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Biomedical subjects

M Nelson

Publications and source records attributed to M Nelson.

At least 163 records · Page 9Linked to original sources
PubMed1999

Endothelin-stimulated ERK activation in airway smooth-muscle cells requires calcium influx and Raf activation.

Endothelin (ET)-1 is a 21-amino-acid peptide that is a potent vasoconstrictor and mitogen. By binding to its G-protein coupled receptor, ET-1 stimulates the proliferation of airway smooth-muscle (ASM) cells, which may be involved in the pathogenesis of asthma. The ETB receptor stimulates activation of the extracellular regulated kinase 2 (ERK2), which is thought to be required for proliferation of ASM cells. Our findings reveal that ET rapidly activates Raf, and that dominant-negative Raf interferes with ET-induced ERK activation in ASM cells. Expression of the amino-terminal Ras-binding domain of Raf inhibited ET-induced ERK activation, suggesting that ET-stimulated Raf activation is a Ras-dependent process. Furthermore, ET-stimulated ERK and Raf activation in ASM cells require calcium influx; chelating extracellular calcium or preventing calcium influx through calcium channels inhibited ET-stimulated, but not phorbol ester-stimulated, ERK and Raf activation.

Animals↗
PubMed1999

What? Me speak in public: what if somebody sees me?

The purpose of this paper is to highlight the specific critical areas of public speaking. It deals with the important and often forgotten areas of the presentation: the objective statement and lesson plan, key platform skills, and the motivational environment.

Communication↗
PubMed1999

Modeling empiric antibiotic therapy evaluation of QID.

At AMIA 1997, we reported on the design and development of a new computer-based tool, called QID, for empiric antibiotic decision support. QID was designed to help physicians identify the antibiotic regimens with the highest probability of covering the pathogens that are most likely to be present in individual patients. QID creates a list of antibiotics, ordered by potential benefit in treatment, for a patient with a suspected infection before culture results are available. Since our initial publication, a "before and after" study has been done using 20 internal medicine residents and the same number of internal medicine attendings. In order to test the hypothesis that physician's would make more appropriate empiric antibiotic choices with the aid of QID, we chose University of Utah physicians and had each evaluate four infectious disease cases that were abstracted from medical record infectious disease cases. Immediately following their initial review and determination of antibiotic therapy for each case, the study participants were presented with QID's antibiotic recommendations on the same case to see if this information would change their initial drug regimen. The tool was shown to have a greater impact on the most difficult cases but statistically improved scores overall (p < .001). Details of our study design and results are presented.

Anti-Bacterial Agents↗
PubMed1998

Identification and chromosomal localization of CTNNAL1, a novel protein homologous to alpha-catenin.

Sodium butyrate (NaB) was shown to induce growth inhibition and apoptosis in a human pancreatic cancer cell line (AsPC-1). To identify the genes that are differentially regulated by NaB, we generated subtracted EST libraries highly enriched for up- or down-regulated transcripts using the suppression subtraction hybridization technique. One of the ESTs identified in the down-regulated library showed significant homology to human alpha-catenin. A cDNA of 2.45 kb that codes for a putative protein of 734 aa was cloned. The cloned cDNA was used as a template in an in vitro transcription-translation reaction. This produced a protein product of about 82 kDa in size. The gene designated as CTNNAL1 (catenin (cadherin-associated protein), alpha-like 1) was found to be ubiquitously expressed in many tissues including pancreas, heart, and skeletal muscle. A human BAC clone containing the gene was isolated and used as a probe for fluorescence in situ hybridization (FISH). Both radiation hybrid and FISH analysis mapped the gene to chromosome band 9q31.2, a region where frequent abnormalities have been observed in bladder carcinoma, esophageal cancers, and several other tumors.

Amino Acid Sequence↗
PubMed1998

Differential loss of heterozygosity at 7q31.2 in follicular and papillary thyroid tumors.

We analysed 42 differentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary thyroid cancers (PTC) and 14 follicular thyroid carcinomas (FTC) with 13 microsatellite markers specific for the long arm of human chromosome 7 within 7q31; this region is deleted frequently in several other tumor types. Overall, 20 of the 42 samples analysed (48%) displayed LOH with one or more of the markers tested. LOH was detected most frequently (78%) in FTC, the most malignant of the thyroid tumors. A smallest common deleted region (SCDR) was defined in this tumor type flanked by markers D7S480 and D7S490. This SCDR is distinct from D7S522, the most commonly deleted locus in many other tumors, which was deleted in only one FTC. D7S522 did show LOH in two of six informative PTCs. None of the PTC and only two of the FAs showed LOH in the FTC SCDR. Since FA is considered a premalignant stage of FTC, our results suggest that inactivation of a putative tumor suppressor at 7q31.2 may be acquired during adenoma to carcinoma progression. The absence of LOH at this locus amongst PTC suggests that inactivation of this tumor suppressor is specific for FTC. In conclusion, LOH at 7q31 is a frequent event in differentiated thyroid cancer, and we have defined a 2 cM SCDR specific for FTC.

Adenoma↗
PubMed1998

Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas.

