γ134.5-deleted HSV-1-expressing human cytomegalovirus IRS1 gene kills human glioblastoma cells as efficiently as wild-type HSV-1 in normoxia or hypoxia.

Pathophysiological hypoxia, which fosters the glioma stem-like cell (GSC) phenotype, is present in high-grade gliomas and has been linked to tumor development, invasiveness and resistance to chemotherapy and radiation. Oncolytic virotherapy with engineered herpes simplex virus-1 (HSV-1) is a promising therapy for glioblastoma; however, the efficacy of γ(1)34.5-deleted HSVs, which have been used in clinical trials, was diminished in hypoxia. We investigated the ability of a chimeric human cytolomegalovirus (HCMV)/HSV-1 virus, which expresses the human CMV protein kinase R evasion gene IRS1 and is in preparation for clinical trials, to infect and kill adult and pediatric patient-derived glioblastoma xenografts in hypoxia and normoxia. Infectivity, cytotoxicity and viral recovery were significantly greater with the chimeric virus compared with the γ(1)34.5-deleted virus, regardless of oxygen tension. The chimeric virus infected and killed CD133+ GSCs similarly to wild-type HSV-1. Increased activation of mitogen-activated protein kinase p38 and its substrate heat-shock protein 27 (Hsp27) was seen after viral infection in normoxia compared with hypoxia. Hsp27 knockdown or p38 inhibition reduced virus recovery, indicating that the p38 pathway has a role in the reduced efficacy of the γ(1)34.5-deleted virus in hypoxia. Taken together, these findings demonstrate that chimeric HCMV/HSV-1 efficiently targets both CD133+ GSCs and glioma cells in hypoxia.

Influence of the amyloid precursor protein locus on dementia in Down syndrome.

BACKGROUND: The amyloid precursor protein (APP) locus on chromosome 21 influences the development of Alzheimer disease. METHOD: The authors investigated the relationship between a tetranucleotide repeat on intron 7 of the APP gene and the age at onset of dementia in Down syndrome (DS). RESULTS: There was a 13-year difference in the age at onset of dementia in DS associated with the number of tetranucleotide repeat alleles in APP. CONCLUSION: APP is an important locus predicting the age at onset of dementia in people with Down syndrome.

Safer haemotherapy: the responsibilities of government, transfusion service, blood donors, and physician-users.

Despite the introduction of new selection, screening and quality assurance procedures, transfusion of allogeneic blood or blood products is not without risk. Iatrogenic bacterial or viral infection and incompletely understood immunological effects remain major concerns. Close communication and cooperation between the major players on the blood transfusion team - government, transfusion service, blood donors, and physician-users - are essential if new developments and technology are to lead to safer and more efficacious haemotherapy.

TSEN: a novel MNS-related blood group antigen.

We report an antibody (anti-TSEN) that recognizes an antigen (TSEN) at the unique amino acid sequence that results from the junction of GPA58 to GPB27 if the GPB carries the S antigen. Red cells from several unrelated donors that possess this specific GP(A-B) hybrid molecule were agglutinated by anti-TSEN. Since a synthetic peptide with the amino acid sequence at this junction (Pro-Glu-Glu-Glu-Thr-Gly-Glu-Met-Gly-Gln-Leu-Val-His-Arg) specifically inhibited anti-TSEN, it must detect an antigen within this novel amino acid sequence. The TSEN antigen has been provisionally assigned the MNS blood group system number 002.033 on behalf of the ISBT Working Party on Terminology for Red Cell Surface Antigens.

Replicate tests for the detection and correction of errors in anti-human globulin (AHG) tests: optimum conditions and quality control.

Replicate blind AHG tests with weak IgG anti-D sensitised red cells revealed that 32% of workers caused 5 per cent or more false negative errors by using excessive agitation in reading techniques. The common quality control procedure of adding strongly sensitised cells to all negative AHG tests cannot reveal this type of error. Furthermore, strongly sensitised control cells may create an illusion of safety because AHG giving a false negative test with weak antibody in a serum sample may still show a reassuringly strong positive in the control test. "In-house" assessment of all staff and automatic cell-washers by blind replicate tests is recommended as an effective way of improving AHG test performance, thus reducing many of the errors involving false negative AHG tests seen year after year in External Proficiency Trials.

