Development of a high through-put spectrophotometric assay to monitor Trypanosoma cruzi trans-sialidase.
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Animals↗
Biomedical subjects
J A Harrison
Publications and source records attributed to J A Harrison.
Correlates of protection induced by live Aro- Salmonella typhimurium vaccines in the murine typhoid model.
Live attenuated salmonella vaccines generally confer better protection than killed vaccines. The immune responses in BALB/c mice elicited by immunization with a live attenuated Aro Salmonella typhimurium vaccine given orally, intravenously or subcutaneously were compared with those elicited by killed whole-cell vaccines (acetone or heat-treated) given subcutaneously. Live vaccines given by all routes elicited higher interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) responses in spleen cells against an alkali-treated whole-cell salmonella lysate than did killed vaccines. Live and killed vaccines elicited high total antibody levels to smooth lipopolysaccharide (LPS) (enzyme-linked immunosorbent assay), but all live vaccine regimes elicited higher IgG2a, suggesting a Th1 response. Oral and intravenous vaccination with live organisms elicited IgA against smooth LPS which subcutaneous vaccination with live or killed salmonellae failed to evoke. Western blots using rough whole-cell lysates showed that all vaccines elicited a varied anti-protein response; however, all groups immunized with live organisms recognized three unidentified bands of MW 52,000, 46,000 and 18,000 which were consistently absent in groups immunized with killed organisms. The results indicate that immunization with live aroA salmonellae elicited a Th1 type of response, including bystander T-cell help to LPS, and a response to proteins not seen in mice that received killed vaccines.
Administration, Oral↗
Expression and immunogenicity of an Echinococcus granulosus fatty acid-binding protein in live attenuated Salmonella vaccine strains.
Fatty acid-binding proteins (FABPs) are candidate molecules for vaccines against several parasitic platyhelminths. A FABP from the cestode Echinococcus granulosus (EgDf1) was expressed in Salmonella vaccine strains as a C-terminal fusion to fragment C of tetanus toxin (TetC) by using expression vector pTECH. The fusion protein was equally expressed in several attenuated vaccine strains derived from bacteria with different genetic backgrounds and different attenuating mutations. Single-dose immunization experiments with the aroA Salmonella typhimurium strain SL3261 carrying the pTECH-EgDf1 construct were conducted with mice, using both the intravenous and the oral routes. Surprisingly, the antibody response to EgDf1 and the antigen-specific cytokine production in spleen cells were stronger in mice immunized orally. Furthermore, immune mouse sera strongly reacted with fixed sections of the worm's larval stage. Analysis of the isotype distribution of the specific anti-EgDf1 antibodies showed similar production of immunoglobulin G1 (IgG1) and IgG2a together with specific IgA antibodies. In addition, stimulation of spleen cells from mice immunized with the different constructs with either Salmonella lysate, TetC, or EgDf1 showed that, together with Th1-related cytokines (gamma interferon and interleukin 2 [IL-2]), significant levels of a Th2 cytokine (IL-5) were produced specifically, indicating a Th2 component to the response to the Salmonella carrier and to the recombinant antigens. Salmonellae expressing the TetC-rEgDfl fusion are currently under evaluation as potential vaccines against E. granulosus.
Animals↗
Down-regulation of hormone-sensitive lipase in sterol ester-laden J774.2 macrophages.
The development of atherosclerotic plaques in arteries is a key step in atherogenesis, with cholesterol ester accumulation in macrophage-derived foam cells being recognized as a major pathogenic event in this process. In this study, the mouse macrophage cell line J774.2 was induced to accumulate intracellular sterol esters by incubation with 25-hydroxycholesterol in the presence of oleic acid. The accumulation of sterol esters in these cells was found to be accompanied by a marked decrease in the activity of the enzyme responsible for their hydrolysis, namely hormone-sensitive lipase (HSL); Western blotting studies revealed a corresponding decrease in the levels of the HSL polypeptide. Similar findings were obtained after incubation with oxidized low-density lipoprotein or very-low-density lipoprotein. These findings suggest that down-regulation of the expression of HSL is important in cholesterol ester accumulation in macrophages.
Animals↗
Protection against oral challenge three months after i.v. immunization of BALB/c mice with live Aro Salmonella typhimurium and Salmonella enteritidis vaccines is serotype (species)-dependent and only partially determined by the main LPS O antigen.
