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Biomedical subjects

I Miller

Publications and source records attributed to I Miller.

106 records · Page 6Linked to original sources

Proteins of rat serum: III. Gender-related differences in protein concentration under baseline conditions and upon experimental inflammation as evaluated by two-dimensional electrophoresis.

We have previously described the major components of rat serum (Electrophoresis 1998, 19, 1484-1492 and 1493-1500). In this report we examine sex-related differences in protein concentrations, both in control animals and upon experimentally induced inflammation. Under baseline conditions approximately one third of the spots resolved in serum by two-dimensional electrophoresis (2-DE) are expressed at levels > or =25% higher in female rats than in male rats and a further 10% at levels > or =25% lower. Inflammation increases the expression of the positive acute-phase reactants: hemopexin, ceruloplasmin, alpha1-antitrypsin (all approximately 2-fold), C-reactive protein (3- to 5-fold), serine protease inhibitor-3 (4- to 5-fold), thiostatin (> 5-fold in females, >20-fold in males), clusterin, orosomucoid, haptoglobin chains and alpha2-macroglobulin. The baseline level of the last four markers is below the detection limit, hence no percent increase can be computed. Conversely, negative acute-phase reactants are reduced on inflammation: alpha1-inhibitor III, alpha2-HS-glycoprotein, kallikrein-binding protein and transthyretin (all reduced to between 1/2 to 1/3 of the baseline levels), retinol-binding protein (to about 1/2 to 1/4) and albumin (to 2/3). Except for thiostatin, the changes in acute-phase protein levels are similar in male and female rats.

Acute-Phase Proteins↗

Proteins of rat serum IV. Time-course of acute-phase protein expression and its modulation by indomethacine.

Changes in the concentration of major serum proteins were monitored from day 0 to day 4 in three experimental groups: rats injected with turpentine, rats receiving the turpentine shot and daily doses of indomethacine, and rats given indomethacine alone. In inflamed animals, peak changes for acute-phase reactants, evaluated by two-dimensional electrophoresis (2-DE), were usually observed between 48 and 72 h after the phlogistic stimulus. By itself, indomethacine was found to affect the synthesis of most proteins (except one of the thiostatin variants and ceruloplasmin); the changes in serum levels, whether positive or negative, were the same as upon inflammation (except for kallikrein-binding protein), but their extent and/or timing usually differed. When inflamed animals were given indomethacine, a clear-cut difference in the concentration of some proteins was observed versus inflamed rats not given medication, at 24 h after the start of the treatments. Proteins mainly affected were alpha2-macroglobulin, alpha2-HS-glycoprotein, C-reactive protein and kallikrein-binding protein.

Acute-Phase Proteins↗

Determination of the optimal imaging parameters of the RODEO pulse sequence by computer simulation.

A computer program has been developed for evaluating the NMR signal response of various imaging parameters and its efficiency in fat suppression of the RODEO (ROtating Delivery of Excitation Off-resonance) pulse sequence. Both spoiled and refocused RODEO pulse sequences have been considered. By numerically solving the Bloch equation modified for a three-dimensional volume of spins, for realistic RF excitations and Lorentzian distribution of the frequency spectrum for both fat and water, the program permits the imaging contrast and fat suppression of the RODEO pulse sequences to be assessed quantitatively. We have found that excellent fat suppression can be achieved by choosing appropriate imaging parameters. Imaging contrast for different tissues can be enhanced by using longer repetition time (TR) in the spoiled scheme. The complex pattern of NMR signal response and imaging contrast has been observed in the refocused scheme.

Adipose Tissue↗

Functional characterization of NGF-secreting cell grafts to the acutely injured spinal cord.

Previously we reported that grafts of cells genetically modified to produce human nerve growth factor (hNGF) promoted specific and robust sprouting of spinal sensory, motor, and noradrenergic axons. In the present study we extend these investigations to assess NGF effects on corticospinal motor axons and on functional outcomes after spinal cord injury. Fibroblasts from adult rats were transduced to express human NGF; control cells were not genetically modified. Fibroblasts were then grafted to sites of midthoracic spinal cord dorsal hemisection lesions. Three months later, recipients of NGF-secreting grafts showed deficits on conditioned locomotion over a wire mesh that did not differ in extent from control-lesioned animals. On histological examination, NGF-secreting grafts elicited specific sprouting from spinal primary sensory afferent axons, local motor axons, and putative cerulospinal axons as previously reported, but no specific responses from corticospinal axons. Axons responding to NGF robustly penetrated the grafts but did not exit the grafts to extend to normal innervation territories distal to grafts. Grafted cells continued to express NGF protein through the experimental period of the study. These findings indicate that 1) spinal cord axons show directionally sensitive growth responses to neurotrophic factors, 2) growth of axons responding to a neurotrophic factor beyond an injury site and back to their natural target regions will likely require delivery of concentration gradients of neurotrophic factors toward the target, 3) corticospinal axons do not grow toward a cellular source of NGF, and 4) functional impairments are not improved by strictly local sprouting response of nonmotor systems.

