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Biomedical subjects

C Thompson

Publications and source records attributed to C Thompson.

At least 235 records · Page 13Linked to original sources
PubMed1993

Characterization of dinY, a new Escherichia coli DNA repair gene whose products are damage inducible even in a lexA(Def) background.

Bacteriophage Mu dX(Ap lac) was used to isolate a mutation in an Escherichia coli lexA(Def) strain representing a previously undescribed gene (dinY) which does not seem to be under the direct control of LexA. The insertion created a dinY::lacZ fusion in which beta-galactosidase expression required a DNA-damaging treatment (UV irradiation or mitomycin) and activable RecA protein. This strain showed a decreased Weigle reactivation of bacteriophage lambda. However, it was fully inducible for UV mutagenesis. Two-dimensional gel electrophoresis analysis identified two spots absent in the mutant which were both UV inducible only in the presence of activated RecA protein (RecA*). This finding suggests that the dinY::lacZ fusion lies in a gene either that is under the direct control of activated RecA or whose product undergoes RecA*-dependent posttranscriptional/posttranslational modification(s). The dinY gene may also control the expression of some other gene(s) and/or lie in an operon. The fusion was mapped at a position between 41 and 41.5 min on the E. coli chromosome, in the vicinity of the ruv operon.

Bacterial Proteins↗
PubMed1993

Detection and comparison of DNA adducts after in vitro and in vivo diesel emission exposures.

Development of methods to evaluate certain classes of polycyclic aromatic compounds (PAC) detected in complex mixtures to which humans are exposed would greatly improve the diagnostic potential of 32P-postlabeling analysis. Identification of DNA adduct patterns or specific exposure-related marker adducts would strengthen associations between observed DNA adducts and exposures to different environmental pollutants (e.g., kerosene, cigarette smoke, coke oven, and diesel). We have compared diesel-modified DNA adduct patterns in various in vitro and in vivo rodent model systems and compared them to DNA reactive oxidative and reductive metabolites of 1-nitropyrene. The formation of nitrated polycyclic aromatic hydrocarbon (nitrated PAH) DNA adducts, derived from the metabolism of diesel extract constituents, was enhanced relative to other PAH-derived DNA adducts via xanthine oxidase-catalyzed nitroreduction. These adducts were detectable only by the butanol extraction version of the postlabeling analysis. Five major DNA adducts were detected in human lymphocytes treated in vitro with diesel extract. A major adduct detected in human lymphocytes treated in vitro with diesel extract comigrated with a major adduct detected in lymphocyte DNA treated with benzo[a]pyrene (BaP) alone. Other adducts that co-migrated with the major BaP-derived adducts were detected in skin and lung DNA isolated from rodents topically treated with (50 mg) diesel extract and the major adduct detected in calf thymus DNA treated with rat liver S9 and diesel particle extract. Postlabeling of lung DNA isolated from rodents exposed via lung inhalation for 24 months to diesel combustion emissions resulted in the formation of a major nuclease-P1-sensitive DNA adduct that did not co-migrate with the major BaP-diol epoxide adduct.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Comparison of DNA adducts from exposure to complex mixtures in various human tissues and experimental systems.

DNA adducts derived from complex mixtures of polycyclic aromatic compounds emitted from tobacco smoke are compared to industrial pollution sources (e.g., coke ovens and aluminum smelters), smoky coal burning, and urban air pollution. Exposures to coke oven emissions and smoky coal, both potent rodent skin tumor initiators and lung carcinogens in humans, result in high levels of DNA adducts compared to tobacco smoke in the in vitro calf thymus DNA model system, in cultured lymphocytes, and in the mouse skin assay. Using tobacco smoke as a model in human studies, we have compared relative DNA adduct levels detected in blood lymphocytes, placental tissue, bronchoalveolar lung lavage cells, sperm, and autopsy tissues of smokers and nonsmokers. Adduct levels in DNA isolated from smokers were highest in human heart and lung tissue with smaller but detectable differences in placental tissue and lung lavage cells. Comparison of the DNA adduct levels resulting from human exposure to different complex mixtures shows that emissions from coke ovens, aluminum smelters, and smoky coal result in higher DNA adduct levels than tobacco smoke exposure. These studies suggest that humans exposed to complex combustion mixtures will have higher DNA adduct levels in target cells (e.g., lung) as compared to nontarget cells (e.g., lymphocytes) and that the adduct levels will be dependent on the genotoxic and DNA adduct-forming potency of the mixture.

