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Biomedical subjects

C Sweeney

Publications and source records attributed to C Sweeney.

At least 55 records · Page 3Linked to original sources
PubMed1994

The relationship between proteoglycan synthesis in Swarm chondrocytes and pathways of cellular energy and UDP-sugar metabolism.

The effect of anaerobic culture conditions and various metabolic inhibitors on 35S-proteoglycan synthesis, UDP-sugar pools, and the ATP pool were investigated in confluent, primary, day 1 cultures of Swarm chondrosarcoma chondrocytes. (i) Incubation under a nitrogen atmosphere for 6 h did not affect 35S-proteoglycan synthesis or the pool size for UDP-glucuronate, other UDP-sugars, or ATP. Incubation with 5 mM sodium azide brought about a 40% reduction of proteoglycan synthesis in the first 30 min but no further change over the subsequent 90 min. UDP-Glucuronate, other UDP-sugar pools, and the ATP level were not affected by azide treatment. The results indicate that proteoglycan synthesis and its energy requirements can be supported entirely by anaerobic metabolism in these cells. (ii) 35S-Proteoglycan synthesis, UDP-sugar production, and nucleotide triphosphate pools were inhibited in a concentration-dependent fashion with sodium iodoacetate. A > 70% reduction of the ATP pool after 30 min treatment suggests that glycolysis is a major target for iodoacetate. Lactate production was inhibited by 40% after 3 h treatment with 10(-4) M iodoacetate. (iii) Glutamine deprivation resulted in a 60% contraction in the UDP-N-acetylhexosamine pool and markedly inhibited 35S-proteoglycan and 3H-protein synthesis. At the same time the UDP-glucose pool expanded to 200%, but the UDP-glucuronate pool was unchanged. The sum of the UDP-N-acetylhexosamine and UDP-hexose pools remained constant. Restoration of glutamine to previously depleted cultures resulted in excessive expansion of the UDP-N-acetylhexosamine pool and excessive contraction of the UDP-hexose pool before both adjusted to normal levels. The UDP-xylose pool was very small. No increases were observed during inhibition of proteoglycan synthesis induced by glutamine deprivation. (iv) 6-Diazo-5-oxo-L-norleucine (DON), a glutamine analogue and amino transferase inhibitor, induced a further contraction of the UDP-N-acetylhexosamine pool and a further decrease in proteoglycan synthesis in glutamine-deprived cultures. Thus cultures use endogenous glutamine during exogenous glutamine deprivation. DON unaccountably stimulated expansion of the UDP-glucuronate pool by 180%, irrespective of whether glutamine was present or not.

Aggrecans↗
PubMed1994

Effects of ethylnitrosourea on expression of proto-oncogene pp60c-src and high-molecular-weight neurofilament protein in rodent embryo central nervous system cells in vitro.

Effects of exposure to ethylnitrosourea (ENU) on expression of proteins that play a role in neuronal differentiation were examined in central nervous system (CNS) micromass embryo cell cultures. ENU is a known developmental toxicant which affects neuronal development. The proteins selected were the protein product of the src proto-oncogene (pp60c-src) and high-molecular-weight neurofilament protein (NF). pp60c-src has marked increases in amount and kinase activity in neurons at the time of differentiation and NF is found in differentiated neurons. CNS micromass cultures are primary cells from Day 12 rat embryo midbrains which are plated at high density and differentiate into neurons during 5 days in culture. Proteins were quantitated by polyacrylamide gel electrophoresis separation of equal amounts of total cell protein followed by transfer to membranes, immunoblotting, and densitometric scanning of blots. Dose-dependent decreases in cell growth and differentiation were confirmed using endpoints of cell number, protein content of cultures, neutral red uptake, hematoxylin staining of differentiated cells, and levels of binding of the neurotransmitter [3H]gamma-aminobutyric acid. Concentrations which inhibited response by 50% compared to controls ranged from 232 to 455 microM ENU. Dose-related decreases in amounts of pp60c-src and NF proteins relative to total protein were seen in CNS cultures treated with ENU. Results confirm the usefulness of the micromass cultures in following chemical effects on neuronal differentiation. The effects of ENU on specific proteins associated with neuronal differentiation were shown.

Analysis of Variance↗
PubMed1994

31P changes as a measure of therapy response in human osteosarcomas implanted into nude mice.

Our objective was to determine whether changes in PME and PCr/Pi can be used to predict lack of tumor response to chemotherapy in a murine model of human osteosarcoma. A chemotherapy-sensitive human osteosarcoma cell line was implanted into the flank of 22 nude mice. Cisplatin was administered to 11 of the mice 9 days postimplantation. 31P MR spectroscopy was performed pre- and post-chemotherapy in both sets of mice. Statistically significant changes in PCr/Pi occur from post-chemotherapy in the treated mice, but not in the untreated mice during the same time. Change in PME parallels changes in tumor volume. Changes in PCr/Pi predict lack of chemotherapy treatment in human osteosarcoma implanted into nude mice with a specificity of 80% and a sensitivity of 63%. The change in PCr/Pi occurs prior to any changes in volume of the tumor [corrected].

