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Biomedical subjects

W Glenn

Publications and source records attributed to W Glenn.

16 recordsLinked to original sources

Signaling through surface IgM in tolerance-susceptible immature murine B lymphocytes. Developmentally regulated differences in transmembrane signaling in splenic B cells from adult and neonatal mice.

During the course of B lymphocyte development, newly emerging surface Ig+ B cells pass through a stage when Ag-Ag receptor interactions lead not to immune responsiveness but to a state of functional tolerance. We have explored the molecular basis of antigenic nonresponsiveness and tolerance susceptibility using tolerance-susceptible surface Ig+ splenic B lymphocytes from neonatal mice and anti-mu chain antibodies as a polyclonal ligand. In this population of cells, surface IgM is uncoupled from the inositol phospholipid (PI)-hydrolysis pathway at a point proximal to the receptor; anti-mu antibodies did not stimulate inositol phosphate generation despite the fact that PI-hydrolysis was observed after treatment with A1F4, implicating the existence of a functional G protein and phospholipase C. Further evidence for a difference early in the signal transduction pathway stems from the finding that anti-mu stimulation does not induce the expression of two immediate/early PKC-linked genes egr-1 and c-fos. This appears to be the primary signaling difference between the mature and immature B cells from the neonatal mouse splenic population, as these cells undergo a G0-G1 cell cycle phase transition when surface IgM is bypassed using phorbol diester and calcium ionophore. Interestingly, despite undetectable levels of PI-hydrolysis, we observed equivalent receptor-mediated changes in intracellular calcium when comparing the immature and mature populations. These results indicate incomplete coupling of surface IgM to the signal transduction machinery operative in mature, immunocompetent B cells and suggests a molecular mechanism accounting for the differential processing of surface IgM signals into activation vs tolerogenic responses observed in these two stages of B cell development.

Aging

Verbal fluency deficits in female alcoholics.

Verbal fluency deficits in female alcoholics (n = 48) were investigated using Thurstone's Word Fluency Test (TWFT) and a category fluency test. Overall, alcoholics performed less well than did controls (n = 36). Simple effects indicate that although controls performed less well on category fluency than on the TWFT, alcoholics did not differ between the two tests. Simple effects also show that controls' performance was superior to that of alcoholics on the category fluency test, but the groups did not differ on the TWFT. The pattern of results suggests that the process of shifting rapidly between categories is more difficult than perusing a mental lexicon. Correlations between these tasks and other tests of cognitive functioning suggest that the TWFT and the category fluency test may be assessing different types of verbal fluency.

Adult

Egr-1 expression in surface Ig-mediated B cell activation. Kinetics and association with protein kinase C activation.

We have studied the expression of an immediate/early type gene, Egr-1, in murine B lymphocyte responses to Ag receptor-generated signals. The Egr-1 gene encodes a zinc finger protein with sequence-specific DNA binding activity and is believed to act as an intracellular "third messenger," to couple receptor-generated signals to activation-associated changes in gene expression. We show here that Egr-1 mRNA expression is rapidly and transiently (returning to basal levels by 6 h) induced after receptor crosslinking with anti-receptor antibodies. Egr-1 protein expression is more prolonged, maintaining detectable levels through 12 h. The induction of Egr-1 is a primary response to Ag receptor signaling, as it is independent of new protein synthesis and is inhibited by actinomycin D. We have also examined the linkage of Egr-1 to known signaling pathways associated with G0 to G1 transition by these cells in response to signals generated through the B cell Ag receptor. Egr-1 mRNA was not induced after elevation of intracellular free Ca2+. In contrast, the pharmacologic agents PMA and SC-9, which directly activate protein kinase C, both cause marked increases in Egr-1 mRNA levels with the same kinetics as observed after anti-receptor antibody stimulation. Further, the protein kinase C inhibitors H7, sangivamycin, and staurosporin block anti-receptor antibody-induced expression of Egr-1, thus, B cell Ag receptor-linked Egr-1 expression is likely coupled to the protein kinase C component of transmembrane signaling. Preliminary promoter mapping studies are consistent with this conclusion, because both PMA and anti-receptor antibody act through the same or overlapping cis-regulatory elements.

Animals

Lateral lumbar spinal canal stenosis: classification, pathologic anatomy and surgical decompression.

The lateral region of the lumbar spinal canal is subject to pathologic alterations which encroach upon the neural structures located within. In order to further understanding and facilitate communication among specialists in diverse disciplines, a subdivision of the lateral region is proposed to comprise three zones: entrance zone, mid-zone and exit zone. The anatomical boundaries of these zones are defined and the pathologic conditions of each are described, and serve as the basis for techniques of surgical decompression when clinically required.

Humans

MRI simulator for instruction in pulse-sequence selection.

An ordinary desk-top microcomputer was programmed to simulate MR images for specified spin-echo pulse sequences. Model pixel maps of proton density and T1 and T2 relaxation times were made from published estimated values for regions of the human head, neck, and spine. Images were generated and displayed from the model maps and user-specified pulse-sequence parameters in less than 30 sec/image. Models for various pathologic conditions, including calcification, subacute hemorrhage, porencephaly, lipoma, and multiple sclerosis, were superimposed on the images of normal anatomy to create unknown cases. Simulated images can easily demonstrate the effect of pulse-sequence selection on the contrast of normal structures and pathologic conditions. Use of simulated images is an excellent technique for gaining experience in pulse-sequence selection. Low-cost microcomputers can provide adequate image detail and reasonable image display time of synthetic MR images for teaching purposes.