Adult↗
PubMed1993

Discordant expression of CD28 ligands, BB-1, and B7 on keratinocytes in vitro and psoriatic cells in vivo.

The process for optimal T-cell activation requires not only engagement of the T-cell receptor/CD3 complex, but also the delivery of additional co-stimulatory signals that synergize with the primary response mediated through the T-cell receptor. Thus, the regulated expression of ligands for such co-stimulatory molecules can be critical in determining whether a cell can effectively activate T cells following the presentation of a foreign antigen. The CD28 antigen has recently been shown to mediate such co-stimulatory signals by interacting with the B7/BB-1 molecule expressed on activated B cells and monocytes. We show in this study that activated keratinocytes, both in vitro and in vivo display a discordance in expression between B7 and BB-1 based on differential monoclonal antibody (MAb) reactivity. Activated keratinocytes in vitro, as well as psoriatic keratinocytes and epithelial cells in the thymus, are reactive with the BB-1 MAb but not anti-B7 MAbs. These BB-1 positive cells fail to express detectable B7 messenger RNA by Northern blot analysis. Furthermore, keratinocytes bind specifically to CD28-transfected COS7 cells, and this binding is inhibited by anti-CD28 and anti-BB-1 but not B7 MAbs. These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28.

Antibodies, Monoclonal↗
PubMed1993

The failure of conventional methods to promote spontaneous transpyloric feeding tube passage and the safety of intragastric feeding in the critically ill ventilated patient.

Nasoenteral tube feedings are often recommended in critically ill patients when gastrointestinal tract function is intact. Conventional methods of placement include turning the patient on the right side and the use of drugs that stimulate peristalsis to promote transpyloric passage. A prospective study was initially performed to assess the success of conventional methods used to promote transpyloric feeding tube placement in patients requiring assisted ventilation admitted to the Surgical Intensive Care Unit (SICU) (Part I of the study). In 68 critically ill ventilated patients, placement of nasoduodenal feeding tubes was attempted. Successful transpyloric placement was achieved in only ten patients. There was no correlation between age, gender, admitting diagnosis, time of tube placement and successful placement. The second part of the study was initiated to assess the safety of nasogastric feeding in critically ill ventilated patients. Forty-two patients admitted to the SICU were considered candidates for gastrointestinal tract feeding and were fed through the gastric route. Twenty-five patients reached enteral feeding goal rate within 72 hours, while 34 patients achieved goal rate by five days. Eight patients required total parenteral nutrition to meet nutritional needs because of an inability to achieve adequate nutritional support enterally. There were 11 complications noted in ten patients, including one episode of aspiration pneumonia. The presence of complications was not related to age, gender, admitting diagnosis, infusion method or type of formula used. Duodenal intubation using conventional methods in critically ill ventilated patients is unsuccessful in most patients. Nasogastric feeding in this group of patients can be safely administered in selected instances.

Critical Illness↗
PubMed1992

Novel form of growth cone motility involving site-directed actin filament assembly.

Regulation of cytoskeletal structure and motility by extracellular signals is essential for all directed forms of cell movement and underlies the developmental process of axonal guidance in neuronal growth cones. Interaction with polycationic microbeads can trigger morphogenic changes in neurons and muscle cells normally associated with formation of pre- and postsynaptic specializations. Furthermore, when various types of microscopic particles are applied to the lamellar surface of a neuronal growth cone or motile cell they often exhibit retrograde movement at rates of 1-6 microns min-1 (refs 3-6). There is strong evidence that this form of particle movement results from translocation of membrane proteins associated with cortical F-actin networks, not from bulk retrograde lipid flow and may be a mechanism behind processes such as cell locomotion, growth cone migration and capping of cell-surface antigens. Here we report a new form of motility stimulated by polycationic bead interactions with the growth-cone membrane surface. Bead binding rapidly induces intracellular actin filament assembly, coincident with a production of force sufficient to drive bead movements. These extracellular bead movements resemble intracellular movements of bacterial parasites known to redirect host cell F-actin assembly for propulsion. Our results suggest that site-directed actin filament assembly may be a widespread cellular mechanism for generating force at membrane-cytoskeletal interfaces.