Animals↗
PubMed1994

Acute ethanol inhibits calcium influxes into esophageal smooth but not striated muscle: a possible mechanism for ethanol-induced inhibition of esophageal contractility.

In both humans and cats, EtOH administered in vivo and acutely decreases contractility of smooth muscle of lower esophageal sphincter (LES) and lower esophagus (LE), but not striated muscle of upper esophagus. To see if these effects are associated with perturbation of Ca++ homeostasis, esophageal muscle slices were incubated in vitro with EtOH and then 45Ca++. At steady-state Ca++ uptake, some slices were exposed to 1 microM carbachol (CCH). Although 100 mM EtOH had no effect on Ca++ uptake into resting or stimulated striated muscle of upper esophagus, it significantly inhibited Ca++ uptake into smooth muscle of LES and LE. For unstimulated LE and resting LES, 100 mM EtOH significantly inhibited both initial uptake and steady-state levels, whereas lower doses had no significant effect. EtOH at 100 mM also affected changes in Ca++ content induced by CCH stimulation. CCH increased total exchangeable tissue Ca++ content in LE, whereas it decreased Ca++ content in LES. EtOH at 100 mM blunted these CCH-induced effects in both LES and LE. In contrast to resting muscle, inhibition of CCH-stimulated LE muscle was not limited to 100 mM EtOH, because substantial and significant inhibition was also seen at EtOH doses of 25 and 50 mM, doses which are relevant even in social drinking. Thus, EtOH inhibition of Ca++ influx into esophageal muscle is selective for smooth muscle, can occur at pharmacologically relevant EtOH doses and could be the underlying mechanism for EtOH's inhibition of contractility of esophageal smooth muscle.

Animals↗
PubMed1993

UDP-sugar metabolism in Swarm rat chondrosarcoma chondrocytes.

UDP-sugars and adenine nucleotides were extracted from freshly isolated chondrocytes and primary cell cultures and analysed by anion-exchange h.p.l.c. The pool sizes of UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine, UDP-glucose-galactose, UDP-glucuronate and UDP-xylose were 2.9, 1.2, 2.5, 0.6 and 0.03 nmol/10(6) freshly isolated chondrocytes. When chondrocytes were maintained in Dulbecco's modified Eagle medium supplemented with 15% foetal-bovine serum, synthesis of [35S]proteoglycan and [3H]protein decreased over the first 48 h in culture, as did the pools of UDP-glucuronate and ATP. In contrast, the size of the UDP-N-acetylhexosamine pools underwent little change during culture. [35S]Proteoglycan and [3H]protein syntheses were stimulated in cultures supplemented with serum or insulin compared with those maintained in medium alone, in agreement with previous results. However, the UDP-sugar pool sizes were the same in both supplemented and non-supplemented cultures. In cultures maintained in the presence of [1-3H]glucose, the UDP-sugars were labelled to a constant 3H specific radioactivity which was very similar to that of the labelling medium. UDP-N-acetylhexosamines were labelled to constant 3H specific radioactivity with [6-3H]glucosamine as a precursor, but only about 1 in 375 of these UDP-sugars was derived from the amino sugar in the presence of glucose. The half-life (t1/2) for UDP-hexoses, UDP-glucuronate and UDP-N-acetylhexosamines was about 12, 12 and 50 min respectively.

Animals↗
PubMed1993

Cavernous haemangiomas (angiomas) of the brain: clinically significant lesions.

A review of 2000 consecutive magnetic resonance imaging (MRI) brain studies identified 18 (0.9%) patients with lesions that satisfied MRI criteria for cavernous haemangiomas. The clinical, computed tomography (CT) and MRI findings in 23 patients with probable cavernous haemangiomas were compared. Thirty-three lesions were identified with multiple lesions in five (22%) patients. In 19 (82%) patients the neurological presentation corresponded to a cavernous haemangioma. The presenting symptoms were: seizures in 11 patients (48%); progressive neurological symptoms and signs in four (17%); and acute symptoms and signs due to haemorrhage in four (17%). T2 weighted images suggested the diagnosis in all cases, with 24 (73%) lesions showing the typical appearance of an area of mixed signal intensity with a rim of low signal intensity. In the absence of acute haemorrhage, CT demonstrated well circumscribed, round or oval hyperdense lesions without significant mass effect and with normal surrounding brain tissue in the majority of cases. Although not diagnostic, these CT features are strongly suggestive of cavernous haemangiomas.

Adolescent↗
PubMed1990

Interactions of the endothelium and mesangium in glomerular injury.

