Search PubMed⌕ Search

Biomedical subjects

D Baker

Publications and source records attributed to D Baker.

At least 289 records · Page 16Linked to original sources
PubMed1990

GTP-binding Ypt1 protein and Ca2+ function independently in a cell-free protein transport reaction.

The 21-kDa GTP-binding Ypt1 protein (Ypt1p) is required for protein transport from the endoplasmic reticulum to the Golgi complex in yeast extracts. Ypt1 antibodies block transport; this inhibition is alleviated by competition with excess purified Ypt1p produced in bacteria. Furthermore, extracts of cells carrying the mutation ypt1-1 are defective in transport, but transport is restored if a cytosolic fraction from wild-type cells is provided. The in vitro transport reaction also requires physiological levels of Ca2+. However, Ypt1p functions independently of Ca2+. First, buffering the free Ca2+ at concentrations ranging from 1 nM to 10 microM does not relieve inhibition by Ypt1 antibodies. Second, consumption of a Ca2+-requiring intermediate that accumulates in Ca2+-deficient incubations is not inhibited by anti-Ypt1 antibodies, although completion of transport requires ATP and an N-ethylmaleimide-sensitive factor. Thus, Ypt1p and Ca2+ are required at distinct steps.

Antibodies↗
PubMed1990

Antigen-restricted antigenic competition induced by 2,4-dinitrochlorobenzene: association with depression of lymphocyte proliferation.

2,4,6-Trinitrochlorobenzene (picryl chloride) and 2,4-dinitrochlorobenzene (DNCB) fail to cross-sensitize with respect to contact sensitivity in mice. Nevertheless, topical exposure of mice to DNCB and other skin-sensitizing dinitrobenzene derivatives was found to result in a significant impairment of draining lymph node cell proliferative responses induced following epicutaneous challenge with picryl chloride 5 days later. The inhibition of picryl chloride induced proliferation was associated with an impairment of contact sensitization to this chemical. The effect of DNCB on subsequent responses to picryl chloride was transient and no longer detectable 15 days following exposure. The inhibition of proliferation and contact sensitization caused by DNCB was largely restricted to picryl chloride. Thus, DNCB failed to influence the development of contact allergy to the unrelated chemical 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone) and exerted a far less pronounced effect on oxazolone-induced proliferative responses. These data, therefore, describe an antigen-restricted form of antigenic competition which is associated with a depression of the primary lymphocyte proliferative response.

Animals↗
PubMed1990

Perforating eye injury in Allegheny County, Pennsylvania.

From 1980 through 1986, acute perforating eye injury (ICD codes 871.0-871.9) was diagnosed in 345 residents of Allegheny County, Pennsylvania. The mean incidence rate was 3.49 per 100,000 person years. There was no significant change in incidence over the seven-year period. The largest number of injuries occurred among individuals working with tools, of which 47 percent were occupational. Males had a 6.5-fold risk of injury relative to females. Blacks had a risk of 2.2 times that of Whites, mainly due to an excess of assaultive injuries. Individuals who had had recent ocular surgery accounted for 4.6 percent of cases overall, and for 31.6 percent of cases in those over age 60.

Adolescent↗
PubMed1990

Assessment of intestinal amino acid availability in cattle by use of the precision-fed cecectomized rooster assay.

The digestibilities of amino acids in duodenal digesta of steers were measured using a precision-fed cecectomized rooster assay. Freeze-dried duodenal digesta from steers fed five different diets were utilized. Amino acids present in digesta of steers fed diets supplemented with corn gluten meal were more digestible than those from digesta of steers fed diets supplemented with soybean meal, blood meal, fish meal, or no true protein source. Measurements of amino acid digestibility in the cecectomized rooster were similar to those obtained previously when measured with reference to chromic oxide in steers fitted with duodenal and ileal cannulae, suggesting that the precision-fed cecectomized rooster assay is an appropriate technique for estimating small intestinal digestibility of amino acids in cattle.

Amino Acids↗
PubMed1990

Requirements for antigenic competition in contact sensitivity.

