PubMed Health⌕ Search

Biomedical subjects

C Briggs

Publications and source records attributed to C Briggs.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mutations affecting the superantigen activity of staphylococcal enterotoxin B.

As a superantigen, staphylococcal enterotoxin B (SEB) possesses the ability to bind to major histocompatibility complex class II molecules and be recognized by T cells bearing certain T-cell receptor (TCR) V beta alleles. Other investigators have utilized site-specific mutagenesis to generate amino acid substitutions to identify residues that may be involved in the interaction with the TCR beta-chain. In an attempt further to define the face of the SEB molecule involved in the interaction with the beta-chain, we have employed a polymerase chain reaction (PCR)-based, site-specific mutagenesis method to generate amino acid substitutions with altered superantigen activity. Our results show that valine at position 169 appears to be involved in the function of this superantigen, since each of several substitutions at this position exhibit a significantly reduced ability to induce T-cell proliferation. Analysis of the responding T cells to the residue 169 substitution shows that the mutant toxins maintain TCR V beta selectivity. At the same time, mutation of the proximal histidine at position 166 does not alter the superantigen activity of SEB. Radiolabelled binding analysis of these H166 and V169 mutants shows that class II-binding activity is not significantly altered. When viewed in the context of other results reported in the literature, combined with the crystal structure of the toxin, our results suggest that the interaction with the TCR probably involves SEB residues which ring a cavity along one side of the toxin molecule.

Animals↗
PubMed1997

Liver torsion and associated bacterial peritonitis in a dog.

A Malamute was examined for acute abdominal pain and collapse. Radiographs of the abdomen showed a pneumoabdomen, and a lucent mass in the region of the liver. Abdominocentesis yielded an inflammatory exudate with bacteria compatible with a Bacillus or a Clostridium sp. A quadrate lobe torsion was found at postmortem.

Abdomen, Acute↗
PubMed1996

Inhibitory effect of a CD4-CDR3 peptide analog on graft-versus-host disease across a major histocompatibility complex-haploidentical barrier.

A structure-based designed peptide has been engineered to exhibit the same molecular surface as a portion of the CDR3-like region in domain 1 of the murine CD4 molecule. Earlier in vitro experiments indicated that this analog, known as rD-mPGPtide, inhibited T-cell proliferation in mixed lymphocyte reactions and blocked activation of both normal CD4+ T cells and T-cell lines after T-cell receptor triggering. In addition, rD-mPGPtide proved to be a potent inhibitor in vivo of CD4+ T-cell-mediated experimental allergic encephalomyelitis disease in the SJL mouse model. In this current report, we have evaluated the potential of rD-mPGPtide for suppressing the development of graft-versus-host disease (GVHD) in an irradiated major histocompatibility complex (MHC)-haploidentical murine bone marrow transplantation (BMT) model [(B6 x DBA/2)F1-->(B6 x CBA)F1 (950 cGy)]. Our results indicated that early administration of rD-mPGPtide was effective in the inhibition of alloreactive responses of the donor T cells against the host and thus delayed or prevented the onset of GVHD. The median survival time of animals treated with rD-mPGPtide was enhanced as much as four-fold with as little as a single dose of peptide at the time of transplant. Decreased alloreactivity was indicated by phenotypic and functional analysis of positively selected thoracic duct lymphocytes 4 days after transplant and by histopathological examination of skin and gastrointestinal tissue samples 4 weeks later. Therefore, the administration of a CD4-CDR3 peptide is an efficacious approach against the development of GVHD during allogeneic BMT.

Acute Disease↗
PubMed1996

Mitochondrial phosphate transport protein. replacements of glutamic, aspartic, and histidine residues affect transport and protein conformation and point to a coupled proton transport path.

