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Biomedical subjects

D A Johnson

Publications and source records attributed to D A Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1986

The effect of enzymatic reaction on dissolution rate: theoretical analysis and experimental test.

The dissolution behavior of N-acetylphenylalanine ethyl ester (1) and N-benzoyltyrosine ethyl ester (2) from a rotating disk into aqueous solutions containing the enzyme alpha-chymotrypsin was investigated. The effect of the bulk enzymatic reaction on the dissolution rates is modeled using the continuity equation where the reaction term is considered a constant throughout the reaction zone. Dimensional analysis on the continuity equation defines the important parameter R* = KcatE0h2/(CsD) which is the ratio of the diffusion time to the reaction time. This parameter correctly predicted the fact that the enzymatic reaction had only a slight impact on the dissolution of the highly soluble 1 while the effect on the less soluble 2 was large. Also predicted by R* is the dissolution dependence on the catalytic rate constant. The variation of this rate constant with pH is consistent with the dependence on pH found for the dissolution rate of 2. It is further demonstrated that the decrease in dissolution rate with solubility can be significantly reduced when the dissolving compound is an enzyme substrate. For the two compounds used in this study the dissolution rate decreased with the square root of solubility, as predicted by the theoretical analysis in the presence of enzyme. Other experiments included the variation of the enzyme concentration and the rotational speed of the spinning disk. All experiments were designed to show how R* could correctly predict the relative importance of the convective, diffusive, and reactive processes.

Diffusion↗
PubMed1986

Pediatric primary sclerosing cholangitis.

An 11-year-old male presented with abdominal pain and emesis. Serum chemistries revealed cholestasis and an ERCP demonstrated sclerosing cholangitis. Secondary causes of this disease process were excluded. Sclerosing cholangitis is distinctly uncommon in the pediatric age group, but it should be considered in evaluation of patients of any age with cholestasis. It appears in some cases that there may be subtle histologic and radiographic features which separate the pediatric and adult forms of the disease.

Bile Ducts, Intrahepatic↗
PubMed1986

Solid-phase gastric emptying in patients with Barrett's esophagus.

Delayed gastric emptying as a pathophysiologic factor in patients with gastroesophageal reflux (GER) is controversial. In order to further evaluate this question, we studied a population with severe reflux, specifically, patients with Barrett's esophagus. Solid-phase gastric emptying was measured in 17 patients and in 17 healthy volunteers using radionuclide imaging. Gastric emptying was variable among these patients with 70% normal, 18% rapid, and only 12% slow studies. From these observations, we conclude that delayed gastric emptying is unlikely to be a major factor in the pathogenesis of Barrett's esophagus.

Adult↗
PubMed1986

Changes in annual tuberculosis notification rates between 1978/79 and 1983 for the population of Indian subcontinent ethnic origin resident in England.

In two national surveys of tuberculosis notifications in England conducted in 1978/79 and 1983 the estimated annual notification rates for the Indian subcontinent (Indian, Pakistani, and Bangladeshi) ethnic groups were considerably higher than the rate for the white ethnic group. The mean annual decline in rates between the surveys appeared to be greater for the Indian and the Pakistani and Bangladeshi ethnic groups, 15% and 16% respectively, than for the white ethnic group (7%). Data from two small sample population surveys, the National Dwelling and Housing Survey in 1978 and the Labour Force Survey in 1983, were used to calculate the rates. However, comparison of the estimates for the population of Indian subcontinent ethnic origin in England from these surveys revealed discrepancies between them. Additional information from the Labour Force Survey on the year of first entry to the United Kingdom (UK) permitted the calculation of new estimates for the 1978 population, and based on these estimates the annual notification rates for 1978/79 were 287 per 100,000 for the Indian and 286 per 100,000 for the Pakistani and Bangladeshi ethnic groups. The rates for 1983 were 178 and 169 respectively, and the mean annual decline between the surveys was 11% for the Indian and 12% for the Pakistani and Bangladeshi ethnic groups. There were important changes in the characteristics of the population of Indian subcontinent ethnic origin in England between 1978 and 1983, and therefore the rates for both surveys have been standardised by the method of direct standardisation to a common reference population. Standardizing for year of entry to the UK, place of birth (UK or abroad), age, and sex reduced the mean annual decline in the notification rate to 4% for the Indian and 9% for the Pakistani and Bangladeshi ethnic groups. The much greater reduction in the rate of decline in the Indian ethnic group is due to the substantial decline between the surveys in the proportion of recent immigrants, the group with the highest annual notification rate, in that population. Future trends will continue to be influenced by immigration patterns, but it will also be important to monitor the rates among the increasing proportion of the population born in the UK or resident in England for more than five years.

