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Biomedical subjects

E B Brown

Publications and source records attributed to E B Brown.

At least 19 recordsLinked to original sources

Multiphoton-excited fluorescence of fluorogen-labeled neurotransmitters.

Fluorescence detection of fluorogen-labeled neurotransmitters is demonstrated using 100 fs pulses from a titanium-sapphire mode-locked laser to achieve molecular excitation by simultaneous absorption of two and three photons of near-IR radiation. Two-photon excitation spectra are determined for the naphthalene-2,3 dicarboxaldehyde derivative of glycine and the fluorescamine derivative of leucine enkephalin, with the peak excitation cross section (o2) approximately equal to 1 x 10(-50) cm4 s/photon for both species. Three-photon-excitation fluorescence is demonstrated for o-phthaldialdehyde-labeled glutamate using excitation wavelengths between 965 and 1012 nm. The three-photon excitation cross section (o3) remains nearly constant in this wavelength range, with an absolute value of approximately 10(-84)-10(-85) cm6 s2/photon 2. Rapid cycling of analytes through the fluorescent excited state and detection that is free from background caused by Rayleigh and Raman scatter combine to make multiphoton-excited fluorescence a highly sensitive approach for detecting trace amounts of neurotransmitters. Measurements of two-photon-excited fluorescence of fluorescamine-labeled bradykinin and analysis of multiphoton-excited background reveal the potential of this method to detect fewer than 1000 neurotransmitter molecules.

Fluorescent Dyes

Comparison of dual photon and dual energy X-ray bone densitometers in a clinic setting.

In clinical practice, decisions must be made about whether and how to convert to newer technologies. To address this issue, two separate studies were conducted. We evaluated the relationships between results of lumbar spine measurements using two dual photon absorptiometry (DPA1 and DPA2) instruments and one dual energy X-ray (DXA) instrument with the same subjects (49 volunteers), and also in 65 patients who were measured on the DPA1 and DXA machines. Second, we measured the lumbar spine and the proximal femur in three groups of 12 female volunteers three times on one instrument within 1 week. We purposely simulated a busy clinic setting with different technologists, older radioactive sources, and a heterogeneous patient group. The comparison study indicated a significant difference between the mean bone density values reported by the machines, but the results were highly correlated (R2 = 0.89-0.96). The short-term precision errors (coefficients of variation) differed among the instruments, ranging from 1.3% (DXA of the spine) to 5.1% (DPA1 of the spine), and in the femoral neck, 2.3% and 2.4% (DXA and DPA1, respectively) versus 3.5% by DPA2. This study emphasizes the differences between instruments, the potential for greater error in busy clinic environments, and the apparent superiority of dual energy X-ray absorptiometry under these less than ideal conditions.

Absorptiometry, Photon

Correlations between vertebral regional bone mineral density (rBMD) and whole bone fracture load.

To assess the significance of regional quantitative computed tomography measurements of bone density with respect to mechanical strength in the human lumbar spine, 58 vertebrae (from 12 males, 10 females) were scanned in vitro with multiple-thin-slice quantitative computed tomography and then compressed to fracture. With computer graphics, 18 specific regions of physical density and 10 combination averages of density were identified within each vertebral body. To ensure the statistical independence of data, the individual vertebral specimens were assigned to one of three groups (T11-L1, L2-L3, or L4-L5). Use of best-subsets procedures resulted in regression models to predict fracture strength. These models used specific regional density values and often the age and sex of the donors. The correlation coefficients that resulted from the multiple regression models ranged from r = 0.88 to r = 0.95. When the density values were multiplied by the minimum cross-sectional area of the vertebral body, similar regional density averages were selected, and the predictive values were slightly improved (r = 0.94-0.97). The heterogeneity of the density samples (measured as standard deviation) in multiple regression fashion also produced strong correlation coefficients (r = 0.88-0.94). The bone density in an anterior cylinder of the midplane region, the location measured most often in quantitative computed tomography densitometry, was strongly correlated (r = 0.85) to fracture load for the T12-L1 group (N = 20), but was not significant for the other two groups of vertebrae. The cancellous bone density from the female data was not found to be significantly different from the male data set.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Risk of systemic reactions in patients taking beta-blocker drugs receiving allergen immunotherapy injections.

