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Biomedical subjects

E Lee

Publications and source records attributed to E Lee.

At least 361 records · Page 20Linked to original sources

Doppler echocardiography and ultrafast cine computed tomography during dynamic exercise in chronic parenchymal pulmonary disease.

In an effort to better understand the cardiac contribution to exercise limitation in chronic lung disease, 21 patients with advanced chronic pulmonary parenchymal disease and 10 normal control subjects were evaluated for changes in right ventricular (RV) pressure, volume and function during incremental, symptom-limited supine bicycle exercise. Patients underwent sequential exercise tests with Doppler echocardiography and ultrafast cine computed tomography (CT). RV systolic pressure during exercise was determined by saline-enhanced Doppler of tricuspid regurgitation. RV ejection fraction, end-diastolic volume, stroke volume and cardiac index were obtained by CT at rest and peak exercise. Sixteen of the 21 study patients also exercised on high-flow oxygen. In the control subjects RV systolic pressure increased from 21 +/- 6 mm Hg (mean +/- standard deviation) at rest to 32 +/- 8 mm Hg at peak exercise, whereas in patients with lung disease, RV systolic pressure increased from 42 +/- 17 to 81 +/- 26 mm Hg (both p less than 0.01). Compared with the control subjects, the patients with lung disease had significantly lower mean values for RV ejection fraction at rest (47 +/- 7 vs 55 +/- 7%) and at peak exercise (47 +/- 9 vs 57 +/- 3%, respectively, both p less than 0.05). The patients who demonstrated oxyhemoglobin desaturation during exercise showed the most abnormal cardiac responses, with marked increases in mean RV systolic pressure, decreases in mean RV ejection fraction and blunted increases in cardiac index and RV stroke volume. Although acute oxygen supplementation was associated with a slight decrease in RV systolic pressure at peak exercise and a longer duration of exercise, there was no significant improvement in RV function. Doppler echocardiography and CT provide complementary and potentially useful information about right-sided heart pressures and RV ejection fraction during exercise in patients with advanced chronic lung disease. Oxyhemoglobin desaturation during exercise is a marker for the most abnormal pulmonary vascular reserve, as indicated by RV contractile dysfunction and limited ability to increase cardiac index.

Aged↗

Retention of chromosome 3 in extrapulmonary small cell cancer shown by molecular and cytogenetic studies.

In small cell lung carcinoma, one of the short arms of chromosome 3 is typically lost. To investigate chromosome 3 in extrapulmonary small cell carcinoma, we used DNA probes that detect restriction-fragment-length polymorphisms at loci on 3p. These probes were used to study DNA extracted from tumors and normal tissues and/or tumor cell lines from five patients with extrapulmonary small cell cancer. Tumor DNA from four of the five patients with extrapulmonary small cell cancer retained heterozygosity at loci on 3p. Cytogenetic studies of the tumor cell lines established from these four patients showed retention of both short arms of chromosome 3. We conclude that the loss of genetic material from 3p observed in small cell lung cancer is not typical in extrapulmonary small cell cancer.

Adult↗

Purification of a sarcoplasmic reticulum protein that binds Ca2+ and plasma lipoproteins.

