Biomedical subjects

B Clancy

Publications and source records attributed to B Clancy.

18 recordsLinked to original sources

PubMed2005

Paraganglioma: the role of genetic counselling and radiological screening.

Paragangliomas are rare tumours of the autonomic nervous system that occur in both sporadic and hereditary forms. They are usually benign tumours with low mortality, but can cause significant morbidity related to mass effect. Genetic predisposition to develop paraganglioma can occur within known tumour syndromes and familial tumours tend to present at a younger age and at multiple sites compared to sporadic tumours. Tumours should be diagnosed and excised as early as possible, as studies have shown morbidity to be directly related to tumour size. We present a case of a 14-year-old boy with multiple paraganglioma and a strong family history of paraganglioma. He suffered significant morbidity at resection of an extra-adrenal retroperitoneal tumour due to late diagnosis and was later unable to undergo excision of a head and neck paraganglioma due to its size and relation to neurovascular structures in the neck. We review the current literature on suggested genetic counselling (psychological counselling and DNA analysis) and radiological screening guidelines and recommend that genetic counselling should be offered to all patients with a family history of paraganglioma from the age of 5 years. Those positive for paternal paraganglioma locus gene should then undergo regular radiological screening with MRI.

Adolescent↗

PubMed2004

Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model.

This study evaluated healing of rabbit bilateral ulnar osteotomies 6 and 8 weeks after surgery in response to percutaneous injection of transgenic adenoviral (Ad) bone morphogenetic protein-6 (BMP-6) vector or green fluorescent protein vector control (Ad-GFP) administered 7 days after surgery compared to untreated osteotomy controls. The amount, composition and biomechanical properties of the healing bone repair tissue were compared among groups and to historical data for intact rabbit ulnae obtained from similar studies at the same institution. Quantitative computed tomography was used to determine area, density and mineral content of the mineralized callus in the harvested ulnae. Maximum torque, torsional stiffness, and energy absorbed to failure were determined at 1.5 degrees /s. Calcified sections of excised ulnae (5 microm) were stained with Goldner's Trichrome and Von Kossa, and evaluated for callus composition, maturity, cortical continuity, and osteotomy bridging. Radiographic assessment of bone formation indicated greater mineralized callus in the ulnae injected with Ad-hBMP-6 as early as 1 week after treatment (2 weeks after surgery) compared to untreated osteotomy ulnae (p < 0.006) and Ad-GFP treated osteotomy ulnae (p < 0.002). Quantitative computed tomography confirmed greater bone area and bone mineral content at the osteotomy at 6 weeks in Ad-BMP-6 treated osteotomy as compared to untreated osteotomy ulnae (p < 0.001) and Ad-GFP treated osteotomy ulnae (p < 0.01). Ad-BMP-6 treated osteotomy ulnae were stronger (p < 0.001 and 0.003) and stiffer (p < 0.004 and 0.003) in torsion at 6 weeks than untreated osteotomy ulnae or Ad-GFP treated osteotomy ulnae, respectively. Maximum torque, torsional stiffness, and energy absorbed to failure were greater in Ad-BMP-6 treated osteotomy ulnae compared to their respective untreated contralateral osteotomy ulnae at 8 weeks [p < 0.03]. Maximum torque and torsional stiffness in the Ad-BMP-6 treated osteotomy ulnae were not different to intact ulnae values at 6 and 8 weeks. These experiments confirm that BMP-6 can be potently osteoinductive in vivo resulting in acceleration of bone repair.

Adenoviridae↗

PubMed2001

Structure and projections of white matter neurons in the postnatal rat visual cortex.

