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Biomedical subjects

R Roth

Publications and source records attributed to R Roth.

At least 37 records · Page 2Linked to original sources
PubMed1996

B7 costimulation and autoantigen specificity enable B cells to activate autoreactive T cells.

This study examines the role of B cells as auto-APCs in activating autoimmune T cells responses. Mice immunized with their own cytochrome c (cyt c) elicit no detectable B or T cell responses. However, mice first primed with a cryptic self peptide, mouse cyt c 81-104, followed at 3 wk with a boost of whole cyt c, elicit autoreactive T cells specific to self cyt c. T cell autoimmunity is not elicited in similarly immunized B cell-deficient (mu MT) mice. The expression of the B7-2 and/or B7-1 costimulatory molecules, as well as specificity to a self Ag, cyt c, enabled B cells to activate T cells to proliferate and to express IFN-gamma, IL-4, IL-5, and IL-10 cytokine mRNAs. In contrast, neither adoptively transferred B7- B cells nor nonspecific B7+ B cells were able to activate naive T cells. Moreover, anti-B7-2 treatment of mice prevented the in vivo expression of the IL-4, IL-5, and IFN-gamma cytokine mRNA responses. Our results suggest a major role of autoantigen-specific, B7-bearing B cells in breaking T cell tolerance to self Ag.

Adoptive Transfer↗
PubMed1996

Comparison of monocytes and B cells for activation of human T helper cell subsets.

Human rye grass allergen Lol p I-specific T helper cell clones of Thp, Th0, Th1 and Th2 subtype were activated with Lol p I and monocytes or B cells as antigen-presenting cells, and cell proliferation, interleukin (IL)-2, interferon-gamma, and IL-4 secretion were measured. Monocytes induced activation of T cell clones of all four T helper cell subsets and were usually more potent antigen-presenting cells than B cells. B cells and monocytes similarly induced proliferation and IL-4 secretion by Th2 clones, whereas B cells, in contrast to monocytes, only weakly activated Th1 clones. However, exceptions to this rule existed within each T helper cell subset suggesting that individual T cell clones, regardless of the subset to which they belong, may have quantitatively and/or qualitatively different requirements for secondary activation signals which are provided by the antigen-presenting cells. The data demonstrate that, in general, monocytes are more effective than B cells in activating human T cell clones of all subtypes and that B cells were efficient antigen-presenting cells only for Th2 cells. However, individual T cell clones of any given T helper cell subset vary with respect to their activation by monocytes or B cells.

Allergens↗
PubMed1996

Carbon monoxide ... the silent killer with an audible solution.

Carbon monoxide (CO) is responsible for more poisoning fatalities each year than any other toxic agent. The often insidious nature of the symptom progression and its ability to imitate many common illnesses may result in the failure to diagnose a potentially fatal outcome. CO detectors equipped with an audible alarm can alert potential victims of CO poisoning before toxic sequelae develop. A study was conducted in which all calls to 911 concerning a CO detector in alarm or regarding possible CO poisoning were investigated by a paramedic crew; 101 possible CO exposures were investigated. CO detectors with audible alarms were the genesis of 59.4% of the calls. Detectable CO levels were found in 69.3% of the investigations, and 80% of the homes with detectors had verifiable CO concentrations. The mean CO concentration in homes with detectors was 18.6 ppm, compared with 96.6 ppm when no detector was available; 63.4% of the victims with no alarm were symptomatic, compared with 13.3% of victims with alarms. CO detectors with audible alarms were effective in alerting the potential victims of CO poisoning to its presence. Persons with CO detectors were less likely to become symptomatic from a CO exposure than those who did not have CO detectors.

Carbon Monoxide↗
PubMed1996

Activation of cloned human CD4+ Th1 and Th2 cells by blood dendritic cells.

Dendritic cells (DC) have been reported to be the most potent antigen-presenting cells (APC) for the activation of naive T cells and to be 10-100-fold more potent APC than monocytes (M phi) in the mixed lymphocyte reaction. In this study the authors compared human blood DC with M phi and B cells for their ability to activate cloned rye grass allergen Lol p I specific CD4+ Th1 and Th2 cells. In the presence of Lol p I, all three types of APC activated Th1 and Th2 cells to a similar extent, as shown by T-cell proliferation and interferon-gamma, interleukin-2 (IL-2) or IL-4 secretion. However, at low APC:T cell ratios, M phi were the most potent APC for both Th1 and Th2 cells followed in decreasing order by DC and B cells. This hierarchy was observed with APC preparations isolated by negative selection or highly purified by positive selection using fluorescent cell sorting for HLA-DR(high)-DC, CD14(pos)-M phi and CD19(pos)-B cells. The data demonstrate that, in contrast to what has been reported for naive T cells, human blood DC activate cloned memory Th1 and Th2 cells to a similar extent as M phi and B cells presumably because the requirements for activation of memory type T cells are less stringent than those for naive T cells.