Actins↗
PubMed1992

Quisqualate neurotoxicity in rat cortical cultures: pharmacology and mechanisms.

Quisqualate is a potent neurotoxin in cortical cultures of the rat. Unlike N-methyl-D-aspartate (NMDA), the toxicity of quisqualate is due to overstimulation of a membrane receptor after the agonist has been removed. This receptor appears to be the 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor since 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) are potent antagonists when added to the post incubation media. NBQX and DNQX are ineffective when present only during quisqualate exposure, indicating the AMPA receptor is not involved in the initial event. Transfer of culture media 30 min after quisqualate exposure to either neuronal or non-neuronal cells was found to cause toxicity in previously untreated neuronal cells. This effect could not be reproduced with NMDA. The neurotoxic chain of events could be interrupted during quisqualate exposure by removal of sodium from the incubation media, suggesting the involvement of a sodium-dependent plasma membrane uptake mechanism. Quisqualate may be continually recycled by internalization and release, causing neurotoxicity by persistent stimulation of the AMPA receptor.

Animals↗
PubMed1992

HIV testing and assessment of risk of other sexually transmitted diseases.

The risk factors for infection with the human immunodeficiency virus (HIV) were assessed in individuals attending two different HIV antibody testing clinics: Genitourinary Medicine (GUM) and an HIV counselling and screening clinic (CSC) The risk of acquiring other sexually transmissible infections (STD) was also assessed, and all patients were offered STD screening. Fewer STDs were found in CSC patients than in GUM patients, but the results highlight the need to be aware of the possibility of other STDs whenever and wherever HIV antibody testing is undertaken.

Adolescent↗
PubMed1992

Evaluation of bacterial polysaccharide immune globulin for the treatment or prevention of Haemophilus influenzae type b and pneumococcal disease.

A human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) has been prepared from plasma donors immunized with Haemophilus influenzae type b (Hib), pneumococcal, and meningococcal vaccines. At a dose of 0.5 ml/kg, BPIG increased levels of antibody to Hib by greater than 0.15 microgram/ml within 4-6 h and by 2-4 micrograms/ml at 72 h. Thereafter, antibody declined, with a mean half-life of 27 days. BPIG treatment of Apache infants did not impair their active antibody responses to concurrently administered diphtheria-tetanus-pertussis or Hib oligosaccharide-diptheria CRM197 conjugate vaccines. In high-risk Apache infants, BPIG given at 2, 6, and 10 months of age provided significant protection from invasive Hib infection during infancy. Thus, BPIG may have utility in the prevention of Hib infections in high-risk patients who cannot be immunized adequately with Hib conjugate vaccines.

Antibodies, Bacterial↗
PubMed1992

Prevention of Haemophilus influenzae type b infections in Apache and Navajo children.

Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos. The attack rate in children less than 5 years of age is 5-10 times higher than in the general US population. Three vaccines were evaluated. Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants. HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses. The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels. PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose. This vaccine was greater than 90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age. Even a single dose achieved a high protective efficacy.

Antibodies, Bacterial↗
PubMed1992

Limulus antilipopolysaccharide factor protects rabbits from meningococcal endotoxin shock.

Limulus antilipopolysaccharide factor (LALF), an 11.8-kDa peptide isolated from amebocytes of Limulus polyphemus, neutralizes meningococcal lipooligosaccharide (LOS)-induced gelation of limulus amebocyte lysate. Rabbits challenged with an LD90 of LOS (10 micrograms/kg) premixed with LALF in vitro (n = 10) had significantly higher mean arterial pressure, arterial pH, serum bicarbonate concentrations, and survival (90% vs. 8%, P = .005) than did rabbits challenged with LOS alone. Relative to untreated controls, rabbits pretreated with LALF intravenously (iv) at 1.2 mg/kg (n = 21) also had significant improvements in physiologic measurements and higher survival (52% vs. 8%, P = .003). Even when LALF (1.2 mg/kg iv) was given 1/2 h after LOS challenge, animals showed significant improvements in physiologic measurements and survival (33% vs. 8% in untreated controls P = .028). LALF-treated animals also had significantly lower circulating endotoxin activity and tumor necrosis factor concentrations. Thus, LALF attenuates the toxic effects of meningococcal LOS in rabbits even when administered after LOS challenge and deserves further evaluation as a potential therapeutic agent for treating gram-negative septic shock.

Animals↗