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Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 235 records · Page 13Linked to original sources

The aeromedical risk associated with asymptomatic cholelithiasis in USAF pilots and navigators.

BACKGROUND: The U.S. Air Force (USAF) aeromedical policy regarding incidentally discovered, asymptomatic cholelithiasis required the aircrew to undergo cholecystectomy prior to being considered for return to flying duties. HYPOTHESIS: The merit of continuing this USAF policy was evaluated at the request of the U.S. Air Force Surgeon General. METHODS: A medical literature review of the natural history of cholelithiasis in the general population was completed. The USAF aircrew waiver file (1972-92) and the Ellingson Aerospace Medicine Consultation Service (ACS) data file (1955-92) were reviewed for cases of USAF pilots and navigators with a diagnosis of cholelithiasis or cholecystectomy. Pilot and navigator annual manpower data were obtained from the Air Force Military Personnel Center (1972-92) and used in calculations involving the USAF aircrew waiver file. Surgical morbidity and mortality information was obtained from the Division of Surgery, Wilford Hall Medical Center. RESULTS: Literature review predicted a 1-4% annual rate of acute events in individuals with previous asymptomatic cholelithiasis. Based on KUB radiographs taken at ACS, the prevalence of asymptomatic cholelithiasis in USAF pilots and navigators was estimated to be 2-3%. Of 11,685 pilots and navigators evaluated at the ACS, 80 (0.7%) were diagnosed with cholelithiasis or cholecystectomy. Between 1972 and 1992, an estimated 16,232 man-years of pilot/navigator exposure to asymptomatic cholelithiasis occurred; however, only 50 cases with a diagnosis of cholecystectomy or cholelithiasis were reported in the USAF waiver file. Mortality and morbidity for cholecystectomy, whether performed by open or laparoscopic technique, were reported as 0.2% and 5%, respectively, in the general population. CONCLUSION: The overall incidence of acute cholecystitis within USAF aircrew would not be changed by aeromedical cholecystectomy being performed on aviators with incidentally detected asymptomatic cholelithiasis.

Adult↗

Leptospirosis.

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Animals↗

The use of epidemiological concepts and techniques to discern factors associated with the nitrate concentration of well water on swine farms in the USA.

This epidemiological study investigates the relationship between various factors associated with swine farms and the nitrate concentration of well water in the USA. Through a random sampling procedure, 605 swine farms located in 18 states were selected for inclusion in this study. A total of 631 well water samples were collected from these farms and tested for a variety of elements and compounds. The concentrations of nitrate, nitrite, sulfate, chloride, sodium, potassium, ammonia, fluoride, bromide and lithium were determined by an ion chromatograph while an inductively coupled argon plasma emission spectrophotometer was used to determine the concentrations of calcium, magnesium, barium, zinc, iron and phosphate. Data concerning various farm factors were gathered via a personally administered questionnaire. The data were examined using both multiple linear regression and logistic regression. Results indicate that 53.6% (338/631) of the wells contained detectable levels of nitrate, 11.7% (74/631) had nitrate levels exceeding 45 ppm and 4.3% (27/631) exceeded 100 ppm. Logistic models demonstrated an association between nitrate concentrations > 45 ppm, increasing water potassium levels and wells < 100 ft deep. Nitrate levels > 100 ppm were related to increasing water concentrations of potassium, magnesium, barium and zinc, wells 6-10 years old, increasing distance from the study farm to the nearest cattle farm and a greater distance to the nearest waterway located off the study farm. A negative association was seen between nitrate concentrations > 100 ppm, the water level of sulfate, and the use of the same well to supply both the household and livestock. Multiple linear regression models revealed a positive association between increasing nitrate concentration and the water levels of chloride, calcium, zinc and the greater number of miles from the study farm to the nearest farm with cattle or sheep. A negative association was noted between the concentration of well water nitrate and the water levels of sulfate and ammonia, the use of water treatment, the number of miles to the nearest farm with poultry, the employment of water treatment and the use of the same well to supply water to both livestock and the household.

Agriculture↗

Phosphorylation of the 61-kDa calmodulin-stimulated cyclic nucleotide phosphodiesterase at serine 120 reduces its affinity for calmodulin.