The homodimeric mitochondrial phosphate transport protein (PTP), which has six transmembrane helices per subunit, catalyzes inorganic phosphate transport in an electroneutral and pH gradient-dependent manner across the inner membrane. We have replaced the Glu, Asp, and His residues of the yeast PTP to assess their role in the transport mechanism. Mutants with physiologically relevant transport activity were identified by their ability to rescue the PTP null mutant yeast from glycerol medium. Five residues appear critical for transport: His-32 in helix A, Glu-126 and -137 in helix C, and Asp-39 and -236 at the matrix ends of helices A and E. These mutant PTPs are expressed at near normal levels in yeast. This yeast PTP and the mutants were expressed in Escherichia coli as inclusion bodies, solubilized, purified, and reconstituted. Their transport activities correlate well with the physiological assays. None of the transport inactivating mutations appear to be due to major protein conformation changes as assayed by the efficiency of PTP incorporation into liposomes. Only the Glu95Gln (cytosolic helices B and C-connecting segment), Glu163Gln and Glu164Gln (matrix helices C and D-connecting segment), and Glu126Asp (helix C) show a near 70% decrease in liposome incorporation efficiency. In addition, mutations at either end of helix D increase phosphate transport 2-fold. We would like to suggest that Glu-126, His-32, and Glu-137 (similar to Asp-96, Lys-216, and Asp-85 of bacteriorhodopsin) form a proton cotransport pathway that is coupled in an as yet undefined manner (possibly via His-32) to a phosphate transport pathway, which may include helix D.

Amino Acid Sequence↗
PubMed1994

Yeast mitochondrial phosphate transport protein expressed in Escherichia coli. Site-directed mutations at threonine-43 and at a similar location in the second tandem repeat (isoleucine-141).

Yeast mitochondrial phosphate transport activity has been reconstituted from the import receptor (MIR) expressed as inclusion bodies in Escherichia coli. This result undermines the suggestion [Murakami, H., et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 3358-3362] that the MIR has been misidentified as the phosphate transport protein (PTP). PTP was solubilized with N-lauroylsarcosinate and Triton X-100 and purified with a yield of about 2 mg/L of induced bacterial culture. This PTP, reconstituted in liposomes, catalyzes phosphate uptake with a Vmax [24.5 degrees C, net (zero trans), pHi = 8.0, pHe = 6.8] of 0.61 mmol of phosphate min-1 (mg of PTP)-1 and a Km of 1.30 mM. This Vmax is higher and the Km about the same as that obtained with PTP purified from mitochondria. Replacement of Thr43 and Ile141 by other amino acids results in three types of PTP: (a) 2.5-5.0% Vmax of wild-type PTP (PTPwt) (Thr43Cys; Thr43Ser; Ile141Cys), (b) < 0.1% Vmax (detection limit of assay) of PTPwt (Thr43Ala; Thr43Asp), and (c) proton transport uncoupled from phosphate transport (Ile141Cys). Km changes are not significant. Activity of Thr43Cys confirms results obtained with mitochondrially expressed protein. Thus, yeast PTP requires Thr43 and mammalian PTP the similarly located Cys42 for high transport activity. Thr43 and Ile141 are each situated between two basic residues (LysThrArg vs ArgIleArg). Cys substitutions in either of these positions confer the same high N-ethylmaleimide sensitivity to the yeast PTPwt as displayed by the mammalian PTP.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Specificity and generality of motivational components in depression: a personal projects analysis.

Features of depression, as measured by the Beck Depression Inventory (BDI), were distinguished from anxiety, as assessed by the Beck Anxiety Inventory (BAI), and were explored from a goals perspective using the Personal Projects Analysis methodology (B.R. Little, 1983). Depression and anxiety were found to reflect a "negative" appraisal pattern characterized by goals rated high in stress and difficulty, and low in structure, control, perceived skill, and positive outcome expectancy. Depression also revealed distinctive features not found in anxiety (e.g., goals that are perceived as being less visible to important others). A goal-based approach to research and diagnosis is presented, and implications for future research are discussed.

Adult↗
PubMed1993

Assessment of reperfusion in myocardial infarction by body surface electrocardiographic mapping.

