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Biomedical subjects

M Scanlon

Publications and source records attributed to M Scanlon.

At least 19 recordsLinked to original sources
PubMed2006

Baseline characteristics and response to GH replacement of hypopituitary patients previously irradiated for pituitary adenoma or craniopharyngioma: data from the Pfizer International Metabolic Database.

OBJECTIVE: To test the hypothesis whether the effects of GH replacement therapy in adults could be affected by prior pituitary irradiation, the baseline characteristics and response to GH were evaluated in adults with severe GH deficiency (GHD), who had received or not irradiation for the treatment of pituitary adenoma or craniopharyngioma. DESIGN: Data from 447 patients, who had received radiotherapy (427 in addition to surgery), and 630 patients, who were operated on but not irradiated for their tumour, were retrieved from Pfizer International Metabolic Database (KIMS) and compared at baseline and 1 and 2 years following the onset of GH replacement. RESULTS: Irradiated and non-irradiated patients exhibited the expected phenotype of GHD at baseline. However, irradiated patients had a greater impairment in the quality of life (QoL), a higher fat mass, lower high-density lipoprotein cholesterol levels and a lower bone mineral content (BMC) than non-irradiated patients. Treatment with GH induced similar changes in both groups. After 1 year of GH replacement, there was an increase in serum IGF-I and fat-free mass, a reduction in fat mass and an improvement in QoL, all changes being equivalent in irradiated and non-irradiated patients. The lipid profile also improved with the irradiated patients showing a better response. These beneficial effects were maintained and the BMC also increased in both groups by the second year of treatment. CONCLUSIONS: This analysis shows that prior irradiation for pituitary adenoma or craniopharyngioma does not compromise the beneficial effects of GH replacement therapy.

Adenoma↗
PubMed2005

Preventing bacterial contamination and proliferation during the harvest, storage, and feeding of fresh bovine colostrum.

The objectives of this study were to identify control points for bacterial contamination of bovine colostrum during the harvesting and feeding processes, and to describe the effects of refrigeration and use of potassium sorbate preservative on bacteria counts in stored fresh colostrum. For objective 1, first-milking colostrum samples were collected aseptically directly from the mammary glands of 39 cows, from the milking bucket, and from the esophageal feeder tube. For objective 2, 15-mL aliquots of colostrum were collected from the milking bucket and allocated to 1 of 4 treatment groups: 1) refrigeration, 2) ambient temperature, 3) refrigeration with potassium sorbate preservative, and 4) ambient temperature with potassium sorbate preservative. Subsamples from each treatment group were collected after 24, 48, and 96 h of storage. All samples underwent bacteriological culture for total plate count and coliform count. Bacteria counts were generally low or zero in colostrum collected directly from the gland [mean (SD) log10 cfu/mL(udder) = 1.44 (1.45)]. However, significant bacterial contamination occurred during the harvest process [mean (SD) log10 cfu/mL(bucket) = 4.99 (1.95)]. No additional bacterial contamination occurred between the bucket and the esophageal feeder tube. Storing colostrum at warm ambient temperatures resulted in the most rapid increase in bacteria counts, followed by intermediate rates of growth in nonpreserved refrigerated samples or preserved samples stored at ambient temperature. The most effective treatment studied was the use of potassium sorbate preservative in refrigerated samples, for which total plate count and total coliform counts dropped significantly and then remained constant during the 96-h storage period.

Animals↗
PubMed2004

Application of a quartz crystal microbalance to evaluate biodegradability of starch by Bacillus subtilis.

Biodegradation of solution-cast starch films by Bacillus subtilis was monitored using a quartz crystal microbalance (QCM). A starch film was formed on the crystal by solution casting and exposed to the Bacillus subtilis culture in a bioreactor. The high sensitivity of the QCM could monitor small weight changes of the starch films on the crystal in the initial stages of biodegradation by secreted exo-enzymes of the bacterium. The feasibility of this approach as a means of quantification and characterisation of biodegradability of different polymeric materials by selected organisms is discussed.

