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Biomedical subjects

M Bennett

Publications and source records attributed to M Bennett.

At least 163 records · Page 9Linked to original sources
PubMed1996

The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts.

We address the mechanism of hybrid resistance (HR) in vitro using NK effector cells and target lymphoblasts from H-2b, H-2d, and H-2b/d mice. The 5E6 (Ly49C)+ subset of F1 NK cells lyse BALB/c (H-2d) but not B6 (H-2b) targets unless either anti-5E6 or anti-H-2Kb MAbs are present. H-2Dd transgenic B6 (D8) targets are not susceptible to F1 Ly49A+ effectors. Furthermore, 5E6+ Ly49A+ F1 effectors lyse B6 and BALB/c targets only in the presence of anti-5E6 and anti-Ly49A MAbs, respectively. Thus, recognition of H-2Kb by 5E6 and H-2Dd by Ly49A transduce independent inhibitory signals. Moreover, anti-5E6 MAbs enable 5E6+ BALB/c NK cells to lyse (BALB/c x B6)F1 targets. These data support the "missing self" and not the "hemopoietic histocompatibility antigen" hypothesis for HR. In addition, 5E6+ NK cells from BALB/c and BALB.B, but not B6 or (BALB/c x B6)F1, mice receive negative signals from both H-2d and Kb class I antigens. Thus, allelic differences in 5E6 (C57BL versus BALB) may regulate recognition events by NK cells.

Alleles↗
PubMed1996

Children's understanding of the distinction between real and apparent emotions: a training study.

The effects of two types of training on 4-year-old children's understanding of the distinction between experienced positive affect and neutral or negative display were examined. One type of training provided first-hand experience of possible discrepancies between facial expression and actual affect. The other training focused on the sorts of motives that might prompt the concealment of positive affect. Compared with a control group, both experimental groups showed modest gains.

Child, Preschool↗
PubMed1996

Others' actions can reflect on the self: a developmental study of extended identity.

This study was an investigation of children's understanding that others' judgments of the self can be based on the actions of another person with whom one is associated. Five-, 8-, and 11-year-old children in Scotland were presented with hypothetical scenarios that indicated that they were responsible for a toddler who breached normative expectations of behavior. The children were required to make a variety of judgments, most notably concerning their likely emotion and its causes, and what others would think of them. The majority recognized that others would make negative judgments of the self. However, emotional self-attributions indicated that only among the 11-year-olds was there a widespread tendency to be self-punitive-that is, to attribute reflexive emotions such as embarrassment. Particularly among the 5-year-olds, punitive responses (e.g., anger) were directed only at the norm-violating toddler, implying that, unlike the oldest children, they did not view the toddler as constituting part of their extended identity. Eight-year-olds appeared to represent an intermediate step between the younger and older groups. In the light of these findings it is suggested that a mature form of extended identity may be a relatively late development.

Anger↗
PubMed1996

Cowpox.

Explore the source record for details and available documents.

Animals↗
PubMed1996

Identification of proteins that interact with exon sequences, splice sites, and the branchpoint sequence during each stage of spliceosome assembly.

We have carried out a systematic analysis of the proteins that interact with specific intron and exon sequences during each stage of mammalian spliceosome assembly. This was achieved by site-specifically labeling individual nucleotides within the 5' and 3' splice sites, the branchpoint sequence (BPS), or the exons with 32P and identifying UV-cross-linked proteins in the E, A, B, or C spliceosomal complex. Significantly, two members of the SR family of splicing factors, which are known to promote E-complex assembly, cross-link within exon sequences to a region approximately 25 nucleotides upstream from the 5' splice site. At the 5' splice site, cross-linking of the U5 small nuclear ribonucleoprotein particle protein, U5(200), was detected in both the B and C complexes. As observed in yeast cells, U5(200), also cross-links to intron/exon sequences at the 3' splice site in the C complex and may play a role in aligning the 5' and 3' exons for ligation. With label at the branch site, we detected three distinct proteins, designated BPS72,BpS70, and BPS56, which replace one another in the E, A, and C complexes. Another dynamic exchange was detected with pre-mRNA labeled at the AG dinucleotide of the 3' splice site. In this case, a protein, AG100,cross-links in the A complex and is replaced by another protein, AG75, in the C complex. The observation that these proteins are specifically associated with critical pre-mRNA sequence elements in functional complexes at different stages of spliceosome assembly implicates roles for these factors in key recognition events during the splicing pathway.

Animals↗
PubMed1996

Proliferation indexes--a comparison between cutaneous basal and squamous cell carcinomas.