Phosphorylation of the 61-kDa isoform of bovine calmodulin (CaM)-stimulated cyclic nucleotide phosphodiesterase (CaM-PDE) by the catalytic subunit of cyclic AMP-dependent protein kinase A (PKA) results in a decrease in the affinity of the enzyme for calmodulin [Sharma, R. K., & Wang, J. H. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 2603-2607]. In the present study, purified 61-kDa CaM-PDE was phosphorylated in the presence of [gamma-32P]ATP and cleaved with a Lys-C endoproteinase. The resultant phosphopeptides were resolved by reverse-phase HPLC and analyzed by electrospray mass spectrometry and Edman sequencing. Serine residues 120 and 138 were identified as the principal sites of phosphorylation. A cDNA encoding the 61-kDa CaM-PDE [Sonnenburg, W. K., Seger, D., & Beavo, J. A. (1993) J. Biol. Chem. 268, 645-652] was used to generate point mutants in which either or both of these serines were replaced with alanine. The mutants were expressed in COS-7 cells, purified, and phosphorylated. Phosphorylation of the mutant Ser 138-->Ala resulted in a decrease in affinity for CaM that was comparable to that seen with the wild-type enzyme. In contrast, phosphorylation of the mutant Ser 120-->Ala had virtually no effect on CaM affinity. We conclude that phosphorylation of serine 120 by PKA is responsible for the reduction in affinity of the 61-kDa CaM-PDE for CaM.

3',5'-Cyclic-AMP Phosphodiesterases↗

The application of a modified nucleotide in aptamer selection: novel thrombin aptamers containing 5-(1-pentynyl)-2'-deoxyuridine.

Combinatorial libraries of nucleic acids are developing into novel sources for lead compounds in drug development. In order to diversify the pool of ss DNA sequences, we have used a modified nucleotide, 5-(1-pentynyl)-2'-deoxyuridine, in place of thymidine in a random nucleic acid library and screened this library against human thrombin. Previously, we described this screening method to identify a novel structural inhibitor (an aptamer) of the coagulation protease thrombin (Bock, L. et. al. (1992) Nature 355 564-566). Using the modified nucleic acid library, we have now isolated a second pool of thrombin inhibitors with strikingly different sequence composition compared to the selection using natural bases. This second class of aptamers is dependent on the presence of the modified nucleotide for protein binding and clotting inhibition. Our method represents a potential strategy to enhance the diversity of libraries for in vitro selection, and thereby increasing the utility of this technique in the identification of molecules with novel biochemical properties.

Base Sequence↗

Where have all the pennies gone? The work of Manchester Medical Audit Advisory Group.

Medical audit has its critics, who point to the large sums of NHS cash that seem to be disappearing down a medical plughole. These criticisms are recognised by medical audit advisory groups but there are many reasons why the work of these groups has not yet resulted in many publications in journals or bumped up health indicators. After discussing the criticism this article describes the work of the medical audit advisory group in Manchester. Real changes in cooperative working with general practice teams and between practices are taking place, and improved relationships between general practice and the hospitals are being helped by joint audit work. The Manchester group is also working to help in setting standards and to cooperate with purchasing. The work of the group is changing as it develops.

Capital Financing↗

Targeted disruption of the c-fos gene demonstrates c-fos-dependent and -independent pathways for gene expression stimulated by growth factors or oncogenes.

The c-fos proto-oncogene is believed to play a pivotal role in transducing growth factor-mediated signals from the extracellular milieu into the nucleus. c-fos protein dimerizes with c-jun and related proteins and mediates transcription via AP-1 sites. Using c-fos-deficient mice generated through gene knockout techniques, we derived 3T3-type cell lines from primary embryonic fibroblasts. The c-fos-deficient cells grow normally under optimal culture conditions and show only a slight reduction in growth rate in low serum culture compared with control cells. They also express mRNA for most of the Fos and Jun family members at normal levels. The overall levels of AP-1 DNA binding activity are normal and several genes (c-jun, MCP1, metallothionein) known to contain functional AP-1 sites are expressed normally in the c-fos-deficient and control cells. In contrast, mRNA for the metalloproteases stromelysin (MMP-3) and type I collagenase (MMP-1), which are often induced by oncogenes and growth factors and have been implicated in tumor invasiveness, cannot be induced by epidermal growth factor or platelet-derived growth factor in c-fos-deficient cells. Transformation of mutant cells with polyoma middle T oncogene essentially restores wild-type levels of stromelysin expression, while transformation with v-src leads to only a weak induction of the metalloprotease. These results clearly demonstrate that some AP-1-dependent genes require c-fos for full expression while others do not; oncogenes may activate expression of metalloproteases via either fos-dependent or fos-independent mechanisms. These results also imply that c-fos may play an important regulatory role in the invasive behavior of malignant tumors, independent of any role this proto-oncogene might play in cell growth per se.

