Biomedical subjects

M D Scott

Publications and source records attributed to M D Scott.

At least 19 recordsLinked to original sources

PubMed2004

Prevalence and diffusion of helmet use at ski areas in Western North America in 2001-02.

OBJECTIVE: The purpose of this study was to examine diffusion of and predictors of helmet use among skiers and snowboarders in the Western United States and Canada. DESIGN: 6400 skiers and snowboarders at 29 ski resorts in the Western United States and Canada were interviewed on chair lifts and observed for helmet use during two consecutive ski seasons (winters 2001 and 2002). SETTING: Skiers and snowboarders were observed and interviewed at 29 ski resorts in Alaska, California, Colorado, Idaho, Montana, New Mexico, Nevada, Oregon, Utah, and British Columbia as part of a sun protection project. SUBJECTS: Participants completing the survey consisted of 3525 adult skiers and snowboarders in the 2002 season and 2978 adult skiers and snowboarders in the 2001 season. MAIN OUTCOME MEASURE: The outcome measure for all analyses was prevalence of helmet use by skiers and snowboarders. RESULTS: Helmet use by skiers and snowboarders is increasing and is most prevalent among snowboarders, experts, and more frequent skiers/snowboarders. No evidence was found for the hypothesis that helmet use is diffusing more rapidly among earlier adopters of helmets than later adopters. CONCLUSIONS: Although controversy remains, helmets are rapidly diffusing as a safety device at western North American ski resorts. Expert and more frequent skiers and snowboarders are more likely to wear helmets, which may indicate that helmets are recognized as a safety device.

Adolescent↗

PubMed2001

Interactions of IgM ABO antibodies and complement with methoxy-PEG-modified human RBCs.

BACKGROUND: RBCs modified with cyanuric chloride activated methoxy-PEG (CmPEG; 5000 Da) are less immunogenic than untreated RBCs, and their use thus may reduce the risk of alloimmunization in chronically transfused patients. STUDY DESIGN AND METHODS: To further examine the potential utility of CmPEG-RBCs, the effects of derivatization on an arm of the immune system that plays an important role in transfusion rejection-the complement system--were determined. RESULTS: When CmPEG-RBCs were incubated in autologous or heterologous ABO-matched serum, no classical or alternative pathway consumption was found, no C3a was generated, no cell-bound C3b or C9 was detected, and no cell lysis occurred. Cell-bound complement regulation was normal for CmPEG-RBCs, as determined by acidified serum or reactive lysis assays. CmPEG-RBCs differed from control RBCs only when incubated in ABO-mismatched serum. In that case, CmPEG modification failed to protect against ABO antibody-dependent complement-mediated lysis. Indeed, cell lysis was actually enhanced at CmPEG concentrations >1.0 mM. CONCLUSION: The enhanced lysis of CmPEG-RBCs in ABO-mismatched serum correlated with increased IgM binding and C3a generation and elevated C3b and C9 membrane deposition. While PEG modification effectively blocks non-ABO antigens, these data show that ABO matching is still required. Once ABO-matched, these modified RBCs retain great potential for the prevention of alloimmunization.

ABO Blood-Group System↗

PubMed2001

Current and future applications of immunological attenuation via pegylation of cells and tissue.

Prevention of immunological rejection of transplanted tissues is of crucial importance in transplantation medicine. Current procedures primarily use pharmacological agents such as cyclosporin, which, while effective, must be typically administered for the life of the individual. Furthermore, the drug-induced global immunosuppression of the patient predisposes the individual to infection and enhances their risk of developing certain forms of cancer. Hence, additional methods are needed to both enhance tissue engraftment and diminish the adverse effects of current immunosuppressive therapy. Studies from blood transfusion (i.e. a specialised form of cellular transplantation) suggest that covalent modification of cells and tissues with methoxypoly(ethylene glycol) [mPEG] can significantly diminish rejection episodes and may further enhance the induction of tolerance to donor tissues. The mechanisms underlying mPEG-mediated immunocamouflage are the loss of antigen recognition, impaired cell-cell interaction, and an inability of endogenous antibodies (e.g. immunoglobulin G) to effectively recognise and bind foreign epitopes. As a consequence of the global camouflage imparted by mPEG, the weak co-stimulation of alloreactive T cells may subsequently induce apoptosis, thus leading to tolerance. Initial studies on the transplantation of pegylated isogeneic rat pancreatic islets demonstrates that mPEG-derivatisation does not impair in vivo cellular signalling and function. Thus, in contrast to the pharmacological inhibition of the recipient's immune response, the mPEG-mediated immunocamouflage directly addresses the inherent antigenicity and immunogenicity of the donor tissue itself while leaving the recipient a fully competent immune system.