Bangladesh↗
PubMed1986

Progressive systemic sclerosis: radionuclide esophageal scintigraphy and manometry.

Radionuclide esophageal scintigraphy (RES) and manometry were used for prospective evaluation of esophageal involvement and disease severity in 11 patients (nine women and two men; median time since diagnosis, 1 year) with progressive systemic sclerosis (PSS). Quantitation of RES included calculation of the percentage of emptying at 30 seconds, while manometry provided measurements of proximal, distal, and lower esophageal sphincter (LES) pressures. The findings of both RES and manometry were abnormal in all 11 patients. There was a high correlation between the percentage of emptying and either distal esophageal pressure (r = .86, P less than .01) or LES pressure (r = .79, P less than .01). No significant correlation was found between the percentage of emptying and proximal esophageal pressure (r = .28, P = .39). RES is a safe, simple procedure that is readily accepted by patients and can be used in place of manometry for the detection and staging of esophageal involvement in PSS.

Adult↗
PubMed1986

Ozone effects on alpha-1-proteinase inhibitor in vivo: blood plasma inhibitory activity is unchanged.

The possible oxidative inactivation of human blood plasma alpha-1-proteinase inhibitor (alpha-1-PI) by inhaled ozone was assessed. Eleven male volunteers (non-smokers) were exposed to 0.5 ppm ozone for four hours on two consecutive days and ten control subjects were exposed to air under the same conditions. Blood plasma samples, drawn before and after treatment, were assayed for total alpha-1-PI, total protein and elastase inhibitory activity. The amount of active alpha-1-PI in plasma samples was quantitated by titrating porcine pancreatic elastase with increasing amounts of plasma. The importance of constructing titration curves for determinations of this type was demonstrated. No differences were noted in the ratios of total alpha-1-PI/total protein or elastase inhibitory activity/total alpha-1-PI in the plasma from ozone exposed individuals relative to controls. Although inhaled ozone did not result in any significant decrease in the activity of blood plasma alpha-1-PI, these findings do not preclude the possibility of oxidative inactivation of a alpha-1-PI in the lung.

Blood Proteins↗
PubMed1986

Stool chemistries in patients with unexplained diarrhea.

In approaching the differential diagnosis of unexplained diarrheal disorders, separation of osmotic and secretory causes is important. The osmotic gap between measured stool osmolality and osmolality calculated from stool sodium and potassium concentrations is low in secretory diarrhea and high in osmotic diarrhea. Cholera, villous adenoma and bile salts are among the causes of secretory diarrhea. Causes of osmotic diarrhea include monosaccharidase deficiency, disaccharidase deficiency, excessive use of sugar-free gum and excessive ingestion of magnesium antacids.

Bicarbonates↗
PubMed1986

Biliary dyskinesia with associated high amplitude esophageal peristaltic contractions.

A 60-yr-old woman with recurrent biliary-type pain and pancreatitis was found to have abnormal biliary manometrics. Sphincter of Oddi basal and phasic contraction pressures were significantly elevated. Esophageal manometrics revealed high amplitude peristaltic contractions that were unassociated with chest discomfort. High amplitude dysmotility syndromes may perhaps represent a spectrum of disease involving the entire gastrointestinal tract.

Ampulla of Vater↗
PubMed1986

Liver involvement in the sulfone syndrome.

A patient being treated with dapsone developed a hypersensitivity reaction with typical features of the "sulfone syndrome," including fever, malalse, and hepatitis. All abnormalities rapidly reversed with discontinuance of the dapsone regimen and institution of prednisone therapy. Hepatic involvement may be a prominent feature of the sulfone syndrome and may be of the hepatocellular or cholestatic type. Based on our review of the Food and Drug Administration reports, this syndrome appears to be relatively uncommon, but physicians need to recognize that expression of this syndrome may be incomplete. More clinical data are necessary to better define the incidence and pathogenesis of sulfone-induced liver disease.