AIMS: To compare differences in cell proliferation indexes and apoptotic indexes between cutaneous basal and squamous cell carcinomas, in an attempt to suggest an explanation for the differences in their biological behaviour. METHODS: Forty cases of cutaneous basal cell carcinoma (BCC) and 40 cases of moderately and well differentiated squamous cell carcinoma (SCC) were retrieved from the archives. Sections, 4 microns thick, were cut from formalin fixed, paraffin wax embedded tissue in each case and stained with haematoxylin and eosin. These were then examined for mitotic and apoptotic figures per 1000 cells. Sections from the same cases were also immunostained with the mouse monoclonal antibody Ki67 (MIB1); positive nuclear staining was counted per 1000 cells. RESULTS: No significant differences were found between the mitotic indexes and apoptotic indexes in these tumours. There was, however, a significant difference in Ki67 (MIB1) staining, with greater staining in the squamous cell carcinomas. CONCLUSION: Estimation of the mitotic and apoptotic indexes did not reveal any differences between these two tumour types. The proliferation indexes, assessed by Ki67 immunostaining, did differ. This may be one of the factors underlying the more aggressive behaviour of SCC.

Apoptosis↗
PubMed1996

Discussing the diagnosis and prognosis with cancer patients.

Effective doctor-patient communication is an integral part of good clinical care. Telling a patient that he/she has cancer can be a daunting task. If done with empathy and sensitivity it can create an important bond between the doctor and patient. If done brusquely and without tact it can create barriers and lasting hostility. Several key steps help make the breaking of bad news easier for doctors and patients. There is not one 'right formula' but appreciation of and responsiveness to the patient's verbal and non-verbal signals are core skills which can be developed.

Clinical Competence↗
PubMed1995

Pleotropic effects of dietary DHEA.

We present data pertaining to some of the in vivo effects associated with dietary DHEA administration to mice and rats. Dietary DHEA leads to: (1) decrease in body weight gain; (2) relative increases in liver weight; (3) liver color change; (4) induction of hepatic peroxisomal enzymes; (5) proliferation of hepatic peroxisomes with increased cross-sectional area; (6) decreased hepatic mitochondrial cross-sectional area; (7) elevated levels of hepatic cytosolic malic enzyme; (8) slight decreases, significant decreases, or significant increases in serum triglyceride levels, depending on mouse strain; (9) increases in total serum cholesterol levels; (10) significant decreases in the hepatic rates of fatty acid synthesis; (11) significant increases in the hepatic rates of cholesterol synthesis; (12) decreases in both protein content and specific activity of hepatic mitochondrial carbamoyl phosphate synthetase-I without concomitant changes in serum urea nitrogen; (13) induction of glutathione S-transferase activity in liver; (14) decrease in hepatic endogenous protein phosphorylation; (15) increase in hepatic AMPase and GTPase activities; (16) formation of 5-androstene-3 beta,17 beta-diol as a major metabolite of DHEA by subcellular fractions of liver, which is reflected in serum and tissue levels; and (17) reduction in serum prolactin levels.

Animals↗
PubMed1995

Rapid rejection of H2k and H2k/b bone marrow cell grafts by CD8+ T cells and NK cells in irradiated mice.

Acute rejection of transplanted bone marrow cell (BMC) grafts can occur within 48 h in unsensitized, lethally irradiated mice, and NK cells have been implicated as the effector cells. Recently, we observed that both CD8+ TCR-alpha beta+ T and NK cells of irradiated mice could rapidly reject allogeneic lymph node cell grafts. In this study, we evaluated the ability of NK and CD8+ T cells to mediate rejection of H2k or H2k/b BMC grafts by pretreating groups of mice with depleting mAbs. H2k BMC were transplanted into syngeneic, B6 (H2b), BALB/c (H2d), NZB (H2d), and (NZB x B6)F1 (NZB6F1, H2d/b) hosts. Proliferation measured 5 days after cell transfer indicated that syngeneic, B6, and BALB/c hosts accepted H2k BMC grafts. However, CD8+ T cells from NZB and poly I:C-treated BALB/c hosts, and NK cells from poly I:C-treated NZB6F1, hosts, rejected H2k BMC grafts. In NZB6F1 hosts, there was an added effect of anti-TCR-alpha beta and anti-NK1.1 mAbs. It is possible that T and NK cells cooperate in rejecting H2k or H2k/b BMC grafts in certain hosts. Transplantation of H2k/b, but not H2k/d, BMC into similar recipients had the same fate as H2k BMC. Thus, certain CD8+ T cells may share a similar recognition system with NK cells.

