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Biomedical subjects

C Orr

Publications and source records attributed to C Orr.

At least 19 recordsLinked to original sources

Multipotent progenitor cells isolated from adult human pancreatic tissue.

The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus.

Adult↗

Inhibition of p38 mitogen-activated protein kinase protects human islets from cryoinjury and improves the yield, viability, and quality of frozen-thawed islets.

The development of an optimal islet cryopreservation method will permit transplantation of islets from multiple donors in a single procedure and contribute to alleviation of the islet shortage. In this study, we have improved human islet cryopreservation methods under serum-free conditions using an intracellular-based islet cryopreservation solution (ICS), especially supplemented with a p38 pathway inhibitor (p38IH) to suppress p38 mitogen-activated protein kinase (MAPK) activation. Three different solutions were compared for freezing and thawing of human islets (1) conventional RPMI1640 medium, (2) ICS, and (3) ICS supplemented with a p38IH, SD-282 (ICS-p38IH). Islet cryopreservation with ICS-p38IH significantly improved islet recovery, viability, and quality after thawing of cryopreserved islets. This improvement may allow the use of cryopreserved islets in clinical islet transplantation.

Cell Culture Techniques↗

The impact of the classroom environment on defining function in school-based practice.

OBJECTIVE: Whether the environment is stressed in function-dysfunction decisions appears to depend on where in the hierarchy of components of complex tasks and of role skills the evaluating therapist is focused. This study examined the intervention planning decisions of occupational therapists who used the Model of Student Role Adaptation, which emphasizes the complex tasks involved in the student role. The purpose of the study was to determine whether these therapists were responding to environmental demands in planning their interventions. METHOD: Special education teachers selected tasks that they believed were the most essential for student functioning within their classroom environments. These selections were compared with the goals and objectives developed by occupational therapists who serve children in these settings. RESULTS: Chi square analysis indicated a significant relationship between tasks designated by the teacher participants as environmental demands and those included in occupational therapy intervention planning. CONCLUSION: The results suggest that the occupational therapist participants were responding to the environmental demands of the classroom when constructing their intervention plans.

Activities of Daily Living↗

Nitrogen kinetics of infectious bovine rhinotracheitis-stressed calves.

Eight crossbred feeder steers were used in two consecutive N balance studies to investigate the effects of infectious bovine rhinotracheitis virus (IBRV) on N kinetics. Balance Study 1, which followed a 10-d acclimation phase, consisted of 7 d of sample collection referred to as the healthy phase (d -7 to d -1). Study 2, the IBRV-infected phase, began 2 d after a nasal IBRV challenge and continued for 6 d (d 2 to d 8). A stable isotope, [15N]-glycine, was used to determine N kinetics in both studies. Steers weighed 203 kg at the beginning of the study, 208 kg at IBRV infection and 194 kg at the end of study. Infection with IBRV increased (P less than .05) urinary N excretion from 17.9 to 31.5 g/d. Daily N balance was reduced (P less than .05) during infection from 21.2 to -3.3 g/d. Total serum proteins increased (P less than .05) during infection from 6.6 to 7.1 g/100 ml, the increase being predominantly in the alpha and gamma globulin fractions. Blood urea-N increased (P less than .05) during infection from 6.5 to 12.9 mg/100 ml. The urine excretion curve of the stable isotope and the N balance data indicated that IBRV infection increased N turnover and altered tissue utilization of N.

Animals↗

Hemispheric asymmetries in phonological processing assessed with probe evoked magnetic fields.

Auditory Evoked Magnetic Fields (EFs) to tonal stimuli were recorded at homotopic maxima over the left and right auditory areas in nine subjects. Recordings were made during two conditions, both involving simultaneous presentation of the probe tone stimuli and a set of tape-recorded verbal material. During the control condition subjects were instructed to attend to the tones and ignore the verbal material. In the phonological processing condition they were instructed to ignore the tones and attempt to identify a phonological target item which was embedded in the verbal material. EFs obtained during both conditions were characterized by an early N1m and a later P2m component corresponding to the N1 and P2 components of auditory evoked potentials (EPs). During the phonological condition, the amplitude of the N1m was significantly reduced in both hemispheres symmetrically whereas the amplitude of the P2m was attenuated to a significantly greater degree in the left hemisphere. These data are in agreement with previous EP evidence of greater interference of linguistic processing with processing of irrelevant probe stimuli in the left hemisphere, indicative of greater left hemisphere involvement in language tasks.

Acoustic Stimulation↗

Status of the myocardium and infarct-related coronary artery in 19 necropsy patients with acute recanalization using pharmacologic (streptokinase, r-tissue plasminogen activator), mechanical (percutaneous transluminal coronary angioplasty) or combined types of reperfusion therapy.