Bacillus subtilis↗
PubMed2001

Role of P glycoprotein in the course and treatment of Encephalitozoon microsporidiosis.

Encephalitozoon microsporidia are obligate intracellular protozoan parasites that proliferate and differentiate within a parasitophorous vacuole inside host cells that are usually epithelial in nature. Isolates of the three species of the Encephalitozoon microsporidia, E. cuniculi, E. hellem, and E. intestinalis, were obtained from AIDS patients and cultured in green monkey (E6) kidney cells. Anti-P-glycoprotein (anti-Pgp) and anti-multidrug resistance-associated protein (anti-MRP) monoclonal antibodies were used to probe for multidrug resistance (MDR) pump epitopes and verapamil- or cyclosporin A- and probenecid-modulated intracellular calcein fluorescence were used to assess the expression of Pgp and MRP respectively in uninfected and infected cells. Pgp, but not MRP, was detected immunocytochemically and by verapamil- and cyclosporin A-potentiated intracellular fluorescence in both host cells and parasite developing stages. When an in vitro infection assay was employed, verapamil and cyclosporin A acted as chemosensitizing agents for the antiparasitic drug albendazole. These observations suggest that inhibiting host cell and perhaps parasite MDR pumps may increase the efficacy of antiparasitic agents in these and other microsporidia species.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Lung carcinoid related Cushing's syndrome: report of three cases and review of the literature.

Three patients with lung carcinoid related Cushing's syndrome (LCRCS) treated at Frenchay Hospital, Bristol between 1984 and 1994 are described. The first patient presented with hyperpigmentation 13 years after bilateral adrenalectomy. The second patient had no recurrence or metastases 14 years after removal of a typical carcinoid tumour. The last patient survived nine years after diagnosis of liver metastasis. The possibility of LCRCS should be considered in every patient proved to have Cushing's disease and bilateral adrenal enlargement on abdominal computed tomography. Biochemical sets of investigation (for example, adrenocorticotrophic hormone (ACTH) stimulation, dexamethasone suppression, and metyrapone response) could be misleading and should not be relied upon solely. Search for an ectopic ACTH source should be called off only when ACTH has been demonstrated in the surgically removed specimen, and most importantly, when the serum ACTH concentration returns to normal after surgery. Lung carcinoid tumours are compatible with long survival, and liver metastasis could prove indolent and slowly growing.

ACTH Syndrome, Ectopic↗
PubMed2001

Cytoskeletal organization and cell motility correlates with metastatic potential and state of differentiation in prostate cancer.

The actin cytoskeleton is the key cellular machinery responsible for cellular movement. Changes in the organization and distribution of actin and actin binding protein are necessary for several cellular processes such as focal adhesion formation, cell motility and cell invasion. Here we examined differences in cytoskeletal protein distribution, cell morphometry and cell motility of metastatic and non-metastatic cells. Correlations were found between metastatic potential phenotypic properties such as cell motility, cell spreading and cytoskeletal organization in prostate cancer. As a cell progresses from a normal state to a malignant state, it loses its ability to function normally and also become poorly differentiated. Differentiation therapy is concerned with the redirection of malignant cells toward a terminal, non-dividing state using non-cytotoxic agents. Two well acknowledged differentiation agents, retinoic acid (RA) and diflouromethylomithine (DFMO) were examined for their ability to alter cellular phenotypes associated with metastatic potential in rat prostate cancer cell lines. The results of these studies indicate that there are sub-cellular differences between non-metastatic and highly metastatic cells relative to cytoskeletal organization. We also show that treatment of highly metastatic cells with either RA or DFMO significantly alters cell morphology, cell morphometry and motility to states similar to non-metastatic cells.

Actins↗
PubMed2000

Effect of filmless imaging on the utilization of radiologic services.