3T3 Cells↗

Sensitive gas-liquid chromatographic method for the determination of loratadine and its major active metabolite, descarboethoxyloratadine, in human plasma using a nitrogen-phosphorus detector.

A sensitive gas-liquid chromatographic (GLC) method was developed for the determination of loratadine, a long-acting tricyclic antihistamine, and its active metabolite, descarboethoxyloratadine, in human plasma. The method involved extraction with organic solvent at neutral and alkaline pH. The organic layer from the neutral pH extraction was evaporated to dryness, reconstituted and injected into the GLC system. On the other hand, to the organic layer from the alkaline pH extraction trifluoroacetic anhydride was added. Following addition of H2O, the mixture was centrifuged and the organic layer was evaporated to dryness, reconstituted and injected onto the GLC system that was equipped with a nitrogen specific detector and a fused-silica capillary column. The linearity for both loratadine and descarboxyloratadine were demonstrated with r > or = 0.998 at concentrations ranging from 0.1 to 30 ng/ml. The results showed that the GLC method was accurate (bias < or = 12%) and precise (coefficient of variation, C.V., < or = 12%) for loratadine and descarboethoxyloratadine. The limit of quantitation was 0.1 ng/ml for loratadine with a C.V. of 9.2% and for descarboethoxyloratadine with a C.V. of 5.3%. The GLC method described has been demonstrated to be useful for the determination of loratadine and descarboethoxyloratadine in plasma samples of pediatric volunteers following oral administration of a single dose of 10 mg of loratadine syrup.

Child↗

Integrative transformation of the mycotoxin-producing fungus, Penicillium paxilli.

A high frequency transformation system has been developed for Penicillium paxilli using pAN7-1. Up to 44% of the primary transformants were heterokaryons. Loss of hygromycin resistance was observed in primary transformants that were sub-cultured on non-selective media, but single spores of these primary transformants were mitotically stable on both selective and non-selective media. A molecular analysis of the transformants generated showed that 78% had single-site integrations, with half of these containing a single copy of pAN7-1. CHEF-gel electrophoresis showed that P. paxilli has at least six chromosomes with a total genome size of about 23.4 Mb.

Chromosomes, Fungal↗

A nation's response to attack: Israelis' depressive reactions to the Gulf War.

We examined Israelis' reactions to the Gulf War and SCUD missile attacks. Four national samples of Israelis (n = 3,204) were interviewed as to depressive mood on four occasions--prior to the Gulf Crisis, as the war approached, during the SCUD missile attacks, and after cessation of hostilities. There was an expected increase in depressive mood during the period of SCUD missile attacks and a quick return to base-line levels following the hostilities. Less educated and older individuals reported higher base-line levels of depressive mood and were at higher risk for clinical depression. Women and men did not differ in depressive mood before or after the SCUD missile attacks. However, women experienced a marked increase in depressive mood when the SCUD missile attacks occurred.

Adjustment Disorders↗

Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer.

OBJECTIVE: This study compares the human placental transport of glyburide, glipizide, chlorpropamide, and tolbutamide. STUDY DESIGN: The recirculating single cotyledon human placenta model tested maternal-to-fetal transport in term placentas perfused immediately after delivery. Drug levels were measured by high-performance liquid chromatography and liquid scintillation spectrometry, and transport rates were calculated by comparing maternal and fetal concentrations. RESULTS: The transport of these substances differed significantly over a tenfold range (analysis of variance, p < 0.0008). A significant association exists by multiple linear regression between drug transfer and molecular weight, dissociation constant, and the octanol-water partition coefficient (R2 = 0.91, p < 0.0001). CONCLUSIONS: There is significant variability in human placental transfer rates of the oral hypoglycemics, which strongly correlates with molecular properties. These data suggest that less fetal exposure may occur with second-generation sulfonylureas and anticipate that regression models may be useful in selecting agents that minimize placental transport to the fetus.