The role of the main LPS O antigen in the specificity of protection as mediated by systemic mechanisms following immunization with live attenuated Aro Salmonella vaccines was studied in mice. Innately Salmonella-susceptible (Itys) BALB/c mice were immunized intravenously with a single dose of either Salmonella typhimurium SL3261 aroA (LPS O4,5,12) or Salmonella enteritidis Se795aroA (LPS O1,9,12), and challenged orally 2-3 months later with either S. typhimurium C5 or S. enteritidis Thirsk. Nearly isogenic transductants of the two challenge strains expressing either their own LPS or that of the other serotype (S. typhimurium C5 O4 or O9, and S. enteritidis Thirsk O9 or O4) were also used. Both vaccines conferred similar high protection against the virulent strain of the homologous serotype expressing its own LPS. There was no protection against the heterologous serotype expressing its own LPS. However, when vaccinated mice were challenged with either the same serotype as the vaccine but expressing the heterologous LPS, or with the heterologous serotype expressing the LPS of the vaccine, protection was always lower than protection against the fully homologous serotype. Anti-smooth LPS antibodies showed higher titres against the homologous LPS, but with significant crossreactivity with the heterologous LPS. Antibodies to O-rough S. typhimurium and S. enteritidis LPS were present following immunization with either of the two vaccine strains. The LPS alone cannot fully account for the specificity of protection in this model; other (protein) antigens may be responsible. It remains to be seen whether there is a T-cell mediated component to the specificity of protection conferred by live Salmonella vaccines.
Animals↗
Prosthodontic management of a combination transosteal/endosteal implant reconstruction: a clinical report.
This is a clinical report of a patient who was not referred for prosthodontic evaluation and treatment until after undergoing Bränemark endosseous implant placement to supplement the previously existing mandibular staple bone plate implant. This supplemental treatment was the surgeon's attempt to resolve the patient's complaint of loose dentures. Creativity with implant biomechanics and prosthodontic design were necessary to restore the patient, in a predictable manner, to normal function. A fixed, detachable cast overdenture bar rigidly connected to all the implants was constructed utilizing resilient attachments to retain the tissue-supported mandibular overdenture. A presurgical prosthodontic evaluation could have averted many of the problems encountered with treatment. More effective conventional prosthodontic treatment may have resolved the patient's complaints and eliminated the need for additional implant placement.
Bone Plates↗
Effect of interleukin 12 neutralization on host resistance and gamma interferon production in mouse typhoid.
Innately resistant (Ityr) A/J mice infected with the virulent Salmonella typhimurium C5 strain suppress the early exponential bacterial growth in the reticuloendothelial system toward the end of the first week of infection, with spleen and liver bacterial counts reaching a plateau phase. In vivo administration of neutralizing anti-interleukin-12 (IL-12) antibodies did not affect early bacterial growth in the tissues (days 1 to 3) but impaired the establishment of the plateau, with higher spleen and liver counts by day 7 of the infection in anti-IL-12 treated mice than in untreated controls. Gamma interferon (IFN-gamma) was detectable in the sera and spleen homogenates of both control and anti-IL-12-treated mice on days 3 and 7 of the infection. Noticeably, IFN-gamma levels were significantly lower in anti-IL-12 treated mice than in control animals. Splenocytes from uninfected A/J mice released IFN-gamma in response to concanavalin A (ConA) or to S. typhimurium C5. In vitro IL-12 neutralization dramatically impaired the IFN-gamma response to S. typhimurium but not to ConA. Splenocytes harvested from infected anti-IL-12 treated mice on day 7 of the infection produced significantly lower amounts of IFN-gamma upon in vitro stimulation with ConA and with a Salmonella protein-rich extract than did cells from similarly infected untreated control animals. Spleen cells from infected mice showed lower proliferative (mitogenic) responses to ConA and to a Salmonella soluble extract than did cells from uninfected mice. In vivo anti-IL-12 treatment significantly restored the ability of splenocytes from infected mice to proliferate in response to the antigens and ConA. In vivo neutralization of IL-12n in innately susceptible BALB/c mice ((ItyS)) immunized with a live attenuated aromatic-dependent Salmonella vaccine reduced host resistance to virulent oral challenge with S. typhimurium C5. Thus, in primary Salmonella infections, IL-12 mediates the suppression of growth of virulent salmonellae in the reticuloendothelial system, positively modulates IFN-gamma production, and is involved in the immunosuppression which accompanies the acute stages of the disease. IL-12 also contributes to host resistance to virulent organisms in secondary infections.