Animals↗

PubMed2000

Camouflaged blood cells: low-technology bioengineering for transfusion medicine?

The small number of studies done on the covalent modification of RBC with PEG, or PEG-derivatives, suggests that the immunocamouflage of intact cells significantly reduces the antigenicity and immunogenicity of the foreign cell. Importantly, this protective immunologic effect can be accomplished without adversely affecting the structure, function, or viability of the modified cell (e.g., RBCs and lymphocytes). As a consequence, PEG-RBC may have significant practical value in the treatment of the chronically transfused patient as a prophylactic measure against allosensitization. The PEG-RBC also may be useful in treating the already allosensitized individual. As shown, preexisting antibodies do not effectively recognize nor bind to the modified donor cells. A finding of further interest to transfusion medicine is that pegylation of contaminating lymphocytes within RBC products may prove efficacious in preventing graft-versus-host disease in the immunocompromised patient. However, the main emphasis of our research continues to be the immunocamouflage of RBC for use in chronic transfusion therapy of the SCD and thalassemic patient.

Blood Component Transfusion↗

PubMed1999

Stealth cells: prevention of major histocompatibility complex class II-mediated T-cell activation by cell surface modification.

Transfusion or transplantation of T lymphocytes into an allogeneic recipient can evoke potent immune responses including, in immunocompromised patients, graft-versus-host disease (GVHD). As our previous studies demonstrated attenuated immunorecognition of red blood cells covalently modified with methoxy(polyethylene glycol) (mPEG), we hypothesized that T-cell activation by foreign antigens might similarly be prevented by mPEG modification. Mixed lymphocyte reactions (MLR) using peripheral blood mononuclear cells (PBMC) from HLA class II disparate donors demonstrate that mPEG modification of PBMC effectively inhibits T-cell proliferation (measured by (3)H-thymidine incorporation) in a dose-dependent manner. Even slight derivatization (0.4 mmol/L mPEG per 4 x 10(6) cells) resulted in a >/=75% decrease, while higher concentrations caused >/=96% decrease in proliferation. Loss of PBMC proliferation was not due to either mPEG-induced cytotoxicity, as viability was normal, or cellular anergy, as phytohemagglutinin (PHA)-stimulated mPEG-PBMC demonstrated normal proliferative responses. Addition of exogenous interleukin (IL)-2 also had no proliferative effect, suggesting that the mPEG-modified T cells were not antigen primed. Flow cytometric analysis demonstrates that mPEG-modification dramatically decreases antibody recognition of multiple molecules involved in essential cell:cell interactions, including both T-cell molecules (CD2, CD3, CD4, CD8, CD28, CD11a, CD62L) and antigen-presenting cell (APC) molecules (CD80, CD58, CD62L) likely preventing the initial adhesion and costimulatory events necessary for immune recognition and response.

Antigen-Presenting Cells↗

PubMed1999

Structural and functional consequences of antigenic modulation of red blood cells with methoxypoly(ethylene glycol).

We previously showed that the covalent modification of the red blood cell (RBC) surface with methoxypoly(ethylene glycol) [mPEG; MW approximately 5 kD] could significantly attenuate the immunologic recognition of surface antigens. However, to make these antigenically silent RBC a clinically viable option, the mPEG-modified RBC must maintain normal cellular structure and functions. To this end, mPEG-derivatization was found to have no significant detrimental effects on RBC structure or function at concentrations that effectively blocked antigenic recognition of a variety of RBC antigens. Importantly, RBC lysis, morphology, and hemoglobin oxidation state were unaffected by mPEG-modification. Furthermore, as shown by functional studies of Band 3, a major site of modification, PEG-binding does not affect protein function, as evidenced by normal SO4- flux. Similarly, Na+ and K+ homeostasis were unaffected. The functional aspects of the mPEG-modified RBC were also maintained, as evidenced by normal oxygen binding and cellular deformability. Perhaps most importantly, mPEG-derivatized mouse RBC showed normal in vivo survival ( approximately 50 days) with no sensitization after repeated transfusions. These data further support the hypothesis that the covalent attachment of nonimmunogenic materials (eg, mPEG) to intact RBC may have significant application in transfusion medicine, especially for the chronically transfused and/or allosensitized patient.