To learn whether patients taking beta-blocker (BB) drugs were at increased risk of having systemic reactions (SRs) from allergen immunotherapy, we prospectively studied 56,105 injection visits in 3178 patients during a 1-year interval. A total of 166 SRs occurred in 144 patients (4.5% of all patients) or 3.0 SRs occurred per 1000 injection visits. Sixty-eight patients were taking BB drugs throughout the year, and only one patient had an SR. By chance, 3.08 patients were expected to have had SRs. We conclude that BB drugs did not increase the frequency of SRs in the patients studied who were receiving immunotherapy (p greater than 0.95). Patients taking BB drugs may still be at increased risk, however, from more severe SRs or their SRs may be more refractory to therapy.

Adrenergic beta-Antagonists

Tungiasis: report of one case and review of the 14 reported cases in the United States.

Tungiasis is a cutaneous parasitic infestation by the fertilized female sand flea Tunga penetrans. It is prevalent in tropical Africa and in Central and South America. Despite increasing air travel to and from these countries, surprisingly the disease is rarely reported in the United States. This report describes another case of tungiasis and reviews the 14 previously reported cases in the United States. Clinical features, differential diagnosis, treatment, and prophylaxis of tungiasis are discussed.

Adult

Iron metabolism: a 40-year overview.

The study of iron metabolism during the past 40 years is summarized. The status of hematology in general, and of the Hematology Division at Washington University in particular, is retrospectively reviewed. From a baseline of accepted information in 1950, the major areas of iron metabolism in humans are examined and significant additions to the fund of knowledge are identified. Progress in most areas is characterized by slow accretion of knowledge rather than by true conceptual breakthroughs.

Food, Fortified

Electron microscopy of the low pH structure of influenza virus haemagglutinin.

Influenza virus haemagglutinin mediates infection of cells by fusion of viral and endosomal membranes, triggered by low pH which induces a conformational change in the protein. We report studies of this change by electron microscopy, neutron scattering, sedimentation and photon correlation on X-31 (H3N2) haemagglutinin, both intact and bromelain cleaved, in various assemblies. HAs in all preparations showed a thinning at low pH, and a marked elongation which was removed on tryptic digestion, revealing altered features in the remaining stem portion of the molecule. A tentative model of the change is proposed, with reference to the known X-ray structure at neutral pH, in which major changes occur in the stem tertiary structure, while the top portion is only affected in its quaternary structure.

Animals

Electron microscopic evidence for the axial rotation and inter-domain flexibility of the Fab regions of immunoglobulin G.

The Fab arms of immunoglobulin G (IgG) have long been known to hinge about their joint with the Fc subunit. Using monoclonal antibodies bound to influenza haemagglutinin (HA) as position markers, we now show that these arms can also rotate about their long axis with respect to Fc. We also show that when two IgGs are bound cyclically with two HA molecules, the arms can bend between the variable and constant domains to accommodate bond angle constraint.

Antigen-Antibody Complex

Tissue effects of iron deficiency in the rat.

Measurements of succinate dehydrogenase and mitochondrial glycerol-3-phosphate dehydrogenase activities, iron, cytochrome c and myoglobin, were made on various hind-leg muscles, fast-twitch red and white muscle and heart and liver of male Wistar rats fed an iron-deficient diet on weaning. Rats fed the same diet and given 20 mg iron intraperitoneally as iron-dextran (Imferon) served as controls. For iron-repletion studies anemic rats (hemoglobin less than 7 g/dl) were given a single injection of 10 mg iron (Imferon) and the time course of change in the above parameters was followed up to 22 days after injection. The iron concentration of most iron-deficient muscles dropped to approx. 35% of control, the heart to 60% and liver to 13%. On repletion, the iron concentration of all tissues increase significantly by 4 days. While the levels of cytochrome c and myoglobin approximated the iron levels in muscle, they did not change significantly in the heart. Succinate dehydrogenase activity dropped profoundly in muscle, to 10-30% of control; on repletion, the activity increased significantly. Mitochondrial glycerol-3-phosphate dehydrogenase activity showed only small changes in iron-deficient tissues.

Anemia, Hypochromic

Electron microscopy of influenza haemagglutinin-monoclonal antibody complexes.