Animals↗
Induction of human factor VIII inhibitors in rats by immunization with human recombinant factor VIII: a small animal model for humans with high responder inhibitor phenotype.
Hemophilia A is a clotting disorder that is due to reduced or absent coagulation factor VIII (FVIII) activity. In approximately 25% of people with severe hemophilia A, standard treatment with intravenous plasma-derived or recombinant FVIII (rFVIII) induces anti-FVIII antibodies that inhibit FVIII activity (inhibitors). We describe the development of a rat model to study the formation of inhibitors. Immunization of rats with human rFVIII in adjuvant induced an anti-human rFVIII antibody response characteristic of an anti-FVIII inhibitor response in hemophilia A patients. The rats exhibited a rapid, polyclonal secondary antibody response to human rFVIII. These antibodies were reactive against epitopes located in the heavy and light chains. All the rFVIII-immunized rats developed antibodies against the FVIII C2 domain, a region of major reactivity in hemophilia A patients with inhibitors. Furthermore, competition ELISAs demonstrated that rat and human anti-FVIII antibodies recognized identical or overlapping epitopes of the FVIII molecule. The rat anti-FVIII antibodies also functioned as human FVIII inhibitors with titers ranging from 120 to 2048 Bethesda Units (B.U.). We propose that this rat model may be useful to investigate immune responses to FVIII and may lead to better therapies for FVIII inhibitors.
Animals↗
Induction of human factor VIII inhibitors in rats 2: Fine mapping of rat anti-human rFVIII antibodies.
Inhibiting antibodies in patients with hemophilia A pose a significant therapeutic dilemma in the treatment of bleeding episodes. The genetic factors which predispose hemophiliacs to inhibitors and the optimal method for inhibitor suppression remain obscure. Hence, an animal model of the human FVIII inhibitor response is of potential value. Sprague-Dawley rats immunized with human recombinant FVIII (rFVIII) subsequently developed abnormal coagulation parameters coincident with the development of an immune response to the human protein. The epitopes for the resultant rat anti-rFVIII antibodies were mapped using a random fragment expression library constructed from the FVIII cDNA. Antigenic regions located within the A1, First and Second Acidic and B domains were mapped. Rat immunoglobulins reactive with the individual epitopes were immunoaffinity purified and assayed for inhibitory activity. Several of the epitopes mapped using the rat antibodies were similar to regions previously shown to be antigenic for human inhibitors. By contrast, no epitopes were mapped to the A2 domain with the techniques used. This may be due to the possible presence of conformational epitopes in this area which cannot undergo fragmentation and still retain antigenicity or the presence of relatively low concentrations of antibodies to this region. The rat model shares some similarity with both the auto- and alloimmune human response to FVIII and therefore may be a valuable model for studies on the induction and suppression of the inhibitor response.
Animals↗
The unidentified interstellar infrared bands: PAHs as carriers?
Infrared emission spectra of gas-phase naphthalene and pyrene have been measured in the range of 3 to 7.5 micrometers with ultraviolet laser desorption-excitation and a spectroscopic technique featuring single-photon counting in the infrared. The spectra were compared with the unidentified infrared emission bands that are observed in many astronomical objects. Marked discrepancies between those observations and the laboratory emission spectra in the wavelengths and relative intensities of principal spectral features led to the conclusion that small neutral unsubstituted polycyclic aromatic hydrocarbons cannot be the carriers of the unidentified infrared emission bands.
Astronomy↗
Role of hns in the virulence phenotype of pathogenic salmonellae.
