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Biomedical subjects

C S Davis

Publications and source records attributed to C S Davis.

At least 73 records · Page 4Linked to original sources
PubMed1987

Neurotoxic esterase: characterization of the solubilized enzyme and the conditions for its solubilization from chicken brain microsomal membranes with ionic, zwitterionic, or nonionic detergents.

Neurotoxic esterase (NTE) is a membrane-bound protein found in highest concentration in brain and lymphocytes. The enzyme has no known physiological function, but its organophosphorylation and aging in neural tissue are thought to trigger the pathogenesis of organophosphorus-induced delayed neuropathy (OPIDN). Solubilization of NTE from microsomal membranes from hen or chick brain was studied with ten detergents encompassing ionic, zwitterionic, or nonionic types. Corrected yields of NTE solubilized over a range of [detergent]/[protein] ratios were determined by dividing the activity not sedimenting in detergent at 100,000 g for 60 min at 4 degrees by the activity in the original microsomal fraction with no detergent present. Highest corrected yields were obtained with sodium cholate (44%), Triton X-100 (48%), and nonyl-GPS (57%). Partial loss of NTE activity occurred in the presence of detergent which could be prevented by the inclusion of asolectin in the solubilization preparation. NTE could not be solubilized by omitting detergent or by substituting 2 M NaCl for detergent. Mipafox pI50 values obtained from complete titration curves carried out on NTE solubilized in Triton X-100, sodium cholate, or sodium cholate/asolectin were indistinguishable from the value for native enzyme from brain homogenate. These results indicate that NTE exhibits the properties of an integral membrane protein with lipid dependence. The enzyme can be solubilized in good yield with a variety of detergents with retention of its characteristic differential inhibition by paraoxon and mipafox, a necessary prelude to bulk purification of the enzymatically active protein.

Animals↗
PubMed1985

Solubilization of hen brain neurotoxic esterase in dimethylsulfoxide.

Neurotoxic esterase is the putative site of initiation of organophosphorus-induced neuropathy. The protein is membrane-associated and will thus require solubilization before it can be purified. Its enzymic activity was retained in hen brain microsomes suspended in 10-60% (v/v in water) dimethylsulfoxide and 5-20% dimethylacetamide, but lost in 5-20% 1- and 2-propanol as well as higher concentrations of dimethylsulfoxide. Soluble activity (100,000 x g, 60 min supernatant) was not obtained with dimethylacetamide, but 24% of the recovered activity (67%) was solubilized in 40% dimethylsulfoxide, with retention of its native response to inhibitors. Solvent extraction of active enzyme is of intrinsic interest and expands the options for its purification.

1-Propanol↗
PubMed1983

Kinetics of esmolol, an ultra-short-acting beta blocker, and of its major metabolite.

Esmolol is an ultra-short-acting beta blocker. Its kinetics was studied in eight healthy subjects after continuous intravenous infusion of 400 micrograms/kg/min over 2 hr. The concentrations of esmolol and its major metabolite, 3-[4-(2-hydroxy-3-[isopropylamino]propoxy)phenyl]propionic acid, in blood and urine were determined by gas chromatographic-mass spectrometric assay and HPLC. The distribution and elimination t1/2s of esmolol averaged 2.03 and 9.19 min. The apparent volume of distribution of esmolol averaged 3.43 l/kg and was four times the volume of the central compartment. The total clearance of esmolol averaged 285 ml/min/kg, indicating that nonhepatic routes play a predominant role in its clearance. The t1/2s of formation and elimination of the metabolite averaged 2.82 min and 3.72 hr. The ratio of the metabolite formation and elimination rate constants of the parent drug (kf/k10) averaged 0.829, suggesting that 82.9% of esmolol was converted to the metabolite (which is consistent with the urinary recovery of 71% of the dose as unconjugated metabolite). The volume of distribution and total clearance of the metabolite averaged 0.411 l/kg and 1.28 ml/min/kg. Esmolol was followed by a significant reduction of isoproterenol-induced increase in heart rate and systolic blood pressure at doses of 50, 150, and 400 micrograms/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Hospital use in a fee-for-service system.

The population of Olmsted County, Minnesota, receives care virtually exclusively from two fee-for-service group practices: the Mayo Clinic and the Olmsted Medical and Surgical Group. Study of the use of acute-care hospital services by this population in 1976 reveals that the hospital discharge rate per 1,000 population, adjusted for age and sex, was 30% less than the national rate; the age-sex-adjusted rate of hospital days per 1,000 population was 38% less than the national rate. Analysis by length of stay, type of hospital service, frequency of selected diagnoses and surgical procedures, and certain demographic and economic characteristics did not explain the differences from national use rates. These rates are comparable, after age and sex adjustment, with those in larger prepaid group practices. The analysis suggests that the organization of medical care may have an important influence on hospital use.

Catchment Area, Health↗
PubMed1982

Laboratory diagnosis of gastrinoma. I. A prospective evaluation of gastric analysis and fasting serum gastrin levels.

In a small percentage of patients with ulcer disease, a gastrinoma may be ultimately discovered. In most institutions, a fasting serum gastrin determination and gastric analysis are as first-line tests to identify this subgroup of patients with ulcer disease. The blood test is relatively inexpensive and well accepted by patients. Gastric analysis is uncomfortable and required a well-equipped facility staffed by skilled personnel. A prospective study designed to assess the diagnostic usefulness of these tests and, particularly, whether combining both tests adds to the individual value of each, revealed that gastric analysis does not improve the diagnostic ability of the fasting serum gastrin test. Therefore, gastric analysis probably is not indicated for determining whether a patient with active ulcer disease has a gastrinoma. The fasting serum gastrin test will suffice, and abnormal values on this test should be verified by the use of other tests such as responses to gastrin provocative tests.