Glomerular mesangial and endothelial cells have key roles in the regulation of glomerular blood flow, both under normal circumstances and in pathologic states. The anatomic structure of the glomerulus is such that the endothelial and mesangial cells are in close proximity to each other and consequently may communicate through a number of cellular mediators. Vasodilatory substances, such as prostacyclin and endothelium-derived relaxing factor, and vasoconstrictive substances, such as endothelin, are released by endothelial cells and can interact with mesangial cells to affect glomerular blood flow. The ability of plasma macromolecules to enter and circulate through the mesangium may play an important role in the development of glomerular injury. Angiotensin II has been shown to increase the uptake and decrease the rate of disappearance of certain macromolecules in the mesangium; this action is blocked, at least partially, by angiotensin II receptor antagonists and by calcium channel blockers. Experimental studies have suggested that angiotensin converting enzyme inhibitors and calcium channel blockers may prevent or arrest progression of renal injury. Angiotensin converting enzyme inhibitors may ave a beneficial effect by decreasing intraglomerular pressure through inhibition of angiotensin II predominant constriction of the glomerular efferent arteriole and possibly by decreasing mesangial trafficking of macromolecules. Calcium channel blockers may have beneficial effects on intracellular events that occur because of injury of either endothelial or mesangial cells.

Angiotensin II↗
PubMed1989

Hyaluronan and hyaluronan-binding proteins in cartilaginous tissues.

Recent developments in the biology of hyaluronan in cartilage are reviewed. The homology between the hyaluronan-binding sites of cartilage proteoglycan and link protein is discussed. Previous reports indicate that an increased concentration of extracellular hyaluronan inhibits 35S-proteoglycan synthesis by several types of chondrocyte. We report data showing that this response varies in its reproducibility and sensitivity to low concentrations of hyaluronan in rat chondrosarcoma chondrocytes and pig laryngeal chondrocytes in suspension culture. Two newly recognized hyaluronan-binding proteins have been isolated from extracts of Swarm rat chondrosarcoma. The major protein has a molecular mass of 102 kDa and the less prominent protein a molecular mass of 91 kDa. The latter may be derived from the former. Neither protein cross-reacts with antisera against cartilage proteoglycan HABR (hyaluronan-binding region), link protein, hyaluronectin or type II collagen.

Animals↗
PubMed1988

Differential regulation by glucocorticoids of mouse pro alpha 2(I) and pro alpha 1(III) DNA-binding proteins.

Multiple procollagen-specific DNA-binding proteins were identified for the alpha 2(I) and the alpha 1(III) procollagen promotor containing gene fragments. The proteins are gene-specific, differing in their relative molecular weights and relative binding specificities. A major finding was the increased DNA-binding with specificity for the procollagen promoter containing DNAs by several nonhistone nuclear proteins in mouse embryo fibroblasts treated with dexamethasone. The previously reported coordinate decrease of type I and type III procollagens by glucocorticoids may involve differential regulation by glucocorticoids of procollagen gene specific DNA-binding proteins.

Animals↗
PubMed1986

Neodymium (Nd):YAG laser surgery in the equine larynx: a pilot study.

Laryngeal surgery in the equine is customarily and routinely performed by means of a ventral laryngotomy incision. Such procedures are usually performed under deep general anesthesia with the horse in dorsal recumbency. The objective of this work was to determine the efficacy of an endoscopic approach coupled to a Nd:YAG laser fiber in performing arytenoidectomy. Arytenoidectomy is commonly indicated in the treatment of arytenoid chondritis and in the failure of prosthetic implantation for left laryngeal hemiplegia. This preliminary study was undertaken to determine the feasibility of the endoscopic laser approach to ablate the most difficult of the structures of the larynx, considering tissue structure and density. This procedure was accomplished by using heavy sedation and local anesthesia and was performed in the standing position. This approach appears to be feasible and makes other adjacent structures accessible via the endoscope coupled to a surgical laser. Indications for future pilot applications of laser surgery in the equine larynx are entrapment of the epiglottis, dorsal soft palate displacement, and the ablation of laryngeal cysts and polyps. This pilot study appears to offer a new modality for discrete surgical ablation of this structure, with minimal postoperative complications and a reduced or equivalent convalescent period in this valuable species of animal.

Animals↗
PubMed1981

Marihuana and alcohol: perinatal effects on development of male reproductive functions in mice.

Marihuana and alcohol have been reported to exert a wide range of effects on reproductive functions in man and laboratory animals. Decreased testosterone levels, suppression of pituitary gonadotropin release, impaired fertility and sexual dysfunction have been observed in adult males exposed to either of these substances. The present studies examined the effects of perinatal exposure to ETOH and THC alone or in combination on the development or reproductive functions in mice. Testes weights and plasma testosterone levels were reduced in adult males perinatally exposed to these substances, alone or in combination. Seminal vesicle weights were reduced only in the THC-exposed mice, while kidney weights were decreased by either ETOH or THC exposure. In ETOH plus THC-exposed animals, plasma LH was reduced while FSH levels were increased. In response to castration, gonadotropin levels were elevated in mice perinatally exposed to THC. In vitro responsiveness to gonadotropin stimulation, as indicated by testosterone production by decapsulated testes, was significantly inhibited in tissue obtained from ETOH-exposed males. Although no simple interactions were observed, it is evident that THC and ETOH, either alone or in combination, can affect the development of male reproductive functions in mice.

Adrenal Glands↗