Search PubMed⌕ Search

Biomedical subjects

C Abrams

Publications and source records attributed to C Abrams.

At least 19 recordsLinked to original sources
PubMed2001

Viral reduction techniques: types and purpose.

Viral reduction techniques help assure the highest level of plasma-product safety that is possible using today's technology. However, worldwide travel and changing demographics could bring new pathogens into focus and thus require plasma-product manufacturers to be continually vigilant in their efforts to refine current reduction techniques and develop and apply new methods. This review focuses on all the currently used viral reduction techniques, why viral reduction continues to be important (even with the use of polymerase chain reaction techniques to improve plasma screening), and possible future directions for viral reduction. When exploring current approaches, including heat treatment (especially pasteurization), solvent/detergent, pH changes, and ultrafiltration, this review also includes (where applicable) the negative impact of these techniques on product integrity and/or viruses not destroyed. Other techniques (eg, chromatography) and the fractionation steps relevant in the production of selected plasma products may also impart viral reduction and are briefly assessed. Relying on an extensive review of current online and printed literature, this article also discusses the current US and European guidelines and regulations that impact viral reduction techniques. This information includes emphasis on the recommendation to use at least 2 reduction techniques (each with a different mode of action) for each plasma product so as to substantially reduce both enveloped and nonenveloped viruses. The approach to validation studies and results from specific studies are reviewed, and future approaches for viral reduction are described.

Guidelines as Topic↗
PubMed2001

The Food and Drug Administration's perspective on plasma safety.

The balance between acceptable plasma-product safety and the demand for those products involves a finite (but very low) level of risk for transmitting infectious diseases. The Food and Drug Administration (FDA) has focused on the use of a triple safety net to provide safe plasma products. This safety net includes donor selection, plasma testing, and inventory hold (look back and retrieval). Although each part of this safety net contributes to reducing the overall viral load in plasma products, each part may not contribute equally to a safe product in all cases. Donor selection is not universally reliable, and plasma antibody testing can be negative for a disease during its seroconversion window period. However, inventory hold (especially for first-time donors) has added to the usefulness of the other safety-net components. This review article provides a brief overview of each safety component and subsequent related improvements, including advances in antibody testing for donor screening and the addition of PCR testing for donor minipools and viral inactivation procedures during plasma-product manufacturing. Dilemmas created by this safety approach are also discussed, including the debate over zero risk of product versus cost and the impact on donors when they test positive for the various diagnostic tests used. Other dilemmas include the decision to include or exclude currently used plasma tests with the advent of polymerase chain reaction (PCR) testing, expanded use of PCR to test for other plasma-transmitted diseases that impart limited risk to recipients, and the role of antigen/antibody interactions in plasma products, especially as the latter relate to plasma-pool and final-product testing.

Consumer Product Safety↗
PubMed2001

The impact of Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease on plasma safety.

Although the true risk of transmitting (classical) Creutzfeld-Jakob Disease (CJD) and variant CJD (vCJD) via transfusion is likely very minimal, a review of prions and the impact of these associated prion diseases is timely because of their current effect on safety policies in the blood-plasma industry. Various types of human and animal prion diseases are outlined and reviewed, with emphasis on the importance of cross-species transmission as is relevant for vCJD. Review of the prion theory focuses on the relationship of prions to disease pathophysiology, prion resistance to protein modification, and potential prion transmission. Causes (with emphasis on iatrogenic CJD) and diagnosis of clinical CJD are described and contrasted with the same for vCJD. The origin of vCJD, the pathophysiologic questions surrounding this condition, and the latest diagnostic tests and research are also reviewed. Comparison of transmission feasibility versus actual transmission of CJD or vCJD by blood or blood products is then explored. Reasons for the discrepancy between theoretic and actual transmission for CJD and the body of evidence provided by look-back studies are examined. When compared with CJD, reasons are provided for the higher theoretic risk of transmitting vCJD by blood products. Studies evaluating transmission by blood products in animals are considered. Transfusion practices that include European and US criteria to prevent vCJD through blood products are reviewed. This includes the debate surrounding product leukoreduction, deferral of donors at high risk either for exposure to vCJD or for contracting CJD, targeted elimination of donor plasma, and how some policies may have contributed to product shortages.

