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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 73 records · Page 4Linked to original sources

Tumor versus vascular photodamage in a rat tumor model.

The [4-(5-nitro-2-furyl)-2-thiazoyl] formamide (FANFT)-induced urothelial tumor in the rat is found to express the mdr gene. The resulting multidrug resistance (MDR) phenotype results in the expression of an outward transport system that prevents cellular accumulation of certain weakly cationic agents. Among the latter is a photosensitizer with known efficacy for the FANFT tumor, the copper benzochlorin iminium salt. FANFT cells are protected from direct cell kill mediated by this drug, suggesting that the substantial delay in tumor regrowth from this tumor/sensitizer combination can be attributed to vascular effects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Selective stimulation of the D1 ATPase domain of N-ethylmaleimide-sensitive fusion protein (NSF) by soluble NSF attachment proteins.

N-Ethylmaleimide-sensitive fusion protein (NSF) is required for most intracellular membrane fusion events. NSF is recruited to membranes by soluble NSF attachment proteins (SNAPs) and membrane-resident SNAP receptor (SNARE) proteins. The 20 S complex of NSF/SNAPs/SNAREs disassembles when NSF hydrolyses ATP, and this disassembly event is believed to be essential for membrane fusion. SNAPs stimulate NSF ATPase activity, but it is not known which of NSF's two ATPase domains (D1 or D2) is affected. Using recombinant mutant NSFs defective in ATP hydrolysis in one domain only, we found that SNAPs stimulate NSF ATPase activity by a selective action on the D1 domain, yet had no effect on the D2 domain. Since the D1 domain of NSF is implicated in 20 S complex disassembly, this supports the idea that SNAP stimulation of NSF ATPase activity is required for membrane fusion.

Adenosine Triphosphatases↗

Analysis of regulated exocytosis in adrenal chromaffin cells: insights into NSF/SNAP/SNARE function.

Many of the proteins that function in regulated exocytosis have now been identified. Several proteins form part of a conserved core machinery that acts in many intracellular vesicular fusion steps and their essential roles confirmed by molecular genetic analysis. In addition, studies with adrenal chromaffin and PC12 cells have demonstrated the function of various proteins in regulated exocytosis and have permitted dissection of the stages of exocytosis in which they act. N-Ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment proteins (SNAPs) are key proteins in exocytosis. Examination of their function has indicated that they have a predocking role most likely as molecular chaperones to prepare the docking/fusion machinery. The exact site and time of action in exocytosis of many of the other identified proteins are unknown. A major emphasis for the future will be analysis of the molecular physiology of regulated exocytosis to permit the assignment of functions to identified proteins in particular stages of the regulated exocytotic pathway.

Adrenal Medulla↗

Acute visual change.

Changes in vision or loss of vision are common complaints for patients presenting to the emergency department. Such complaints may represent a simple problem related to recent trauma, early evidence of a systemic disease, or may be a vision-threatening lesion. A logical and organized approach to the history and the physical examination of the patient with eye complaints is key to the diagnosis and treatment of the more significant causes of these complaints. This article reviews an organized approach to the patient with complaint of visual loss and considers the wide differential diagnosis. It focuses specifically on the evaluation of the patient complaining of visual changes resulting from central retinal artery occlusion, central retinal vein occlusion, retinal detachment, acute angle-closure glaucoma, giant cell temporal arteritis, and retrobulbar hemorrhage.

Acute Disease↗

The promoter of the plant defensin gene PDF1.2 from Arabidopsis is systemically activated by fungal pathogens and responds to methyl jasmonate but not to salicylic acid.