A protein in the sarcoplasmic reticulum of rabbit skeletal and cardiac muscle was identified because of its ability to bind 125I-labeled low density lipoprotein (LDL) with high affinity after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein, referred to as the 165-kDa protein, is restricted to striated muscle. It was not detected in 14 other tissues, including several that contain smooth muscle, but it appears in rat L6 myoblasts when they differentiate into myocytes. Immunofluorescence and immunoelectron microscopic studies revealed that the protein is present throughout the sarcoplasmic reticulum and the terminal cisternae. It binds 45Ca2+ on nitrocellulose blots and stains metachromatically with Stains-all, a cationic dye that stains Ca2+-binding proteins. It does not appear to be a glycoprotein, and it appears slightly larger than the 160-kDa glycoprotein previously described in sarcoplasmic reticulum. The 165-kDa protein binds LDL, beta-migrating very low density lipoprotein, and a cholesterol-induced high density lipoprotein particle that contains apoprotein E as its sole apoprotein with much higher affinity than it binds high density lipoprotein. The protein is stable to boiling and to treatment with sodium dodecyl sulfate, but it becomes sensitive to these treatments when its cystine residues are reduced and alkylated. The protein was purified 1300-fold to apparent homogeneity from rabbit skeletal muscle membranes. It differs from the cell surface LDL receptor in that 1) its apparent molecular weight is not changed by reduction and alkylation; 2) it is present in Watanabe-heritable hyperlipidemic rabbits, which lack functional LDL receptors; 3) binding of lipoproteins is not inhibited by EDTA; and 4) it is located within the lumen of the sarcoplasmic reticulum where it has no access to plasma lipoproteins. It is unlikely that this protein ever binds lipoproteins in vivo; however, its lipoprotein binding activity has facilitated its purification to homogeneity and suggests that this protein has unusual structural features. The role of the 165-kDa protein in Ca2+ homeostasis in the sarcoplasmic reticulum, if any, remains to be determined.

Adrenal Glands↗

Metabolic behavior of cell surface biotinylated proteins.

The turnover of proteins on the surface of cultured mammalian cells was measured by a new approach. Reactive free amino or sulfhydryl groups on surface-accessible proteins were derivatized with biotinyl reagents and the proteins solubilized from culture dishes with detergent. Solubilized, biotinylated proteins were then adsorbed onto streptavidin-agarose, released with sodium dodecyl sulfate and mercaptoethanol, and separated on polyacrylamide gels. Biotin-epsilon-aminocaproic acid N-hydroxysuccinimide ester (BNHS) or N-biotinoyl-N'-(maleimidohexanoyl)hydrazine (BM) were the derivatizing agents. Only 10-12 bands were adsorbed onto streptavidin-agarose from undervatized cells or from derivatized cells treated with free avidin at 4 degrees C. Two-dimensional isoelectric focusing-sodium dodecyl sulfate gel electrophoresis resolved greater than 100 BNHS-derivatized proteins and greater than 40 BM-derivatized proteins. There appeared to be little overlap between the two groups of derivatized proteins. Short-term pulse-chase studies showed an accumulation of label into both groups of biotinylated proteins up until 1-2 h of chase and a rapid decrease over the next 1-5 h. Delayed appearance of labeled protein at the cell surface was attributed to transit time from site of synthesis. The unexpected and unexplained rapid disappearance of pulse-labeled proteins from the cell surface was invariant for all two-dimensionally resolved proteins and was sensitive to temperature reduction to 18 degrees C. Long-term pulse-chase experiments beginning 4-8 h after the initiation of chase showed the disappearance of derivatized proteins to be a simple first-order process having a half-life of 115 h in the case of BNHS-derivatized proteins and 30 h in the case of BM-derivatized proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminocaproates↗

Effect of prostaglandin F3 alpha on gastric mucosal injury by ethanol in rats: comparison with prostaglandin F2 alpha.

In humans eicosapentaenoic acid can be converted to 3-series prostaglandins (PGF3 alpha, PGI3, and PGE3). Whether 3-series prostaglandins can protect the gastric mucosa from injury as effectively as their 2-series analogs is unknown. Therefore, we compared the protective effects of PGF3 alpha and PGF2 alpha against gross and microscopic gastric mucosal injury in rats. Animals received a subcutaneous injection of either PGF3 alpha or PGF2 alpha in doses ranging from 0 (vehicle) to 16.8 mumol/kg and 30 min later they received intragastric administration of 1 ml of absolute ethanol. Whether mucosal injury was assessed 60 min or 5 min after ethanol, PGF3 alpha was significantly less protective against ethanol-induced damage than PGF2 alpha. These findings indicate that the presence of a third double bond in the prostaglandin F molecule between carbons 17 and 18 markedly reduces the protective effects of this prostaglandin on the gastric mucosa.

Alprostadil↗

Thermal conduction effects associated with temperature measurements in proximity to radiofrequency electrodes and microwave antennas.