Chemical and Drug Induced Liver Injury↗
PubMed1985

Human lung mast cell tryptase fails to activate procollagenase or degrade proteoglycan.

Pig synovial and human skin fibroblast procollagenases were treated with highly purified tryptase, the major proteinase of human mast cells, to determine whether this trypsin-like proteinase could activate the latent form of collagenase and so be involved in connective tissue breakdown. No significant activation of either human or pig procollagenase was found, but the highest concentration of tryptase partially destroyed procollagenase. Tryptase did not degrade type I collagen or proteoglycan. These data indicate that human mast cell tryptase does not contribute to connective tissue breakdown via procollagenase activation or via proteoglycan degradation.

Animals↗
PubMed1985

Human bronchial leucocyte proteinase inhibitor. Rapid isolation and kinetic analysis with human leucocyte proteinases.

Bronchial leucocyte proteinase inhibitor (BLPI) is an 11 000 Mr protein found in human mucous secretions. This inhibitor apparently controls the serine proteinases elastase and cathepsin G, released from extravascular polymorphonuclear leucocytes. A simple, single-step chromatographic procedure for the isolation of BLPI based on its affinity for chymotrypsin was developed. The purified inhibitor was homogeneous by electrophoresis and gel filtration. Amino acid analyses were in close agreement with previous reports, and showed BLPI to be rich in proline and cystine, but lacking histidine. We have further characterized the role of BLPI with respect to human leucocyte elastase and cathepsin G by close examination of the kinetic parameters. Additionally, we have determined the kinetics of association (kon) and dissociation (koff) for BLPI with bovine trypsin and chymotrypsin. Equilibrium dissociation constants (Ki) of 1.87 X 10(-10) M, 4.18 X 10(-9) M, 8.28 X 10(-9) M and 2.63 X 10(-8) M were obtained for human leucocyte elastase, cathepsin G, bovine trypsin and chymotrypsin, respectively. These results are discussed with respect to BLPI's possible function in vivo and its role relative to other inhibitors in bronchial secretions.

Amino Acids↗
PubMed1985

Solute accessibility to N epsilon-fluorescein isothiocyanate-lysine-23 cobra alpha-toxin bound to the acetylcholine receptor. A consideration of the effect of rotational diffusion and orientation constraints on fluorescence quenching.

To obtain information on the disposition of alpha-toxin when bound to the acetylcholine receptor (AChR), we evaluated the accessibility of solutes to fluorescein isothiocyanate (FITC) conjugated to alpha-toxin (siamensis 3) at lysine 23 (FITC-toxin) by measuring the rate constants for iodide quenching of the fluorescence of fluorescein free in solution and FITC-toxin free in solution and bound to AChR. Relative to the free fluorescein, we observed a 55% reduction in the quenching rate constant for the unbound FITC-toxin and 80% reduction for the AChR-bound FITC-toxin. It is tempting to interpret a decrease in the quenching rate constant as due to an increase in the masking of the labeling fluorophore, which in our case would then be indicative of masking of fluorescein conjugated to the free toxin and masking of FITC-toxin, in the region of lysine 23, when bound to AChR. However, elementary considerations indicate that the quenching rate depends not only on geometrical masking factors but also on the translational and rotational mobilities of the labeled molecules as well as orientational constraints. To evaluate these effects we have established quantitative relations between the rate of fluorescence quenching, the degree of masking of fluorophore, translational and rotational rates, and orientational constraints of the labeled macromolecules, using recent formulations for the rate of reaction between asymmetric molecules (Shoup et al., 1981, Biophys. J., 36:619-714). These relations predict that the decrease in quenching constant observed for the labeled FITC-toxin as well as the AChR-bound FITC-toxin is largely due to differences in translational and rotational rates and orientational constraints and not to significant increases in geometrical masking. Our theoretical formulation shows that the quenching rate can be decreased by a factor of 2-5 merely by immobilizing a fluorophore on the surface of a large protein without any significant increase in geometrical masking.

Animals↗