Transient contributions of subplate neurons to the initial development of the cortex are well-characterized, yet little data are available on a subpopulation of subplate neurons that persist in the white matter (WM) of the cerebral cortex across development. To characterize the WM neurons, differential interference contrast and Nomarski optics were used to visualize individual cells in the WM in slices of rat visual cortex at postnatal ages 9-23. Soma-dendritic morphology and local axonal projection patterns, including probable synaptic innervation sites of their axons, were identified by intracellular filling with biocytin during electrophysiologic recordings. Dendritic branches of all WM neurons, tripartitioned here into upper, middle, and deep divisions, extend throughout the WM and frequently into the overlying cortex. Axonal arborizations from most WM neurons, including apparent boutons, project into adjacent WM with many also innervating overlying cortical layers, whereas some project into the stratum oriens/alveus of the hippocampal formation. Processes of a subset of WM neurons appear to be confined to the WM itself. By using antimicrotubule associated protein (MAP2) immunostaining to quantify the density of WM neurons in rat visual cortex, we find that their overall numbers decrease to approximately 30% of initial levels during postnatal development. During this same developmental period, an increasing percentage of WM neurons contain the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), as evaluated by immunostaining. Thus, WM neurons that survive the initial perinatal period of cell death are positioned under the laminae of the maturing cortex to potentially modulate the integration of visual signals through either conventional synaptic or nonconventional (diffusible NO signaling) mechanisms.

Action Potentials↗

PubMed2001

Translating developmental time across mammalian species.

Conservation of the order in which events occur in developing mammalian brains permits use of regression theory to model the timing of neural development. Following a small adjustment to account for a systematic variability in primate cortical and limbic systems, the model is used to generate a 95-event/nine-species matrix that predicts aspects of neurogenesis and axonal outgrowth in the brains of developing mice, hamsters, rats, spiny mice, rabbits, ferrets, cats, monkeys, and humans. Although data are compiled from species in which the timing of birth and the rate of maturation vary widely, the model proves statistically accurate, with practical implications for improving estimation of milestones of neural development, particularly for humans. Using the three-factor model (species, neural events, and primate adjustments), we produce predictions for the timing of 493 neural occurrences in developing mammalian brains that either have not yet been, or cannot be, empirically derived. We also relate the timing of neural events across the nine species in the form of a reference table calibrated to the development of laboratory rats. This 'translation' table will assist in attempts to equate the neurodevelopmental literature across species with either large or small differences in gestation and maturation, and also permit studies done in a variety of mammals to be applied to better understand human development. The comparative data indicate that humans, although conventionally considered an altricial species, are neurally advanced at birth relative to the other species studied.

Aging↗

PubMed2000

The development of peritumoral stroma required for IL-12 induced tumor regression depends on the T cell/IFN-gamma-involving host-tumor interaction.

T cell migration into tumor masses is a critical process in the scenario of IL-12-induced tumor regression. Our previous study showed that this depends on the development of peritumoral stroma prior to IL-12 therapy. The present study investigated the regulation of the development of peritumoral stroma in comparison with tumor-parenchymal stroma. In the OV-HM and CSA1M tumor models, tumor regression associated with T cell migration was induced following IL-12 treatment. Both OV-HM and CSA1M tumor masses growing in syngeneic mice developed peritumoral stroma before IL-12 treatment. However, peritumoral stroma was not observed in these two types of tumor masses generated in nude mice, T cell-depleted syngeneic mice, anti-IFN-gamma mAb-treated mice or IFN-gamma-deficient mice. In contrast, parenchymal stroma formation did not appear to be affected because tumors generated in these groups of mice exhibited rather higher growth rates than those of tumors in normal syngeneic mice. Importantly, the lack of peritumoral stroma in tumor masses was associated with the failure of T cells to migrate to these tumor masses: splenic T cells prepared from IL-12-treated tumor-bearing mice migrated into the corresponding tumor mass growing in untreated syngeneic recipient mice, whereas portions of the same donor cells failed to migrate into the above stroma-negative tumor masses. These results indicate that the development of peritumoral and parenchymal stroma is differentially regulated; there exist functional differences in the two types of stroma; and the formation of peritumoral stroma requires components of the host's immune system such as IFN-gamma and T cells.

Animals↗

PubMed1999

Widespread projections from subgriseal neurons (layer VII) to layer I in adult rat cortex.

