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Biomedical subjects

M Carroll

Publications and source records attributed to M Carroll.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of crosslinking UHMWPE on its tensile and compressive creep performance.

The in vitro quasi-static tensile and compressive creep properties of three sets of GUR 1050 ultra-high-molecular-weight polyethylene (UHMWPE) specimens were obtained. These sets were: control (as-received stock); "low-gamma" (specimens were crosslinked using gamma radiation, with a minimum dose of 5 Mrad); and "high-gamma" (specimens were crosslinked using gamma radiation, with a minimum dose of 15 Mrad). The % crystallinity (%C) and crosslink density (rho(x)) of the specimens in the three sets were also obtained. It was found that, in both tension and compression, crosslinking resulted in a significant depreciation in the creep properties, relative to control. The trend in the creep results is explained in terms of the impact of crosslinking on the polymer's %C and rho(x). The present results are in contrast to literature reports that show that crosslinking enhances the wear resistance of the polymer. The implications of the present results, taken together with the aforementioned literature results, are fully discussed vis-a-vis the use of crosslinked UHMWPE for fabricating articular components for arthroplasties.

Biocompatible Materials↗
PubMed2000

Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks.

PURPOSE: To identify a recommended phase II dose for the second generation glycinamide ribonucleotide transformylase (GARFT) inhibitor, AG2034, administered by intravenous bolus every 3 weeks without folate supplementation and to describe AG2034 pharmacokinetics. METHODS: Adults with advanced malignancies were enrolled in cohorts of three per dose level with expansion to six upon observation of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was defined as the dose at which two of up to six patients experienced DLT. Upon identification of an MTD and evidence of cumulative toxicity, a lower intermediate dose was explored as a candidate phase II dose. AG2034 plasma concentrations were measured using an ELISA assay. RESULTS AND CONCLUSIONS: The recommended phase II dose is 5.0 mg/m2. DLTs were anemia, thrombocytopenia, mucositis, diarrhea, hyperbilirubinemia, fatigue, and insomnia. Toxicities were modestly cumulative over three courses. Pharmacokinetic analysis showed a dose-AUC0-24 relationship and a progressive increase in AG2034 AUC0-24 over three courses. Both pharmacokinetic and pharmacodynamic factors may contribute to the modest cumulative toxicity observed with AG2034.

Adult↗
PubMed2000

Routine intragastric feeding following traumatic brain injury is safe and well tolerated.

BACKGROUND: Delayed gastric emptying following traumatic brain injury (TBI) has led some to advocate jejunal feeding. Our purpose was to review our experience with percutaneous endoscopic gastrostomy (PEG) and intragastric feeding in TBI patients to assess safety and effectiveness. METHODS: All patients on a TBI clinical pathway at our institution were targeted for early PEG. After PEG, standard enteral nutrition was initiated. Abdominal examination and gastric residual volumes were used to assess tolerance. RESULTS: There were 118 patients with moderate to severe TBI. The average age was 36 years. Mean Injury Severity Score (ISS) was 25. Enteral access was obtained and intragastric feeding was initiated on day 3. 6. Intragastric feeding was tolerated without complication in 111 of 114 (97%) patients. Five patients aspirated, but had no evidence of intolerance prior to the event. CONCLUSIONS: PEG provided reliable enteral access in moderate to severe TBI patients. Intragastric feeding was well tolerated with a low complication rate (4%).

Adolescent↗
PubMed2000

TEL/PDGFbetaR fusion protein activates STAT1 and STAT5: a common mechanism for transformation by tyrosine kinase fusion proteins.

OBJECTIVE: TEL/PDGFbetaR is a tyrosine kinase fusion protein associated with the pathogenesis of chronic myelomonocytic leukemia. The following experiments were undertaken to understand the mechanisms whereby TEL/PDGFbetaR transforms cells. MATERIALS AND METHODS: Activation of JAK and STAT proteins was studied in an interleukin 3 (IL-3)-dependent cell line, Ba/F3, transformed to IL-3 independence by TEL/PDGFbetaR. RESULTS: TEL/PDGFbetaR activates STAT1 and STAT5 in transformed Ba/F3 cells through a JAK-independent pathway. Activation of STAT proteins requires the kinase activity of TEL/PDGFbetaR. JAK1, JAK2, JAK3, and TYK2 are not phosphorylated by TEL/PDGFbetaR. However, TEL/PDGFbetaR can phosphorylate STAT5 in transiently transfected COS cells, suggesting that TEL/PDGFbetaR may itself be the kinase involved in tyrosine phosphorylation of STAT proteins. In contrast, native PDGFbetaR stimulated by PDGF ligand does not activate STAT proteins to a significant degree in this hematopoietic context. STAT1 and STAT5 also are activated by TEL/ABL and TEL/JAK2 fusion proteins associated with human leukemia. CONCLUSIONS: STAT activation may be a common mechanism of transformation by leukemogenic tyrosine kinase fusion proteins.