Animals↗
PubMed1995

NK cell subsets in the regulation of murine hematopoiesis. I. 5E6+ NK cells promote hematopoietic growth in H-2d strain mice.

NK cells are able to reject bone marrow allografts in lethally irradiated mice. 5E6 is a marker expressed on a subset of NK cells that is responsible for the rejection of H-2d homozygous bone marrow cell (BMC) allografts. This suggests that the 5E6+ NK cell subset somehow recognizes and is deleterious for H-2d BMC. However, unlike Ly-49+ NK cells, 5E6+ cells are not deleted or even down-regulated in H-2d-homozygous mice. We wanted to determine, therefore, the role of the 5E6+ and 5E6- NK cell subsets in the normal physiologic regulation of hematopoiesis in H-2d strains of mice. Surprisingly, both in vivo depletion studies of normal mice and studies in which the subsets were purified and cultured with syngeneic BMC in vitro demonstrated that in H-2d mice, the 5E6+ subset of NK cells did not inhibit, but instead promoted, growth of H-2d BMC. Depletion of the 5E6+ subset also resulted in decreased marrow engraftment after syngeneic bone marrow transplantation in H-2d mice. Analysis of the cell culture supernatants of the purified subsets indicated that the functional effects of the subsets on hematopoiesis correlated with the relative amounts of hematopoietic growth-promoting cytokines produced by the NK cells. These results demonstrate that physiologically relevant subsets of NK cells exist that are involved in the homeostatic regulation of hematopoiesis and that they can be distinguished on the basis of 5E6 expression.

Animals↗
PubMed1995

Cloning and functional characteristics of murine large granular lymphocyte-1: a member of the Ly-49 gene family (Ly-49G2)

Large granular lymphocyte (LGL) 1 is a cell surface glycoprotein expressed on a subset (50%) of C57BL/6 natural killer (NK) cells. Immunoprecipitation experiments reveal that the LGL-1 protein exists as a disulfide-linked 40-kD homodimer. Functional studies of LGL-1+ cells indicate that selected H-2d target cells are not lysed efficiently by these interleukin (IL)-2-cultured NK cells. These findings suggested that LGL-1 may be a member of the Ly-49 gene family. Here we report the molecular cloning of the LGL-1 cDNA from a severe combined immunodeficient-adherent lymphokine-activated killer cell library transfected into Cos-7 cells and find LGL-1 to be homologous to the Ly-49 gene at both the nucleotide (85%) and amino acid levels (73%). Sequencing of our LGL-1 cDNA has revealed it to be nearly identical to the Ly-49G2 cDNA recently isolated by cross-hybridization with an Ly-49 probe. LGL-1 represents a type II transmembrane protein of 267 amino acids with its carboxyl end exposed extracellularly. The LGL-1 protein contains 11 highly conserved cysteine residues and a 25-amino acid transmembrane region. Southern blot analysis demonstrates that there are a number of homologous genes in mouse DNA that hybridize strongly to LGL-1. Northern analyses using poly A+ RNA from LGL-1+ NK cells indicate that LGL-1 is expressed as a 1.4 kb mRNA. Two-color flow cytometry analysis (FCA) of C57BL/6 splenic NK cells demonstrates that LGL-1 and Ly-49 label overlapping subsets of cells. FCA identifies four subsets of NK cells as defined by LGL-1 versus Ly-49 staining. We have sorted these individual subsets, expanded them in IL-2, and performed cytotoxicity experiments to determine their target cell profiles in relation to class I expression. Results of these studies are complex, but indicate that Ly-49 may not be the only molecule that recognizes class I as an inhibitory signal for cytotoxicity. LGL-1+ cells also fail to lyse several H-2d-expressing tumor targets and concanavalin A lymphoblasts from BALB/c but not C57BL/6 mice. This inhibition of lysis by LGL-1+ NK cells is negated by addition of monoclonal antibody (mAb) 4D11 that recognizes the LGL-1 protein. When mAbs to the class I molecules H-2Dd and H-2Ld (alpha 1 alpha 2 domains only) are added to cytotoxicity assays, LGL-1+ cells lyse H-2d targets very effectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Cloning and characterization of 5E6(Ly-49C), a receptor molecule expressed on a subset of murine natural killer cells.