Animals↗
PubMed2000

Adaptation of the Diabetes Health Profile (DHP-1) for use with patients with Type 2 diabetes mellitus: psychometric evaluation and cross-cultural comparison.

AIMS: To adapt the Diabetes Health Profile (DHP-1) for use with English speaking patients with Type 2 diabetes mellitus and to evaluate the psychometric properties of the adapted measure in a UK and Danish sample of insulin, tablet and diet-treated patients with Type 2 diabetes. METHODS: Following linguistic adaptation using the forward-backward translation procedure, the 32-item DHP-1 was sent to 650 and 800 consecutively selected UK and Danish patients with Type 2 diabetes. Construct validity was assessed using principal axis factoring. Factor stability was assessed across language groups using the coefficient of congruence. Reliability was evaluated using Cronbach's alpha and multi-trait analysis, including item convergent/discriminant validity. Subscale discriminant validity was assessed through known groups with one-way ANOVA and post hoc Scheffe tests for multiple comparisons. RESULTS: Eighteen items (56.25%) were retained following initial item analysis. A three-factor solution accounting for 45.6% and 40.3% of the total explained variance was identified in the UK and Danish samples, respectively. Factors were interpreted as psychological distress (PD), barriers to activity (BA) and disinhibited eating (DE). Factor congruence between language groups ranged from 0.98 to 0.99 and Cronbach's alpha ranged between 0.70 and 0.88. Item scaling success for both language versions was 88.9%. BA scores discriminated between treatment groups in both language groups (F = 24.24, P < 0.001; F = 7.68, P < 0.001) and PD scores in the UK sample (F = 20.97, P < 0.001). CONCLUSIONS: The DHP-18 developed for use with patients with Type 2 diabetes has been shown to have satisfactory internal reliability and validity and measurement equivalence across language groups.

Affect↗
PubMed2000

The effectiveness and safety of brimonidine as mono-, combination, or replacement therapy for patients with primary open-angle glaucoma or ocular hypertension: a post hoc analysis of an open-label community trial. Glaucoma Trial Study Group.

The purpose of this study was to determine the effectiveness and safety of brimonidine 0.2% (Alphagan, Allergan Inc., Irvine, CA) as mono-, combination, or replacement therapy for reducing intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. The study method was an open-label, comparative clinical evaluation involving 2335 patients. During the 2-month trial, data were collected at baseline (visit 1), month 1 (visit 2), and month 2 (visit 3). Various parameters were evaluated, including glaucoma medications (visit 1), IOP (visit 1-visit 3), and adverse events. A subset cohort of 1254 patients was selected that met specific study criteria. Data from these 1254 patients were used to evaluate adverse events and the change in IOP from visit 1 to visit 3. Patient data were grouped according to specific drug regimen, and drug regimens were categorized into supergroups of mono-, combination, and replacement therapy. The results of the study revealed that the overall mean change in IOP for 1) monotherapy (n = 240) was -5.07 mm Hg (-20.2%), 2) combination therapy (n = 554) was -4.01 mm Hg (-16.9%), 3) replacement therapy (n = 460) was -2.33 mm Hg (-9.8%), and 4) overall (n = 1254) was -3.59 mm Hg (-14.9%) (p < 0.001 for all changes). Overall, 6.0% of the subjects reported adverse events, with no hypersensitivity or unexpected systemic or ocular adverse events. Eighty-five percent (85%) of clinicians rated brimonidine as "good" to "excellent". In conclusion, brimonidine is safe and effectively lowers IOP when used as mono-, combination, or replacement therapy as observed in a large community population.

Adrenergic alpha-Agonists↗
PubMed2000

Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.

Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.

Aged↗
PubMed1998

The development of a risk-adjusted capitation payment system: the Maryland Medicaid model.

This article describes the risk-adjusted payment methodology employed by the Maryland Medicaid program to pay managed care organizations. It also presents an empirical simulation analysis using claims data from 230,000 Maryland Medicaid recipients. This simulation suggests that the new payment model will help adjust for adverse or favorable selection. The article is intended for a wide audience, including state and national policy makers concerned with the design of managed care Medicaid programs and actuaries, analysts, and researchers involved in the design and implementation of risk-adjusted capitation payment systems.

Ambulatory Care↗
PubMed1995

Proteolysis of the human platelet and endothelial cell thrombin receptor by neutrophil-derived cathepsin G.