A TnphoA-generated mutant C5060, attenuated for virulence, was derived from the mouse-virulent Salmonella typhimurium strain C5. This mutation, designated hns-112::TnphoA, harbours the transposon in the 3' end of hns, with the alkaline phosphatase open reading frame in the opposite orientation to that of hns. Bacterial strains harbouring hns-112::TnphoA were mucoid and had altered levels of DNA supercoiling, as monitored using pUC18 as a reporter plasmid. Transduction of hns-112::TnphoA into mouse virulent strains, including S. typhimurium SL1344 and Salmonella enteritidis Se795, resulted in attenuation. When an independent hns mutation, harbouring a kanamycin-resistance cassette inserted into the Kpnl site at base pair 237 of the hns gene, was introduced into S. typhimurium C5, the isolates were also attenuated. S. typhimurium C5 isolates harbouring the multicopy plasmid pGB651, which encodes the Escherichia coli hns gene, were partially attenuated in mice. Transductional analysis, using Tn10 insertions located close to the hns gene, showed that virulence could be restored in genetic crosses that eliminated the resident hns mutations. However, some hns+ transductants were still attenuated, suggesting that secondary attenuating lesions can accumulate in hns-deficient strains. These studies show that the hns locus plays a role in Salmonella virulence.
Animals↗
Toxicity of lipopolysaccharide and of soluble extracts of Salmonella typhimurium in mice immunized with a live attenuated aroA salmonella vaccine.
Mice immunized intravenously 10 days earlier (but not those immunized 2 months earlier) with an attenuated Salmonella typhimurium SL3261 aroA live vaccine and tested for delayed-type hypersensitivity by injection of crude Salmonella extracts in the footpad can die within 24 to 48 h of an unexplained allergic reaction. The lethal reaction could be prevented by prior administration of anti-tumor necrosis factor alpha serum. Injection of lipopolysaccharide (LPS) (either purified phenol-water-extracted [Westphal] LPS or protein-rich trichloracetic acid-extracted [Boivin] LPS) was also lethal for mice immunized 10 days before. An LPS-rich crude Salmonella extract was more toxic than one which contained less LPS, suggesting that LPS may have been involved in the lethal reactions to crude antigens. Mild alkaline hydrolysis removes O-linked acyl groups from lipid A and eliminates many toxic effects of LPS; however, both Boivin LPS and Westphal LPS remained toxic for immunized mice after alkaline hydrolysis. In contrast, alkaline hydrolysis of crude whole Salmonella extracts (which caused marked protein degradation) reduced the lethal toxicity of the extracts, especially for an LPS-rich preparation. Mice immunized orally with the live vaccine did not show hypersensitivity to either LPS or crude extracts. The results suggest that the lethal reaction to crude Salmonella antigens in mice immunized 10 days earlier is complex, that tumor necrosis factor alpha is involved, and that allergic reactions to crude antigens (but not to LPS alone) can be reduced by mild alkaline hydrolysis.
Animals↗
Height, infant-feeding practices and cardiovascular functioning among 3 or 4 year old children in three ethnic groups.
Barker recently hypothesized that factors affecting prenatal and infant growth are related to adult blood pressure and CVD mortality. Predictions from Barker's hypothesis in regard to infant feeding were tested among a sample of 3 or 4 year old children. The relationship of infant-feeding characteristics (duration of breast-feeding, times of introduction of high fat, high carbohydrate, high potassium foods and table salt) to indicators of cardiovascular functioning (resting blood pressures and heart rates, and heart rate response to graded activity) while controlling for anthropometric (height, sum of seven skinfolds, BMI) and demographic (ethnicity, gender, social status) characteristics revealed that infant-feeding practices were not related to CV functioning in the predicted directions among this sample of 3 or 4 year old children. Furthermore, the positive relationship between height and systolic blood pressure was inconsistent with the Barker hypothesis.
Black or African American↗
A community-based epidemiologic study of health sequelae of exposure to hydrofluoric acid.
An accident at an oil refinery in Texas City, Texas, released around 40,000 lb of hydrogen fluoride, exposing the community to the highly toxic and corrosive substance. A population-based epidemiologic study was conducted to evaluate the impact of the accident on the health of the community. Exposure assessment was done using a multipronged approach through a door-to-door survey of 10,811 individuals. A symptom survey resulting in 1994 completed interviews was conducted with a stratified random sample selected from the exposure study database. The sampling was balanced with respect to age, gender, and predisposition across the three ordinal exposure categories. The results show a strong dose relationship (P < 10(-4)) between the exposure and symptoms reported following the accident and 2 years later, most notably breathing and eye symptoms. However, substantial improvement in health was reported over the 2-year period regardless of the level of exposure. Problems of recall bias and behavioral sensitization are considered and it is recognized that the study may have overestimated the effect. It is also recognized that the study may not have completely unraveled the relative importance of exposure and host response in health outcome, since the two were probably conflated in the exposure measure. Nevertheless, the independence of predisposition and reported level of exposure, the magnitude of effect and its consistency, the unmistakable dose response, the large sample size, and the mutual corroboration of various findings make it difficult to dismiss the interpretation that the hydrofluoric acid exposure indeed caused health problems in the community that continued for at least 2 years after the accident.