The smearing effects due to thermal conduction along various, nonenergized, interstitial devices were quantified in a flow cell-thermal step gradient. An insulated cylindrical flow cell with a high (ca 45 degrees C, 1.12 cm i.d., 1.6 cm o.d.) temperature region surrounded by a low (ca 37 degrees C) temperature region was used to compare temperature profiles measured with a thermocouple sensor inside a Stanford radiofrequency (RF) hyperthermia/brachytherapy catheter, a BSD instrumented microwave (MW) antenna (i.e., thermistor integrated into a dipole antenna) and a Dartmouth MW antenna with a juxtaposed optical sensor. Two parameters were used to quantify the thermal smearing of each interstitial device in the flow cell: (a) the maximum temperature difference (MTD) and (b) the full- width- half-maximum (FWHM) of the high temperature region. The "true" temperature maximum (45.4 degrees C) and distribution (FWHM = 1.65 +/- 0.06 cm) were measured with an optical sensor. These data indicate that the BSD instrumented MW antenna significantly smeared the true temperature profile (MTD = 2.7 degrees C, FWHM = 2.1 cm), as did the Dartmouth MW antenna (MTD = 1.5 degrees C, FWHM = 1.7 cm). The Stanford RF catheter, when insulated, resulted in minimal smearing (MTD = 0.3 degrees C, FWHM = 1.9 cm). Moreover, when the insulation was removed so the RF electrode was exposed to the thermal step gradient, smearing was again minimal (MTD = 0.3 degrees C, FWHM = 1.9 cm).

Brachytherapy↗

Potential exposure of cooks to airborne mutagens and carcinogens.

Recent case-control and proportionate mortality studies in Canada, the United States, Britain, and Denmark have shown that cooks and other food-service workers may have elevated risks of cancers of the nasopharynx, buccal cavity, esophagus, lung, and bladder. The purpose of this pilot study was to determine if there might be airborne products of cooking which may be risk factors for these cancers in cooks. Eight air samples were taken in four restaurants and subsequently analyzed for mutagenicity using the Ames assay, and for carcinogens using gas chromatography/mass spectrometry. All four samples taken in the restaurant cooking areas were mutagenic to TA98 without metabolic activation, and two were mutagenic to TA100 also without metabolic activation. Of the four dining area samples, one was mutagenic to TA100 and one to TA98, both without metabolic activation. Compounds tentatively identified by mass spectrometry did not include known carcinogens. The ventilation systems in all four restaurants allow the exposure of cooks to both the air from dining room smoking areas and the volatile products of cooking.

Air Pollutants, Occupational↗

Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin.

Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen-glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full-thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 microns, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was greater than 5 x 10(4) cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physiochemical structure, functioning as a transient basal lamina during morphogenesis of skin.

Animals↗

Effects of fish oil on gastric mucosal 6-keto-PGF1 alpha synthesis and ethanol-induced injury.

Fundic mucosal content and synthesis of 6-ketoprostaglandin F1 alpha, the major prostanoid in the rat gastric mucosa, were determined after rats had ingested a diet containing 10% fish oil or 10% corn oil for 4 wk. 6-Ketoprostaglandin F1 alpha content and synthesis in rats fed a fish oil-supplemented diet were reduced significantly compared with rats receiving a corn oil-supplemented diet (P less than 0.05). However, rats receiving 10% fish oil for 8 wk sustained significantly less gastric mucosal injury after intragastric challenge with 15% and then with absolute ethanol than rats receiving 10% corn oil or regular chow for 8 wk (P less than 0.05). Thus fish oil ingestion protected the gastric mucosa even though fish oils reduced mucosal prostaglandin synthesis.

6-Ketoprostaglandin F1 alpha↗

Noninvasive evaluation of pulmonary artery pressure during exercise by saline-enhanced Doppler echocardiography in chronic pulmonary disease.

