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Biomedical subjects

D A Weber

Publications and source records attributed to D A Weber.

At least 19 recordsLinked to original sources
PubMed1992

Sequences in both class II major histocompatibility complex alpha and beta chains contribute to the binding of the superantigen toxic shock syndrome toxin 1.

Class II major histocompatibility complex (MHC) molecules present peptides derived from processed antigen to antigen-specific CD4-positive T cells. In addition, class II molecules bind with high affinity another class of antigens, termed superantigens. T cell stimulation by superantigens depends almost exclusively on the V beta segment expressed by the T cell receptor (TCR). Mapping of the superantigen binding site on class II molecules should provide valuable information on how MHC and TCR molecules interact. Recombinant mouse I-A class II molecules expressed on transfected L cells were analyzed for their ability to bind the toxic shock syndrome toxin 1. Polymorphic residues in the alpha helices of both the alpha and beta chains of I-A contributed to quantitative toxin binding, suggesting that the toxin binds to either a combinatorial or a conformational site on class II MHC molecules.

Animals↗
PubMed1992

Effect of pattern of aerosol inhalation on clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid from the lungs of normal humans.

The clearance rate of inhaled aerosols of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from the lungs provides a rapid, clinically useful, noninvasive index of pulmonary epithelial permeability. In order to identify a method that minimizes intrasubject and intersubject variability and thereby provides a reliable means to identify patients with abnormal values, we administered a submicronic aerosol of 99mTc-DTPA to 10 healthy, nonsmoking male subjects with either tidal breathing (Vtidal) or multiple vital capacity maneuvers (VVC). Subjects then spontaneously breathed room air while counting continued for 30 min. Monoexponential clearance rates over 7, 15, and 30 min were compared with a two-compartment, biexponential analysis over 30 min. Intrasubject reproducibility was evaluated by repeating clearance 2 to 156 days later. Monoexponential clearance following VVC at 30 min equaled 1.36 +/- 0.55%/min compared with 0.83 +/- 0.25%/min for Vtidal (p less than 0.025). VVC inhalations resulted in a larger fast compartment of 16 +/- 12% compared with 3 +/- 2% with tidal breathing (p less than 0.01). The least intrasubject variability with coefficient of variation (CV) of +/- 18% was obtained with monoexponential analyses after Vtidal during 15 min of scanning and with either breathing maneuver over 30 min. Monoexponential clearance for 30 min with Vtidal gave the least scatter between subjects, with CV of +/- 30%. These data show that simple tidal inhalations of 99mTc-DTPA followed by a monoexponential analysis of the 30-min time-activity curve from both lungs minimize the degree of variability between and among subjects and provide a predicted normal value of clearance of 0.83 +/- 0.25%/min. The development of a more rapid curvilinear clearance followed by delivery VVC suggests that several deep breaths transiently increase epithelial permeability or reduce the volume of liquid in the alveolar subphase in some regions. Resting for 20 min prior to inhaling the aerosol of 99mTc-DTPA is recommended to avoid alterations in clearance rates from deep breathing.

Administration, Inhalation↗
PubMed1992

Enhanced healing of cutaneous wounds in rats using beads with positively charged surfaces.

The efficacy of electrical fields in soft-tissue repair is unclear. Materials with a charged surface provide a localized charged environment. We examined the effects of surface-charged particles in wound healing in rats with paired dorsal incisions with one side serving as a control. Tensiometry demonstrated that after 10 days, wounds with positively charged particles were 53 percent stronger (p less than 0.001) than controls (10 rats, 30 wound strips), whereas differences with negatively charged (6 rats, 15 strips) or uncharged beads (11 rats, 33 strips) were insignificant. Histologically, wounds with positively charged particles were characterized by large quantities of collagen-rich connective tissue and by prominent bead-associated giant cells. At 94 days, no differences in wound strength were noted. This method of creating charged local environments has potential clinical implications and may add insights into the behavior of cells in response to charged stimuli.

Analysis of Variance↗
PubMed1991

Measuring body fat: calibrating the rulers. Intermethod comparisons in 389 normal Caucasian subjects.

A systematic study of 389 normal Caucasians stratified for sex and age compared all of the traditional methods for measuring fat: body water, underwater weighing, body potassium, and anthropometrics and the newer methods of dual-photon absorptiometry, bioimpedance analysis, and total body electrical conductivity. Measurements by all methods are highly intercorrelated, but methods differences show the population means for fat percent to range from 26 to 35% of body weight across eight methods. All methods show increasing fat (as % body weight) with age in both sexes but vary in secular slope. The goal of this report is to provide direct translations between each of the eight methods. Intermethod comparison equations are given as simple linear regressions by using each method both as dependent and independent variable for each sex, permitting translation for results by any method to any other.