Animals↗

PubMed1998

Cellular camouflage: fooling the immune system with polymers.

Immunological recognition of foreign cells is a primary concern in both transfusion and transplantation medicine. Our unique approach to this problem is to globally camouflage the surface of the foreign cell using nonimmunogenic, long chain polymers such as methoxypoly(ethylene glycol) [mPEG]. mPEG-modification of red blood cells effectively attenuates both antibody binding to surface epitopes and decreases the inherent immunogenicity of foreign, even xenogeneic red cells. These cells exhibit normal structural and functional characteristicsin vitro and exhibit normal in vivo survival in animal models. Pegylation of white blood cells (particularly antigen presenting cells and T lymphocytes) surprisingly prevents recognition of foreign class II molecules and prevents T cell proliferation in response to foreign MHC molecules. Potential applications for the covalent binding of nonimmunogenic, long chain polymers (e.g., PEG) to intact cells include, but are not limited to: 1) derivatized RBC to diminish transfusion reactions arising from sensitization to minor blood group antigens (allosensitization) in the chronically transfused (e.g., sickle and thalassemia patients); 2) use of mPEG modification of "passenger" lymphocytes to prevent immune recognition and graft versus host disease; and 3) derivatization of the vascular endothelium of donor tissues prior to transplantation to prevent/diminish acute tissue rejection. In contrast to highly specific blocking mechanisms (e.g., anti-CD4; proteolytic removal of RBC A/B antigens), the generation of globally camouflaged (i.e., stealth) cells may more effectively prevent the often complex and redundant events leading to immune recognition of foreign cells.

Antigens, Surface↗

PubMed1997

Chemical camouflage of antigenic determinants: stealth erythrocytes.

In a number of clinical circumstances it would be desirable to artificially conceal cellular antigenic determinants to permit survival of heterologous donor cells. A case in point is the problem encountered in transfusions of patients with rare blood types or chronically transfused patients who become allosensitized to minor blood group determinants. We have tested the possibility that chemical modification of the red blood cell (RBC) membrane might serve to occlude antigenic determinants, thereby minimizing transfusion reactions. To this end, we have covalently bound methoxy(polyethylene glycol) (mPEG) to the surface of mammalian RBC via cyanuric chloride coupling. Human RBC treated with this technique lose ABO blood group reactivity as assessed by solution-phase antisera agglutination. In accord with this, we also find a profound decrease in anti-blood group antibody binding. Furthermore, whereas human monocytes avidly phagocytose untreated sheep RBC, mPEG-derivatized sheep RBC are ineffectively phagocytosed. Surprisingly, human and mouse RBC appear unaffected by this covalent modification of the cell membrane. Thus, mPEG-treated RBC are morphologically normal, have normal osmotic fragility, and mPEG-derivatized murine RBC have normal in vivo survival, even following repeated infusions. Finally, in preliminary experiments, mPEG-modified sheep RBC intraperitoneally transfused into mice show significantly improved (up to 360-fold) survival when compared with untreated sheep RBC. We speculate that similar chemical camouflage of intact cells may have significant clinical applications in both transfusion (e.g., allosensitization and autoimmune hemolytic disease) and transplantation (e.g., endothelial cells and pancreatic beta cells) medicine.

Animals↗

PubMed1997

Physiologic responses during functional electrical stimulation leg cycling and hybrid exercise in spinal cord injured subjects.