In acute myocardial infarction, myocardial salvage is dependent on rapid restoration of blood flow. Pharmacologic (streptokinase, recombinant tissue-type plasminogen activator), mechanical (percutaneous transluminal coronary angioplasty, guide wire perforation) or combined forms of reperfusion therapy can accomplish this goal, but their effects on infarcted myocardium and vessel occlusion site have not been compared at necropsy. The heart of 19 necropsy patients who had received various forms of acute reperfusion therapy was studied: 14 had pharmacologic or combined forms of reperfusion therapy (13 streptokinase and 1 tissue-type plasminogen activator, including 4 with combined balloon angioplasty) and 5 had had purely mechanical (balloon angioplasty) reperfusion therapy. Reperfusion was initially clinically successful in all 19 patients with the average time from onset of symptoms to reperfusion being 3.7 hours. Necropsy observations separated the 19 patients into distinct subgroups based on changes in the myocardium and infarct-related coronary arteries. Of the 19 patients, 14 (74%) had hemorrhagic myocardial infarction and they all received pharmacologic or combined forms of reperfusion therapy. The remaining five patients (26%) had nonhemorrhagic (anemic) infarction and were treated with balloon angioplasty therapy alone. Increased luminal cross-sectional area was present in 8 of 9 patients with acute balloon angioplasty but severe coronary atherosclerotic plaque remained in 9 of 10 patients without acute balloon angioplasty. Severe hemorrhage surrounded angioplasty sites in all four patients who also received streptokinase or tissue-type plasminogen activator. Severe bleeding at the angioplasty site compromised the dilated coronary lumen in one patient. No patient with angioplasty alone had intraplaque bleeding. Thus, acute coronary balloon angioplasty reperfusion therapy alone appears to avoid the potentially adverse effects of myocardial and intraplaque hemorrhage while simultaneously increasing luminal cross-sectional area at the site of acute occlusion.

Adult↗

The sensitivity of different coagulation reagents to the presence of lupus anticoagulants.

The sensitivity and responsiveness of seven activated partial thromboplastin time reagents to the presence of lupus anticoagulants (LAs) was evaluated with a panel of 50 well-characterized LA plasmas. The results document that some reagents are clearly less responsive and sensitive to LAs; however, there is considerable variability between individual LA samples in these features. In addition, with 16% of these samples, immediate mixing studies showed correction of the activated partial thromboplastin time to the normal range with a 1:1 mixture of normal and LA plasma and 8% to 10% showed either a normal platelet neutralization procedure or a normal tissue thromboplastin inhibition procedure. Together, these findings provide further evidence of the laboratory heterogeneity of these inhibitors. The effect of this variability on the diagnosis of these inhibitors is discussed.

Blood Coagulation Disorders↗

BIOETHICSLINE: an overview for searchers.

The BIOETHICSLINE File (BIOETHICS) is a bibliographic database produced at the Kennedy Institute of Ethics, Georgetown University, and made available online through the the National Library of Medicine's MEDLARS system. BIOETHICS provides multidisciplinary coverage of the ethical, legal, and public policy aspects of medicine, health care, and biomedical and behavioral research. This article describes the content and development of the database, suggests effective strategies for searching, and presents illustrative searches. An appendix lists selected major indexing terms (Keywords) from the controlled vocabulary of the Bioethics Thesaurus.

Bioethical Issues↗

Inhibition by deoxycytidine, cytidine, and beta-cytosine arabinoside of the induction of alkaline phosphatase activity in HeLa cells.

The main objective of these experiments was the further examination of whether the induction of alkaline phosphatase activity in HeLa cells by 5-iodo-2'-deoxyuridine (IdUrd) depends on the incorporation of IdUrd into DNA. Thymidine (dThd), deoxycytidine (dCyd), cytidine, and beta-cytosine arabinoside (Ara-C) inhibited a dose-dependent manner the induction of alkaline phosphatase activity by IdUrd in HeLa cells, and 5-iodo-2'-deoxycytidine induced activity in a dose-dependent manner at concentrations similar to those of IdUrd. Three of these compounds, dThd, dCyd, and Ara-C, were studied with regard to degree of inhibition of induction and IdUrd incorporation into DNA. Although the various doses of these three compounds decreased the incorporation of IdUrd into DNA, there was no apparent linear correlation between the extent of inhibition of IdUrd incorporation and the degree of inhibition of the induction of alkaline phosphatase activity. dCyd also inhibited a dose-dependent manner the induction of alkaline phosphatase by hydrocortisone, sodium butyrate, and choline chloridee. These results, although not unequivocal, support the idea that IdUrd induction of alkaline phosphatase activity in HeLa cells does not require IdUrd incorporation into DNA. The dCyd altered the thermostability for alkaline phosphatase activity from control or IdUrd-treated cells, and for controls cells the change in thermostability occurred without a change in the enzyme specific activity.

Alkaline Phosphatase↗