Computer-Assisted Instruction

Anatomic-ultrasound correlations for intraoperative open chest imaging of coronary artery atherosclerotic lesions in human beings.

This study was performed to further validate a method for intraoperative ultrasound imaging of coronary arteries. Ultrasound images of coronary atherosclerotic lesions were compared with anatomic specimens of the coronary arteries obtained from open chest human subjects. The anatomic specimens were derived from four cardiac transplant recipients, accepted as candidates for transplantation because they had severe diffuse atherosclerotic disease, and one patient who died in the early postoperative period after a coronary artery bypass procedure. Twenty-six ultrasonically imaged atherosclerotic areas of the coronary arteries in these patients were compared with formalin-fixed and decalcified anatomic specimens. Specific ultrasound appearances for atherosclerotic lesions were observed, including 1) discrete (focal) stenosing fibrous/atheromatous plaques; 2) diffuse nonobstructive fibrous/atheromatous disease (detectable even in anatomically small vessels); 3) complete occlusion by fibrous/atheromatous lesions or organizing thrombus; and 4) "shadowing," an ultrasound pattern characteristic of significant calcification within atherosclerotic plaques. As part of this study, a new 12 MHz water path probe was evaluated for coronary artery scanning. The new probe allowed improved access to coronary arteries and increased detail of anatomic visualization. Both the performance of the new high resolution probe and the knowledge gained by the anatomic correlations obtained in this study should aid the development of intraoperative coronary artery scanning for surgical localization of atherosclerotic disease during coronary bypass surgery.

Adult

Foot-pounds of torque of the normal knee and the rehabilitated postmeniscectomy knee.

Foot-pounds of torque of the knee flexors and knee extensors of eight rehabilitated patients who had had meniscectomies were obtained isometrically and at 60 and 210 degrees per second by use of an isokinetic apparatus. Our purpose was to test the null hypothesis that no significant difference in torque would be manifested between the rehabilitated postmeniscectomy knee and the normal knee. Mean torque developed by the rehabilitated postoperative knee was 10 to 12 percent less than the mean torque developed by the normal knee. We found a significant difference between means of torque of the normal knee and the rehabilitated knee for isometric flexion, rapid dynamic flexion, and rapid dynamic extension. Means of torque of knee extension for the three types of contraction for both knees of the subjects demonstrated similar patterns in which torque developed isometrically was greater than torque developed by slow dynamic tension, which in turn was greater than torque developed by rapid dynamic contraction. Means of torque of knee flexion for the three types of contraction for both knees of the subjects created patterns in which torque developed isometrically was essentially equal to torque developed by slow dynamic tension, and both these measurements exceeded torque developed by rapid dynamic contractions. Overall, the results suggest that physical therapists need to use rehabilitative techniques that promote muscular power and muscular endurance in addition to muscular strength and that more attention needs to be directed to the rehabilitation of knee flexors.

Adolescent

Utilization of computed tomography scanners and the health planning issue: a process data summary.

Studies were made of the computed tomography (CT) scanning process at three hospitals. The data collected, while of interest to hospital administrators and radiologists, are particularly significant in view of the current structure of health planning guuielines. The data show clearly that the utilization potential of a particular CT scanner is a function of patient demand, scan time, the ratio of head to body procedures, and medical practice insofar as contrast medium administration is concerned. This paper summarizes the results of the hospital studies and documents the implications of the data for health planning guidelines.

Adult

The comparative effects of (Ca2+) and (Mg2+) on on tension generation in the fibers of skinned frog skeletal muscle and mechanically disrupted rat ventricular cardiac muscle.

The effects of intracellular Mg2+ on Ca2+-activated isometric tension generation in rat cardiac muscle fibers and frog skeletal muscle were compared. The membranous sarcolemmal barrier was removed from rat cardiac muscle fibers by mechanical disruption and from frog skeletal muscle by skinning. Tension was recorded in the fibers in bathing solutions of different Ca2+ concentrations and either 5 X 10(-5) M or 1 X 10(-3) M Mg2+ concentration (the same concentrations used in a previous study on single skinned frog skeletal muscle fibers [3]). The amount of Ca2+ required to activate the muscle increased with Mg2+ concentration for both rat ventricular muscle and frog skeletal muscle. These data indicate that intracellular Mg2+ concentration could strongly modulate Ca2+-activated tension in cardiac muscle and that very similar molecular mechanisms are responsible for Ca2+-activated tension in rat ventricular muscle and frog skeletal muscle. The possible sites of action of Mg2+ on Ca2+-activated tension are discussed.

Animals

Pacemaker synchronization.

A method using the standard radio-frequency receiver was developed to telemeter biopotentials across the intact body Wall; it can be employed to program a stimulus to the heart at any phase of the cardiac cycle. The small variations of potential across the electrodes of the implanted cardiac pacemaker change the natural resonant frequency of the receiver in direct relation to the electrical activity of the heart.

Animals

Computer processing of CT images: advances and prospects.

Computerized tomography (CT) images are created by computer and as such are inherently amenable to computer image processing techniques. Advances have been made in the areas of alternative visualization (coronal views, etc.), image enhancement, feature extraction, and computer analysis of the extracted information. Further advances await imaginative application of these techniques and time; others will depend upon necessary advances in image processing methods.

Computers