OBJECTIVES: (1) To determine if a hybrid exercise (leg plus arm) training program performed immediately after functional electrical stimulation (FES) leg cycle exercise (LCE) training would further improve aerobic capacity when compared with FES leg cycle training alone, and (2) to compare the submaximal responses occurring during both FES-LCE alone and hybrid exercise in the same SCI subjects. DESIGN: Nonrandomized control trial whereby subjects act as their own control. SETTING: Outpatient rehabilitation in a primary care hospital. PATIENTS: A volunteer sample (n = 11) of men 20 to 50 years old with complete spinal cord injury, free from cardiovascular and metabolic disease with spasticity. INTERVENTIONS: Three phases of exercise training: phase I, progressive FES-LCE to 30 minutes of exercise (n = 11); phase II, 35.2 +/- 16.2 sessions of FES-LCE (n = 11); phase III, 41.4 +/- 17.7 30-minute sessions of hybrid exercise (n = 8). MAIN OUTCOME MEASURES: (1) Aerobic capacity-a further increase after hybrid exercise when compared with FES-LCE alone; (2) submaximal physiologic parameters (oxygen uptake [VO2], heart rate [HR], blood lactate [BLa-])-measurement of these during constant work rate exercise and a training effect. RESULTS: VO2 (the body's ability to utilize oxygen) significantly improved (p < .05) after both FES-LCE and then further after hybrid training. Hybrid exercise training resulted in significantly (p < .05) greater work rates and VO2 values than both FES-LCE at baseline and training work rates. CONCLUSION: These subjects demonstrated that hybrid exercise performed twice a week provided sufficient intensity to improve aerobic capacity and provide a medium whereby patients with SCI can burn more calories than via FES-LCE alone. This has important implications for improving the health and fitness levels of individuals with SCI and may ultimately reduce their risk of cardiovascular disease.

Adult↗

PubMed1997

Comparison of reconstruction nails for high subtrochanteric femur fracture fixation.

Subtrochanteric osteotomies were created in 18 matched pairs of embalmed cadaveric femora. The femora were stabilized with a Synthes, Zimmer, or Richards second generation femoral reconstruction nail with retrograde blade or screws. The femoral pairs were randomly assigned to groups based on nails used: Synthes versus Zimmer, Synthes versus Richards, and Zimmer versus Richards. The reconstructions were cyclically loaded in bending for 2000 cycles and then loaded to failure. The mean stiffness of the Synthes, Zimmer, and Richards reconstructions was 17%, 40%, and 40% of the intact femora, respectively. The Richards construct was the strongest, and predominately failed by fracture at the distal interlocking screw hole. The Zimmer construct failed by bending of the nail at the osteotomy site and fracture of the proximal femoral shaft. The Synthes construct was the most flexible and least strong and failed by bending of the spiral, retrograde blade with concomitant fracture of the femoral neck. This study indicates that fixation of subtrochanteric femur fractures with a Synthes spiral blade or Richards or Zimmer reconstruction nails provides stable fixation for postoperative loading conditions. However, the Richards and Zimmer nails were able to withstand higher loads than was the Synthes nail before failure.

Adult↗

PubMed1997

Liability issues with the Papanicolaou smear: an insurance industry perspective.

To better understand the sources of cervicovaginal cytology malpractice insurance losses, summaries of all new pathology claims for 25 consecutive months at one malpractice insurer were examined. In 56 claims (out of a total of 335), the interpretation of gynecologic smears was a central issue. The estimated dollar value of these claims was about 25% of the estimated value of all new pathology claims during that interval. Some common characteristics of these cases, as well as factors influencing their outcome, are discussed along with the special problems that cytology poses for malpractice insurers.

Female↗

PubMed1996

Phospholipid composition and organization in model beta-thalassemic erythrocytes.

The membrane phospholipid organization in human red blood cells (RBC) is rigidly maintained by a complex system of enzymes. However, several elements of this system are sensitive to oxidative damage. An important component in the destruction of beta-thalassemic RBC is the generation of reactive oxygen species and the release of redox-active iron by the unpaired alpha-hemoglobin chains. Consequently, we hypothesized that the presence of this oxidative stress to the RBC membrane could lead to alterations in membrane lipid organization. Model beta thalassemic RBC, prepared by the introduction of excess alpha-globin in the cell, have previously been shown to exhibit structural and functional changes almost identical to those observed in beta-thalassemic cells. After 24 hr at 37 degrees C, the model beta thalassemic cells exhibited a significant loss of deformability, as measured by ektacytometric analysis, indicative of extensive membrane damage. However, a normal steadystate distribution of endogenous phospholipids was found, as evidenced by the accessibility of membrane phospholipids to hydrolysis by phospholipases. Similarly, the kinetics of transbilayer movement of spin-labeled phosphatidylserine (PS) and phosphatidylethanolamine (PE) in all samples was in the normal range and was not affected by the presence of excess alpha-globin chains. In contrast, a faster rate of spin-labeled phosphatidylcholine (PC) transbilayer movement was observed in these cells. While control RBC exhibited a complete loss of their initial (2 mol%) lysophosphatidylcholine (LPC) levels following 24 hr of incubation at 37 degrees C, 1.5 mol% LPC was still present in model beta-thalassemic cells, suggesting an altered phospholipid molecular species turnover, possibly as a result of an increased repair of oxidatively damaged phospholipids.