Cell Line↗
PubMed2000

Universal newborn hearing screening with automated auditory brainstem response: a multisite investigation.

OBJECTIVE: The purpose of the study was to assess the feasibility of performing universal newborn hearing screening in different clinical settings and tracking the infants who did not pass initial screening through their confirmatory testing. STUDY DESIGN: Between December 1996 and December 1997, a total of 11,711 infants were enrolled from five clinically different study sites. Universal newborn hearing screening was performed using automated auditory brainstem response (AABR) testing. Infants who did not pass the initial screening were tested again prior to discharge. Data regarding the rate of referral for follow-up testing, age of infant at screening, the duration of time required for screening, and type of personnel performing the test were collected. Formal audiology appointments were made prior to discharge for infants who required follow-up testing, and letters were sent with phone calls made to those who failed to keep their appointments for repeat testing. Outpatient testing consisted of a repeat AABR and, if necessary, a diagnostic auditory brainstem-evoked response, otoacoustic emission testing, and tympanometry. RESULTS: At the time of hospital discharge, the refer rate was < 2% (215 of 11,711 newborns) using AABR screening. Sensorineural hearing loss (SNHL) was confirmed in 32 of these infants, resulting in an overall incidence of confirmed SNHL of 2.7 per thousand newborns. The false-positive rate ranged from 0.3% to 2.5%, with a cumulative false-positive rate of 0.9% (1.5% if all infants lost to follow-up are included as false-positives). No false-negatives were identified. The average time of testing was 7.1 minutes independent of the personnel performing the testing and the age of testing was < 24 hours in 70% of the infants tested. The total number of infants lost to follow-up was 61 (29% of patients referred or 0.5% of the study population). CONCLUSION: This study demonstrated that the refer rate for universal hearing screening with the AABR was acceptably low when performed by a variety of personnel in typical nursery settings within the first 24 hours after birth. A low rate of screening failures with the AABR minimizes costs associated with subsequent follow-up assessments and lessens any potential impact of false-positive screening on the parent-newborn relationship.

Audiology↗
PubMed2000

Adrenomedullin receptor is found exclusively in noradrenaline-secreting cells of the rat adrenal medulla.

Adrenomedullin, originally identified in the adrenal medulla, has binding sites in the adrenal gland; however, its role in the adrenal medulla is unclear. This study was designed to characterise adrenomedullin binding sites in the rat adrenal medulla, using ligand binding studies, immunocytochemistry, and mRNA analysis. A single population of specific adrenomedullin receptors was identified in adrenal medullary homogenates. 125I-Adrenomedullin was displaced only by adrenomedullin1-50 and not by calcitonin gene-related peptide or amylin at concentrations up to 100 nmol/L. The receptor K(D) was 3.64 nmol/L with a receptor density of 570 fmol/mg of protein. Analysis of mRNA revealed that the genes encoding both the putative adrenomedullin receptors, termed calcitonin receptor-like receptor (CRLR) and L1, were expressed in the rat adrenal medulla. Dual-colour indirect-labelled immunofluorescence was used to localise phenylethanolamine N-methyltransferase (PNMT) and the adrenomedullin receptor in the same section. PNMT is the enzyme that converts noradrenaline to adrenaline and is not expressed in noradrenaline-secreting cells. These studies revealed that both CRLR and L1 were expressed only in cells that did not express PNMT, suggesting that adrenomedullin receptors are only found in noradrenaline-secreting cells. Further evidence to support this conclusion was provided by the demonstration of colocalisation of adrenomedullin receptors with dopamine beta-hydroxylase, confirming the presence of the receptors in medullary chromaffin cells. Taken together, these data suggest that adrenomedullin acts through a specific adrenomedullin receptor in the rat adrenal medulla. RT-PCR and northern blot analysis revealed greater abundance of mRNA for L1 than for CRLR, possibly suggesting that L1 may be the major adrenomedullin receptor expressed in this tissue. As it has been reported that adrenomedullin is synthesised predominantly by adrenaline-secreting cells, it appears likely that adrenomedullin is a paracrine regulator in the adrenal medulla.