Theories of information processing and plasticity in mammalian cortex often rely on knowledge of intracortical networks studied in rodent cortex. Accordingly, the contribution of all cells involved in this circuitry is potentially significant, including connections from a subset of neurons that persist from the developmental subplate, called subgriseal neurons in the present study. Ascending corticocortical connections from subgriseal neurons were identified by using in vivo transport of fluorescent retrograde tracers from discrete applications confined to cortical layer I (approximately 1 mm2) or from injections placed into superficial cortical layers. Applications restricted to cortical layer I can be identified by a subsequent retrograde labeling pattern that includes neurons in layers II/III and V but not those in layer IV. In contrast, when retrograde tracer is deposited in layers II/III, layer IV cells are also labeled. By using this identification technique in juvenile and adult rats, widespread interareal projections to superficial layers, including unequivocal connections to cortical layer I, were found to originate from a tangential band of neurons directly below the conventionally identified gray matter (i.e., subgriseal) and from a smaller number of cells in the white matter (WM) proper. Subgriseal and WM neurons were labeled below application and injection sites in somatosensory, auditory, visual, motor, frontal, and adjacent areas at distances of more than 4 mm. However, the subgriseal-to-superficial pathway was not sensitive to nonfluorescent retrograde tracers including horseradish peroxidase. Because neurons in the deeper cortical layers can be strongly influenced through input to their apical dendritic extensions in cortical layer I, the widespread connections described in the present study indicate that the ascending subgriseal projections should be considered in models of mature cortical function.

Aging↗

PubMed1998

Reduction of background autofluorescence in brain sections following immersion in sodium borohydride.

Autofluorescence of aldehyde-fixed neural tissue often obscures perikaria and fine processes labeled with fluorescent anterograde or retrograde tracers. In particular, this autofluorescence hinders the detectability of fine axonal projections labeled with the convenient anterograde tracer, tetramethylrhodamine dextranamine. Background fluorescence was notably reduced by immersion of free-floating brain tissue sections in a solution of sodium borohydride (NaBH4, 0.1%), a chemical which is known to neutralize Schiffs bases through reduction of amine-aldehyde compounds into non-fluorescent salts. The reversible and renewable immersion technique was most effective in paraformaldehyde-fixed tissue where the preservation quality was improved such that labeled axons remained detectable for more than 1 year after initial preparation.

Amidines↗

PubMed1998

Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I.

We have studied the origin and extent of axons within layer I of the primary somatosensory cortex (SI) of rats by using retrograde and anterograde tracers with an emphasis on reciprocal connections to layer I of SI from ipsilateral cortical areas that are the target of SI projections. Small crystals of 1,1',dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) labeled horizontal axons projecting in all directions within layer I, which extended for up to 4 mm with numerous terminal branches. Applications of horseradish peroxidase, Diamidino yellow, or fast blue to the pial surface of SI labeled a characteristic pattern of neurons below the application site that excluded neurons in layer IV of the barrel fields, unless the dye penetrated deeper than layer II. This provided a control for the effective depth of the layer I dye applications. Retrograde transport from layer I of SI was traced to the primary motor area, the lateral parietal areas, including the secondary somatosensory (SII) and agranular insular cortex ipsilaterally, as well as the homotopic areas of SI contralaterally. Injections of the anterograde tracer dextran amine at the same site as the SI surface application labeled dense fiber terminations in middle layers of these same secondary areas in the primary motor cortex (MI) or SII in the midst of cells labeled by retrograde transport from layer I of SI. Injections of dextran amine into these secondary cortical areas labeled fibers that coursed through deep layers to SI, where they ascended to layer I. These reciprocal corticocortical inputs to SI were concentrated in layer I, where they branched and extended horizontally across several SI barrels.

Animals↗

PubMed1998

The manufacturing process for recombinant factor IX.

Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance the capacity of cells to remove the amino-terminal propeptide from rFIX) into Chinese hamster ovary cells; (2) selection of a cell line that was capable of expressing high amounts of active rFIX while growing in bioreactors containing a completely defined culture medium that does not contain blood or plasma products; and (3) inclusion of four independent chromatography steps, none of which require monoclonal antibodies. Furthermore, rFIX has been extensively tested to demonstrate similarity to plasma-derived factor IX and has been shown to be a consistent, high-purity product. For example, a high-specific-activity product (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and high-purity source of factor IX treatment for patients with hemophilia B.

Animals↗

PubMed1991

Reducing the leakage of body-worn incontinence pads.

The aim of this research was to evaluate the effect of various absorbent materials (fluff pulp and superabsorbent) on the leakage performance of incontinence pads. A shaped pad-and-pant system was used as the basic design and four pad types made to different specifications were compared using a double-blind technique. Forty-five elderly hospital residents who were incontinent of urine used all four pad types in a randomly allocated order. Data were recorded on more than 5000 pads over a 2-month period. Leakage was reduced by adding a second layer of fluff pulp and, whilst the addition of a superabsorbent material tended to reduce leakage further, we found no clear relationship between the amount of superabsorbent and the reduction of leakage. Other data indicated the importance of securing the pad in place with the appropriate net pants and the leakage rates of pads in relation to the amount of urine they contained. This research suggests that superabsorbent materials have great potential for reducing the leakage rate of incontinence pads but that the way in which they are incorporated into the pad, the amount of fluff pulp and the design of the pad also play an important part.

Absorption↗

PubMed1989

No more guesswork! Choosing incontinence products.

Explore the source record for details and available documents.

Bedding and Linens↗

PubMed1981

Labeling of preformed liposomes with Ga-67 and Tc-99m by chelation.

We have synthesized a long-chain hydrocarbon covalently coupled to diethylene-triaminepenta-acetic acid (stearylamine-DTPA) and have incorporated this compound in liposomes during their preparation. The lipophilic hydrocarbon chain anchors the molecule in the lipid bilayer, exposing the DTPA groups on the surface for chelation. Ethanolic solutions of the lipids are evaporated to dryness under nitrogen in multidose vials; the lipids are suspended in the vial by adding a small volume of distilled water followed by sonication. The liposomes are then labeled by transcomplexation in the case of Ga-67 and by conventional stannous reduction in the case of Tc-99m, by adding the activities directly to the vial. These liposomes bind 95 +/- 5% of Ga-67 and Tc-99m activity, as determined by paper chromatograph assay, eliminating the need for a purification step. The labeled liposomes release about 5% of their Ga-67 activity, and about 30% of their Tc-99m activity after 2 hr of incubation in 50% human plasma at 37 degrees C. Activity released from liposomes labeled with Ga-67 or Tc-99m oxine is much greater under the same conditions. In normal mice the labeled liposomes show biodistributions that are comparable with that obtained with liposomes labeled by conventional techniques.

Amines↗

PubMed1980

Investigations of a new, highly negative liposome with improved biodistribution for imaging.

An attractive feature of liposomes is the wide range of lipid composition that can lead to liposome formation, coupled with the observation that liposome biodistribution may be altered by varying lipid composition. For instance, adding charged lipids to neutral lecithin will alter the biodistribution of the resulting charged liposomes. We have prepared highly negative liposomes by replacing lecithin with negatively charged cardiolipin. The liposomes have been labeled in the lipid phase with Ga-67 and Tc-99m oxine and their properties evaluated. The expected high negative charge of the resulting liposomes was confirmed by an ion-exchange chromatographic technique. Using paper chromatography, the stability of the label was determined during incubation in saline and serum. Finally, biodistributions were determined at 2 hr in mice, and the results compared with those for negative lecithin liposomes. Accumulated activities in liver and spleen were reduced by factors of five and 20, respectively, over lecithin liposomes. Since preferential accumulation of activity in these organs constitutes the biggest limitation to the use of lecithin liposomes, cardiolipin liposomes may prove to be more useful carriers of radioactivity in imaging applications. More importantly, however, these results illustrate the value of studying novel liposome types as potential radiopharmaceuticals.

Amines↗

PubMed1973