The requirements for the induction of antigenic competition in murine contact sensitivity have been examined. Experiments with a variety of skin-sensitizing chemicals revealed a correlation between immunogenicity and the ability to inhibit subsequent responses to an unrelated contact allergen, oxazolone. Previous studies have suggested that, in contact sensitivity at least, antigenic competition is the consequence of a reduced lymphocyte proliferative response to the second antigen. We investigated whether the regulatory events which impair proliferation following exposure to the second antigen are induced as the result of a strong proliferative response to the first (competitor) antigen. It was found, however, that significant inhibition of the primary proliferative response to picryl chloride, by pretreatment of mice with either picryl sulphonic acid or 2,4-dinitrochlorobenzene, failed to prevent picryl chloride inducing antigenic competition for oxazolone. Our studies suggest that following topical exposure to potent skin allergens events other than proliferation in draining lymph nodes induce active immunoregulatory processes, one consequence of which is the appearance of antigenic competition.

Animals↗
PubMed1990

Is maintenance antiparkinsonian treatment necessary?

The authors designed a three-phase prospective trial in which only those patients who developed an acute, neuroleptic-induced extrapyramidal side effect (EPSE) received benztropine (BZ) at 2 mg i.m. and then 1 mg p.o. b.i.d. for 2 days after their symptoms were rated for severity and type (Preparatory Phase 1). They were then randomly assigned under double-blind conditions to continue BZ or be switched to placebo for 8 days (Experimental Phase 2). Finally in Phase 3 (Followup), all patients continued on placebo in a single-blind design until Day 30. If the patient re-experienced an acute EPSE that was of sufficient severity to require immediate BZ administration, he or she was rated, treated, and then dropped from the study. EPSE scores and dropout rates did not differ in Phase 2 between the placebo- and BZ-treated groups. Implications for the continuation, cessation, or intermittent use of antiparkinsonian (AP) drugs are discussed.

Adult↗
PubMed1990

Effect of joint motion on experimental calcium pyrophosphate dihydrate crystal induced arthritis.

We studied the effects of joint movement and immobilization on acute and chronic calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis in lapine knee joints. Exercised CPPD injected joints, in both acute (single 10 mg CPPD intraarticular (IA), duration: 5 h) and chronic (repeated 10 mg CPPD IA, duration: 20 and 42 days) experiments, demonstrated a more intense histologic synovitis compared to cast immobilized knees (p = 0.0001). In chronic experiments, both CPPD injected and noninjected immobilized knees showed greater cartilage histopathologic-histochemical abnormalities (p less than 0.004) and significant reduction in cartilage hexosamine content (p less than 0.005), compared to exercised joints. CPPD injected knees, both exercised and immobilized, demonstrated an initial phase of increased cartilage biosynthetic activity (35S incorporation) at 20 days, compared to noninjected knees (p = 0.02), followed by a decline at 42 days (p less than 0.005). Our data indicate that joint movement enhances acute and chronic experimental CPPD crystal induced synovitis. Articular cartilage is more adversely affected by joint immobilization than by chronic crystalline inflammation. An optimum balance between exercise and rest seems necessary for patients with arthritis so that cartilage can be preserved but pain from active inflammation also controlled.

Animals↗
PubMed1989

Differential expression of guinea pig class II major histocompatibility complex antigens on vascular endothelial cells in vitro and in experimental allergic encephalomyelitis.

Previous studies have shown that vascular endothelial cells do not normally express major histocompatibility complex (MHC) Class II antigens either in vivo or in vitro. In this investigation it was found that endothelial in the central nervous system (CNS) of normal guinea pigs constitutively express MHC Class II antigens recognized by the monoclonal antibodies HLA-DR, 27E7, and MSgp8. This phenotype is retained when these CNS-derived endothelial cells are propagated in tissue culture. Furthermore, examination of CNS tissue taken from animals in the acute phase of chronic relapsing experimental allergic encephalomyelitis shows that additional epitopes of the MHC Class II antigen, detected by the monoclonal antibodies CI.13.1 and 22C4, are present during the diseased state. This study not only demonstrates constitutive expression of certain MHC Class II determinants by guinea pig endothelial cells, but also shows that other Class II determinants can be differentially expressed in certain disease states.

Animals↗
PubMed1989

A simple and rapid method for determining the linearity of a flow cytometer amplification system.

We describe a simple and rapid method for determining the linearity of a flow cytometer amplification system. The method is based on a fundamental characteristic of linear amplifiers: The difference between two amplified signals increases linearly with increasing amplifier gain. Two populations of beads or cells, differing slightly in fluorescence intensity, are analyzed by the flow cytometer at increasing photomultiplier tube high-voltage settings. The distribution of the populations' mean difference versus mean position is a straight line intersecting the origin for linear amplifiers. Although some types of nonlinearities cannot be detected with this technique, deviations from linearity indicate nonlinear components in the flow cytometer amplification system. The correlation coefficient is used to quantify degree of nonlinearity. We also describe a method for amplifier nonlinearity compensation.