PURPOSE: To determine the effect of a large-scale picture archiving and communication system (PACS) on in- and outpatient utilization of radiologic services. MATERIALS AND METHODS: Data were collected at the Baltimore Veterans Affairs (VA) Medical Center (BVAMC) before and after implementation of an enterprise-wide PACS; the numbers and types of imaging examinations performed for fiscal years 1993 and 1996 were evaluated. These data were compared with those from a similar academic medical center, the Philadelphia VA Medical Center (PVAMC), and with aggregate data obtained nationally for all VA hospitals over comparable periods. RESULTS: Inpatient utilization, defined as the number of examinations per inpatient day, increased by 82% (from 0.265 to 0.483 examinations per patient day) after a transition to filmless operation at BVAMC. This is substantially greater than the increases of 38% (from 0.263 to 0.362 examinations per patient day) and 11% (from 0.190 to 0.211 examinations per patient day) at the film-based PVAMC and nationally, respectively. Outpatient utilization, defined as the number of examinations per visit, increased by 21% (from 0.108 to 0.131 examinations per visit) at BVAMC, compared with a 1% increase (from 0.087 to 0.088 examinations per visit) at PVAMC and a net decrease of 19% (from 0. 148 to 0.120 examinations per visit) nationally. CONCLUSION: The transition to filmless operation was associated with increases in inpatient and outpatient utilization of radiologic services, which substantially exceeded changes at PVAMC and nationally over the same interval.

Academic Medical Centers↗
PubMed2000

VCAM-1-induced inwardly rectifying K(+) current enhances Ca(2+) entry in human THP-1 monocytes.

Hyperpolarization in human leukemia THP-1 monocytes adherent to vascular cell adhesion molecule (VCAM)-1 is due to an induction of inwardly rectifying K(+) currents (I(ir)) (Colden-Stanfield M and Gallin EK, Am J Physiol Cell Physiol 275: C267-C277, 1998). We determined whether the VCAM-1-induced hyperpolarization is sufficient to augment the increase in intracellular free calcium ([Ca(2+)](i)) produced by Ca(2+) store depletion with thapsigargin (TG) and readdition of external CaCl(2) in fura 2-loaded THP-1 monocytes. Whereas there was a 2.1-fold increase in [Ca(2+)](i) in monocytes bound to glass for 5 h in response to TG and CaCl(2) addition, adherence to VCAM-1 produced a 5-fold increase in [Ca(2+)](i). Depolarization of monocytes adherent to VCAM-1 by I(ir) blockade or exposure to high [K(+)] abolished the enhancement of the peak [Ca(2+)](i) response. In monocytes bound to glass, hyperpolarization of the membrane potential with valinomycin, a K(+) ionophore, to the level of hyperpolarization seen in cells adherent to VCAM-1 produced similar changes in peak [Ca(2+)](i). Adherence of monocytes to E-selectin produced a similar peak [Ca(2+)](i) to cells bound to glass. Thus monocyte adherence to the physiological substrate VCAM-1 produces a hyperpolarization that is sufficient to enhance Ca(2+) entry and may impact Ca(2+)-dependent monocyte function.

Calcium↗
PubMed2000

A primary culture of guinea pig gallbladder epithelial cells that is responsive to secretagogues.

We have developed a cell culture of guinea pig gallbladder epithelial cells with which to study ion transport. When grown on permeable supports, the cultured epithelia developed a transepithelial resistance (R(t)) of approximately 500 Omega. cm(2). The epithelial cell origin of the cell culture was further confirmed by immunocytochemical localization of cytokeratin. Ionomycin and forskolin increased transepithelial voltage and short-circuit current (I(sc)) and decreased R(t). The response to ionomycin was transient, whereas that to forskolin was sustained. Both were attenuated by replacement of Cl(-) and/or HCO(3)(-). Mucosal addition of the anion transport inhibitors DIDS or diphenylamine-2-carboxylic acid (DPC) blocked the response to ionomycin. The response to forskolin was blocked by DPC but not by DIDS. Ionomycin, but not forskolin, increased intracellular Ca(2+) concentration in fura 2-loaded cells. PGE(2), histamine, vasoactive intestinal polypeptide, and secretin elicited a sustained increase in I(sc). Responses to ATP and CCK were transient. Thus cultured guinea pig gallbladder epithelia display the range of responses observed in the native tissue and are an appropriate model for studies of ion transport in gallbladder and intestinal epithelia.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Dural arteriovenous fistulas of the craniocervical junction.