The plant defensin PDF1.2 has previously been shown to accumulate systemically via a salicylic acid-independent pathway in leaves of Arabidopsis upon challenge by fungal pathogens. To further investigate the signalling and transcriptional processes underlying plant defensin induction, a DNA fragment containing 1184 bp and 1232 bp upstream of the transcriptional and translational start sites, respectively, was cloned by inverse PCR. To test for promoter activity this DNA fragment was linked to the beta-glucuronidase (GUS)-encoding region of the UidA gene as a translational fusion and introduced into Arabidopsis ecotype C-24. Challenge of the transgenic plants with the fungal pathogens Alternaria brassicicola and Botrytis cinerea resulted in both local and systemic induction of the reporter gene. Wounding of the transgenic plants had no effect on GUS activity. Treatment of the transgenic plants with either jasmonates or the active oxygen generating compound paraquat strongly induced the reporter gene. In contrast, neither salicylate nor its functional analogues 2,6-dichloroisonicotinic acid and 1,2,3-benzothiodiazole-7-carbothioic acid S-methyl ester resulted in reporter gene induction. These results are consistent with the existence of a salicylic acid-independent signalling pathway, possibly involving jasmonates as regulators, that is triggered by pathogen challenge but not by wounding. The transgenic plants containing the PDF1.2-based promoter-reporter construct will provide useful tools for future genetic dissection of this novel systemic signalling pathway.

Acetates↗

Psychosocial factors associated with depression: a study of socially disadvantaged women with young children.

This study aims to use valid measures to a) estimate the prevalence of depressive disorder and b) identify psychosocial factors associated with depression in a sample of socially disadvantaged women with children. One hundred ninety-three women, recruited through a doorknock of public housing estates completed an interview that included the Diagnostic Interview Schedule to identify cases of depression and the Mannheim Interview for Social Support. The women also completed self-report questionnaires assessing psychological morbidity, life events, perceptions of intimate relationships, and personality factors. The 6-month prevalence of major depression was 17% and the lifetime prevalence 29%. Major depression was associated with perceptions of low parental care during childhood and low care from current partner, vulnerable personality style, increased reporting of life events, and an unsatisfactory social support network.

Adolescent↗

Clinical decision support, systems methodology, and telemedicine: their role in the management of chronic disease.

In this paper, the design and evaluation of decision support systems, including those incorporating a telematic component, are considered. It is argued that effective design and evaluation are dependent upon the adoption of appropriate methodology set firmly within a systemic framework. Systems modeling is proposed as an approach to system design, with evaluation adopting an approach incorporating evaluability analysis and formative and summative evaluation, including the use of stakeholder matrix analysis. The relevance of such systemic methodology is demonstrated in the context of diabetes and end-stage renal disease as examples of the generic clinical problem of the management of chronic disease.

Chronic Disease↗

Holism in nursing.

This article explores the concept of holism in nursing in terms of what it is and what it has to offer.

Health Knowledge, Attitudes, Practice↗

Stimulation of NSF ATPase activity by alpha-SNAP is required for SNARE complex disassembly and exocytosis.

N-ethylmaleimide-sensitive fusion protein (NSF) and alpha-SNAP play key roles in vesicular traffic through the secretory pathway. In this study, NH2- and COOH-terminal truncation mutants of alpha-SNAP were assayed for ability to bind NSF and stimulate its ATPase activity. Deletion of up to 160 NH2-terminal amino acids had little effect on the ability of alpha-SNAP to stimulate the ATPase activity of NSF. However, deletion of as few as 10 COOH-terminal amino acids resulted in a marked decrease. Both NH2-terminal (1-160) and COOH-terminal (160-295) fragments of alpha-SNAP were able to bind to NSF, suggesting that alpha-SNAP contains distinct NH2- and COOH-terminal binding sites for NSF. Sequence alignment of known SNAPs revealed only leucine 294 to be conserved in the final 10 amino acids of alpha-SNAP. Mutation of leucine 294 to alanine (alpha-SNAP(L294A)) resulted in a decrease in the ability to stimulate NSF ATPase activity but had no effect on the ability of this mutant to bind NSF. alpha-SNAP (1-285) and alpha-SNAP (L294A) were unable to stimulate Ca2+-dependent exocytosis in permeabilized chromaffin cells. In addition, alpha-SNAP (1-285), and alpha-SNAP (L294A) were able to inhibit the stimulation of exocytosis by exogenous alpha-SNAP. alpha-SNAP, alpha-SNAP (1-285), and alpha-SNAP (L294A) were all able to become incorporated into a 20S complex and recruit NSF. In the presence of MgATP, alpha-SNAP (1-285) and alpha-SNAP (L294A) were unable to fully disassemble the 20S complex and did not allow vesicle-associated membrane protein dissociation to any greater level than seen in control incubations. These findings imply that alpha-SNAP stimulation of NSF ATPase activity may be required for 20S complex disassembly and for the alpha-SNAP stimulation of exocytosis.