BACKGROUND: Osteochondroma most frequently arises sporadically and as a solitary lesion, but also may arise as multiple lesions characterizing the autosomal dominant disorder hereditary multiple exostoses (HME) and the contiguous gene syndromes Langer-Giedion and DEFECT-11 syndromes. HME is genetically heterogeneous with association of three loci including 8q24.1 (EXT1), 11p11-12 (EXT2), and 19p (EXT3). Constitutional chromosomal microdeletions of 8q24.1 and 11p11-12 are features of the Langer-Giedion and DEFECT-11 syndromes, respectively. Cytogenetic studies of osteochondroma are rare. METHODS: Cytogenetic analysis was performed on 34 osteochondroma specimens from 22 patients with sporadic lesions and 4 patients with HME utilizing standard methodologies. Fluorescence in situ hybridization with chromosome specific probes was performed on three cases to define structural rearrangements further. RESULTS: Clonal abnormalities were detected in ten cases. Notably, deletion of 11p11-13 was observed in one case (a sporadic tumor) and loss or rearrangement of 8q22-24.1 in eight cases (seven sporadic and one hereditary tumor). CONCLUSIONS: These findings: 1) confirm previous observations of 8q24.1 karyotypic anomalies in sporadic osteochondroma, 2) reveal the presence of somatic chromosomal anomalies in hereditary osteochondromata, 3) suggest that similar to hereditary lesions, sporadic osteochondromas also are genetically heterogeneic (involvement of both 8q24.1 and 11p11-12), and 4) support the hypothesis that loss or mutation of EXT1 and EXT2, two putative tumor suppressor genes, may be important in the pathogenesis of sporadic as well as hereditary osteochondromata.

Adolescent↗
PubMed1998

A comparison of manual versus computer-assisted radiographic measurement. Intraobserver measurement variability for Cobb angles.

STUDY DESIGN: A comparison between computer-assisted measurement using digitized radiographs, which has the potential to reduce error, and manual measurement using standard radiographs. OBJECTIVE: To assess measurement variability for the Cobb method on digital radiographs and compare it with that of manual measurements on standard radiographs. BACKGROUND DATA: Studies of the Cobb method have demonstrated multiple sources of error leading to significant intraobserver measurement variability. Estimates for the 95% confidence interval for intraobserver variability range from 2.8 degrees to 10 degrees. METHODS: Twenty-four scoliosis radiographs were measured by six examiners. Two measurement sets were done manually ("manual set"), and two measurement sets were done on digitized images using a computer mouse ("computer set"). RESULTS: For the manual set, the 95% confidence interval for intraobserver variability was 3.3 degrees (range, 2.5-4.5 degrees). For the computer set, the value was 2.6 degrees (range, 2.3-3.3 degrees). This difference in 95% confidence intervals between the manual and computer sets was statistically significant (P < 0.001). CONCLUSIONS: The results of this study demonstrate that intraobserver variability for manual and computer Cobb angle measurements yield a 95% confidence interval of approximately 3 degrees, with the computer having a slightly lower variability. The computer technique removes sources of intrinsic error, e.g., the variability introduced by using different manual protractors, the inaccuracy of standard protractors, and the use of wide-diameter radiographic markers. Identical digital images can be shared electronically between centers, without having to duplicate and mail films. Multicenter studies in which different examiners will be measuring Cobb angles may consider using the computer as a measuring device to reduce intrinsic measurement errors.

Arthrography↗
PubMed1998

Chlorella virus NY-2A encodes at least 12 DNA endonuclease/methyltransferase genes.

The 380-kb chlorella virus NY-2A genome is highly methylated; 45% of the cytosines are 5-methylcytosine (5mC) and 37% of the adenines are N6-methyladenine (6mA). Based on the sensitivity/resistance of NY-2A DNA to 80 methylation-sensitive DNA restriction endonucleases, the virus is predicted to encode at least 10 DNA methyltransferases: 7 6mA-specific methyltransferases, M.CviQI (GTmAC), M.CvQII (RmAR), M.CviQIII (TCGmA), M.CviQIV (GmATC), M.CviQV (TGCmA), M.CviQVI (GmANTC), and M.CviQVII (CmATG): and 3 5mC-specific methyltransferases, M.CviQVIII [RGmC(T/C/G)], M.CviQIX (mCC), and M.CviQX (mCGR). Five of the 6mA methyltransferase genes, M.CviQI, M.CviQIII, M.CviQV, M.CviQVI, and M.CviQVII, were cloned and sequenced. In addition, 2 site-specific endonuclease activities, R.CviQI (G/TAC) and NY2A-nickase (R/AG), were detected in cell-free extracts from NY-2A virus-infected chlorella. Therefore, the NY-2A genome contains at least 12 DNA methyltransferase and endonuclease genes which, altogether, compose about 3-4% of the virus genome.

Amino Acid Sequence↗
PubMed1998

Critical care provided in an urban emergency department.