Dural arteriovenous fistulas (DAVF) involving the craniocervical junction are uncommon lesions that may result in neurological deficits referable to posterior fossa structures and/or the spinal cord. We report on two patients with craniocervical junction DAVF whose venous drainage involved the cervical spinal cord. Both cases presented with progressive quadriparesis and parenchymal magnetic resonance signal abnormality of the cervical spinal cord. Both patients improved following embolization of the fistulas. AVF of the craniocervical junction are an uncommon, but important cause of treatable neurological deficits referable to this region of the nervous system.

Journal Article↗
PubMed1999

A marine snail neurotoxin shares with scorpion toxins a convergent mechanism of blockade on the pore of voltage-gated K channels.

kappa-Conotoxin-PVIIA (kappa-PVIIA) belongs to a family of peptides derived from a hunting marine snail that targets to a wide variety of ion channels and receptors. kappa-PVIIA is a small, structurally constrained, 27-residue peptide that inhibits voltage-gated K channels. Three disulfide bonds shape a characteristic four-loop folding. The spatial localization of positively charged residues in kappa-PVIIA exhibits strong structural mimicry to that of charybdotoxin, a scorpion toxin that occludes the pore of K channels. We studied the mechanism by which this peptide inhibits Shaker K channels expressed in Xenopus oocytes with the N-type inactivation removed. Chronically applied to whole oocytes or outside-out patches, kappa-PVIIA inhibition appears as a voltage-dependent relaxation in response to the depolarizing pulse used to activate the channels. At any applied voltage, the relaxation rate depended linearly on the toxin concentration, indicating a bimolecular stoichiometry. Time constants and voltage dependence of the current relaxation produced by chronic applications agreed with that of rapid applications to open channels. Effective valence of the voltage dependence, zdelta, is approximately 0.55 and resides primarily in the rate of dissociation from the channel, while the association rate is voltage independent with a magnitude of 10(7)-10(8) M-1 s-1, consistent with diffusion-limited binding. Compatible with a purely competitive interaction for a site in the external vestibule, tetraethylammonium, a well-known K-pore blocker, reduced kappa-PVIIA's association rate only. Removal of internal K+ reduced, but did not eliminate, the effective valence of the toxin dissociation rate to a value <0.3. This trans-pore effect suggests that: (a) as in the alpha-KTx, a positively charged side chain, possibly a Lys, interacts electrostatically with ions residing inside the Shaker pore, and (b) a part of the toxin occupies an externally accessible K+ binding site, decreasing the degree of pore occupancy by permeant ions. We conclude that, although evolutionarily distant to scorpion toxins, kappa-PVIIA shares with them a remarkably similar mechanism of inhibition of K channels.

Animals↗
PubMed1999

Impact of filmless radiology on frequency of clinician consultations with radiologists.

OBJECTIVE: The purpose of the study was to determine the impact of filmless operation on the relative frequency of in-person consultations in the radiology department between radiologists and clinicians. CONCLUSION: The transition to filmless operation at the Baltimore Veterans Affairs Medical Center was associated with an 82% reduction in the in-person consultation rate for general radiography and a 44% reduction for cross-sectional imaging despite an increase in the volume of studies. The major reason for this decrease was the convenient access to current and prior images provided by the PACS (picture archiving and communication system). Radiology departments contemplating a transition to filmless operation should prepare for communication with clinicians to shift from being mostly in person to being conducted more and more through electronic forms of communication.