Adipose Tissue↗
PubMed1991

Increased lung permeability following long-term use of free-base cocaine (crack).

The clearance of inhaled 99mTc DTPA aerosol from the lungs is used as an index of lung epithelial permeability. Using the radioaerosol method, we investigated the effects of long-term "crack" (free-base cocaine) inhalation on lung permeability in 23 subjects. Eighteen control subjects (12 nonsmokers and 6 cigarette smokers) with no history of drug use were also studied. Subjects inhaled approximately 150 muCi (approximately 5.6 MBq) of 99mTc DTPA aerosol and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 minutes. Regions of interest (ROIs) were selected to include the following: (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc DTPA lung clearance was determined from the slopes of the respective time-activity plots for the different RIOs. Radioaerosol clearance half-times (T1/2) for the seven nonsmoking crack users (61.5 +/- 18.3 minutes) were longer than for the seven cigarette-smoking crack users (27.9 +/- 16.9 minutes) and nine cigarette-smoking crack plus marijuana users (33.5 +/- 21.6 minutes). T1/2 for the nonsmoking crack users was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 minutes). T1/2 for the cigarette-smoking drug users was similar to that of the cigarette-smoking control group (33.1 +/- 17.8 minutes), suggesting a similar mechanism of damage from the smoke of crack and tobacco. From these groups, one nonsmoker and 11 cigarette smokers displayed biexponential 99mTc DTPA clearances, indicative of greater lung injury than found in the usual cases of monoexponential clearance. The upper lungs of all crack users groups cleared faster than the lower lungs. The faster and biexponential clearance properties of inhaled 99mTc DTPA aerosol were the principal functional abnormalities found in all the drug users. In contrast, 19 of 23 crack users had normal spirometry and gas exchange. These results indicate that 99mTc DTPA may provide a sensitive and useful assay to evaluate the physiologic effects of cocaine inhalation in the lung.

Adult↗
PubMed1991

Imaging of cocaine-induced global and regional myocardial ischemia.

Severe and often fatal cardiac complications have been reported in cocaine users with narrowed coronary arteries caused by atherosclerosis as well as in young adults with normal coronaries. We have found that in normal dogs cocaine induces severe temporary hypoperfusion of the left ventricle as indicated by a significantly lower 201Tl concentration compared to the baseline state. The most significant decrease in uptake occurred 5 min after injection and was more pronounced in the septal and apical segments. Following intravenous administration of cocaine, instead of gradual disappearance of 201Tl from the left ventricle, there was continuous increase in 201Tl concentration in the left ventricle. These imaging experiments indicate that the deleterious effects of cocaine on the heart are probably due to spasm of the coronaries and decreased myocardial perfusion. Since spasm of the large subpericardial vessels does not seem to explain the magnitude of the increased coronary resistance and decreased coronary flow after cocaine as described in the literature, it is suggested that microvascular spasm of smaller vessels plays a major role in the temporary decrease in perfusion. The data may also suggest that severe temporary myocardial ischemia is probably the initiating factor for the cardiac complications induced by cocaine.

Animals↗
PubMed1991

Effects of visual stimulation on the redistribution of iodine-123-IMP in the brain using SPECT imaging.

A study was performed to validate the assumption that redistribution and clearance of [123I]IMP localization in the brain are unaffected by changes in ambient light levels and visual stimulation occurring after radiopharmaceutical is administered and deposited in the brain. Serial SPECT and planar imaging studies were performed on six healthy, volunteer, adult male subjects under resting, nonactivation conditions. Studies were repeated 7 days later with each subject exposed to strobe light stimulation prior to delayed SPECT procedures at 3 hr. Redistribution and clearance of 123I-IMP in the brain were examined in cortical, subcortical, and cerebellar regions on transaxial slices for the two sets of serial procedures in each subject. Visual stimulation following the initial uptake of [123I]IMP did not affect the distribution or clearance of [123I]IMP in the brain, including the visual cortex, and therefore should not influence the interpretation of delayed SPECT images.

Adult↗
PubMed1990

High precision in-vivo neutron activation analysis: a new era for compartmental analysis in body composition.

We have focused on two topics in body composition research. The first is basic: we must quantitatively define the interrelationships of the body compartments to one another in health before studying these relationships in disease. The precisions now available can enable us to get to do this work, over the full range of age, race, and occupational diversity. The second direction is more modest and more technical, but nonetheless important. It is the calibration and validation of surrogate measurement methods suitable for field research conditions, doctors' offices, intensive care units, etcetera. Our methods have advanced in fundamental ways. We have an obligation to see them applied effectively.

Adipose Tissue↗
PubMed1990

Cross-modal functions in alcoholism and aging.