Adrenal Medulla↗
PubMed2000

Immunization with a modified vaccinia virus expressing simian immunodeficiency virus (SIV) Gag-Pol primes for an anamnestic Gag-specific cytotoxic T-lymphocyte response and is associated with reduction of viremia after SIV challenge.

The immunogenicity and protective efficacy of a modified vaccinia virus Ankara (MVA) recombinant expressing the simian immunodeficiency virus (SIV) Gag-Pol proteins (MVA-gag-pol) was explored in rhesus monkeys expressing the major histocompatibility complex (MHC) class I allele, MamuA*01. Macaques received four sequential intramuscular immunizations with the MVA-gag-pol recombinant virus or nonrecombinant MVA as a control. Gag-specific cytotoxic T-lymphocyte (CTL) responses were detected in all MVA-gag-pol-immunized macaques by both functional assays and flow cytometric analyses of CD8(+) T cells that bound a specific MHC complex class I-peptide tetramer, with levels peaking after the second immunization. Following challenge with uncloned SIVsmE660, all macaques became infected; however, viral load set points were lower in MVA-gag-pol-immunized macaques than in the MVA-immunized control macaques. MVA-gag-pol-immunized macaques exhibited a rapid and substantial anamnestic CTL response specific for the p11C, C-M Gag epitope. The level at which CTL stabilized after resolution of primary viremia correlated inversely with plasma viral load set point (P = 0.03). Most importantly, the magnitude of reduction in viremia in the vaccinees was predicted by the magnitude of the vaccine-elicited CTL response prior to SIV challenge.

Animals↗
PubMed2000

Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV.

Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al., J. Virol. 70:3741-3752, 1996). This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines as compared with animals that received nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly, the reduction in levels of viremia resulted in a significant increase in median (P < 0.05 by Student's t test) and cumulative (P = 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS.

Animals↗
PubMed2000

Sensing a purpose.

Explore the source record for details and available documents.

Cardiopulmonary Resuscitation↗
PubMed2000

Automatic extraction of protein interactions from scientific abstracts.

This paper motivates the use of Information Extraction (IE) for gathering data on protein interactions, describes the customization of an existing IE system, SRI's Highlight, for this task and presents the results of an experiment on unseen Medline abstracts which show that customization to a new domain can be fast, reliable and cost-effective.

Abstracting and Indexing↗
PubMed2000

Fatal myeloproliferation, induced in mice by TEL/PDGFbetaR expression, depends on PDGFbetaR tyrosines 579/581.

The t(5;12)(q33;p13) translocation associated with chronic myelomonocytic leukemia (CMML) generates a TEL/PDGFbetaR fusion gene. Here, we used a murine bone marrow transplant (BMT) assay to test the transforming properties of TEL/PDGFbetaR in vivo. TEL/PDGFbetaR, introduced into whole bone marrow by retroviral transduction, caused a rapidly fatal myeloproliferative disease that closely recapitulated human CMML. TEL/PDGFbetaR transplanted mice developed leukocytosis with Gr-1(+) granulocytes, splenomegaly, evidence of extramedullary hematopoiesis, and bone marrow fibrosis, but no lymphoproliferative disease. We assayed mutant forms of the TEL/PDGFbetaR fusion protein - including 8 tyrosine to phenylalanine substitutions at phosphorylated PDGFbetaR sites to which various SH2 domain-containing signaling intermediates bind - for ability to transform hematopoietic cells. All of the phenylalanine (F-) mutants tested conferred IL-3-independence to a cultured murine hematopoietic cell line, but, in the BMT assay, different F-mutants displayed distinct transforming properties. In transplanted animals, tyrosines 579/581 proved critical for the development of myeloproliferative phenotype. F-mutants with these residues mutated showed no sign of myeloproliferation but instead developed T-cell lymphomas. In summary, TEL/PDGFbetaR is necessary and sufficient to induce a myeloproliferative disease in a murine BMT model, and PDGFbetaR residues Y579/581 are required for this phenotype.