Acute Disease↗

Grafts of genetically modified Schwann cells to the spinal cord: survival, axon growth, and myelination.

Schwann cells naturally support axonal regeneration after injury in the peripheral nervous system, and have also shown a significant, albeit limited, ability to support axonal growth and remyelination after grafting to the central nervous system (CNS). It is possible that Schwann cell-induced axonal growth in the CNS could be substantially increased by genetic manipulation to secrete augmented amounts of neurotrophic factors. To test this hypothesis, cultured primary adult rat Schwann cells were genetically modified using retroviral vectors to produce and secrete high levels of human nerve growth factor (NGF). These cells were then grafted to the midthoracic spinal cords of adult rats. Findings were compared to animals that received grafts of nontransduced Schwann cells. Spinal cord lesions were not placed prior to grafting because the primary aim of this study was to examine features of grafted Schwann cell survival, growth, and effects on host axons. In vitro prior to grafting, Schwann cells secreted 1.5+/-0.1 ng human NGF/ml/10(6) cells/day. Schwann cell transplants readily survived for 2 wk to 1 yr after in vivo placement. Some NGF-transduced grafts slowly increased in size over time compared to nontransduced grafts; the latter remained stable in size. NGF-transduced transplants were densely penetrated by primary sensory nociceptive axons originating from the dorsolateral fasciculus of the spinal cord, whereas control grafts showed significantly fewer penetrating sensory axons. Over time, Schwann cell grafts also became penetrated by TH- and DBH-labeled axons of putative coerulospinal origin, unlike control cell grafts. Ultrastructurally, axons in both graft types were extensively myelinated by Schwann cells. Grafted animals showed no changes in gross locomotor function. In vivo expression of the human NGF transgene was demonstrated for periods of at least 6 m. These findings demonstrate that primary adult Schwann cells 1) can be transduced to secrete augmented levels of neurotrophic factors, 2) survive grafting to the CNS for prolonged time periods, 3) elicit robust growth of host neurotrophin-responsive axons, 4) myelinate CNS axons, and 5) express the transgene for prolonged time periods in vivo. Some grafts slowly enlarge over time, a feature that may be attributable to the propensity of Schwann cells to immortalize after multiple passages. Transduced Schwann cells merit further study as tools for promoting CNS regeneration.

Animals↗

Performance of current procedural terminology codes by oncology nurses: a report to the ONS board of directors.

At the request of the ONS Board of Directors, a survey was conducted to determine the degree to which oncology nurses performed services listed in the Physicians Current Procedural Terminology manual--services for which physicians are reimbursed. Using a format modeled on a similar study of nurses in general, 100 randomly selected ONS members were asked to describe the degree to which they performed a list of 90 coded procedures compiled by four oncology nurse experts. Response rate was 43%. Respondents, who were representative of the ONS membership on all demographic variables except education, performed an average of 32 of the procedures with very little, if any, direct physician supervision. Study results reflect trends found among nurses in general and raise important questions about patterns of reimbursement and healthcare delivery.

Abstracting and Indexing↗

Acute stroke patients comparing outcomes with and without case management.

Stroke represents a major human and economic challenge to society. The literature suggests that interdisciplinary clinical pathways maximize stroke patient outcomes, whether care is delivered in a designated stroke unit or in a general medical service. In this article, the authors describe the case management model implemented at Columbus Regional Hospital, a 325-bed rural referral hospital in southeastern Indiana. A retrospective chart review compared 23 patients with non-hemorrhagic strokes using two different models of care delivery: unit-based nursing case management and standard nursing care. Differences in outcomes are reported in relation to interdisciplinary utilization, timeliness of referrals, patient education, discharge dispositions, home safety assessments, next-site-of-care communications, length of hospital stay, and patient satisfaction.

Acute Disease↗