Two experiments were performed to measure separate aspects of cross-modal functions in normal and alcoholic research participants: matching, and utilization of concepts. In Experiment 1, cross-modal equivalence-matching was measured, i.e. the ability to select in a second modality (e.g. vision), the same stimulus that was first presented in a different modality (e.g. touch). Experiment 2 measured cross-modal transfer of information about stimulus dimensions, i.e. the ability to recognize and use the concepts of texture and form, based upon prior experience solving tactual problems, to solve visual problems. Fifty-five normal and alcoholic research participants comprised the following five groups: 13 young normals (YN) and 10 young alcoholics (YA), 28-48 years of age; 13 older normals (ON) and 14 older alcoholics (OA), 50-71 years of age; and 5 alcoholic Korsakoff patients (K), 55-68 years of age. Separate subgroups of 9 age-matched ONs and 9 OAs were devised for purposes of statistical analyses of data involving the 5 Ks. Results of the experiments indicated that aging is associated with decline in tactual discrimination ability. Further, cross-modal functions appear to be compromised by alcoholic Korsakoff's disease, and--to a lesser extent--by the combined effects of alcoholism and normal chronological aging. Brain mechanisms important for normal cross-modal functions are discussed.

Adult↗
PubMed1990

A novel chromosomal TEM derivative and alterations in outer membrane proteins together mediate selective ceftazidime resistance in Escherichia coli.

A clinical Escherichia coli isolate (MG32) resistant to ceftazidime but susceptible to other third-generation cephalosporins was previously examined and found to harbor TEM-1 and exhibit alterations in outer membrane proteins. Reexamination of this isolate revealed the additional presence of a novel TEM-1 derivative, now designated TEM-12. Evaluation of ceftazidime and cefotaxime minimum inhibitory concentrations for isogenic derivatives demonstrated a major role for TEM-12 in the decreased susceptibility observed. This was selectively enhanced for ceftazidime resistance by the altered porins of E. coli MG32. TEM-12 appeared identical to TEM-101, an in vitro TEM derivative, in both isoelectric point (pI 5.25) and substrate profile. Hybridization and cloning of the TEM-12 determinant revealed that, unlike other TEM derivatives, TEM-12 is chromosomally encoded, not plasmid-encoded.

Bacterial Outer Membrane Proteins↗
PubMed1990

Emotional perception and memory in alcoholism and aging.

The ability to identify and recognize emotional materials was studied in 10 male alcoholic Korsakoff patients, 27 male non-Korsakoff alcoholics, and 31 male nonalcoholic controls, across a wide age range (23 to 77 years). Stimulus materials were presented in two sensory modalities; the materials were photographs of faces expressing one of four emotions (happy, sad, angry, or neutral), and recordings of sentences with emotional intonations or semantic meanings expressing the same four emotions. Results of the experiments showed consistently severe deficits in emotional functions in the Korsakoff patients, but only minor alterations in the non-Korsakoff alcoholics. Older subjects, whether or not they had a history of alcoholism, also exhibited significant deficits on most of the tasks. Results of the study did not provide strong support for the premature aging hypothesis of alcoholism, which suggests that alcoholism accelerates aging, beginning either at the onset of heavy drinking early in adult life, or later in life after the normal manifestations of aging have begun to appear. Results are related to brain mechanisms in emotional perception and memory functions.

Adult↗
PubMed1990

Diverse potential of beta-lactamase inhibitors to induce class I enzymes.

The ability of various beta-lactamase inhibitors to induce class I beta-lactamases was assessed. Clavulanate was the most active compound, inducing Morganella morganii, Aeromonas caviae, and Enterobacter aerogenes over a broad concentration range and Citrobacter freundii, Pseudomonas aeruginosa, and Serratia marcescens at high concentrations. Disk approximation tests paralleled these results, with clavulanate, but not sulbactam or tazobactam, antagonizing the activity of several beta-lactams against these organisms.

Anti-Bacterial Agents↗
PubMed1990

Beta-lactamase production in members of the family Enterobacteriaceae and resistance to beta-lactam-enzyme inhibitor combinations.

