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Biomedical subjects

A Brownell

Publications and source records attributed to A Brownell.

9 recordsLinked to original sources
PubMed2000

Interferon-gamma receptor polymorphisms determine strain differences in accessibility of activated lymphocyte NK-triggering antigens to recognition by self-reactive NK cells.

The "NK-triggering-antigen regulator" (Nktar) gene is a locus identified in the C57BL/6 genome which regulates the ability of unlabeled activated Con A blasts to compete for recognition of labeled syngeneic Con A blasts by BALB/c NK cells. Linkage analysis on Con A blasts from (BALB/c x CByB6F1) N2 backcross progeny for (1) relative level of competitive inhibition of BALB/c NK lysis of syngeneic Con A blasts and (2) genotypes at polymorphic microsatellite markers distributed throughout the mouse genome mapped the Nktar gene locus to a 5-cM region of chromosome 10 containing the interferon-gamma receptor (Ifngr) gene locus. N2 Con A blasts exhibited an inverse relationship between (a) their cell surface density of IFN-gammaR molecules detected by FACS with monoclonal anti-CD119 and (b) their cold target inhibition of BALB/c NK self-reactivity. Con A blasts from Ifngr(-/-) knockout mice showed a relatively high level of inhibition of BALB/c NK self-lysis and a relatively low level of class I MHC, which were both reversed by transient transfection with the Ifngr gene. Sequencing studies showed that Balb/c Ifngr encodes a Gly(69) whereas C57BL/6 Ifngr encodes Glu(69) due to a difference at nucleotide 284. Sequencing studies of N2 progeny demonstrated 100% concordance between their Nktar inhibitory phenotype and their Ifngr genotype. These findings demonstrate that the Nktar and Ifngr loci are identical. They further indicate that polymorphisms related to the Ifngr locus and affecting expression of cell surface IFN-gammaR may underlie genetic differences in the availability of NK-triggering antigens (NKTAgs) to recognition by self-reactive BALB/c NK cells by differentially affecting the ability of IFN-gammaR molecules to mediate up-regulation of NKTAg-masking class I molecules.

Animals↗
PubMed1998

IL-2-activated murine newborn liver NK cells enhance engraftment of hematopoietic stem cells in MHC-mismatched recipients.

To explore the modulatory effects of IL-2-activated NK cells on hematopoietic stem cell (HSC) engraftment further, we used fresh newborn liver cells (NLC) and IL-2-activated newborn liver cells (ANLC) as combined sources, respectively, of transplanted HSC and IL-2-activated NK cells free of contaminating CD3+ T cells. As previously found with adult IL-2-activated spleen cells, NLC cultured with IL-2 for 7 days exhibited lymphokine-activated killer (LAK) activity, veto activity, and natural suppressor activity, and enhanced both short-term and long-term stem cell engraftment by intact co-injected syngeneic and allogeneic NLC in totally MHC-mismatched lethally irradiated recipients. However, unlike adult IL-2-stimulated adult spleen cells, IL-2-activated NLC lacked CD3+ T cells and failed to induce lethal GVHD. FACS analysis and cell sorting experiments showed that the cells in ANLC which enhanced short-term HSC engraftment belonged to the relatively immature CD3-NK1.1-2B4+ NK cell subset. By contrast, cells belonging to the more mature CD3-NK1.1+2B4+ NK cell subset showed no HSC-enhancing effects. Identification and isolation in humans of similar NK cell enhancers of HSC could lead to a new approach to improving stem cell engraftment in MHC-mismatched recipients without increasing the risk of GVHD.

Animals↗
PubMed1988

Feasibility of validating survey self-reports of mental health service use.

Survey respondents may inaccurately report mental health service utilization for motivational and cognitive reasons. There is little evidence on accuracy of self-reports of mental health service use, and this evidence suggests that respondents tend to underreport inpatient utilization. This study addressed the question of self-report accuracy by comparing survey data from a large probability sample to data from computerized records of publicly funded mental health services. Few inaccuracies in self-reporting were detected. However, despite the use of data bases that were unusually appropriate for verifying self-reports, several problems limited the feasibility of validation. Suggestions are offered for increasing the feasibility of validation in future studies.

Adult↗
PubMed1986

Serum ferritin concentration in sickle cell crisis.

Serum ferritin, aspartate aminotransferase (AST), alkaline phosphatase and hydroxybutyrate dehydrogenase (HBD) were studied during 21 vaso-occlusive crises in 12 adults with sickle cell disease (11 SS, 1 S beta degrees). The patients comprised three groups: those who had been untransfused (4), those who had received occasional exchange transfusion in crisis (3), and those who had been multiply transfused (5). Serum ferritin concentrations in crisis were compared with those of the steady state value. Rises in serum ferritin concentrations occurred in all crises in all groups. Although AST, alkaline phosphatase, and HBD rose, there was no correlation between these and log ferritin concentrations. The clinical impression was that the degree of rise in ferritin related to the severity of the particular crisis, and the above results showed that haemolysis and liver damage were not causally related to this rise. An estimate of serum ferritin cannot be used to assess the state of iron balance in sickle cell disease unless the patient is in the steady state. The considerable rise in serum ferritin concentration found in crisis, however, may be a useful marker of the extent of vaso-occlusion and tissue damage.

Adolescent↗
PubMed1986

An unusual variant of T-CLL: evidence for the existence of a hitherto unrecognized T cell subset.

A case of T-cell chronic lymphocytic leukaemia (T-CLL) with an unusual mature membrane phenotype: E+, CD3+, CD4+, CD8-, M1+, Leu-15+, Fc gamma+, is described. The cells were large granular lymphocytes with slight immature features. Functionally these cells lacked helper, suppressor and NK activity but possessed normal levels of K activity. These findings demonstrate several features not previously described in T-CLL: the coexpression of the antigens detected by T4, M1 and Leu-15 the presence of Fc gamma receptors on CD4+ lymphocytes and the lack of NK activity in M1+, Fc gamma+ cells. This study broadens the known heterogeneity of T-CLL and suggests the existence of a hitherto unrecognized normal T-lymphocyte subset with the same functional and phenotypic characteristics as in the case described here.

Antibodies, Monoclonal↗