Amplifiers, Electronic↗
PubMed1989

Androgen and glucocorticoid receptor-mediated inhibition of cell proliferation by medroxyprogesterone acetate in ZR-75-1 human breast cancer cells.

Medroxyprogesterone acetate (MPA) is a synthetic progestin, currently used in the adjuvant treatment of advanced breast cancer, which induces remission rates (30-40%) comparable to those obtained with other types of endocrine therapies. Since, in addition to its progestin-like action, MPA exhibits androgen- and glucocorticoid-like activities in other tissues, the present study was designed to assess the relative contribution of the different steroid receptor systems in the direct action of MPA on breast cancer cell growth, using the ZR-75-1 human mammary carcinoma cell line as an in vitro model. Unlike pure progestins, MPA potently inhibited the proliferation of ZR-75-1 cells in a concentration-dependent manner either in the presence or in the absence of estrogens, and the addition of insulin had only marginal effects on its growth-inhibitory activity. On the other hand, both hydroxyflutamide (OHF, a non-steroidal monospecific antiandrogen) and RU486 (a potent antiglucocorticoid and antiprogestin also endowed with antiandrogenic activity) competitively reversed MPA antiproliferative effects. MPA further decreased the growth of ZR-75-1 cells co-incubated with maximally inhibitory concentrations of either 5 alpha-dihydrotestosterone (DHT) or dexamethasone (DEX), although at about 300-fold higher MPA concentrations with DHT-treated than with DEX-treated ZR-75-1 cells, thus demonstrating a highly predominant androgenic effect. However, MPA had no effect on the growth of ZR-75-1 cells co-incubated with DHT and DEX simultaneously, thus supporting the predominant role of androgen and glucocorticoid receptors in MPA action. A 12-day preincubation of ZR-75-1 cells with increasing concentrations of MPA (10(-12) to 3 x 10(-6)M) decreased the specific uptake of [3H]estradiol (E2) by intact cell monolayers to the same extent as 10 nM DHT, an effect which was competitively blocked by the addition of OHF (3 microM). MPA action on ZR-75-1 cell growth also significantly differed from that of progestins in being additive to the inhibition of E2-stimulated growth by the steroidal antiestrogen ICI164384. The present data indicate that the main action of MPA on ZR-75-1 human breast cancer cell growth is due to its androgen receptor-mediated inhibitory action, while its glucocorticoid-like activity could play an additional role at high concentrations.

Breast Neoplasms↗
PubMed1989

Rheumatoid arthritis synovial fluid phospholipase A2 activating protein (PLAP) stimulates human neutrophil degranulation and superoxide ion production.

Rheumatoid arthritis is characterized by excessive eicosanoid production, and phospholipase enzymes are the rate limiting step in eicosanoid synthesis. We have shown previously that cells from patients with rheumatoid arthritis express enhanced phospholipase A2 enzyme activities. Recently, we have isolated a phospholipase A2 activating protein termed PLAP from rheumatoid synovial fluid. This novel human protein shares biochemical and antigenic similarities with melittin, a bee venom phospholipase activating protein. Because melittin has been shown to induce neutrophil degranulation and superoxide formation, and because exuberent release of lysosomal enzymes and superoxide have been implicated in the pathogenesis of rheumatoid arthritis, we examined the role of PLAP on inducing these neutrophil functions.

Arthritis, Rheumatoid↗
PubMed1989

Antigen-specific regulation of T lymphocyte proliferative responses to contact-sensitizing chemicals in the guinea pig.

Skin painting of guinea pigs with either 4-ethoxymethylene-2-phenyloxazol-5-one or 2,4-dinitrofluorobenzene induced not only a primary proliferative response in the draining lymph node but also the systemic suppression of subsequent proliferative responses to topically applied hapten. The inhibition of lymphocyte proliferation, as assessed by the incorporation of [3H]-thymidine and the presence of large pyroninophilic cells in the paracortex, was hapten-specific and long-lasting. This study demonstrates that, in common with the mouse, the sensitization of guinea pigs results in the induction of a hapten-specific suppressor mechanism, which serves to control the proliferative response following reexposure to hapten. However, the antigen-nonspecific suppression of proliferation observed in the mouse following exposure to some potent contact sensitizers was not, under the conditions employed, detectable in the guinea pig.