Adenosine Triphosphatases↗

Histologic correlation of image-guided core biopsy with excisional biopsy of nonpalpable breast lesions.

OBJECTIVE: To examine the histologic correlation between image-guided large-core needle biopsy (LCNB) and excisional biopsy of nonpalpable breast lesions. DESIGN: Histologic findings of LCNB and excision specimens were reviewed for patients who underwent image-guided LCNB of nonpalpable breast lesions from April 1, 1993, to March 31, 1996. Histologic diagnosis of the excision specimen was used as a criterion standard. Follow-up ranged from 1 to 4 years. SETTINGS: A dedicated breast imaging clinic on the campus of an urban community hospital. PATIENTS: Five hundred fifty-two patients with nonpalpable mammographically detected abnormalities. MAIN OUTCOME MEASURES: Histologic diagnoses of LCNB and excision specimens (part of a prospectively designed, ongoing quality audit process). RESULTS: Histologic findings were benign in 389 LCNB specimens (70.5%) and abnormal in 163 (29.5%). The benign LCNB specimens remained benign on clinical and radiologic follow-up, with 1 missed malignant diagnosis. One hundred seventy-three patients underwent excision following LCNB, resulting in 10 benign and 163 abnormal specimens. Diagnoses of 102 LCNB specimens showing invasive cancer were confirmed on excision. Of 54 patients in whom LCNB specimens showed ductal carcinoma in situ (DCIS), 10 showed DCIS plus invasive cancer on excision. Of 6 patients in whom LCNB specimens showed atypical duct hyperplasia (ADH), 1 was benign, 1 showed ADH and invasive cancer, 3 showed ADH and DCIS, and 1 remained ADH exclusively on excision. The histologic diagnosis for 10 benign LCNBs remained benign after excision. Correlation coefficient was 0.93 (P < .001). CONCLUSIONS: Benign disease and invasive cancer of the breast can be diagnosed with a high level of confidence using image-guided LCNB. The histologic diagnosis for patients whose LCNB specimens show ADH or DCIS may change after excision.

Biopsy↗

Common mechanisms for regulated exocytosis in the chromaffin cell and the synapse.

Chromaffin granule exocytosis differs in many physiological respects from neuronal synaptic vesicle exocytosis, which has led to the assumption that the two processes occur by distinct mechanisms. While different mechanisms are certainly in operation for the biogenesis of granules and synaptic vesicles, it is now becoming clear that similar mechanisms are used by both beyond this stage. The similarities extend to various aspects of regulated exocytosis, including regulation of the number of vesicles released in response to cell stimulation. Most strikingly, it now appears that the same proteins mediate the docking and fusion of both chromaffin granules and synaptic vesicles, and that homologues of these proteins act similarly in constitutive membrane traffic throughout evolution.

Journal Article↗

A comparison of Medicare reimbursement and results for various imaging-guided breast biopsy techniques.

BACKGROUND: The Medicare population makes up a large proportion of the patients who undergo evaluation and treatment of mammographically detected breast lesions. In the past, the standard approach for obtaining a histological specimen for definitive diagnosis has been wire localization followed by open surgical excision (WL-OSE). In recent years, however, imaging-guided large core needle biopsy (LCNB) has been investigated as a more cost effective and less invasive alternative. METHODS: The authors examined accuracy and reimbursement of ultrasound-guided LCNB, stereotactic-guided LCNB, and WL-OSE in 139 Medicare patients who demonstrated abnormalities on screening mammograms in 1994 and 1995. RESULTS: Ultrasound-guided LCNB was used to diagnose 20% of these cases, sterotactic LCNB was used to diagnose 68% of the cases, and the remaining 12% were diagnosed using WL-OSE. Histological diagnoses for 54 LCNBs (20 ultrasound-guided and 34 stereotactic-guided) were 98% accurate when compared with a subsequent surgical excision specimen. Ultrasound-guided LCNB was the most cost-effective approach, showing an average savings of $1,960 per procedure over WL-OSE and $211 over stereotactic-guided LCNB. Stereotactic-guided LCNB was significantly more cost effective than WL-OSE, showing an average savings of $1,750 per procedure. CONCLUSIONS: These data indicate imaging-guided LCNB to be a reasonable alternative to WL-OSE for definitive histological diagnosis of nonpalpable breast lesions. Ultrasound-guided imaging was shown to be applicable in 20% of the cases and is the least expensive to the Medicare system. The stereotactic approach can be used for a much larger percentage of these patients and although not as cost effective as ultrasound, it is considerably more cost effective than open excisional biopsy. Both core biopsy techniques provided accurate histological diagnoses.