Accidents, Occupational↗
A meta-analysis of studies of the Health Belief Model with adults.
The Health Belief Model (HBM) relates a socio-psychologic theory of decision making to individual health-related behaviors. We conducted a meta-analysis of the relationships between four HBM dimensions (Susceptibility, Severity, Benefits and Costs) and health behavior on 16 studies that measured all four of the dimensions, measured a behavioral dependent variable and included some measures of reliability, minimal criteria for establishing the validity of the dimensions. Mean effect sizes were computed for all the studies, subgroupings representing studies of screening, risk reduction and adherence to medical regimen, and prospective and retrospective study designs. Of 24 mean effect sizes, 22 were found to be positive and statistically significant. The actual variance accounted for ranged from 0.001 to 0.09. Homogeneity was rejected for 15 of the 22, however, suggesting that the same underlying construct was not measured. Retrospective studies were found to have significantly large effect sizes for benefits and costs and smaller effect sizes for severity when compared to prospective studies. The weak effect sizes and lack of homogeneity indicate that it is premature to draw conclusions about the predictive validity of the HBM as operationalized in these studies. Our finding of only 16 studies meeting minimal criteria for valid representation of the HBM dimensions indicates that future studies should focus more on such issues.
Adult↗
Sunscreens with low sun protection factor inhibit ultraviolet B and A photoaging in the skin of the hairless albino mouse.
We examined the chronic effect of long daily suberythemal, fluorescent solar-stimulated radiation (FSSR; ultraviolet B (UVB)+A(UVA)) and UVA alone on female Skh-1 hairless albino mouse skin. Mice were dorsally irradiated 8 h every weekday for 16 weeks with FSSR or UVA, or 32 weeks with UVA alone. Various topical, low concentration, UVB and/or UVA sunscreens were applied before irradiation. Damage was assessed by skin-fold thickness, histology and biochemically by changes in the proportion of type III collagen. All FSSR-exposed mice showed increased skin thickening, elastic fibre hyperplasia, collagen damage and an increased proportion of type III collagen. Application of the UVB sunscreen (2.00%) resulted in marked protection for all nonbiochemical endpoints. There was no obvious advantage of adding 0.75% UVA sunscreen to the UVB sunscreen, but adding 2.00% UVA sunscreen reduced biochemical changes and connective tissue damage. Sixteen weeks of UVA irradiation caused skin thickening and laxity but the histology and biochemistry were indistinguishable from the controls. The mice irradiated with UVA for 32 weeks showed slight elastic fibre hyperplasia and collagen damage histologically, and increased skin thickening and laxity; these changes were unmodified by the 0.75% UVA sunscreen. These mice showed a significant increase in the proportion of type III collagen against which the UVA sunscreen offered protection. Our data suggest that UVA may be important in photoaging and that the use of low sun protection factor UVB+ UVA sunscreens on a day-to-day basis may offer some protection from solar photoaging.
Administration, Cutaneous↗
A profile of women in dental education.
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Adult↗
Accuracy of maternal dietary recall for preschool children.
We assessed the effects of socioeconomic status and amount of time mother and child were together during the day on the accuracy of the mother's 24-hour recall report of her 3- or 4-year-old child's dietary intake. Accuracy of the mother's report was compared for nutrients and foods with dietary intake recorded by an observer. Neither socioeconomic status nor amount of time mother and child were together were related to any of the nutrient indicators of accuracy. Although socioeconomic status and amount of time mother and child were together were not related to the indicators of food accuracy, only 64.8% agreement was obtained between mothers and observers on foods consumed. Mothers were more likely to underreport (17.7%) than overreport (10.4%) foods. The low mean difference scores for nutrient indicators supported the use of the 24-hour recall method when collecting group data. The substantial disagreement on foods, however, suggests that previous studies assessing agreement on nutrients have overestimated the accuracy of the 24-hour recall method.
Chi-Square Distribution↗