To determine the efficacy of body surface potential mapping to detect and quantify reperfusion in acute infarction, 66 patients were studied by repeated body surface potential mapping before and after administration of the thrombolytic agent. The QRS and ST-segment were analyzed and compared to the arterial patency as assessed by arteriography within 10 days. The infarct-related vessel was patent in 50 patients and occluded in the remaining 16. In 6 of the 15 patients in whom thrombolytic therapy was started within 2 hours of the onset of chest pain the ST-segment changed from that of an acute infarction pattern to that of a normal pattern, and the QRS pattern either remained normal or recovered prior to discharge. In two additional patients the QRS pattern returned to normal prior to discharge from the hospital. In the 51 patients with later thrombolytic therapy (> or = 2 hours) the degree of ST elevation and depression decreased more than either the control infarction group (36 inferior and 73 anterior patients) or the group in whom reperfusion attempts were unsuccessful, but the pattern of the map remained that of an infarction. The QRS maps showed that in the first 48 hours recovery of potential was insufficient to distinguish those with successful thrombolysis. Early reperfusion could be detected by body surface potential mapping and the eventual damage predicted from the degree of change in the QRS map. Later reperfusion could be surmised but not quantified.

Electrocardiography↗
PubMed1991

A68930: a potent agonist selective for the dopamine D1 receptor.

A68930, (1R,3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman HCl, is a potent (EC50 = 2.5 nM), partial (intrinsic activity = 66% of dopamine) agonist in the fish retina dopamine-sensitive adenylate cyclase model of the D1 dopamine receptor. In the rat caudate-putamen model of the D1 dopamine receptor, A68930 is a potent (EC50 = 2.1 nM) full agonist. In contrast, A68930 is a much weaker (EC50 = 3920 nM) full agonist in a biochemical model of the dopamine D2 receptor. The orientation of the 3-phenyl substituent in the molecule is critical for the affinity and selectivity of the molecule towards the dopamine D1 receptor. A68930 also displays weak alpha 2-agonist activity but the molecule is virtually inactive at the alpha 1- and beta-adrenoceptors. When tested in rats bearing a unilateral 6-OHDA lesion of the nigro-neostriatal neurons, A68930 elicits prolonged (greater than 20 h) contralateral turning that is antagonized by dopamine D1 receptor selective doses of SCH 23390 but not by D2 receptor selective doses of haloperidol. In this lesioned rat model, A68930 increases 2-deoxyglucose accumulation in the lesioned substantia nigra, pars reticulata. When tested in normal rats, A68930 elicits hyperactivity and, at higher doses, produces a forelimb clonus.

Adenylyl Cyclases↗
PubMed1990

A68930: a potent and specific agonist for the D-1 dopamine receptor.

A68930 (5,6-dihydroxy-3-phenyl-1-aminomethyl-isochroman) is a potent (EC50 = 2.5 nmol/L) partial agonist at the D-1 dopamine receptor. In contrast, A68930 is a much weaker agonist (EC50 = 3,920 nmol/L) at the D-2 dopamine receptor. The orientation of the 3-phenyl substituent in the molecule is critical for the affinity and selectivity of the molecule towards the D-1 receptor in vitro and in vivo. The role of the D-1 receptor in the functioning of the basal ganglia is discussed.

Animals↗
PubMed1989

Deletion mutants of the Escherichia coli K-12 mannitol permease: dissection of transport-phosphorylation, phospho-exchange, and mannitol-binding activities.

We have constructed a series of deletion mutations of the cloned Escherichia coli K-12 mtlA gene, which encodes the mannitol-specific enzyme II of the phosphoenolpyruvate (PEP)-dependent carbohydrate phosphotransferase system. This membrane-bound permease consists of 637 amino acid residues and is responsible for the concomitant transport and phosphorylation of D-mannitol in E. coli. Deletions into the 3' end of mtlA were constructed by exonuclease III digestion. Restriction mapping of the resultant plasmids identified several classes of deletions that lacked approximately 5% to more than 75% of the gene. Immunoblotting experiments revealed that many of these plasmids expressed proteins within the size range predicted by the restriction analyses, and all of these proteins were membrane localized, which demonstrated that none of the C-terminal half of the permease is required for membrane insertion. Functional analyses of the deletion proteins, expressed in an E. coli strain deleted for the chromosomal copy of mtlA, showed that all but one of the strains containing confirmed deletions were inactive in transport and PEP-dependent phosphorylation of mannitol, but deletions removing up to at least 117 amino acid residues from the C terminus of the permease were still active in catalyzing phospho exchange between mannitol 1-phosphate and mannitol. A deletion protein that lacked 240 residues from the C terminus of the permease was inactive in phospho exchange but still bound mannitol with high affinity. These experiments localize sites important for transport and PEP-dependent phosphorylation to the extreme C terminus of the mannitol permease, sites important for phospho exchange to between residues 377 and 519, and sites necessary for mannitol binding to the N-terminal 60% of the molecule. The results are discussed with respect to the fact that the mannitol permease consists of structurally independent N- and C-terminal domains.