Adult↗

Acid leaching studies of chrysotile asbestos from mines in the Coalinga region of California and from Quebec and British Columbia.

The dissolution of magnesium (Mg) and silicon (Si) from various samples of chrysotile asbestos was measured in N HCl at 25 degrees C. Nine samples were used, five from Canada and four from the Coalinga deposit in California. With milled samples from Quebec, the fraction of Mg dissolving was linearly related to the square root of the leaching time until at least 65% had dissolved. With a hand-picked sample of ore from Quebec, the sample from British Columbia and all the Californian samples, the Mg leaching patterns were sigmoid. The leaching patterns for Si were sigmoid in shape for all the materials tested. Mean Mg dissolution rates were calculated for each leaching period. Considerable differences were observed between samples from the different mining regions and also between hand-picked and milled samples from the same mine. Initially, Mg dissolved more rapidly from milled Quebec chrysotiles than from the Coalinga samples. This difference is due in part to the rapid dissolution of non-structural brucite, present in all the samples from Quebec but not in those from California. An additional cause is greater damage to the fibre surfaces resulting from the milling to which the less readily-opened fibres, typical of the Quebec mining area, were subjected. Once this readily-available Mg had dissolved, there was little difference in leaching rates between milled and unmilled samples from the different regions. When the fraction of Mg dissolving is plotted against that of Si, all the materials follow a similar pattern, suggesting that the dissolution of Si (as silica) is the rate-controlling step in the dissolution of Mg.

Asbestos, Amphibole↗

Acid leaching studies of neutron-irradiated chyrsotile asbestos.

Samples of chrysotile from Quebec (UICC B and Jeffrey 4T-30) and from the Coalinga region of California (Calidria RG-144) were irradiated with thermal neutrons in a reactor. The main activation products induced were 46Sc, 51Cr, 59Fe and 60Co. Accurately weighed samples of the irradiated materials were dispersed in N HCl by hand shaking for 10 s. After leaching for predetermined periods at 25 degrees C, the samples were filtered and the concentrations of Mg determined in the filtrates by inductively-coupled plasma atomic emission spectrometry (IPC-AES) and the activities of the four radionuclides by high resolution gamma-ray spectrometry. Similar measurements were made on solutions obtained by refluxing samples of irradiated chrysotile with 2N HCl for 2 h. The specific activities of each of the four activation products were calculated in arbitrary units and, as the concentrations of Sc, Cr, Fe and Co in the UICC B sample had already been determined, it was possible to estimate the concentrations of these elements in the other two samples. Similarities in the leaching patterns of magnesium and of the activation products showed that with all samples, high proportions of the parent trace elements were present in the form of isomorphous substitutes for magnesium in structural brucite. Agreement was closest with the Calidria chrysotile in which all the radionuclides had a similar pattern. With the Jeffrey and UICC B samples, the presence of a high proportion of the iron as relatively insoluble magnetite accounted for the observed discrepancy in behaviour between 59Fe and Mg. More detailed calculation of leaching rates over specific time intervals showed that, initially, 51Cr and 60Co dissolved more rapidly than Mg but that this was followed by a period in which the opposite was the case. It was concluded that the Calidria RG-144 sample is an ideal candidate for studies of magnesium dissolution in vivo.

Asbestos, Amphibole↗