Allergens↗
PubMed1989

A quantitative immunocytochemical study of the infiltrating lymphocytes in the spinal cord of guinea pigs with chronic relapsing experimental allergic encephalomyelitis.

The production and characterization of an anti-guinea pig B cell monoclonal antibody is described. Immunocytochemical techniques using this antibody and others recognizing a Pan T cell antigen and T cell subsets were employed to study frozen sections of spinal cord from guinea pigs with chronic relapsing experimental allergic encephalomyelitis. T and B cells were found in both perivascular lesions and the central nervous system parenchyma, with the major T cell infiltration occurring by the end of the acute phase of disease. The distribution of T cell subsets suggests a phenotypic selectivity in favour of the transport of CT6 (putative CD8)+ve cells across the blood-brain barrier.

Animals↗
PubMed1989

Regulation of lymphocyte proliferation in contact sensitivity: homeostatic mechanisms and a possible explanation of antigenic competition.

Epicutaneous exposure of mice to the contact sensitizing chemicals 4-ethoxymethylene-2-phenyl-oxazol-5-one (oxazolone) and 2,4,6-trinitrochlorobenzene (picryl chloride) causes an inhibition of proliferative responses induced following subsequent topical challenge. The effects on lymphocyte proliferation comprise both transient antigen non-specific and more persistent hapten-specific mechanisms. Pretreatment of mice with one chemical 5 days prior to sensitization with a second, at which time antigen non-specific influences on proliferative responses are manifest, results in depression of contact sensitization as measured by changes in ear thickness following challenge. If, however, the period between pretreatment and sensitization is extended the inhibition of contact sensitization disappears in parallel with a decline in the antigen non-specific depression of lymph node cell proliferation. These data reveal that there exist two homeostatic mechanisms which control proliferation in response to challenge with at least some antigens, and that the extent of lymphocyte proliferation directly influences the degree of contact sensitization achieved. Moreover these results demonstrate that, in some instances at least, competition between antigens may be a function of immunoregulatory influences on lymphocyte proliferation.

Animals↗
PubMed1989

Presentation of myelin basic protein by normal guinea-pig brain endothelial cells and its relevance to experimental allergic encephalomyelitis.

Previous studies have shown that endothelial cells in the central nervous system (CNS) of normal guinea-pigs constitutively express certain MHC class II determinants, whilst the expression of other determinants is apparent during the acute phase of chronic relapsing experimental allergic encephalomyelitis (CREAE). The expression of MHC class II determinants is retained by endothelial cells derived from normal guinea-pig brain tissue and maintained in culture. This present study demonstrates that the MHC class II molecules on these cells can be recognized by allogeneic lymphocytes, resulting in a proliferative response which is enhanced by the addition of exogenous IL-2. The endothelial cells were incapable of presenting either purified protein derivative or ovalbumin, but they could present autologous myelin basic protein (MBP), an encephalitogen implicated in the pathogenesis of EAE. The resulting lymphocyte proliferative response was of the same magnitude as that obtained when a control population of macrophages was used to present MBP. These results, therefore, suggest that cerebrovascular endothelia have the potential to play a role in the pathogenesis of EAE.

Animals↗
PubMed1988

Reconstitution of SEC gene product-dependent intercompartmental protein transport.

Transport of alpha-factor precursor from the endoplasmic reticulum to the Golgi apparatus has been reconstituted in gently lysed yeast spheroplasts. Transport is measured through the coupled addition of outer-chain carbohydrate to [35S]methionine-labeled alpha-factor precursor translocated into the endoplasmic reticulum of broken spheroplasts. The reaction is absolutely dependent on ATP, stimulated 6-fold by cytosol, and occurs between physically separable sealed compartments. Transport is inhibited by the guanine nucleotide analog GTP gamma S. sec23 mutant cells have a temperature-sensitive defect in endoplasmic reticulum-to-Golgi transport in vivo. This defect has been reproduced in vitro using sec23 membranes and cytosol. Transport at 30 degrees C with sec23 membranes requires addition of cytosol containing the SEC23 (wild-type) gene product. This demonstrates that an in vitro inter-organelle transport reaction depends on a factor required for transport in vivo. Complementation of sec mutations in vitro provides a functional assay for the purification of individual intercompartmental transport factors.

Adenosine Triphosphate↗