Binding Sites↗
PubMed1988

Nonrandom X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency.

X chromosome-linked severe combined immunodeficiency (XSCID) is characterized by markedly reduced numbers of T cells, the absence of proliferative responses to mitogens, and hypogammaglobulinemia but normal or elevated numbers of B cells. To determine if the failure of the B cells to produce immunoglobulin might be due to expression of the XSCID gene defect in B-lineage cells as well as T cells, we analyzed patterns of X chromosome inactivation in B cells from nine obligate carriers of this disorder. A series of somatic cell hybrids that selectively retained the active X chromosome was produced from Epstein-Barr virus-stimulated B cells from each woman. To distinguish between the two X chromosomes, the hybrids from each woman were analyzed using an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. In all obligate carriers of XSCID, the B-cell hybrids demonstrated preferential use of a single X chromosome, the nonmutant X, as the active X. To determine if the small number of B-cell hybrids that contained the mutant X were derived from an immature subset of B cells, lymphocytes from three carriers were separated into surface IgM positive and surface IgM negative B cells prior to exposure to Epstein-Barr virus and production of B-cell hybrids. The results demonstrated normal random X chromosome inactivation in B-cell hybrids derived from the less mature surface IgM positive B cells. In contrast, the pattern of X chromosome inactivation in the surface IgM negative B cells, which had undergone further replication and differentiation, was significantly nonrandom in all three experiments [logarithm of odds (lod) score greater than 3.0]. These results suggest that the XSCID gene product has a direct effect on B cells as well as T cells and is required during B-cell maturation.

Alleles↗
PubMed1986

A study of the haematological and haemorheological consequences of venesection.

A study has been made of a number of haematological and haemorheological factors following venesection therapy. Haematocrit was very effectively reduced by the venesection regimen and led to a fall in whole blood viscosity in spite of the microcytosis that was eventually induced in all the subjects. No clinically significant coagulation changes were observed. It is concluded that a simple venesection regimen without volume replacement is a safe procedure for improving blood rheology.

Aged↗
PubMed1984

Breed and swine lymphocyte antigen haplotype differences in agglutination titers following vaccination with B. bronchiseptica.

Genetic differences in immune response to B. bronchiseptica after vaccination with a commercial B. bronchiseptica bacterin were investigated in 1,069 8-wk-old pigs. These pigs were from 65 litters born in the spring and 66 litters born in the fall of 1982 and were purebreds from the Chester White (n = 128), Duroc (n = 281), Hampshire (n = 143), Landrace (n = 309) and Yorkshire (n = 208) breeds. Each litter was raised separately. Individual pigs were vaccinated im at 4 and 6 wk of age with 2 ml of B. bronchiseptica bacterin. At 8 wk of age, 8 ml of blood were collected from each animal and serum prepared to determine agglutinating antibody titers against B. bronchiseptica bacterin by a bacterial agglutination method. In addition, lymphocytes were separated from 1 ml of heparinized blood and used to determine Swine Lymphocyte Antigen (SLA) haplotypes by using cytotoxic antibodies against the SLA complex. Antisera for 3 SLA haplotypes were made available by the National Institutes of Health. Results indicated that breed of pig (P less than .01) and dam of pig (P less than .01) affected the immune response of the pig after B. bronchiseptica vaccination. Higher immune response was also associated (P less than .05) with one of the SLA haplotypes tested. Heritability estimates for immune response following vaccination were .10 +/- .12 (half-sib) and .42 +/- .19 (full-sib). Results suggest that the relationship of the SLA complex to immune response in the pig and nonadditive genetic and maternal effects on immune response should be further investigated.

Agglutination Tests↗