Adenosine Triphosphate↗

PubMed1996

Pain and depression in acute traumatic spinal cord injury: origins of chronic problematic pain?

OBJECTIVE: To examine the relationship between pain and depression over time during acute phases of traumatic spinal cord injury (SCI). Theoretical models of the pain-depression relationship provided the framework: (1) pain causes depression; (2) depression causes pain; (3) pain and depression are independent sequelae to SCI. Understanding the pain-depression relationship provides treatment implications and hypotheses for origins of chronic pain in SCI. DESIGN: A repeated measures design assessing subjects at admission and discharge from rehabilitation. SETTING: Subjects were admitted to a large public hospital in Southern California which is a member of the Model Spinal Cord Injury System. Rehabilitation occurred on two 30-bed units. PARTICIPANTS: Complete admission and discharge data sets were collected from 68 acute traumatic SCI patients who served as subjects. One hundred twenty-one patients initially agreed to participate in a larger study of adjustments to SCI. Thirty-three did not have pain data at admission, 16 dropped out, and 4 had incomplete discharge data. Subjects volunteered and were paid a fee. INTERVENTION: A standard rehabilitation program for SCI. MEASURES: Pain assessment used a 101-point numerical rating scale. Depression assessment used the Center for Epidemiological Studies-Depression Scale(CESD). RESULTS: Pain and depression were independent at admission. At discharge, they were significantly related. Changes in pain affected depression more than changes in depression affected pain. CONCLUSIONS: Relationships between pain and depression develop over time. Reduced pain will have a greater effect on reducing depression than reduced depression will have on pain. Pain described as "burning" during the acute phase does not represent difficult to treat dysesthetic pain, as it may in chronic SCI pain.

Acute Disease↗

PubMed1995

Thalassaemic erythrocytes: cellular suicide arising from iron and glutathione-dependent oxidation reactions?

Both beta-thalassaemic red blood cells and normal red blood cells (RBC) artificially loaded with unpaired alpha-haemoglobin chains exhibit increased amounts of membrane-bound haem and iron. In the model beta-thalassaemic RBC the amount of free haem and iron was as much as 20 times that which could have been contributed by the entrapped alpha-haemoglobin chains alone. This excess haem/iron arises from destabilization of haemoglobin via reactions between ferric iron (Fe3+), initially contributed by the unpaired alpha chains, and cytoplasmic constituents, primarily reduced glutathione (GSH). Indeed, in the presence of Fe3+ (100 microM) addition of even small amounts of GSH (0.5 mM) to dilute RBC haemolysates (0.15 mg haemoglobin/dl) greatly accelerated methaemoglobin formation. In contrast, lysates from GSH-depleted RBC demonstrated a significantly reduced rate of iron-mediated haemoglobin oxidation which was reversible by addition of GSH. The initiation, and subsequent propagation, of Fe(3+)-mediated haemoglobin oxidation was significantly inhibited by iron chelators. Finally, Fe(3+)-driven haemoglobin oxidation was synergized by low amounts of H2O2, an oxidant spontaneously generated in thalassaemic RBC. To summarize, the release of small amounts of free iron from unpaired alpha-haemoglobin chains in the beta-thalassaemic RBC can initiate self-amplifying redox reactions which simultaneously deplete cellular reducing potential (e.g. GSH), oxidize additional haemoglobin, and accelerate the red cell destruction.

Cell Death↗

PubMed1995

Functional expression of falcipain, a Plasmodium falciparum cysteine proteinase, supports its role as a malarial hemoglobinase.

Erythrocytic malaria parasites degrade hemoglobin as a principal source of amino acids for parasite protein synthesis. We have previously shown that a Plasmodium falciparum trophozoite cysteine proteinase, now termed falcipain, is required for hemoglobin degradation, and we have hypothesized that this proteinase is responsible for initial cleavages of hemoglobin. To further evaluate the biological role of falcipain, we expressed the enzyme in bacterial and viral expression systems. After expression in the baculovirus system, falcipain was enzymatically active and had biochemical properties very similar to those of the native proteinase. Recombinant falcipain rapidly hydrolyzed both denatured and native hemoglobin. Hemoglobin hydrolysis was blocked by cysteine proteinase inhibitors but not by inhibitors of other classes of proteinases. Our results support our hypothesis that falcipain is a critical malarial hemoglobinase that is responsible for both initial cleavages of hemoglobin and the subsequent hydrolysis of globin into small peptides.