Administration, Oral↗

A test of brain electrical source analysis (BESA): a simulation study.

The present report summarizes the results of a simulation study on the accuracy of Scherg's implementation of spatio-temporal analysis (BESA) for estimating the parameters (wave shape, location, orientation) of the intracranial sources of event-related brain potentials (ERPs) recorded from the scalp. In view of the subjective factors that might influence a solution, 10 subjects, ranging from those with much experience with ERPs and extensive background in the use of BESA to those with little experience with BESA and/or no knowledge of ERPs, independently analyzed a set of simulated somatosensory ERP data. The simulation contained wave forms from 32 electrode sites generated by a combination of 10 dipole sources. The primary question was how faithfully the different subjects would depict the source wave shapes, locations and orientations. Based on the 9 subjects who were familiar with ERPs, the grand-average cross-correlation coefficient between subjects' estimated and actual source wave shapes was 0.89 (standard deviation (S.D.) = 0.17). The grand-average location error, based upon a head diameter of 17 cm, was 1.4 cm (S.D. = 1.0 cm). The grand-average orientation error was 24.4 degrees (S.D. = 20 degrees).

Brain↗

Lymphocyte colony formation by aleukemic sheep infected with bovine leukemia virus.

The objective of this study was to investigate the effects of bovine leukemia virus (BLV) infection in sheep. A prospective study of the serologic, hematologic, and histologic changes of sheep infected with BLV was conducted. Antibodies to BLV were detectable in the sheep 3 weeks after exposure to blood from an infected cow and persisted during a 120 week examination period, whereas all control sheep remained seronegative. There were no statistically significant differences between the leucocyte counts, lymphocyte counts, and lymphocyte percentages of the infected and control sheep during the first 120 weeks of this study. However, one sheep did develop a leukopenia and lymphopenia 95 weeks after it became infected and died of histologically-confirmed lymphosarcoma 10 days later. A lymphocyte colony assay was used to study the effects of BLV infection on colony formation by sheep lymphocytes in vitro. There was no significant difference in the number of lymphocyte colonies formed by BLV infected and control sheep. Nor was there a significant difference in the number of colonies formed by lymphocytes from the BLV infected sheep, when the autologous sheep serum was replaced with either pooled serum from the infected sheep or with pooled serum from the control sheep. BLV infection in aleukemic sheep does not appear to have an adverse affect on colony formation by lymphocytes in vitro.

Animals↗

A lymphocyte colony assay for culture of sheep lymphocytes.

A procedure for culturing sheep peripheral blood lymphocytes in soft agar was standardized. The variables that were evaluated included the type of T lymphocyte mitogens, mitogen doses, cell number, distribution of the cells in the culture vessel and the duration of the culture. Both concanavalin A (CON A) and phytohemagglutinin A (PHA) stimulated the formation of lymphocyte colonies. However, CON A consistently produced more and larger colonies. The doses of CON A and PHA which yielded the maximum number of colonies were 35 and 61 micrograms/ml, respectively. The optimum number of cells per well as 1.36 x 10(6). Adherence of the cells to the floor of the culture vessel was required for the colonies to form. The maximum number of colonies was attained between day 5 and day 6 of culture. The lymphocyte colony assay may be a useful adjunct to other immunologic assays for studying cell-mediated immunity of sheep.

Animals↗

A tribological study of a series of retrieved accord knee explants.

A tribological study of a series of 27 retrieved Accord meniscal bearing knee joints has been carried out. The roughness of the articulating surfaces of the meniscal and the femoral components was investigated, and the penetration into the polyethylene meniscal component was determined. There was generally little damage to the highly polished metallic femoral components. A general polishing and smoothing of the ultra high molecular weight polyethylene meniscal components was observed, although there was some subsequent deterioration of the polyethylene surfaces in certain cases. The penetration rate of the femoral components into the menisci was low, and was found to be similar to that reported for other meniscal knee joints.

Adult↗

Determinants of resting energy expenditure in young children.