Two examples of a new low-frequency red cell antigen, JFV.

A new low frequency red cell antigen JFV has been found in two families, one of German and one of Dutch origin. JFV is inherited as an autosomal dominant character. Family studies showed that JFV is not controlled by the Rh, MNS, Lu, Fy, or Jk loci and that it is not X- or Y-borne.

Dihydromatricariate-based triglycerides, glyceride ethers, and waxes in the australian soldier beetle,Chauliognathus lugubris (Coleoptera: Cantharidae).

The soldier beetleChauliognathus lugubris is shown to contain triglycerides and glyceride ethers of 8-dihydromatricaria acid, and waxes of the C12 homolog, of this acid, as well as the previously reported free acid. The triglycerides contain one, two, or three dihydromatricariate moieties, with any remaining positions esterified with normal fatty acids. The glyceride ethers were monostearyl ethers of glycerol esterified with dihydromatricaria acid and oleic or linoleic acid. The waxes, which also include a dihydromatricaria chromophore in the alcohol moiety, occur only in the females and are present in paired accessory glands in the abdomen. The ethers are restricted to females and appear to be associated with developing eggs. The triglycerides are much more abundant in females than males. Triglycerides, glyceride ethers, and waxes represent about 95% of the dihydromatricariate moiety (average, ca. 590 µg) in females with free acid the remainder; in males free acid is present to over 50% (ca. 22 µg) and the remainder is triglyceride (ca. 15 µg). Larvae contain mainly tridihydromatricariate-substituted triglyceride and a smaller quantity of the free acid.

RASM, a "new' low-frequency blood group antigen.

A 'new' low-frequency red cell antigen, RASM, was found in 3 generations of a Caucasian family. It is inherited as a Mendelian dominant character. The propositus, a newborn, had a positive direct antiglobulin test; overt haemolytic disease of the newborn was not present.

Good laboratory practice before and after blood transfusion.

Among the general principles that govern good laboratory practice before and after blood transfusion, there are two aspects which receive little attention: the importance of transfusion medicine as a distinct discipline; and the interrelationships within the hospital needed to make the "Blood Bank" effective.

A family demonstrating inheritance of the Leach phenotype: a Gerbich-negative phenotype associated with elliptocytosis.

The proposita of a Canadian family and 2 of her sibs have the rare Leach phenotype and provide the first evidence that the Leach phenotype is an inherited condition. Their red cells are Ge: -2, -3 and fail to react, by the antiglobulin test, with the monoclonal antibodies GERO, BRIC 4 and BRIC 10. The minor sialoglycoproteins beta, beta 1 and gamma are apparently absent from their red cell membranes. A proportion of their red cells are elliptocytes indicating that beta and/or beta 1 and/or gamma have a function in maintaining normal red cell shape.

Comparison of a modified manual hexadimethrine bromide (Polybrene) and a low-ionic-strength solution antibody detection technique.

Manual hexadimethrine bromide (Polybrene) tests (Polybrene in low-ionic medium) were used in parallel with manual low-ionic-strength solution (LISS) procedures for the routine testing of patient samples referred to a general hospital blood bank. Of 5646 consecutive sera tested, 5167 (91.5%) did not react with either technique; 320 sera (5.7%) reacted in both methods. The Polybrene technique detected 63 antibodies which did not react in the LISS methods. One hundred sera did not react in the Polybrene test, but did react in the LISS methods. Sera showing discrepant results between the two methods were further tested in a reference laboratory. Polybrene tests appeared to be better in avoiding reactions due to clinically nonsignificant antibodies. The LISS methods, however, appeared to be more sensitive in detecting antibodies of potential clinical significance.