Animals↗

PubMed1994

Single extraction method for the spectrophotometric quantification of oxidized and reduced pyridine nucleotides in erythrocytes.

A simplified and reliable assay for the determination of erythrocyte pyridine nucleotide (NAD and NADP) concentrations, as well as the ratio of the reduced [NADH/NADPH] to oxidized [NAD+/NADP+] nucleotide, is important in understanding both normal and abnormal red blood cells (RBC). However, previously published methods for quantitating pyridine nucleotides are inappropriate for RBC, difficult to use, or inaccurate. The method described within this paper provides for both improved reliability and ease of use. In addition, we have documented that significant pools of NADPH and NADH are tightly bound to proteins (e.g., catalase) and not detectable by many of the assay systems previously used. This results in a significant change in not only total RBC pyridine nucleotide content but also in the ratio of reduced to nonreduced nucleotide.

Erythrocytes↗

PubMed1994

Intravascular (angiotropic) large cell lymphoma: determination of monoclonality by polymerase chain reaction on paraffin-embedded tissues.

Angiotropic lymphoma is a rare, aggressive, intravascular non-Hodgkin's lymphoma, usually of B-cell phenotype. Because lymphoma is often clinically unsuspected, the small skin or muscle biopsies typically obtained for evaluation make assessment of lymphoid clonality through cell surface markers or Southern blot hybridization analysis difficult or impossible. The recent development of polymerase chain reaction methodologies to detect chromosomal translocations and immunoglobulin heavy chain gene rearrangement on paraffin-embedded tissue offers an attractive alternative for ascertaining the clonality of lymphoproliferative processes. We report a case of B-cell angiotropic lymphoma in which a monoclonal variable diversity joining region rearrangement of the immunoglobulin heavy chain locus was detected by polymerase chain reaction in both ante- and postmortem, formalin-fixed, paraffin-embedded skeletal muscle. The use of polymerase chain reaction in assessing clonality in angiotropic lymphoma is enhanced by the general absence of a background of reactive B-lymphoid cells in angiotropic lymphoma, which can obscure the monoclonal band and/or compromise sensitivity. No amplification product was obtained for t(14;18) involving the bcl-2 major breakpoint region. It is interesting to note that this case exhibited rare circulating lymphoma cells and more extensive bone marrow involvement (more than 100 tumor cells/high magnification field) than has been previously described.

Aged↗

PubMed1993

Decreased catalase activity is the underlying mechanism of oxidant susceptibility in glucose-6-phosphate dehydrogenase-deficient erythrocytes.

Historically, it has been theorized that the enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes arises as a direct consequence of an inability to maintain cellular glutathione (GSH) levels. This study alternatively hypothesizes that decreased NADPH concentration leads to impaired catalase activity which, in turn, underlies the observed oxidant susceptibility. To investigate this hypothesis, normal and G6PD-deficient erythrocytes and hemolysates were challenged with a H2O2-generating agent. The results of this study demonstrated that catalase activity was severely impaired upon H2O2 challenge in the G6PD-deficient cell while only a transient decrease was observed in normal cells. Supplementation of either normal or G6PD-deficient hemolysates with purified NADPH was found to significantly (P < 0.001) inhibit catalase inactivation upon oxidant challenge while addition of NADP+ had no effect. Analysis of these results demonstrated direct correlation between NADPH concentration and catalase activity (r = 0.881) and an inverse correlation between catalase activity and erythrocyte oxidant sensitivity (r = 0.906). In contrast, no correlation was found to exist between glutathione concentration (r = 0.170) and oxidant sensitivity. Analysis of NADPH/NADPt ratio in acatalasemic mouse erythrocytes demonstrated that NADPH maintenance alone was not sufficient to explain oxidant resistance, and that catalase activity was required. This study supports the hypothesis that impaired catalase activity underlies the enhanced oxidant sensitivity of G6PD-deficient erythrocytes and elucidates the importance of NADPH in the maintenance of normal catalase activity.

Animals↗