Recent reports that members of the family Enterobacteriaceae that produce high levels of certain beta-lactamases are often resistant to ticarcillin-clavulanate prompted this study to assess the relationship between type and amount of enzyme produced and susceptibility to ticarcillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam. Agar dilution MICs were determined by using 73 strains of Enterobacteriaceae that produced a single beta-lactamase that had been characterized and quantified and a beta-lactamase-negative control strain of Escherichia coli. For E. coli and Klebsiella pneumoniae, MICs of each combination increased as levels of TEM, SHV-1, or class IV enzymes increased. However, the percentage of strains that were resistant was highest for ticarcillin-clavulanate (32%), with only 18 and 6% resistant to piperacillin-tazobactam and cefoperazone-sulbactam, respectively. Strains producing PSE-1, regardless of level, were resistant or moderately susceptible to ticarcillin-clavulanate but were susceptible to piperacillin-tazobactam and cefoperazone-sulbactam. HMS-1 and OHIO-1 beta-lactamases were associated with resistance to ticarcillin-clavulanate and piperacillin-tazobactam, respectively. High levels of class IV enzymes in Klebsiella oxytoca were associated with resistance to all three combinations. These results indicate that the level and type of beta-lactamase produced by members of the family Enterobacteriaceae are important determinants of susceptibility to beta-lactam-inhibitor combinations, especially ticarcillin-clavulanate.

Anti-Bacterial Agents↗
PubMed1990

Class II MHC molecules are spontaneously internalized in acidic endosomes by activated B cells.

The antibody response to protein antigens requires specific cooperation between B and T cells. In order to deliver the helper signal, T cells must recognize, in the context of Class II MHC, processed antigen on the membrane of B cells. Processed antigen is in the form of peptides bound in a given site of the Class II MHC molecule; in order to address the question of where, in the B cell, the complex of Class II MHC and processed antigen is formed, we studied the subcellular localization of these two molecules. Since the formation of this complex is the crucial step in antigen processing and presentation, the answer to this question is central to the whole problem of the physiology of antigen handling by B cells. To collect information pertinent to the question, we have compared, in B cells, the intracellular traffic of Class II MHC and of monovalent and divalent anti-immunoglobulin antibodies used as protein ligands of the membrane immunoglobulins. We have done so by two-color immunofluorescence microscopy, and we have detected extensive confluence of Class II MHC molecules with the immunoglobulin ligand, both mono- and bi-valent, in the endosomes of LPS-activated murine B cells. Whereas the ligand clearly reaches the endosomes by internalization from the cell membrane, the Class II MHC molecules could reach the same location either by endocytosis from the membrane or through targeting to the endosomes of newly synthesized Class II MHC molecules. We have collected quantitative evidence for endocytosis of Class II MHC by following, with the fluorescence activated cell sorter, the quenching of the fluorescence of fluoresceinated Fab' anti Class II MHC in LPS-activated murine B cells; this quenching indicates the entry of the label into an acidic intracellular compartment. Together with the results of others, obtained with different methods, our observations support the concept that, at least in mature activated B cells, Class II MHC molecules reach the organelles where they meet processed protein antigens, mainly through the endocytic route. Since activated B cells endocytose their membrane Class II MHC, and not their membrane Class I, our results contribute to the understanding of how B cells present antigens, that have bound to their membrane immunoglobulins, to Class II-restricted helper T cells and not to Class I-restricted cytolytic T cells.

Animals↗
PubMed1989

Differential endocytosis of IgM and IgD in murine B cell lines.

The internalization of surface immunoglobulin (Ig) by B lymphocytes is the first step in the antigen-presenting function performed by these cells. Mature B cells coexpress on their surface IgM and IgD. At this time, there is controversy over whether these two isotypes serve different functions in the antigen-presenting process. The results presented here show that the intracellular pattern of distribution of IgM and IgD after internalization is strikingly different in the B cell lines studied. These findings support the hypothesis that the role of the two Ig classes in the antigen-presenting function may be different.

Animals↗
PubMed1989

Studies of a new fatty acid analog (DMIVN) in hypertensive rats and the effect of verapamil using ARG microimaging.

Studies of myocardial utilization of fatty acids and analogs has focused on coronary heart disease. This study addresses the topic of radioiodinated fatty acid utilization in hypertensive-cardiomyopathy. The new fatty acid analog 19-iodo-3,3-dimethyl-18 nonadecenoic acid (DMIVN) was studied by autoradiographic microimaging (ARG) in salt-sensitive (S) hypertensive (salt-fed) and in salt-sensitive (S) normotensive (low-salt diet), Dahl-strain rats. A salt fed, S-strain group was treated with verapamil and the results were compared to those in a hypertensive, non-treated group. The distribution of DMIVN in the hearts of normotensive rats was uniform. In the myocardium of hypertensive rats nonuniform DMIVN concentration was seen in the subendocardial and mid-layers of the left ventricle (LV). Verapamil given to salt-fed rats prevented hypertension and uniform DMIVN uptake similar to normotensive controls was seen. The data suggest that DMIVN may be suitable for the detection of hypertension induced myocardial changes and for assessing therapy. The distribution and clearance characteristics of DMIVN indicate that DMIVN may be a useful agent for SPECT imaging in man.

Animals↗