To determine the feasibility of noninvasive determination of right ventricular systolic pressure (RVSP) during a graded-exercise protocol, saline contrast-enhanced Doppler echocardiography of tricuspid insufficiency was performed in 36 patients with chronic lung disease and 12 normal controls. In the patients with chronic pulmonary disease, symptom-limited, incremental supine bicycle exercise and pulse oximetry were performed on and off high-flow oxygen. Technically adequate Doppler studies were initially obtained in 20 patients (56%) at rest and 14 (39%) on exercise; these numbers increased to 33 (92%) and 32 (89%), respectively, after enhancement with agitated saline (both p less than 0.001). In 10 patients with chronic lung disease who had simultaneous hemodynamic monitoring during exercise, the correlation between Doppler and catheter measurements of pulmonary artery systolic pressure was close (r = 0.98). Among controls, RVSP increased from 22 +/- 4 at rest (mean +/- SD) to 31 +/- 7 mm Hg at peak exercise. In patients with chronic lung disease, RVSP increased from 46 +/- 20 to 83 +/- 30 mm Hg (both p less than 0.001 vs. controls). Despite normal resting values for RVSP in 28% of study patients, nearly all showed abnormal increases in RVSP during supine bicycle exercise. Increases in RVSP during exercise were greatest in patients who showed oxyhemoglobin desaturation. The short-term administration of oxygen significantly blunted the increase in RVSP during exercise. Saline contrast-enhanced Doppler evaluation of tricuspid insufficiency seems a potentially valuable noninvasive method of determining the exercise response of RVSP in patients with chronic pulmonary disease.

Adult↗

Chloroperoxidase-catalyzed oxidation of aminopyrine.

Although in the absence of halide ion chloroperoxidase did not catalyze the ethylhydroperoxide (EHP)-supported oxidation of aminopyrine, in the presence of Br- or Cl-, chloroperoxidase did catalyze the oxidation of aminopyrine, generating the aminopyrine cation radical (AP+). The initial rate of AP+ formation was determined by monitoring the absorbance at 565 nm. The pH optimum of the reaction was centered around 5.0. The rate of AP+ formation showed typical Michaelis-Menten saturation kinetics with respect to EHP, aminopyrine and Br-. The rate of formation of bromine in the chloroperoxidase-EHP-Br- system was also determined by measuring the change in absorbance at 267 nm. In the system containing 1 mM EHP and 0.2 M KBr at pH 5.0, the rate was 1.8 nmol of bromine/s/micrograms of chloroperoxidase, which was slower than that of AP+ formation under the same conditions. The present results suggest that the formation of AP+ is initiated by the halogenation of the N,N-dimethylamino group followed by the homolysis of the haloammonium cation, and that the most likely halogenating reagent is an enzyme-bound halogenating intermediate.

Aminopyrine↗

Functional human CD4 protein produced in milk of transgenic mice.

The soluble form of human CD4, an HIV receptor molecule first detected on the surface of T cells, binds glycoprotein gp120, a coat protein of human immunodeficiency virus, and has potential value for the treatment of AIDS. As a first step toward providing the necessary quantities of this protein at an affordable price we report here on the production of functional, soluble human CD4 in transgenic mice. In these animals, a regulatory region derived from a murine gene encoding the whey acidic protein directs synthesis of human CD4 protein to the mammary gland of lactating animals where it is secreted into milk.

Acquired Immunodeficiency Syndrome↗

Bone marrow peroxidase in mice: determination of the level and the catalytic activity.

The level of myeloperoxidase and the peroxidase activity in the bone marrow were determined in the various strains of mice. The levels of myeloperoxidase, which was determined by a immunostaining coupled with sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE), were ranged from 3 to 5 micrograms per mg protein in the bone marrow of various strains of mice. No strain difference of the enzyme activity toward guaiacol was observed among mice. On the other hand, the activity toward KI of C3H/He mice was lower than C57BL/6, Balb/c and ddY mice.

Animals↗

Ambulatory and intraoperative transesophageal echocardiography.

Transesophageal echocardiography is a relatively new imaging technique that is rapidly evolving into a major tool for general cardiac imaging in a variety of venues. This article focuses on the current probe technology, the technique of performing transesophageal echocardiography, standard anatomic image views used, and currently accepted indications for intraoperative and ambulatory transesophageal echocardiography.