Resting energy expenditure (REE) in adults is influenced by fat-free mass (FFM) and fat mass (FM), and is significantly higher in men than in women. There are limited data, however, on the physiologic determinants of REE in children. We therefore measured REE in 113 prepubertal children (39 white girls, 41 white boys, 21 Mohawk girls, and 12 Mohawk boys), 3.9 to 7.8 years of age, representing a wide range of body weight (14.7 to 34.0 kg), height (0.97 to 1.30 m), FFM (10.3 to 25.0 kg), and FM (1.7 to 13.7 kg; 9.4% to 40.3%). The REE was measured in duplicate by indirect calorimetry (range, 830 to 1405 kcal/day) while the children were in a postprandial state and viewing a cartoon film. The FM and FFM values were determined by bioelectrical resistance by means of the Kushner equation. In stepwise regression analysis, the combination of FFM (p < 0.001; partial r = 0.77), sex (p = 0.001; partial r = 0.12), and FM (p = 0.01; partial r = 0.16) explained 63% of the variation in REE. The regression coefficients were 31.9 kcal/kg FFM, 53 kcal for boys, 0 for girls, and 13 kcal/kg FM. Mohawk background, age, fat distribution, heart rate, and physical activity were not independently associated with REE. After REE was adjusted for the aforementioned significant factors, there were no significant correlations with parental factors (body composition, physical activity, age, and REE) other than normalized maternal REE (r = 0.19; p = 0.05). We conclude that the effects of FFM, sex, and FM on REE in children are similar to those in adults. The higher REE in young boys suggests that the previously reported higher REE in adult men cannot be explained entirely by differences in sex hormones. Finally, our data do not support the hypothesis that REE in children is negatively influenced by obesity in children or in parents.

Adipose Tissue↗

Event-related brain potential evidence for a verbal working memory deficit in multiple sclerosis.

Memory deficits are frequently identified in patients with multiple sclerosis. Both working (short-term) and long-term memory appear affected, particularly on free-recall tasks. The focus of our study was to examine neurophysiological correlates of working memory processes and to identify the specific components responsible for the working memory deficits reported in multiple sclerosis. Event-related brain potentials (ERPs) were recorded from the scalp of mildly afflicted multiple sclerosis patients and their matched normal controls during the performance of phonological and visuo-spatial working memory tasks. Neuropsychological test, behavioural performance and ERP data all indicated that verbal working memory is especially susceptible to impairment by multiple sclerosis, while visuospatial working memory is less susceptible. The pattern of results further indicated that the verbal working memory dysfunction in multiple sclerosis is at least partially due to impairment in the phonological loop, a rehearsal mechanism for retaining verbal information in working memory.

Adult↗

Continuous assessment and improvement in quality of care. A model from the Department of Veterans Affairs Cardiac Surgery.

OBJECTIVE: The authors organized the Department of Veterans Affairs (VA) Continuous Improvement in Cardiac Surgery Study (CICSS) to provide risk-adjusted outcome data for the continuous assessment and improvement of quality of care for all patients undergoing cardiac surgery in the VA. BACKGROUND: The use of risk-adjusted outcomes to monitor quality of health care has the potential advantage over consensus-derived standards of being free of preconceived biases about how health care should be provided. Monitoring outcomes of all health care episodes, as opposed to review of selected cases (e.g., adverse outcomes), has the advantages of greater statistical power, the opportunity to compare processes of care between good and bad outcomes, and the positive psychology of treating all providers equally. These two concepts, together with a pre-existing peer committee (the VA Cardiac Surgery Consultants Committee) to review, interpret, and act on the risk-adjusted outcome data, form the primary design considerations for CICSS. METHODS: Patient-level risk and outcome (operative mortality and morbidity) data are collected prospectively on each of the approximately 7000 patients undergoing cardiac surgery in the VA each year. These outcomes, adjusted for patient risk using logistic regression, are provided every 6 months to each cardiac surgery program and to a national peer review committee for internal and external quality assessment and improvement. RESULTS: For the most recent 12-month period with complete data collection, observed-to-expected (O/E) ratios ranged from 0.2 to 2.2, with eight centers falling outside of the 90% confidence limits for an O/E ratio equaling 1.0. The O/E ratio for all centers has fallen by 14% over the 4.5-year period of this program (p = 0.06). CONCLUSIONS: A large-scale, low-cost program of continuous quality improvement using risk-adjusted outcome is feasible. This program has been associated with a decrease in risk-adjusted operative mortality.

Cardiac Surgical Procedures↗