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Biomedical subjects

L Hood

Publications and source records attributed to L Hood.

440 records · Page 25Linked to original sources
PubMedDate not supplied

Direct evidence for chromosomal inversion during T-cell receptor beta-gene rearrangements.

A germline T-cell receptor variable region (V beta) gene segment (V beta 14) has been mapped 10 kilobases to the 3' side of the constant region (C beta 2) gene. The V beta 14 gene segment is in an inverted transcriptional polarity relative to the diversity-region (D beta) and joining-region (J beta) gene segments and the C beta genes. Analyses of a T-cell clone (J 6.19), which has productively rearranged the V beta 14 gene segment, indicate that the productive V beta-D beta-J beta rearrangement and its reciprocal flank recombination product are linked and located at either border of a chromosomal inversion. These data demonstrate for the first time a linkage between mammalian V and C genes and verify that a functional T-cell receptor V beta gene can be constructed through a chromosomal inversion.

Amino Acid Sequence↗
PubMedDate not supplied

Predominant use of a V alpha gene segment in mouse T-cell receptors for cytochrome c.

The T-cell receptor is a cell surface heterodimer consisting of an alpha and a beta chain that binds foreign antigen in the context of a cell surface molecule encoded by the major histocompatibility complex (MHC), thus restricting the T-cell response to the surface of antigen presenting cells. The variable (V) domain of the receptor binds antigen and MHC molecules and is composed of distinct regions encoded by separate gene elements--variable (V alpha and V beta), diversity (D beta) and joining (J alpha and J beta)--rearranged and joined during T-cell differentiation to generate contiguous V alpha and V beta genes. T-helper cells, which facilitate T and B cell responses, bind antigen in the context of a class II MHC molecule. The helper T-cell response to cytochrome c in mice is a well-defined model for studying the T-cell response to restricted antigen and MHC determinants. Only mice expressing certain class II molecules can respond to this antigen (Ek alpha Ek beta, Ek alpha Eb beta, Ev alpha Ev beta and Ek alpha Es beta). Most T cells appear to recognize the C-terminal peptide of cytochrome c (residues 81-104 in pigeon cytochrome c). We have raised helper T cells to pigeon cytochrome c or its C-terminal peptide analogues in four different MHC congenic strains of mice encoding each of the four responding class II molecules. We have isolated and sequenced seven V alpha genes and six V beta genes and analysed seven additional helper T cells by Northern blot to compare the structure of the V alpha and V beta gene segments with their antigen and MHC specificities. We have added five examples taken from the literature. These data show that a single V alpha gene segment is responsible for a large part of the response of mice to cytochrome c but there is no simple correlation of MHC restriction with gene segment use.

Animals↗
PubMedDate not supplied

Novel submicroscopic extrachromosomal elements containing amplified genes in human cells.

In previous work, several methotrexate (MTX)-resistant variants were isolated frm the human cell line HeLa BU25, which exhibited a high degree of dihydrofolate (DHFR) gene amplification (estimated to be 250- to 300-fold). These variants did not contain any chromosome with a homogeneously staining region (HSR) and exhibited only a small average number of minute chromosomes per cell: these two types of karyotypic abnormalities generally accompany selective gene amplification. We now report that structures containing amplified DHFR genes in one of these variants (HeLa BU25-10B3) can be isolated by pulsed-field gradient or field-inversion gel electrophoresis as homogeneous DNA molecules of approximately 650 kilobases (kb). Electron microscopy of metaphase spreads from these cells reveals chromatin fibres with a similar DNA content, which are probably related to the above elements. These represent a novel type of extrachromosomal structures in mammalian cells.

Drug Resistance↗
PubMedDate not supplied

Debate: a teaching strategy to improve verbal communication and critical-thinking skills.

Debate is presented as a valuable learning activity for teaching critical thinking and improving communication skills. Included in the discussion are a brief history of the use of debate as a teaching strategy, the responsibilities of the teacher and learner when using debate in the classroom, and its many advantages for developing competencies in communication and critical thinking.

Clinical Competence↗
PubMedDate not supplied

Phase II study of human lymphoblastoid interferon in patients with advanced renal carcinoma.

Twenty-two patients with measurable metastatic renal carcinoma were treated with human alpha lymphoblastoid interferon (Wellferon) (3 million units/m2 of body surface area) im three times a week for 6 weeks; 21 were evaluable for response and toxicity. One patient had a partial regression of disease lasting 39 weeks and another had a minor response. Six patients had partial or minor response in one area but no change in the disease elsewhere (mixed response); they were classified as having stable disease. An additional seven patients had no change in measurable disease and in six the disease progressed. The tumor regressions by metastatic site were four of 14 patients, pulmonary; three of four, soft tissue; one of nine, bone (? soft tissue); none of three, mediastinal; none of four, renal; none of five, liver; and none of ten, other abdominal sites of tumor. The side effects were fever (101 degrees F-103 degrees F), chills, malaise, anorexia, minor (10%-20%) decrease in performance status, and weight loss. We concluded that interferon had some activity against metastatic renal carcinoma, although clinically useful responses were quite infrequent. While lung metastases appeared to be more responsive than those at other sites, careful examination of the data suggests that this simply reflects differences in the bulk of the metastatic disease. Smaller metastases appear more likely to respond than bulky metastases.

Adult↗