Animals↗
PubMed2000

Actions of neuropeptide Y on the rat adrenal cortex.

Although several studies have demonstrated the presence of neuropeptide Y (NPY) in nerves supplying the mammalian adrenal cortex, its function in this tissue remains unclear, with reports of both stimulatory and inhibitory effects on aldosterone secretion apparently depending on the tissue preparation used. In the present study the effects of NPY on rat adrenal capsular tissue were investigated. NPY significantly stimulated aldosterone secretion in a dose-dependent manner, and this effect was abolished by atenolol, a beta1-adrenergic antagonist. NPY also stimulated the release of catecholamines from intact rat adrenal capsular tissue with the same dose-dependent relationship as the stimulation of aldosterone release. These observations suggest that the actions of NPY may be mediated by the local release of catecholamines from chromaffin cells within adrenal capsular tissue, as we have previously described for vasoactive intestinal peptide. The second part of this study concerned the NPY receptor subtype mediating the actions of NPY on the adrenal cortex. It was found that peptide YY stimulated aldosterone release with a comparable potency to NPY, whereas pancreatic polypeptide (PP) was without effect. The Y1 selective NPY analog Leu31Pro34NPY had a greater effect on aldosterone release than the Y2 selective analog NPY18-36. Studies using the specific Y1 receptor antagonist BIBP 3226 showed significant attenuation of the aldosterone response to NPY, but no effect on the response to added norepinephrine. Binding studies carried out using [125I]NPY revealed the presence of a single population of NPY-binding sites with a Kd of 12.25 nmol/liter and a binding capacity of 623 fmol/mg protein. Competition studies revealed displacement of [125I]NPY specific binding by NPY, peptide YY, and Leu31Pro34NPY, but not by other peptides. Messenger RNA analysis revealed the presence of messenger RNA coding for both the Y1 receptor and the Y4 receptor, but not the other subtypes. Taken together these data suggest that the effects of NPY on the rat adrenal cortex are mediated by the Y1 receptor subtype.

Adrenal Cortex↗
PubMed1999

Role of complement receptors CD21/CD35 in B lymphocyte activation and survival.

In summary, the complement system has evolved an important function in regulation of humoral immunity to T-dependent antigens. Covalent attachment of activated C3 to antigen alters its fate by enhancing uptake on the surface of FDC via CD21/CD35; and by enhancing signal transduction via the B cell coreceptor CD21/CD19/Tapa-1. In the absence of complement receptors CD21/CD35 or C3 ligand, naive B cells bearing low affinity BCR fail to effectively survive within the lymphoid follicle following contact with antigen and death is mediated by a Fas-dependent mechanism. Alternatively, B cells sufficiently activated to initiate a GC reaction fail to survive in the absence of CD21-CD21L interaction.

Animals↗
PubMed1999

Memory dissociation and metamemory in multiple sclerosis.

A previous study by Scarrabelotti and Carroll [60] was the first to use Jacoby's process dissociation procedure [31] with an MS group to investigate memory function, and the first to obtain metamemory judgments about recall under inclusion and exclusion instructions. Twelve months later using different words, 49 MS and 39 matched controls were readministered a word stem completion task, and made metamemory judgments about their performance. The California Verbal Learning Test (CVLT) [18], Stroop [64], and Reitan's Word Finding Test (WFT) [57], tests considered to particularly rely on conscious processing, were also readministered. At year one testing no group differences were identified in word stem completion under indirect, inclusion, or exclusion instructions, nor in conscious and automatic estimates. By contrast in year two, MS subjects remembered significantly fewer words under inclusion, and employed significantly less conscious processing than the control group to achieve remembering. However, estimates of automatic memory processing were the same for both groups. MS subjects equalled controls in the prospective and retrospective monitoring of words they consciously recalled under inclusion instructions, in both years. By contrast, each group was poor at monitoring words completed automatically under exclusion instructions; and by year two, MS subjects were even less able to monitor such material than controls. Finally by the second year, reduced conscious processing was also related to reduced performance on the Stroop, WFT, and CVLT recall and use of semantic clustering. Taken together, these findings indicate that automatic memory processing is intact in MS, but impairment in memory, metamemory, and other cognitive tasks becomes evident over time when they rely on conscious processes.

Adult↗