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Biomedical subjects

L Collins

Publications and source records attributed to L Collins.

At least 19 recordsLinked to original sources

Status of kappa L chain gene rearrangements and c-kit and IL-7 receptor expression in stromal cell-dependent pre-B cells.

Studies from several laboratories have provided evidence that distinct stromal cell-derived signals are involved in the maturation of pre-B cells into surface Ig expressing B lymphocytes. In order to define the stage of development at which these stimuli act, various polymerase chain reaction strategies were used to characterize the status of kappa L chain gene rearrangements in nontransformed, stromal cell dependent pre-B cells. These cells were obtained from lymphoid colonies whose growth was potentiated by factors from a stromal cell line. kappa L chain genes in cells from many of these colonies were rearranged, and analysis of the Jk genes used indicated a bias toward the most 3' loci. However, the use of a reverse transcriptase PCR strategy failed to detect mature kappa transcripts, indicating that stromal cell mediators exist that allow pre-B cells to progress to the stage at which L chain genes are rearranged but not expressed. Reverse transcriptase PCR further revealed that no transcripts for c-kit (the receptor for kit-ligand) and the IL-7R could be detected in these cells. This suggests that these receptors are no longer expressed by the time cells have undergone kappa rearrangements and minimize a role for stromal cell-derived kit-ligand and IL-7 in mediating the pre-B to B cell transition.

Animals

Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies.

The molecules essential to the continual morphogenesis and shedding of the opsin-containing disks of vertebrate photoreceptors are largely unknown. We describe a 37 kd protein, rom-1, which is 35% identical and structurally similar to peripherin/retinal degeneration slow (rds). Like peripherin, rom-1 is a retina-specific integral membrane protein localized to the photoreceptor disk rim. The two proteins are similarly oriented in the membrane, and each has a highly conserved (15/16 residues) cysteine- and proline-rich domain in the disk lumen. Although both rom-1 and peripherin form disulfide-linked dimers, they do not form heterodimers with each other, but appear to associate noncovalently. These results suggest both that rom-1 and peripherin are functionally related members of a new photoreceptor-specific protein family and that rom-1, like peripherin, is likely to be important to outer segment morphogenesis. The association of mutations in RDS with retinitis pigmentosa indicates that ROM1 is a strong candidate gene for human retinopathies.

Adult

Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy.

To evaluate the effect of thrombin on the dynamics of thrombolysis, we infused rabbits with heparin or hirudin alone or in conjunction with tissue-type plasminogen activator (t-PA) and monitored the kinetics of fibrinolysis and changes in ex vivo platelet aggregation responses over time. Both heparin and hirudin enhanced total fibrinolysis in an ex vivo arteriovenous shunt preparation: 82 +/- 2% and 79 +/- 2%, respectively, compared with 51 +/- 8% for t-PA alone (P less than 0.05) and 50 +/- 4% for t-PA plus aspirin (p less than 0.05). Heparin coadministered with t-PA significantly reduced the half-time for clot lysis compared with t-PA alone (p less than 0.05), whereas hirudin coadministered with t-PA significantly reduced the half-time for clot lysis compared with that for t-PA alone, t-PA plus aspirin, and t-PA plus heparin (5.5 +/- 0.6 versus 12.1 +/- 2.0 versus 12.6 +/- 2.2 versus 10.0 +/- 0.8 minutes, respectively; p less than 0.05). Both heparin and hirudin prevented the increase in ADP-induced platelet aggregation normally seen with t-PA alone (p less than 0.01 by t test; p less than 0.05 by two-way analysis of variance). These data demonstrate that selective, antithrombin III-independent thrombin inhibitors can enhance the efficacy of thrombolysis by modulating the dynamics of the process and preventing platelet activation associated with plasminogen activator therapy.

Animals

MRI-PET correlation in three dimensions using a volume-of-interest (VOI) atlas.

Quantitative interpretation of functional images (PET or SPECT) is hampered by poor spatial resolution, low counting statistics, and, for many tracers, low contrast between different brain structures of interest. Furthermore, normal tracer distributions can be severely disrupted by such gross pathologies as stroke, tumor, and dementia. Hence, the complementary anatomical information provided by CT or MRI is essential for accurate and reproducible regional analysis of functional data. We have developed methods for the simultaneous three-dimensional display and analysis of image volumes from MRI and PET. A general algorithm for defining the affine transformation between two equivalent point ensembles has been adapted for the purpose of registering MRI and PET image volumes by means of a simple fiducial arrangement. In addition, we have extended previous MRI-based computerized atlas methodology to three dimensions. The native atlas planes were spaced at 2 mm intervals, sufficient axial sampling to permit the generation of oblique planar sections through the atlas space. This will allow for an infinite number of angulations and axial offsets in two-dimensional region-of-interest (ROI) templates, all derived from the same master three-dimensional volume-of-interest (VOI) atlas and therefore maintaining topographical consistency throughout. These ROI templates may be selected to match the image orientation for conventional two-dimensional segmentation and data extraction.