Ambulatory Care↗

Isolation and sequence analysis of serine protease cDNAs from mouse cytolytic T lymphocytes.

Three new cDNA clones (designated MCSP-1, MCSP-2, and MCSP-3) encoding mouse serine proteases were isolated from cloned cytolytic T lymphocytes (CTL) by a modified differential screening procedure. The putative mature proteins of MCSP-2 and MCSP-3 are each composed of 228 amino acids with molecular weights of 25,477 and 25,360, respectively. NH2-terminal amino acids of MCSP-2- and MCSP-3-predicted proteins were identical to those reported for granzyme E and F, respectively. The third species, MCSP-1, was closely related to the two other cDNA species but approximately 30 amino acids equivalents of the NH2-terminal portion of the cDNA were not cloned. The amino acids forming the active sites of serine proteases were well conserved among the three predicted proteins. The active site pocket residue positioned six residues before the active-site Ser184 is alanine in MCSP-1, threonine in MCSP-2, and serine in MCSP-3, indicating that both MCSP-2 and MCSP-3 may have chymotrypsin-like specificity. There are three potential asparagine-linked glycosylation sites in MCSP-1 and MCSP-3, and four in MCSP-2-deduced amino acid sequences. Amino acid comparison of MCSP-1 with four other reported serine proteases whose active site pocket residue is alanine revealed that MCSP-1 was substantially different from the other molecules, indicating that MCSP-1 may be a new member of mouse T cell serine protease family. Antibodies made against a MCSP-1 lacZ gene fusion protein stain granules of CTL and react on immunoblots with two distinct granule protein bands of 29 and 35-40 kD. Only the 35-kD species labels with [3H]DFP. Since a protease cascade may play a key role in cytolytic lymphocyte activation, our isolation of cDNAs representative of unique serine esterases should help to investigate such a cascade process.

Amino Acid Sequence↗

Inactivation of peroxidases of rat bone marrow by repeated administration of propylthiouracil is accompanied by a change in the heme structure.

Myeloperoxidase and eosinophil peroxidase were isolated from the bone marrow cells of rats treated with or without propylthiouracil (PTU) which caused bone marrow depression. PTU treatment decreased the activity of myeloperoxidase but not of eosinophil peroxidase using guaiacol as the electron donor. However, when KI,N-N'-dimethyl-p-phenylenediamine and pyrogallol were used as the electron donor, the activity of only eosinophil peroxidase was inhibited by PTU treatment. EPR spectra indicated that the structure of myeloperoxidase surrounding the heme iron changed from a rhombic form into an axial one by the repeated administration of PTU. Therefore, the inactivation of peroxidases by PTU treatment was accompanied by an alteration of their structures surrounding the heme.

Animals↗

Relationship between Campylobacter pylori and gastritis in healthy humans after administration of placebo or indomethacin.

Endoscopic and microscopic appearances of antral and fundic mucosa were correlated with the presence or absence of Campylobacter pylori--and with plasma immunoglobulin G antibodies to that organism--in 23 healthy volunteers, 12 of whom had received indomethacin and 11 of whom had received no medication. Antral C. pylori, found in 9 of 23 biopsy specimens (3 of 11 controls, 6 of 12 indomethacin-treated patients; not significantly different), correlated strongly with histologic evidence of active superficial antral gastritis (p less than 0.005), but not with the endoscopic appearance of the antrum. In contrast to the antrum, fundic C. pylori, found in 14 of 23 biopsy specimens (61%), were frequently associated with histologically and endoscopically normal fundic mucosa. Campylobacter pylori-associated active antral gastritis occurred only in subjects whose fundus harbored this organism. Plasma immunoglobulin G antibody titers to C. pylori were highest in subjects with Campylobacter-associated antral gastritis and lowest in subjects without gastric Campylobacter. These studies suggest that healthy humans may harbor C. pylori in their proximal stomach without apparent ill effects. In some of these individuals, the organism also involves the antrum and is associated with active gastritis.

Adult↗