Cathepsin G is a neutrophil-derived protease that has been shown to inhibit the effects of thrombin on some cells expressing thrombin receptors while acting as an agonist on others. The present studies examine whether cleavage of the thrombin receptor by cathepsin G can account for these diverse effects. When added to cells that normally respond to thrombin, cathepsin G prevented a subsequent cytosolic Ca2+ increase caused by thrombin, but had no effect on responses to the thrombin receptor agonist peptide, SFLLRN. These effects were observed in cells in which cathepsin G had little or no agonist effect (human umbilical vein endothelial cells and HEL cells), as well as in cells in which cathepsin G acted as an agonist (platelets and CHRF-288 cells). Binding studies using monoclonal antibodies with defined epitopes within the first 60 residues of the thrombin receptor N-terminus showed that incubation of platelets and endothelial cells with cathepsin G abolished the binding of all of the antibodies, while thrombin abolished only the binding of antibodies whose epitopes were N-terminal to the known thrombin cleavage site between Arg41 and Ser42. Analysis of peptide proteolytic fragments identified three potential cleavage sites for cathepsin G: Arg41-Ser42, Phe43-Leu44, and Phe55-Trp56. Cleavage at Phe55-Trp56 would account for both the observed loss of all of the antibody binding sites and the inhibition of receptor activation by thrombin. Two approaches were used to determine whether a solitary cleavage at Arg41-Ser42 could result in receptor activation. In the first, HEL cells were exposed to cathepsin G or thrombin in the presence of an antibody whose epitope includes Phe55. The antibody inhibited responses to thrombin, but augmented the response to cathepsin G. In the second, COS-1 cells were transfected with variant thrombin receptors in which Phe55 and Trp56 were mutated to alanine. Transfected wild-type receptors responded to thrombin, but not cathepsin G, while the variant receptors responded to both proteases. These results 1) suggest that the ability of cathepsin G to inhibit responses to thrombin, but not SFLLRN, is due to cleavage of the receptor at Phe55-Trp56, deleting the tethered ligand domain, and 2) show that cathepsin G can activate thrombin receptors, but only if the cleavage site at Phe55-Trp56 is mutated or otherwise protected.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1994

Determinants of specificity of a baculovirus-expressed antibody Fab fragment that binds selectively to the activated form of integrin alpha IIb beta 3.

PAC1 is an IgM kappa murine monoclonal antibody that, like the Arg-Gly-Asp-containing ligand fibrinogen, binds to integrin alpha IIb beta 3 only on activated platelets. The unique binding properties of PAC1 may be determined by its large size, its multivalency, and by variable region sequences, including an Arg-Tyr-Asp at residues 100A-C in H-CDR3. To study the molecular determinants of PAC1 function, baculoviruses containing cloned cDNA for the Fd heavy and kappa light chains of PAC1 were used to co-infect Sf9 insect cells. Infected cells secreted a soluble, monovalent, 50-kDa Fab fragment that bound saturably to agonist-stimulated platelets but not to resting cells. Fab binding was inhibited > 85% by 10 mM EDTA, 1 mM RGDS, 1 mM fibrinogen gamma 397-411, or 12 microM fibrinogen, but not by 1 mM RGES. Compared to PAC1 IgM, a 60-fold higher molar concentration of PAC1 Fab was required for half-maximal binding to platelets or for half-maximal inhibition of fibrinogen binding. PAC1 Fab bound to an activated form of alpha IIb beta 3 expressed in Chinese hamster ovary cells, but not to the resting form of the receptor in these cells or to alpha v beta 3 in human endothelial cells. Conversion of Asp100C to Glu by site-directed mutagenesis rendered the antibody inactive, indicating that the Arg-Tyr-Asp sequence in H-CDR3 is essential for PAC1 recognition of alpha IIb beta 3. Binding of fibrinogen or PAC1 IgM to platelets induced tyrosine phosphorylation of a 140-kDa platelet protein, but binding of PAC1 Fab did not. These studies demonstrate that the specificity of PAC1 for activated alpha IIb beta 3 is determined by an integrin recognition sequence within H-CDR3. However, the strength of this binding interaction and the ability of PAC1 to trigger signaling in platelets also depend on antibody valency.

Amino Acid Sequence↗
PubMed1994

Distinct p53/56lyn and p59fyn domains associate with nonphosphorylated and phosphorylated Ig-alpha.