Antigen-Presenting Cells↗
PubMed1996

[Endovascular therapy of visceral aneurysms].

Sixteen cases of endovascular treatment of aneurysms and pseudoaneurysms were reported; five patients had true aneurysms, 11 presented pseudoaneurysms of splanchnic arteries. In all cases embolization was performed with coils; in one case we used coils in combination with Ethibloc. In 14 of 16 patients definite occlusion of the aneurysms was achieved without further surgical intervention.

Adult↗
PubMed1995

Activation of complement by human hemoglobin and by mixtures of hemoglobin and bacterial endotoxin.

Purified human hemoglobin is being developed as an alternative to transfusions of homologous erythrocytes. However, toxicity associated with infusion of hemoglobin has limited the development of this resuscitation fluid. Some observed toxicities, including activation of the complement cascade, have been associated with contamination of hemoglobin solutions by bacterial endotoxin. Recent studies have demonstrated complex formation between hemoglobin and endotoxin, and have documented a resultant increase in the ability of endotoxin to activate coagulation, stimulate tissue factor production by human peripheral blood mononuclear cells, and stimulate tissue factor activity and protein synthesis in cultured human endothelial cells. The process of hemoglobin enhancement of endotoxin toxicity suggests a possible mechanism by which the consequences of endotoxin contamination of hemoglobin solutions, including complement activation, could be magnified. Therefore, we studied the potential of hemoglobin to either fix complement directly, or modify the ability of endotoxin to fix complement. Human crosslinked and native hemoglobins, at concentrations between 0.2 mg/ml and 3 mg/ml, were shown to fix complement. Complement fixation by hemoglobin was identical in normal human serum or in factor B-depleted serum, suggesting that fixation occurred via the classical pathway of complement activation. Complement fixation then was examined with a battery of smooth and rough endotoxins tested in the absence and presence of hemoglobin. Addition of hemoglobin to a solution of a rough Salmonella endotoxin partial structure, from which a single fatty acid had been hydrolyzed from the lipid A portion of the macromolecule, resulted in decreased efficiency of complement fixation. However, addition of hemoglobin had little or no effect on the intrinsic complement fixing abilities of eight other smooth endotoxins, rough endotoxins, or endotoxin partial structures. Our results demonstrated the ability of hemoglobin to fix complement at hemoglobin concentrations which would be achieved during infusion for resuscitation, but failed to demonstrate a reproducible effect of hemoglobin on the activation of complement by endotoxin.

Bacterial Toxins↗
PubMed1995

FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae.

Type 1 pili are heteropolymeric mannosebinding fibers produced by all members of the Enterobacteriaceae family. The bulk of the fiber is composed of FimA. Two macromolecular complexes responsible for mediating an interaction with mannose-containing receptors were purified from fimA- Escherichia coli by mannose affinity chromatography and ion-exchange chromatography. One complex contained only the mannose-binding adhesin, FimH, associated with FimG, a minor component of the type 1 pilus. In the other complex the FimG-FimH moiety was loosely associated with a chaperone-minor subunit complex (FimC-FimF), possibly representing an intermediate in tip fibrilla assembly. The FimC chaperone has also been shown to form a preassembly complex with FimH that has been purified and characterized previously. Purified FimC did not bind to the FimG-FimH complex but did recognize FimH dissociated from the FimG-FimH complex. Quick-freeze deep-etch electron microscopy revealed that the FimG-FimH complex had a thin fibrillar architecture. High-resolution electron microscopy of type 1 pili revealed that a 16-nm fibrillar tip structure with an architecture identical to that of the FimG-FimH complex was joined end-to-end to the pilus rod. In a fimH- deletion mutant, the tip fibrillae joined to pilus rods were approximately 3 nm in length. The full-length tip fibrilla was restored by complementation with the fimH gene in trans. The bipartite nature of the type 1 pilus was also demonstrated on pili purified from clinical isolates of members of the Enterobacteriaceae family arguing that it is a conserved feature of the type 1 pilus.

Adhesins, Escherichia coli↗
PubMed1995

Effects of a heterogeneous set of xenobiotics on RNA synthesis of yeast cells.

