Publications by authors named "Hedrick S"

Chalcone synthase (CHS) catalyzes the first and key regulatory step in the branch pathway of phenylpropanoid biosynthesis specific for synthesis of ubiquitous flavonoid pigments and UV protectants. In bean (Phaseolus vulgaris L.) and other members of the Leguminoseae, chalcone synthase is also involved in the synthesis of the isoflavonoid-derived phytoalexin antibiotics characteristic of this family.

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We have studied the relationship between major histocompatibility complex (MHC)-restricted antigen recognition and alloreactivity by examining T cell receptor (TCR) alpha and beta gene expression in cytochrome c-specific, Ek alpha:Ek beta (Ek)-restricted helper T cell clones derived from B10.A mice. The clones could be segregated on the basis of four distinct alloreactivity patterns.

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17 T cell clones and 3 T cell lines, specific for pigeon cytochrome c, were analyzed for fine specificity and rearranged T cell receptor (TCR) gene elements. Clones of similar fine specificities were grouped into one of four phenotypes, and correlations between phenotype differences and gene usage could be made. All the lines and clones rearranged a member of the V alpha 2B4 gene family to a limited number of J alpha regions.

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The derived amino-acid sequences of the heterodimeric antigen receptors expressed by a series of murine T-cell clones are presented. A comparison of the receptor sequences indicates that several mechanisms for generating receptor diversity can influence T-cell specificity, including junctional diversity, combinatorial joining, and combinatorial chain associations.

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The effect of home care on patient outcomes and costs of care has been controversial. This information synthesis summarizes results from studies of home care using experimental or quasi-experimental designs, explicitly including judgments of methodologic soundness in weighing the results. In 12 studies of programs targeted at chronically ill populations, home care services appear to have no impact on mortality, patient functioning, or nursing home placements.

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In 1982, the Veterans Administration established Health Services Research field programs in each of the six VA regions. Herein, we describe the historical origins, organization, responsibilities, activities, and early accomplishments of one of these programs--the Northwest Regional HSR&D field program. Special reference is made to this program's commitment to health services research relevant to geriatrics and gerontology, including the development of a system-wide agenda for research, information syntheses in geriatrics-relevant health services research topics, and the conduct of funded projects pertinent to care of the elderly.

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Using the murine cDNA clone for the beta chain of the T cell antigen receptor, we have examined four highly cytotoxic rat large granular lymphocyte (LGL) leukemia lines for the expression of unique rearrangements and mRNA transcription of the genes coding for the T cell antigen receptor. In contrast to normal rat T cells and nine rat T cell lines, the LGL leukemia lines exhibited no detectable gene rearrangements in the beta chain locus after digestion of LGL DNA by four restriction enzymes. Northern blots containing RNA from these LGL tumor lines demonstrated a low level of aberrant or nonrearranged beta chain transcription (less than 10 copies per cell) but virtually no translatable 1.

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The restriction enzyme Eco RI reveals DNA cleavage sites that serve to distinguish the gene locus believed to encode the beta subunit of the major histocompatibility complex (MHC)-restricted, antigen-specific receptor of the T cell in BALB/c mice from that of SJL/J mice. A monoclonal antibody, KJ16-133, also distinguishes BALB/c and SJL/J, because it recognizes an allotypic marker present on a cell-surface heterodimer believed to function as the MHC-restricted, antigen-specific T cell receptor. This study has shown that these two markers cosegregate in a set of BALB/c X SJL/J recombinant inbred (RI) mouse strains, permitting the conclusion that they are linked to within 3 centimorgans of each other, and to the kappa locus on chromosome 6.

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The striking number of human and murine immunodeficiency disorders which map to the X chromosome suggests that genes localized on this chromosome must have important roles in lymphocyte development. At least seven distinct disorders in the human and two in the mouse disrupt lymphocyte maturation, particularly that of B cells, at characteristic stages. As functional genes mapping to the X chromosome in one mammal are found on the X chromosome in all other mammals, the same genes regulating lymphocyte development are expected to be found on the X chromosome in mouse and man.

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The functionally defined sets of T lymphocytes--helper T cells, cytotoxic T cells, and suppressor T cells--were examined for the possible involvement of a recently identified T-cell receptor beta gene locus in receptor formation. Since gene rearrangements are required for functional gene expression, cloned T-cell lines from each of the groups were surveyed for the expression of unique gene rearrangements. In addition, cell lines that showed gene rearrangements were further tested for the expression of the mature 1.

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We undertook a controlled random double-blind comparing gold and penicillamine. Of the 50 patients with rheumatoid arthritis entered into the study, 34 completed the protocol. We found no significant differences in the clinical results, laboratory variables, or toxicity.

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We have studied a family in which the proband had systemic lupus erythematosus and selective incomplete deficiency of the fourth component of complement (C4) (2-5% of the normal level). An additional six healthy family members also had low C4 levels (2.4-24.

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We describe here our efforts to develop a systematic strategy for the enumeration and isolation of genes encoding T cell-specific, membrane-associated polypeptides. Of particular importance among the cDNA clones that we have isolated is one which encodes the beta chain of the murine T cell receptor for antigen. The gene product is strikingly similar to immunoglobulin in its variable (V), constant (C), joining (J), and diversity (D) - like elements and the ability of the latter three types of element to assort independently during differentiation.

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Southern blot analysis of somatic cell hybrid lines indicates that the beta chain of the T cell receptor for antigen maps to chromosome 6 of the mouse. An experiment testing hybridization of the constant region of this gene to DNA from a hybrid cell line containing a translocation of chromosome 6 supports the localization of this gene to the proximal (centromeric) one-third of chromosome 6, in the same general region as the immunoglobulin kappa chain locus. This may be another indication of the shared evolutionary origins of the genes encoding both T and B cell antigen recognition.

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Comparison of the sequence of a cloned T cell-specific cDNA with those of cross-reacting cloned cDNAs isolated from a thymocyte library indicates the presence of variable, constant and joining regions remarkably similar in size and sequence to those encoding immunoglobulin proteins. Together with the evidence for somatic gene rearrangements reported in the accompanying paper, this strongly suggests that the TM86 cDNA clone encodes one chain of the T-cell receptor for antigen.

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Of 10 distinct cloned DNA copies of mRNAs expressed in T lymphocytes but not in B lymphocytes and associated with membrane-bound polysomes, one hybridizes to a region of the genome that has rearranged in a T-cell lymphoma and several T-cell hybridomas. These characteristics suggest that it encodes one chain of the elusive antigen receptor on the surface of T lymphocytes.

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In this report we examine the effects of binding antigen directly to Ia molecules during immunization and stimulation of T cells in culture. To accomplish this we characterize the T cell response to Igh-1j-encoded IgG2a antibodies in C57BL/10 H-2 congenic mice. In contrast to the response to the closely related Igh-1a-encoded IgG2a antibodies, high responder mice were (C57BL/10 X B10.

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The activation of proliferative T lymphocytes normally involves the simultaneous recognition of a particular foreign antigen and a particular Ia molecule on the surface of antigen-presenting cells, the phenomenon of major histocompatibility complex (MHC) restriction. An analysis of T cell clones specific for pigeon cytochrome c, from B10.A and B10.

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