Biomedical subjects

D A Mallory

Publications and source records attributed to D A Mallory.

4 recordsLinked to original sources

PubMed2000

The use of dimethylmethylene blue for virus photoinactivation of red cell suspensions.

Phenothiazine dyes and light have been known to have virucidal properties for over seventy years. This review will describe recent progress in the use of one phenothiazine dye, dimethyl-methylene blue, for photo-inactivation of a number of RNA and DNA viruses in red cell suspensions under conditions that minimally affect red cell in vitro properties during 42-day 1-6 degrees C storage. Dimethylmethylene blue has a higher affinity for nucleic acid than the closely related phenothiazine, methylene blue. Virus photoinactivation appears to be mediated by singlet oxygen. The kinetics of photoinactivation depends on the virus studied, but for a given virus, is similar for both intracellular and extracellular forms. The similarity for inactivation of intracellular and extracellular virus suggests that a common target, such as nucleic acid, is involved. Finally, lymphocytes, which can harbour transfusion-associated viruses and can mediate transfusion-associated-graft-versus host disease, are sensitive to dimethylmethylene blue photoinactivation under virucidal conditions.

Animals↗

PubMed1998

Preservation of red cell properties after virucidal phototreatment with dimethylmethylene blue.

BACKGROUND: All published reports have described methods for virus photoinactivation which significantly alter red cell (RBC) properties during storage. In order to improve virucidal activity and reduce damage to RBCs, a series of phenothiazine derivatives were either synthesized or purified and screened for bacteriophage inactivation and red cell potassium efflux. One compound, 1,9-dimethylmethylene blue (dimethyl-methylene blue), had superior screening results and was chosen for further characterization. STUDY DESIGN AND METHODS: White cell reduced RBC suspensions (30% hematocrit) were deliberately inoculated with extracellular virus or virus-infected VERO cells, incubated with 4 microM dimethyl-methylene blue and illuminated with cool-white fluorescent light. Control and treated samples were titered for virus inactivation. In parallel studies, RBC suspensions were exposed to dimethylmethylene blue and light under identical conditions and assayed for in vitro RBC storage properties. RESULTS: Phototreatment of RBC suspensions inactivated > 4.4 log10 of extracellular vesicular stomatitis virus (VSV), > 3.0 log10 of intracellular VSV, > 5.0 log10 of extracellular pseudorabies virus (PRV), > 4.8 log10 of intracellular PRV, > 4.7 log10 of extra-cellular bovine virus diarrhea virus, 5.8 log10 of bacterio-phage phi 6 and > 7 log10 of bacteriophage R17. Encephalo-myocarditis virus, a nonenveloped picornavirus, was resistant to photoinactivation. Virucidal conditions resulted in no detectable IgG binding in 11 of 13 samples, unchanged RBC morphology, normal banding patterns of RBC membrane proteins on SDS PAGE, and unaltered characteristics of 12 of 13 RBC antigens during storage as measured by antibody titrations. In addition, minimal changes were observed in RBC osmotic fragility, lysis, potassium efflux, ATP and 2,3-DPG levels, and the strength of one RBC antigen during storage of phototreated samples compared with controls. CONCLUSION: Dimethylmethylene blue photo-treatment can inactivate several intracellular and extracellular model viruses under conditions which minimally alter RBC properties during 42 days storage at 1-6 degrees C.

2,3-Diphosphoglycerate↗

PubMed1997

Rh haplotypes that make e but not hrB usually make VS.

BACKGROUND AND OBJECTIVES: The Rh phenotypes hrB- and VS+ are both rare in Whites but more common in Blacks. The high-incidence antigen hrB is present on most red cells that are e+. The presence of VS on red cells is associated with an aberrant expression of e, often called eS. MATERIALS AND METHODS: Using conventional serologic methods, including a monoclonal anti-hrB-like antibody, we studied 65 e+ samples that were apparently hrB-. RESULTS: Of the 65, we found that 59 (91%) were VS+. Recent findings have indicated that in VS+ persons a change from leucine to valine occurs at amino acid 245 of the RHCE-encoded polypeptide. While this residue is predicted to lie within the red cell membrane bilayer, the change presumably affects alanine 226 (that is present when e is expressed) in such a way that eS is seen. CONCLUSIONS: Our findings suggest that the change from e to eS may result in nonexpression or marked depression of expression of hrB that is, perhaps, an epitope of e. While the molecular basis of the hrB-phenotype is not known, it is unlikely that the leucine-to-valine change at residue 245, resulting in the aberrant from of e, explains all hrB-samples. First, hrB-VS+ and hrB- VS- samples must differ. Second, some hrB- VS+ samples are C+, some are C-. Presumably diverse molecular bases are involved in hrB-phenotypes.

Black People↗

PubMed1993

Red cell alterations associated with virucidal methylene blue phototreatment.

Several red cell storage properties were evaluated following phototreatment with methylene blue (MB) under conditions that inactivated > or = 6 log10 of added vesicular stomatitis virus. Red cell 2,3 DPG levels were similar to untreated controls throughout conventional 42-day storage at 4 degrees C. Plasma hemoglobin levels were elevated approximately twofold in MB-phototreated samples, and morphology scores were 5 percent lower after 42-day storage. ATP levels declined 30 percent in phototreated samples and in a control sample containing MB and not exposed to light. Lipid peroxidation was not observed in treated or control cells, nor were differences observed in sodium dodecyl sulfate-polyacrylamide gel electrophoresis of ghost membranes derived from phototreated and control samples. Phototreated cells exhibited enhanced ion permeability; sodium and potassium levels approached equilibrium with the suspending medium within 4 to 7 days after treatment. Direct agglutination tests using rabbit anti-human IgG or rabbit anti-human serum albumin on MB-phototreated cells indicated that serum proteins had absorbed to the surface of treated red cells. Plasma depletion by washing red cells prior to phototreatment did not prevent protein binding upon subsequent addition of untreated autologous or group AB plasma. To a much smaller extent, phototreatment of plasma resulted in IgG association with untreated red cells. The addition of glutathione to red cell suspensions prevented IgG binding to phototreated red cells but did not prevent enhanced ion permeability. Taken together, these data suggest that the red cell surface is altered by virucidal MB phototreatment of vesicular stomatitis virus.

2,3-Diphosphoglycerate↗