Among the earliest detectable events in B-cell antigen receptor-mediated signal transduction are the activation of receptor-associated Src-family tyrosine kinases and the tyrosine phosphorylation of Ig-alpha and Ig-beta receptor subunits. These kinases appear to interact with resting B-cell antigen receptor complexes primarily through the Ig-alpha chain antigen receptor homology 1 (ARH1) motif. Recent studies showed a dramatic increase in the amount of Src-family kinase p59fyn bound to Ig-alpha when ARH1 motif tyrosines were phosphorylated. To explore the submolecular basis of these interactions, we conducted mutational analysis to localize sites in p53/56lyn and p59fyn that bind nonphosphorylated and phosphorylated Ig-alpha. Here we report that distinct regions within these kinases bind nonphosphorylated and phosphorylated Ig-alpha ARH1 motifs. The N-terminal 10 residues mediate binding to the nonphosphorylated Ig-alpha ARH1 motif. Association with the phosphorylated Ig-alpha ARH1 motif is mediated by Src homology 2 domains. These findings suggest a mechanism whereby ligand-induced Ig-alpha tyrosine phosphorylation initiates a change in the orientation of an associated kinase that may alter its activity and/or access to substrates and other effectors.

Amino Acid Sequence↗
PubMed1994

Unprocessed foot-and-mouth disease virus capsid precursor displays discontinuous epitopes involved in viral neutralization.

A foot-and-mouth disease virus (FMDV) cDNA cassette containing sequences encoding the capsid precursor P1, peptide 2A and a truncated 2B (abbreviated P1-2A) of type C FMDV, has been modified to generate the authentic amino terminus and the myristoylation signal. This construct has been used to produce a recombinant baculovirus (AcMM53) which, upon infection of Spodoptera frugiperda insect cells, expressed a recombinant P1-2A precursor with a high yield. This polyprotein reacted with neutralizing monoclonal antibodies (MAbs) that bind to continuous epitopes of the major antigenic site A (also termed site 1) of capsid protein VP1. Unexpectedly, it also reacted with neutralizing MAbs which define complex, discontinuous epitopes previously identified on FMDV particles. The reactivity of MAbs with P1-2A was quantitatively similar to their reactivity with intact virus and, in both cases, the reactivity with MAbs that recognized discontinuous epitopes was lost upon heat denaturation of the antigen. The finding that a capsid precursor may fold in such a way as to maintain discontinuous epitopes involved in virus neutralization present on the virion surface opens the possibility of using unprocessed capsid precursors as novel antiviral immunogens.

Animals↗
PubMed1992

Lung function in fire fighters.

Lung function tests were performed on 49 fire fighters of the city of New Haven. Their mean age was 36.4 years, with a mean of 11.7 years as fire fighters. The lung function tests were compared to a control group with a mean age of 33.4 years. There was no significant difference between the mean normal pulmonary function tests of the fire fighters and the control group. The results showed that in this group of fire fighters long-term occupational exposure was not associated with pulmonary function abnormalities.

Adolescent↗
PubMed1991

A community-based feasibility study using wheat bran fiber supplementation to lower colon cancer risk.

METHODS: In this feasibility study, free-living older adults (n = 180; means = 67.5 years old) were randomly assigned to one of three levels of a 3-month standardized compliance enhancement program. RESULTS: Regarding subject compliance with the 18 g/day wheat bran fiber supplement, the high compliance enhancement group had a superior regimen compliance rate (88%) versus the medium and low groups, (66 and 29%, respectively) (P = 0.01), with similar attrition rates. CONCLUSION: No significant gastrointestinal side effects and changes in body weight were reported. For similar efficacy, the comprehensive compliance enhancement group had the greatest cost effectiveness.

Adult↗
PubMed1990

Kearns-Sayre syndrome presenting as renal tubular acidosis.

Renal tubular acidosis and tetany were the 1st manifestations of Kearns-Sayre syndrome in a 5-year-old child. Subsequently, he developed progressive external ophthalmoplegia, ptosis, retinopathy, heart block, and endocrinopathy. There was a 7.5-kb deletion of mitochondrial DNA documented in muscle, kidney, skin fibroblasts, and leukocytes, providing evidence for a multisystem mitochondrial cytopathy.

Acidosis, Renal Tubular↗