Adolescent↗
PubMed1981

Some results of screening for early lung cancer.

Screening for lung cancer is somewhat controversial in that very few evaluations of the screening process have been made, and even fewer have involved the use of concomitant, unscreened controls. This report of the Mayo Lung Project provides evaluation of a randomly selected 4500 clinic patients, offered screening for lung cancer at four-month intervals for six years. Another 4500 randomly selected controls not offered screening were merely observed. Good screening is defined, the Mayo project is evaluated, and puzzling results are presented and discussed. From the screened group, 98 new cases of lung cancer have been detected, 67 by study screening and 31 by spontaneous reporting of symptoms (15) or by x-ray examinations (16) done in other than study circumstances. From the controls, 64 new lung cancer cases have been detected, 43 by symptoms and 1 by other methods. Lung cancer mortality is 39 for study patients and 41 for controls. There is thus no evidence at this time that early case finding hs decreased mortality from lung cancer.

Adenocarcinoma↗
PubMed1981

The Mayo three-community hypertension control program. V. Cost-effectiveness of intervention.

This paper compares the costs of a categorical clinic model for community hypertension intervention with the costs of two less resource-intensive hypertension programs. Three categories of costs are measured for each program: program costs, patient costs, and time costs. Total costs are expressed in terms of costs per hypertensive patient controlled under each program. When adjusted for differences in hypertension prevalence and screening costs in the three community programs, the cost-effectiveness of the categorical clinic model is questionable. These results suggest that careful analyses of the categorical clinic model in other communities should be conducted before public resources are committed to the establishment of such models on a widespread basis.

Community Health Services↗
PubMed1981

Survival of patients surgically treated for stage I lung cancer.

When the TNM staging system of the American Joint Committee (AJC) for Cancer Staging and End-Results Reporting was applied to 3,912 patients seen during a 6 year period at the Mayo Clinic, 624 (16%) fulfilled the criteria for postsurgical pathological Stage I non-small cell bronchogenic carcinoma. Of these 624 patients, 129 were excluded from further survival analysis for various reasons. The remaining 495 consisted of two groups: 350 patients who were enrolled within 30 days into a prospective postoperative 4 monthly follow-up program and 145 patients who were enrolled later or were followed less frequently. Because no significant difference was noted in survival rates between these groups, data were pooled. Of the combined group of 495 patients, 84% survived lung cancer for 2 years and 69% of 5 years (actuarial estimation). The survival of patients classified T1 N0 M0 (91% alive at 2 years and 80% at 5 years) is so good that it seems unlikely that adjuvant therapy in this group could demonstrate improved survival. In addition to TNM classification, age at operation, sex, and extent of operation were important determinants of survival.

Adult↗
PubMed1981

The Mayo three-community hypertension control program. IV. Five-year outcomes of intervention in entire communities.

Beginning in 1974, the Mayo three-community hypertension control program initiated intervention studies in three southeastern Minnesota communities. This paper reports on the blood pressure outcomes 5 years after the inception of graduated programs involving public and professional education, detection, referral, and, in one community, systematic stepped care. Despite differences in local physician-population ratios and organization of medical care, perseverant long-term reductions of blood pressure were noted in all communities. However, the mean diastolic pressures were lower and the number of individuals at goal (diastolic blood pressure 90 mm Hg or less) was higher in the community offering categorical care. These data suggest that while programmatic efforts to control hypertension resulted in favorable blood pressure declines, the outcomes were particularly impressive in the community with a categorical hypertension clinic model offering systematic management of hypertensive patients.

Adult↗
PubMed1978

The measurement of phosphatidate phosphohydrolase in human amniotic fluid.

Phosphatidate phosphohydrolase (EC 3.1.3.4) activity can be found in late gestational human amniotic fluid and is thought to originate in type II alveolar cells of the fetal lungs where it plays an important role in lung surfactant synthesis. In the present study, phosphatidate phosphohydrolase activity was detected and characterized in a 105 000 X g pellet of amniotic fluid using either [32P]phosphatidate or a water-soluble analog, 1-O-hexadecyl-rac-[2-(3)H]glycerol 3-phosphate as substrate. With either substrate, enzyme activity was optimal at pH 6.0. The soluble analog was hydrolyzed with a Km value of 163 micrometer and a V of 30 nmole/min per mg of protein, and offered several advantages over phosphatidate as a substrate for assaying phosphatidate phosphohydrolase in amniotic fluid. Using the synthetic analog, phosphatidate phosphohydrolase activity was measured in the 700 X g supernatant fraction of 30 human amniocentesis samples and compared with another index of fetal lung maturity, the phosphatidylcholine/sphingomyelin ratio. The results suggest that the new phosphohydrolase assay may be clinically useful in the assessment of fetal lung development.

Amniotic Fluid↗
PubMed1978

Synthesis and hypotensive activity of a series of 2-substituted 5,6-dimethoxyindazoles.

The synthesis and hypotensive activity in the dog of a series of 2-substituted 5,6-dimethoxyindazoles are reported. Structure-activity relationships for this class of compounds are discussed. Indazoles containing the diethylaminoethyl, 3-pyridyl, and hydroxyethyl functions in the 2-position were the most effective in lowering blood pressure for the longest times (greater than 270 min).

Animals↗