The molecular locations of antibody binding sites on the haemagglutinin of influenza virus X-31 were investigated by electron microscopy of haemagglutinin-monoclonal antibody complexes. Evidence was obtained for different sites of binding of different antibodies and direct correspondence was observed between these sites and the locations of antigenic sites A, B, and E (D. C. Wiley, I. A. Wilson, and J. J. Skehel (1981). Nature (London) 289, 373-378) defined by determining the amino acids recognized by the specific antibodies.

Amino Acids

Effect of body temperature on salicylate-induced hyperventilation.

Hyperventilation and hyperpyrexia occur simultaneously during acute salicylate intoxication. The present experiments were designed to investigate the stimulatory effect of increased body temperature on respiration in this pathological state. Acute salicylate intoxication was produced in mongrel dogs by intravenous infusion of 200 mg sodium salicylate/kg body weight, and the effect of body temperature on salicylate-induced hyperventilation was studied by comparing the respiration of hyperthermic animals with the respiration of animals maintained normothermic during acute salicylate intoxication by bathing them in cold water. The minute volume of ventilation increased greatly over control levels in both normothermic and hyperthermic animals, but this increment was much larger in hyperthermic animals. The increase in ventilation of normothermic animals can be explained as a rise in alveolar ventilation which results in hypocapnia despite large increases in carbon dioxide production and oxygen consumption during acute salicylate intoxication. The further augmentation of ventilation in hyperthermic animals can be explained as a rise in deadspace ventilation in response to increased body temperature during acute salicylate intoxication.

Animals

Thalassemia.

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Chelating Agents

Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion.

A conformational change in the hemagglutinin glycoprotein of influenza virus has been observed to occur to pH values corresponding to those optimal for the membrane fusion activity of the virus. CD, electron microscopic, and sedimentation analyses show that, in the pH range 5.2-4.9, bromelain-solubilized hemagglutinin (BHA) aggregates as protein-protein rosettes and acquires the ability to bind both lipid vesicles and nonionic detergent. Trypsin treatment of BHA in the pH 5.0-induced conformation indicates that aggregation is a property of the BHA2 component and that the conformation change also involves BHA1. The implications of these observations for the role of the glycoprotein in membrane fusion are discussed.

Bromelains

Psychological changes during a controlled trial of rehabilitation in chronic respiratory disability.

Thirty-four men with chronic respiratory disability took part in a randomised, controlled trial of physical training. The control group also undertook exercise training after their control period. During the study measurements were made of exercise tolerance (12-minute walking distance) and the men completed two psychology questionnaires. Walking distance improved significantly more in the treatment group than in the control group. Both groups recorded scores suggesting psychological "improvement" and the changes in the two groups were not significantly different from each other. There were no consistent associations between the increase in walking distance and changes in psychological scores. Initial psychological scores were not useful in predicting changes in walking distance. The results suggest that the effect of treatment on walking distance was not psychological.

Clinical Trials as Topic

Physiological and biochemical effects of iron deficiency on rat skeletal muscle.

Young rats were made iron deficient by feeding them a low-iron diet for 8 wk. Iron deficiency resulted in a 50% decrease in cytochrome c and cytochrome oxidase and a 26% decrease in mitochondrial glycerol-3-phosphate dehydrogenase activity in skeletal muscle. Respiratory capacity of muscle homogenates was reduced 55%. After 8 days of iron treatment, respiratory capacity, cytochrome c, cytochrome oxidase, and glycerol-3-phosphate dehydrogenase had returned 50% toward normal. Maximum O2 uptake of contracting hindlimb muscles averaged 8.5 mumol O2.min-1.g-1 in control, 4.3 mumol O2.min-1.g-1 in iron-deficient, and 6.2 mumol O2.min-1.g-1 in the 8-day-iron-repleted rats. Muscle fatigue during 10 min of stimulation was greater in the iron-deficient group. Lactate concentration in red muscle was higher in iron-deficient than in control rats after stimulation. The muscle fatigue and lactate responses returned 50% toward normal during 8 days of iron treatment. We conclude that iron deficiency results in a decrease in skeletal muscle capacity for aerobic metabolism and, by this mechanism, increases susceptibility to fatigue.

Animals