The emergency department (ED) provides a substantial amount of critical care. The purpose of this study was to quantitate the critical care provided in an urban ED. The study was performed at a large urban hospital with an annual ED volume of 70,000 patients. All patients requiring critical care in the ED or hospital were prospectively observed between September 1 and November 30, 1993. Patients requiring recovery room care or neonatal intensive care were excluded. Data collected included age, disposition, length of stay, triage acuity assignment in the ED, primary diagnosis, and critical care procedures. During the study, 11,989 patients were examined in the ED with 500 (5%) requiring admission, 340 (3%) requiring a critical care intervention, and 96 (1%) being admitted to an intensive care unit (ICU). Ten percent of patients receiving critical care in the ED were admitted to the floor for lack of bed space. Triage assignment of emergent life-threatening or urgent potentially life-threatening condition predicted critical care need and waiting time to examination. The spectrum of critical care procedures performed in the ED and ICU were similar except for advanced life support intervention, which was more common in the ED (17 versus 3), and arterial line placement, which was more common in the ICU (14 versus 1). The spectrum of diagnoses reflected the age of patients with cardiovascular illnesses (33%), metabolic illnesses (18%), and trauma (16%) common in adults (age > or = 17) and infectious illnesses (46%) or metabolic illnesses (21%) more common in pediatric patients. Overall, 14% of adult critical care, 23% of pediatric critical care, and 15% of all critical care provided in the areas studied occurred in the ED. A significant proportion of critical care is provided in the ED, and triage acuity assignment reflects this need. A significant proportion of critically ill patients was admitted to the floor for lack of bed space, which highlights the financial constraints in urban hospitals such as the one studied.

Adult↗
PubMed1998

Serum creatinine and blood urea nitrogen over a six-year period in the very old. Creatinine and BUN in the very old.

In a population of 141 very elderly subjects, there was a small but significant decline in BUN and creatinine at 3 years, which persisted at 6 years although partially attenuated. A similar pattern of falling BUN and creatinine was seen in the 31 subjects who began the study with mild azotemia. There was no significant change in the subjects' mean Body Mass Index during the 6-year period of observation. The azotemic subjects had a rate of death or dropout from the study similar to that of the entire cohort. Mean systolic blood pressure fell by 5.4 mm Hg (p < 0.05) and diastolic blood pressure by 2.1 mm Hg (p = NS) by 6 years. Users of diuretics or NSAID had a mean BUN and creatinine comparable to those not taking these medications. We conclude that BUN and serum creatinine do not necessarily increase with time in the old old, even in those with mild azotemia, hence, several determinations of these parameters may be needed to ensure accuracy. While renal function in the elderly probably does not improve with time, it may stabilize due to improvement in blood pressure. Use of diuretics and NSAID by functioning elderly individuals is not necessarily associated with worsening azotemia.

Aged↗
PubMed1998

Comparison between nasolacrimal syringing/probing, macrodacryocystography and surgical findings in the management of epiphora.

AIMS: Macrodacryocystography (MDCG) has been shown to be highly sensitive in evaluating the lacrimal drainage system. We aimed to compare the results of syringing/ probing with MDCG, and with surgical findings where available. We also aimed to determine whether MDCG is advisable in addition to syringing/probing when investigating epiphora. METHODS: In a retrospective study, we looked at the records of 76 consecutive patients (86 eyes) presenting with epiphora over a period of 2 years (January 1993 to December 1994). All patients underwent syringing/probing and subsequent MDCG to determine the presence and level of nasolacrimal block. The results were then compared with surgical findings where available (46 eyes, 53%). RESULTS: Surgical findings were predicted by MDCG in 95.5% of cases but in only 54% by probing. Probing findings agreed with MDCG in only 51% of cases. The main areas of disagreement were the presence of canalicular blocks and the presence of more than one block at different levels. CONCLUSION: A combination of syringing/ probing and MDCG provides the most accurate pre-operative lacrimal assessment and should predict all the canalicular stenoses requiring intubation. In addition, MDCG can predict physiological duct blocks beyond canalicular blocks and thus alter surgical management.

Humans↗
PubMed1998

Cerebral haemodynamics and embolization during carotid angioplasty in high-risk patients.

BACKGROUND: Patients with symptomatic internal carotid artery (ICA) stenosis greater than 70 per cent in association with a contralateral ICA occlusion may have an increased risk of stroke following carotid endarterectomy. Such patients might benefit from the theoretically shorter ischaemic time offered by carotid angioplasty and stenting. METHODS: Nine patients who underwent carotid angioplasty and stenting were monitored using near-infrared spectroscopy, continuous jugular venous oximetry and transcranial Doppler ultrasonography to detect both haemodynamic ischaemia and embolic events. RESULTS: Significant ischaemia occurred in four of the nine patients once the stenosis had been crossed by the guidewire (spectroscopy and oximetry). Inflation of the angioplasty balloon resulted in a brief period of ischaemia and showers of emboli in all patients (ultrasonography) and this persisted for more than 3 min after balloon deflation in three patients. One patient had a major disabling stroke due to ICA thrombosis. CONCLUSION: Angioplasty and stenting in these high-risk patients may not confer any advantage over conventional surgery in terms of both haemodynamic ischaemia and embolization.

Aged↗