Previously the toxicity of 45 heterogeneous environmental chemicals on growth and membrane functions in Saccharomyces cerevisiae and Chinese hamster ovary (CHO) cells (Cascorbi et al., 1993) was examined. In this study the inhibitory effects of the same set of chemicals on yeast RNA synthesis rate, measuring [2-14C]uracil uptake during cell proliferation are presented. The sensitivity of this test system was three to six times higher than that of the proliferation rate assay. In addition, the range of the EC20 values were similar to the range from the mammalian CHO cell proliferation test. The relatively good correlation with the yeast cell growth rate (r = 0.78, P = 0.0001) suggests that yeast RNA synthesis is a simple and rapid method of detecting a wide range of toxic compounds without the disadvantage of the insensitivity of the growth rate assay.

Allyl Compounds↗
PubMed1995

Developmental toxicity study of clarified slurry oil (CSO) in the rat.

Pregnant CD rats were exposed dermally to 0.05, 1, 10, 50, and 250 mg/kg/day of Clarified Slurry Oil (CSO) on Days 0-19 of gestation to determine its potential developmental toxicity. Untreated and vehicle controls were included in the study. Day 20 of gestation Caesarean-derived fetuses were examined for gross, external, and visceral or skeletal alterations. Dosages of 1 mg/kg/day and higher significantly decreased maternal body weight, body weight gain, feed consumption, gravid uterine weight, and live litter size and significantly increased resorption rate. These dosages also significantly reduced fetal weights and retarded development of the brain, kidney, thoracic and caudal vertebrae, metacarpals, and hindpaw phalanges in dosage groups with live fetuses (high dosage group dams resorbed all conceptuses). The 50- and 250-mg/kg/day dosage group dams had only placentas and/or dark red viscous fluid in the uterus or vagina and significant body weight loss (associated with resorption). The highest dosage also caused emaciation, slight dehydration, and swollen dark anogenital areas. These results indicate that CSO produces adverse developmental effects at maternally toxic dosages. The maternal and developmental NOAELs (no observed adverse effect levels) were 0.05 mg/kg/day. In a second study, groups of 10 mated female rats were exposed to "pulse" exposures and dosages of 1, 50, or 250 mg/kg/day of CSO applied dermally for 2- or 3-day intervals that spanned the gestation period. All dosages reduced maternal feed consumption and body weight gain during the treatment period. Dosages of 50 and 250 mg/kg/day also produced early resorptions when administered on Days 6 through 8 and 9 through 11 of gestation. However, no increase in fetal alterations occurred, indicating that the effects on embryo-fetal development were due to early death and not to the death of malformed conceptuses.

Abnormalities, Drug-Induced↗
PubMed1994

Characterization and partial purification of an ATPase and inorganic pyrophosphatase of the archaebacterium Methanobacterium thermoautotrophicum.

ATPase and inorganic pyrophosphatase (PPase) activities have been detected in several methanogenic bacteria. These activities are believed to play a crucial role in energy metabolism. In the present study we have investigated some characteristics of the ATPase and the inorganic PPase activities of Methanobacterium thermoautotrophicum. Although these proteins migrate identically on non-dissociating gels, they are catalyzed by distinct enzymes which are separable by biochemical purification methods. The partially purified enzymes are composed of at least two subunits. The ATPase subunits have molecular masses of about 43 and 33 kDa and the inorganic PPase such of about 31 and 25 kDa. After purification, the PPase and the ATPase did not hydrolyze ATP and PP(i), respectively. The membrane-bound ATPase and PPase activities are distinguished in response to sodium fluoride, by the effects of divalent cations, by the temperature ranges for activities and the solubilization behaviour by different extractants. Most investigated catalytic and structural properties of the ATPase do not suit the current criteria for classifying this enzyme under either the F-, V- or P-ATPases.

Adenosine Triphosphatases↗
PubMed1993

Golgi membrane dynamics imaged by freeze-etch electron microscopy: views of different membrane coatings involved in tubulation versus vesiculation.

We used high resolution three-dimensional electron microscopy to visualize Golgi cisternal structure and analyze morphological transitions induced by various in vitro incubations. Our images show that Golgi cisternae have two distinct surface coatings with different distributions and apparent functions. The first type, probably a coatomer coat, consists of tightly packed approximately 10 nm surface particles. These are localized exclusively to sites of membrane budding and are as intimately involved in bud formation as clathrin or caveolin coats. When this coating is exaggerated by GTP gamma S, the periphery of all cisternae is partitioned into coated vesicles that remain attached at their sites of formation. A second, much finer coating is evenly distributed over the periphery of cisternae, including tubules enclosing the fenestrae. It appears to stabilize the membrane curvature associated with tubules and edges. These different coatings must be considered in further attempts to unravel Golgi membrane trafficking mechanisms.

Animals↗