundly reduced, as determined by Oil Red O staining and transmission electron microscopy, and fewer hepatocytic microvilli were evident, indicating impaired lipoprotein endocytosis. Levels of apolipoprotein (APO) E bound to mutant sinusoidal networks were significantly reduced, and fluorescently-labeled murine remnant lipoproteins injected into the blood stream failed to accumulate in the space of Disse and diffuse into hepatocytes, providing evidence that reduced hepatocellular lipid levels in mutant livers are due to impaired lipoprotein uptake. Temporal downregulation of VEGF signaling revealed that it is crucial at all developmental stages of hepatic vascular morphogenesis, and repression of the dominant-negative effect can rescue the phenotype. These findings provide the first genetic evidence that VEGF dynamically regulates SEC fenestration during liver organogenesis, a process that is required for lipoprotein uptake by the liver.

Animals↗
PubMed2004

Disclosing a dementia diagnosis: a review of opinion and practice, and a proposed research agenda.

PURPOSE: The ethical and practical issues in disclosing a dementia diagnosis remain subjects of some debate. In this review of the literature we document previous opinion and practice in the area of diagnostic disclosure. DESIGN AND METHODS: We identified sources for this review with a MEDLINE and PsycINFO database search, followed by collection of additional articles from reference lists. RESULTS: Across sources we were able to identify a broad list of arguments both for and against diagnostic disclosure. We briefly discuss some of the ethical principles that undergird those reasons. IMPLICATIONS: Practice guidelines and professional opinion regarding disclosure appear to depart from the actual experience reported by clinicians, patients, and family members. At a more detailed level, process issues in disclosure, such as who is told, how and what they are told, and the impact of disclosure, are poorly understood. Sensitivity to individual differences may promote an optimal approach to disclosure. Research in this area is sparse and often contradictory, and throughout the review we propose research questions that, when answered, could clarify issues in disclosure that are essential to sound dementia care.

Attitude of Health Personnel↗
PubMed2004

BASP1 is a transcriptional cosuppressor for the Wilms' tumor suppressor protein WT1.

The Wilms' tumor suppressor protein WT1 is a transcriptional regulator that plays a key role in the development of the kidneys. The transcriptional activation domain of WT1 is subject to regulation by a suppression region within the N terminus of WT1. Using a functional assay, we provide direct evidence that this requires a transcriptional cosuppressor, which we identify as brain acid soluble protein 1 (BASP1). WT1 and BASP1 associate within the nuclei of cells that naturally express both proteins. BASP1 can confer WT1 cosuppressor activity in transfection assays, and elimination of endogenous BASP1 expression augments transcriptional activation by WT1. BASP1 is present in the developing nephron structures of the embryonic kidney and, coincident with that of WT1, its expression is restricted to the highly specialized podocyte cells of the adult kidney. Taken together, our results show that BASP1 is a WT1-associated factor that can regulate WT1 transcriptional activity.

Adult↗
PubMedDate not supplied

Evaluation of fibula free flap donor site morbidity.

OBJECTIVE: To evaluate foot and ankle function in a series of patients undergoing fibula microvascular free tissue transfer. STUDY DESIGN: A nonrandomized, nonblinded analysis was performed using the ankle-hindfoot scale as well as radiographic analysis to determine donor site morbidity. RESULTS: Overall, foot ankle function was deemed to be good in this series of patients. Average ankle-hindfoot score was 84.82 of a possible 100 (range, 55-100). Radiographic analysis of donor and contralateral ankles showed no difference in the syndesmotic space or medial clear space. Only 1 patient had increased talar tilt compared with the contralateral side, although this patient had preservation of stability. CONCLUSION: Fibula free flap harvest appears to be associated with acceptable donor site morbidity and preservation of good foot and ankle function in most individuals.

Aged↗
PubMedDate not supplied

Adding stability to the crescentic basilar first metatarsal osteotomy.

Crescentic basilar osteotomies for metatarsus primus varus and hallux valgus allow for substantial correction of the first intermetatarsal angle and the hallux valgus angle. Crescentic osteotomies have two well-documented pitfalls: sagittal plane instability and difficulty in fixation. We describe the addition of a plantar shelf to crescentic basilar osteotomy that allows for easier fixation and less risk of elevation of the first metatarsal postoperatively. This plantar shelf is made in the metaphyseal portion of the first metatarsal, which provides the benefit of better bone healing. In 20 patients, we found an average reduction in the intermetatarsal angle of 9.3 degrees and an average reduction in the hallux valgus angle of 21.8 degrees. Eight weeks postoperatively, only one patient showed elevation of the first metatarsal.

Biomechanical Phenomena↗
PubMedDate not supplied

Bone matrix therapy for aneurysmal bone cysts.

Aneurysmal bone cysts are unique pathologic entities that cause pain and local osseous destruction. Many surgical treatment modalities have been described. This article reports on the case of a 16-year-old high school athlete with left heel pain due to an aneurysmal bone cyst in the calcaneus. Curettage of the bone cyst was performed, and the void was filled with a commercially available mixture of cancellous bone and demineralized bone matrix. Early return to athletic activity was achieved, with no recurrence noted at 3-year follow-up.

Adolescent↗