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Biomedical subjects

H Farmer

Publications and source records attributed to H Farmer.

16 recordsLinked to original sources
PubMed2005

Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer.

Individuals harboring germ-line mutations in the BRCA1 or BRCA2 genes are at highly elevated risk of a variety of cancers. Ten years of research has revealed roles for BRCA1 and BRCA2 in a wide variety of cellular processes. However, it seems likely that the function of these proteins in DNA repair is critically important in maintaining genome stability. Despite this increasing knowledge of the defects present in BRCA-deficient cells, BRCA mutation carriers developing cancer are still treated similarly to sporadic cases. Here we describe our efforts, based on understanding the DNA repair defects in BRCAdeficient cells, to define the optimal existing treatment for cancers arising in BRCA mutation carriers and, additionally, the development of novel therapeutic approaches. Finally, we discuss how therapies developed to treat BRCA mutant tumors might be applied to some sporadic cancers sharing similar specific defects in DNA repair.

Animals↗
PubMed2004

Novel fluorescence-based approaches for the study of biogenic amine transporter localization, activity, and regulation.

Pre-synaptic norepinephrine (NE) and dopamine (DA) transporters (NET and DAT) terminate catecholamine synaptic transmission through reuptake of released neurotransmitter. Recent studies reveal that NET and DAT are tightly regulated by receptor and second messenger-linked signaling pathways. Common approaches for studying these transporters involve use of radiolabeled substrates or antagonists, methods possessing limited spatial resolution and that bear limited opportunities for repeated monitoring of living preparations. To circumvent these issues, we have explored two novel assay platforms that permit temporally resolved quantitation of transport activity and transporter protein localization. To monitor the binding and transport function of NET and DAT in real-time, we have investigated the uptake of the fluorescent organic compound 4-(4-diethylaminostyryl)-N-methylpyridinium iodide (ASP+). We have extended our previous single cell level application of this substrate to monitor transport activity via high-throughput assay platforms. Compared to radiotracer uptake methods, acquisition of ASP+ fluorescence is non-isotopic and allows for continuous, repeated transport measurements on both transfected and native preparations. Secondly, we have extended our application of small-molecule-conjugated fluorescent CdSe/ZnS nanocrystals, or quantum dots (Qdots), to utilize antibody and peptide ligands that can identify surface expressed transporters, receptors and other membrane proteins in living cell systems. Unlike typical organic fluorophores, Qdots are highly resistant to bleaching and can be conjugated to multiple ligands. They can also be illuminated by conventional light sources, yet produce narrow, gaussian emission spectra compatible with multiple target visualization (multiplexing). Together, these approaches offer novel opportunities to investigate changes in transporter function and distribution in real-time with superior spatial and temporal resolution.

Antibodies↗
PubMed2001

Nisoldipine increases the bioavailability of endothelial NO.

Different observations suggest that dihydropyridine calcium antagonists alter endothelial NO release. Therefore, in a first step we investigated whether part of the nisoldipine (a dihydropyridine calcium antagonist with a possible selectivity for coronaries)-induced vasorelaxation was due to an NO release from the endothelium in porcine coronary arteries. Secondly, we directly measured whether nisoldipine increased NO release from rabbit aorta or the nisoldipine enantiomers (Bay R 1223, Bay R 1224) from rat aorta. Thirdly, we determined whether nisoldipine exerted antioxidative properties in segments of porcine aorta with intact endothelium. Blocking endothelial NO synthase with N-nitro-L-arginine resulted in a significant shift of the relaxation curve to higher concentrations. Accordingly, nisoldipine induced a concentration-dependent release of NO (direct electrochemical detection) from native endothelium which already started at a therapeutical level (1 nmol/l nisoldipine/6.5 +/- 1.2 nmol/l NO). To evaluate whether this effect was due to an antioxidative protection of NO, we examined the influence of nisoldipine on a hyperglycemia (30 mmol/l, 20 min)-induced reactive oxygen species release of vascular endothelium from porcine coronary arteries. Nisoldipine concentration-dependently reduced the reactive oxygen species release (>50%; 10 micromol/l). Moreover, a carbachol-induced NO release (rabbit aorta) which was significantly diminished by hyperglycemia was completely restored in the presence of nisoldipine (3 micromol/l). We conclude that nisoldipine increases the NO bioavailability which may result in an ameliorated endothelial function.

Animals↗
PubMed1986

Pancreatic duct obstruction in a stunting syndrome of broiler chickens.

Broilers suffering from stunting syndrome from three farms were shown to have pancreatic atrophy and fibrosis similar to that seen in pancreatic duct obstruction in chickens and mammals. Interlobular and intercalated ducts were found to be stenotic or occluded with inflammation and necrosis of the epithelium and wall. Inclusion bodies were seen in some duct cells. It is suggested that pancreatic duct obstruction is responsible for the maldigestion and pancreatic lesions seen in stunting syndrome.

Animals↗
PubMed1980

The use of amitraz (N1-(2,4-dimethylphenyl)-N-[(2,4-dimethylphenyl)imino)-methyl]-N-methylmethanimidamide) in demodecosis in dogs.

Amitraz topically applied as an 0.025 or 0.05% aqueous suspension once or twice weekly for up to 8 weeks cured 3 cases of generalised squamopapular to pustular demodectic mange and effectively controlled the condition in a fourth dog. Three of these dogs were Dobermans in which the disease was refractory to standard therapy with ronnel. A single wash in 0.025% amitraz suspension was sufficient to cure each of 5 dogs affected with localized demodecosis within 2 to 4 weeks. At these dose levels the drug is non toxic and non irritant to skin and mucous membranes. Recommendations for the use of amitraz include a thorough prewash of the entire skin surface with soap and water followed by application of the drug suspension with vigorous scrubbing, the compound then being allowed to dry on the animal's skin. The availability of amitraz therapy appears to provide a favourable prognosis for the control of severe long standing mange in the dog.

Animals↗
PubMedDate not supplied

Low-profile dynamic splints: a solution to the friction problem.

To find a solution to the problem of friction between the nylon fishing line and the outrigger of a low-profile dynamic splint, a jig was manufactured to bend notches in 2.5-mm copper-coated welding rod. This type of outrigger was compared with an adjustable stainless-steel outrigger to determine which of the two types produces the least amount of friction. As one of each type of outrigger was covered with a layer of Teflon paint, four different outriggers were compared with each other: welding rod only, welding rod with Teflon, stainless steel with Teflon, and stainless steel only. Equal traction units were attached to each of the outriggers and the amount of elongation of a 50-mm tension spring was measured when a 300-g weight was hooked onto it. This was compared with the elongation of the same spring when no friction was present. The results show that the Teflon-covered outriggers displayed significantly (on a 5% level) less friction than did the uncovered outriggers. The stainless-steel outrigger with Teflon performed slightly better than the welding-rod outrigger with Teflon. However, there was no significant difference between these two outriggers, and because the welding-rod outrigger is cheaper and more readily available, it is recommended for clinical use.

Equipment Design↗