Adult

Longitudinal splitting of the peroneus brevis tendon: an anatomic and histologic study of cadaveric material.

Gross and microscopic examinations of 21 split and 10 intact cadaveric peroneus brevis tendons were performed in an effort to determine the pathogenesis of longitudinal splitting of this tendon. The split regions were centered over the posterior margin of the distal fibula and were characterized by splaying of the collagen bundles with accompanying proliferation of blood vessels and fibrovascular connective tissue. Inflammatory infiltrates were not present. Regions of the tendons that were not altered had normal cellularity and orientation of the collagen. The findings of this study suggest that the splitting of the tendon develops through a mechanical mechanism.

Adult

Theory Z as a framework for the application of a professional practice model in increasing nursing staff retention on oncology units.

Recruitment and retention of nurses is the most significant issue facing nursing administrators, educators, researchers and clinicians in the ongoing nursing shortage in the United States today. It has been cited in the literature that American nurses feel that job satisfaction is a major issue in retaining qualified nurses in hospitals. Satisfaction occurs when nurse expectations are matched with the hospital's vision and values. It is for this purpose that the authors have chosen theory Z as a hospital management model to coincide with the institution of the Marker Professional Practice Model to increase job satisfaction (autonomy) in hospital-based nurses. There are four 'hidden' challenges in health care today. They are: (a) fundamental changes occurring within the profession and practice of nursing; (b) the expanded role of women in management; (c) ethical dilemmas related to advances in medical technologies; and (d) the difficulty for health care managers in the United States to make changes related to the above three challenges. The authors feel that it is inherent to the nursing profession to combine existing theories and models to enhance the retention of nurses to the profession.

Hospital Units

Integration of stereoscopic DSA with three-dimensional image reconstruction for stereotactic planning.

Following 4 years of experience using a microcomputer-based system for the planning of stereotactic neurosurgery, we have now developed a workstation with the capability of displaying and analyzing three-dimensional images for this purpose. In addition to viewing volumetrically rendered three-dimensional computer tomograms and magnetic resonance images, we may directly view and analyze stereoscopic digital angiograms. In addition to each set of images being viewed in isolation, we may also combine the three-dimensional anatomical images with the stereoscopic angiograms. This new system is based on a computer equipped with a light polarization switched screen capable of displaying stereoscopic images directly to the observer, thus permitting him to interact with the three-dimensional volume directly, determining coordinates and positioning probe trajectories.

Angiography, Digital Subtraction

Magnetoencephalography and late component ERPs.

The recent emergence of magnetoencephalography is a development that is already yielding results. Its intrinsic sensitivity to the actual source activity, rather than to volume currents, means that its particular value lies in source localization. As well as having proven value in research relating to early evoked response and epilepsy, biomagnetic measurements have been applied to later components. For example, results for the auditory P300 potential indicate the source to lie either in the temporal cortex or the hippocampus. More definite conclusions await further development of the instrumentation. Also, there is much scope for more sophisticated analysis of the magnetic fields, of the electric potentials, or ideally of both together. This is likely to elucidate the largely unknown functional circuitry corresponding to the late components of the response.

Brain Diseases

Clinical applications of integrated 3-D stereoscopic imaging in neurosurgery.

Stereotactic neurosurgery planning, an intrinsically three-dimensional procedure, is generally performed on the basis of two-dimensional tomographic or projection images. We present extensions to these conventional approaches that use stereoscopic digital subtraction angiography, three-dimensional volume rendered computed tomography or magnetic resonance images, or a combination of these modalities. The stereoscopic DSA images are analysed interactively on a 3-D workstation. This system employs a liquid-crystal polarizing shutter to display alternate left- and right-eye views to a user wearing polarized glasses. Quantitative planning operations may be performed on the basis of the angiograms alone, or in conjunction with tomographic images of the anatomy. We also describe the procedures used to produce volume-rendered three-dimensional images from MR and CT data-sets, as well as the methodology for combining the stereoscopic angiograms with the volumetric anatomical images.

Algorithms

Stereotactic neurosurgery planning on a personal-computer-based work station.