5E6 is a cell surface molecule expressed on a subpopulation of murine natural killer (NK) cells that are involved in the specific rejection of H-2d or H-2f (hemopoietic histocompatibility determinant 2) bone marrow cell grafts. Here, we isolated and cloned the gene encoding 5E6 and determined the nucleotide sequence of the cDNA. 5E6 is nearly identical to Ly-49C; the deduced amino acid sequence reveals a polypeptide of 266 amino acids with a molecular weight of 31,284 that contains multiple cysteine residues to explain its disulfide-linked homodimer structure and five potential N-linked glycosylation sites. 5E6 is a type II integral membrane protein with an extracellular carbohydrate recognition domain characteristic of C-type (Ca(2+)-dependent) animal lectins. Chromosomal mapping indicates that 5E6 is located within the NK gene complex on chromosome 6. The sequence of 5E6 mRNA and the degree of glycosylation of 5E6 protein are under genetic control. Immunoprecipitation before removal of N-linked sugars reveals different size molecules. There are several nucleotide differences among BALB/c, B6, and NZB mRNAs; however, none of them would be expected to affect N-glycosylation. Of particular interest are two findings: (a) BALB/c, B6, and (BALB/c x B6)F1 5E6 reduced molecules are approximately 65, 54, and 54 kD, and (b) the cDNA sequence of (BALB/c x B6)F1 is identical to B6. Thus, there appears to be allelic exclusion of 5E6 expression that may be related to the ability of F1 hybrid mice to reject parental H-2d bone marrow cell grafts.

Amino Acid Sequence↗
PubMed1995

Bone marrow cell transplants involving donors and hosts with haplotypes derived from spretus mice.

Intra-H2 recombinant inbred mice derived from matings between B10 (H2b) and B10.SP2 (H2sp2) mice, with an H2 haplotype derived from Mus spretus, have been used to map genes at H2. Recombinants 10115, 10484, R40, 9347, and 9950 were used as donors or hosts in bone marrow cell (BMC) transplants in irradiated mice. From previous studies of Mus musculus mice, the antigens (Ag) on BMC appear to be inherited recessively. The mechanisms offered include codominant inheritance of transacting genes that regulate expression of BMC Ag (Hh hypothesis) and codominant inheritance of class I Ag motifs capable of sending "negative signals" to effector natural killer (NK) cells (missing self hypothesis). Our results indicate that stem cell donors that express the same class I Ag, but differ at genes between Bat2 and Tnfa in the H2-S/D interval, can differ in immunogenicity of transplanted stem cells. The structural gene for the H2sp2 Ag appears to map telomeric of Bat2 and is codominantly inherited. An H2b gene capable of inhibiting expression of the H2sp2 Ag (or contributing to class I motifs capable of inhibiting NK cell mediated lysis of H2sp2 BMC) maps in the Bat2/Tnfa gene segment, but requires homozygosity for this function and may require the H2-Db gene as well. Although H2sp2 hosts reject H2b BMC, hosts (10115, 10484, R40, and 9347 strain) that are H2b in the centromeric, and H2sp2 in the telomeric, portion of H2 accept H2b BMC grafts. These two observations have not been made with haplotypes entirely of Mus musculus origin. The data do not support the Hh hypothesis, and are consistent with the missing self hypothesis only if the gene (requiring homozygozity for function) in the Bat2/Tnfa region codes for a particular protein or peptide that associates with Db to generate a "protective motif."

Animals↗
PubMed1995

Hybrid and allogeneic resistance to T cell grafts mediated by murine NK and CD8+ T cells.

Lethally irradiated mice can reject H-2 allogeneic or parental strain stem cells in bone marrow cell (BMC) grafts within 48 h after transplantation. This rapid rejection of BMC grafts occurs without prior sensitization and is mediated by NK1.1+ NK cells. One hypothesis to account for the ability of host NK cells to mediate acute rejection of allogenic and parental stem cells is that these effector cells recognize hemopoietic histocompatibility (Hh-1) Ags on the donor stem cells. T cells present in the donor BMC can prevent NK cell-mediated rejection. However, lethally irradiated mice can also reject T cells present in lymph node cell preparations that respond to alloantigens of the host. T cell grafts from H-2k/Hh-1k, H-2r/Hh-1null, and H-2ia1/Hh-1null donors were rejected by CD8+ NK1.1- T cells. Ags other than Hh-1 Ags appeared to be recognized by these CD8+ T cells. In contrast, host NK cells rejected H-2d/Hh-1d T cell grafts, whereas both NK cells and CD8+ TCR-alpha beta + T cells rejected H-2b/Hh-1b T cell grafts. Therefore, both CD8+ TCR-alpha beta T cells and NK cells mediate allogeneic and hybrid resistance to T cell grafts.

Animals↗