Baltimore↗
PubMed1997

Role of intracellular calcium in the angiotensin II-mediated tyrosine phosphorylation and dephosphorylation of PLC-gamma 1.

Angiotensin II induces the rapid temporal tyrosine phosphorylation and activation of phospholipase C-gamma 1 (PLC-gamma 1) and the elevation of intracellular calcium levels. To investigate the relationship of these intracellular signaling events, rat aortic smooth muscle cells were treated with the calcium chelator BAPTA-AM, the calcium channel blocker verapamil, the intracellular calcium antagonist TMB-8, and the calcium ionophore ionomycin. The effects of these agents on PLC-gamma 1 tyrosine phosphorylation were then measured. We found that treatment of these cells with the calcium inhibitors augmented the basal level of PLC-gamma 1 tyrosine phosphorylation, without changing the peak level of tyrosine phosphorylation induced by angiotensin II. The rapid dephosphorylation of PLC-gamma 1 that follows angiotensin II stimulation was prevented by these calcium antagonists. In contrast, angiotensin II-induced tyrosine phosphorylation of PLC-gamma 1 was inhibited by ionomycin. These results suggest that the angiotensin II-induced tyrosine phosphorylation of PLC-gamma 1 is calcium-independent, while the dephosphorylation is calcium-dependent.

Angiotensin II↗
PubMed1997

Use of a fluorescent probe to assess the activities of candidate agents against intracellular forms of Encephalitozoon microsporidia.

Microsporidia are obligate intracellular protozoan parasites. Three species of the genus Encephalitozoon are among the microsporidia that infect immunodeficient humans. These species, Encephalitozoon cuniculi, Encephalitozoon hellem, and Encephalitozoon intestinalis, all develop in a parasitophorous vacuole within a host cell. The present study describes a method that uses the fluorescent probe calcein and confocal microscopy to detect drug-induced effects in Encephalitozoon-infected green monkey kidney cells. The effects were as follows: (i) changes in parasite organization within the parasitophorous vacuole; (ii) swelling and gross morphological changes of parasite developing stages in situ; (iii) killing of developing parasite stages in situ, detected by their uptake of the fluorescent probe; and (iv) reduction in the viability of the host cell population, assessed by the loss of the probe. Verapamil and itraconazole were used to increase the vital dye loading by both uninfected and infected cells. Agents with known antimicrosporidial activity, albendazole and fumagillin, caused all three types of parasite changes at concentrations that had no detectable effect on host cell viability. The effective doses of albendazole and fumagillin that caused swelling and disorganization of parasite developing stages were 5 x 10(-7) and 10(-6) M respectively. Killing of developing stages was detected at 10-fold-higher concentrations for these agents and at 10(-5) M for metronidazole. This method can be used to screen candidate antimicrosporidial agents in infected cultured cells.

Albendazole↗
PubMed1994

The glutamate inhibition of carbachol stimulated inositol phosphate production in rat cortical cells is mediated through an ionotropic NMDA receptor.

Carbachol (0.1 mM) stimulated accumulation of inositol monophosphate (IP1) (3-4 fold of basal, P < 0.001) in fetal rat cortical cells is attenuated by glutamate (at 0.1 mM, 40-70% of carbachol alone, P < 0.001). This inhibition by glutamate was reduced by 2-amino-5-phosphonopentanoic acid (AP5), but not by gamma-D-glutamylaminomethyl sulphonic acid (GAMS) [corrected] or 2-amino-3-phosphonopropionic acid (AP3). The metabotropic receptor agonist (1S,3R)-1-aminocyclopentane-1-3-dicarboxylic acid [(1S,3R)-ACPD] (up to 0.1 mM) had no effect upon carbachol stimulated IP1. Staurosporine and quinacrine were unable to prevent the inhibition of carbachol stimulated IP1 by glutamate. These data suggest that the inhibition of carbachol-stimulated IP1, by glutamate in rat cortical cells is mediated through an NMDA ionotropic receptor.

Animals↗