Stereotactic surgery requires knowledge of cerebral structures derived from more than one image source. We have developed a PC-AT-based workstation that accepts patient images, made with the stereotactic frame in place, from CT, MRI, and DSA modalities. Reference markers on the frame are identified in the images to establish the coordinate geometry for each modality. Target points may be identified on each image type and trajectories of probe paths to these points defined. Targets identified on one set of images may be transferred automatically to other images of the same patient in order to guarantee a vessel-free path of approach to a target point deep within the brain. To date several hundred patients have had stereotactic surgery performed on the basis of plans using this system. Procedures included biopsy and aspiration of lesions, implantation of electrodes for the recording of deep EEG signals, and radiosurgical techniques. We present clinical examples of the use of this system in typical stereotactic neurosurgery procedures, address stereoscopic applications, and discuss the results of intermodality tests to establish the accuracy of the technique.

Angiography, Digital Subtraction

Lasers in medicine--some current issues.

Although lasers have been applied to medical and surgical problems for many years, it is only recently that a significant momentum has been created. Lasers are now a routine part of many medical and surgical procedures. This article surveys a selection of current technical issues in this rapidly changing field, including applications in angioplasty, gastroenterology, dentistry, gynaecology, ophthalmology, lithotripsy, biostimulation and safety. As far as possible, only work published in the last three years is covered.

Equipment Safety

Identification of specific residues of human interleukin 2 that affect binding to the 70-kDa subunit (p70) of the interleukin 2 receptor.

Analogs of interleukin 2 containing defined amino acid substitutions and deletions were assayed for bioactivity and for competitive binding to the high-affinity human interleukin 2 receptor complex and its two component subunits, a 55-kDa subunit (p55 or TAC) and a 70-kDa subunit (p70). Substitution of Asp20 or deletion of Phe124 resulted in inactive analog proteins that were unable to interact with the high-affinity p55/p70 complex or the intermediate-affinity p70 subunit of the interleukin 2 receptor. These analogs, however, retained the capacity to compete for binding to the low-affinity p55 subunit. The presence of the carboxylic acid in the side chain of Asp20 was necessary for effective binding to the p70 protein. In contrast, substitution of Trp121 and Leu17 created analogs that were inactive in the bioassay and all three binding assays. The effects of these mutations on protein conformation were assessed by circular dichroism. These results demonstrate that specific residues in the NH2 and COOH termini of interleukin 2 are crucial for its structure and activity.

Binding, Competitive

Structure-function analysis of human interleukin-2. Identification of amino acid residues required for biological activity.

To locate functional domains of the interleukin-2 (IL-2) protein, a cDNA clone encoding biologically active human IL-2 was mutagenized using synthetic oligonucleotides to incorporate defined amino acid substitutions and deletions in the mature protein. The IL-2 analogs were then produced in Escherichia coli and assayed for the ability to induce proliferation of IL-2-dependent cells and the ability to compete for binding to the IL-2 receptor. Our analysis of over 50 different mutations demonstrated that the integrity of at least three regions of the IL-2 molecule is required for full biological activity: the NH2 terminus (residues 1-20), the COOH terminus (residues 121-133), and 2 of the 3 cysteine residues (58 and 105). Deletion of the NH2-terminal 20 amino acids or the COOH-terminal 10 amino acids resulted in the loss of greater than 99% of bioactivity and binding. Amino acid substitutions at specific positions in these regions also resulted in proteins which retained less than 1% activity. The NH2 terminus and an adjacent internal region were recognized by neutralizing anti-IL-2 antibodies. In combination with the results from epitope competition analysis with neutralizing antibodies, these data are consistent with the IL-2 protein being folded such that the NH2 terminus, the COOH terminus, and the internal 30- to 60-region are juxtaposed to form the binding site recognized by the IL-2 receptor.

Amino Acid Sequence

Time series analyses of respiratory responses to indoor and outdoor environmental phenomena.

A time series analysis was utilized to evaluate respiratory responses to outdoor and indoor air pollutant and aeroallergen exposures in potentially sensitive adults in a dry arid environment. Daily symptoms and peak flows were recorded in populations of asthmatics, allergic individuals, those with chronic lung disease symptoms, and asymptomatic individuals (total sample size of 204) over a period of a few years. Meteorology and ambient pollutant concentrations were measured in the basin. Indoor pollutant measurements were made for particulates and CO, indicating that gas stoves and tobacco smoking were the predominant indoor sources. Time series analysis helped determine appropriate lags between environmental stimuli and health responses. Asthmatics showed that most respiratory responses while asymptomatics showed no significant responses. Outdoor ozone, nitrogen dioxide, aeroallergens and meteorology, and indoor gas stoves were significantly related, independently and interactively, with symptoms and peak flow.

Air Pollutants