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Biomedical subjects

E Johnson

Publications and source records attributed to E Johnson.

At least 109 records · Page 6Linked to original sources

Consumption of freshwater fish in Kahnawake: risks and benefits.

Kahnawake is a Mohawk community located on the south shore of the Saint Lawrence River near Montreal. A comprehensive study was conducted in 1996-1997 to address the local concern regarding health risks of contaminant exposure associated with freshwater fish consumption. Forty-two participants, including most of the identified active fishermen (n=33), were interviewed. Walleye, perch, bullhead, and smallmouth bass were the species most consumed. Average daily intake of locally caught fish was 23 g/day. Nutrient and contaminant levels of locally collected fish were analyzed. Fish were good sources of protein, polyunsaturated fatty acids (particularly omega-3 fatty acids), calcium, zinc, and iron. Levels of cadmium, lead, arsenic, polychlorinated biphenyls (PCBs), and other chlorinated pesticides were at least 10 times lower than the guideline levels. Mercury levels of some predatory fish exceeded the guideline of 0.5 microgram/g. Average daily intakes of all contaminants were below the guideline levels by a factor of 10 except for mercury. Average mercury intake rate was about one-third that of the guideline level (200 micrograms/week). Contrary to residents' perception, Kahnawake fish were not particularly contaminated. In view of the nutritional as well as cultural benefits, fishing and fish consumption may be promoted.

Adolescent↗

Failure of anti-Forssman antibodies to induce rejection of mouse heart xenografts.

The Forssman antigen has been proposed to be a target for the xenograft reaction in selected species combinations, including the rat and mouse, which are Forssman-negative and -positive species respectively. The mouse represents an important experimental model for a variety of immune-mediated disease processes, and the availability of a simple, inexpensive target antigen could provide an important tool for studying a selected portion of the immunologic basis for the rejection of xenografts. We have examined the potential that antibodies directed against mouse Forssman antigen could cause the hyperacute rejection of mouse heart xenografts in naive rat recipients. The Forssman antibodies tested included rat anti-mouse (R-anti-M) antiserum, R-anti-M antiserum depleted of anti-Forssman (anti-F) antibodies, rat anti-sheep red blood cell (SRBC) antiserum containing anti-F antibodies and a rat monoclonal anti-F IgM antibody. Our results demonstrate that the R-anti-M antiserum at day 4 post transplantation displayed significant titers (1:512-4096) of hemagglutinating antibodies for SRBC and mild to moderate levels of IgM that specifically binds to Forssman glycolipid (GalNAcalpha1-3GalNAcbeta1-3Galalpha1-4Galbeta1- 4Glcbeta1-1ceramide) as measured by an enzyme-linked immunosorbent assay (ELISA). Passive transfer of the R-anti-M serum to rats receiving mouse cardiac grafts immediately after transplantation caused hyperacute rejection of the xenografts. Sequential immunoabsorption of R-anti-M sera with SRBCs resulted in total removal of the anti-Forssman activity (as defined by negative hemagglutination titer and minimal binding to Forssman glycolipid in ELISA). The anti-F Ab-depleted R-anti-M antisera, however, retained the capacity to induce hyperacute rejection of the mouse hearts [n = 6, median survival time (MST) 13 min] when passively transferred to rat recipients. Anti-Forssman antibodies induced by immunization of LEW rats with SRBCs or a rat anti-Forssman monoclonal antibody, mAb M.1.22.25, exhibited substantial anti-Forssman activity (hemagglutinating titer 1:512-4096 and moderate-to-strong binding to Forssman glycolipid in ELISA respectively). These antibodies also failed, however, to trigger hyperacute rejection of mouse cardiac xenografts. In conclusion, our results suggest that the rat anti-Forssman antibodies, including those stimulated by mouse cardiac xenografts, do not appear to play a role in the immediate (hyperacute) rejection of mouse heart xenografts.

Animals↗

Genetic line and major histocompatibility complex effects on primary and secondary antibody responses to T-dependent and T-independent antigens.

The effects of MHC and nonMHC (background) genetics on the kinetics of primary and secondary antibody responses to T-cell-dependent (SRBC) and T-cell-independent [Brucella abortus (BA)] antigens were investigated. Eight genetic groups were represented, with four homozygous MHC haplotypes [B1-IrGATlow (IrGAT = immune response to GAT locus); B1-IrGAThigh; B19-Ir-GATlow; B19-IrGAThigh] on two genetic backgrounds, the S1 and G lines. Birds were injected simultaneously with BA and SRBC at 4 and 7 wk of age, and blood samples were taken weekly from 4 to 10 wk of age for measurement of total agglutinating serum antibody levels. A quadratic equation and its first derivative were computed for each bird to approximate individual curve parameters: y max, the maximum titer; t max, the time required to achieve y max; and c coefficient, the rate of decline in the titer. Curve parameters of birds from different lines were analyzed separately by using the General Linear Model procedure. A second analysis that included line effect evaluated the nonMHC gene effects and their interactions with erythrocyte antigen B locus (Ea-B) or IrGAT. In the S1 line, there was an interaction (P < 0.05) between MHC haplotypes and sex for primary response to BA. In contrast, there were no significant main effects nor interactions in the G line background for primary and secondary responses to BA and SRBC. There was an effect (P < 0.05) of line background on y max for primary BA and for secondary SRBC responses. A positive correlation (P < 0.05) was found between the c coefficients of BA and SRBC secondary responses, suggesting that the rate of decline in the secondary response is similar between these T-dependent and T-independent responses. The overall results of this study indicate complex interactions between specific MHC alleles and the nonMHC background of the lines in which they are studied.

Animals↗

CD4(+) T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice.

In this study, we used a mouse model to examine the role of the adaptive immune response in alveolar bone loss induced by oral infection with the human gram-negative anaerobic bacterium Porphyromonas gingivalis. Severe combined immunodeficient mice, which lack B and T lymphocytes, exhibited considerably less bone loss than did immunocompetent mice after oral infection, suggesting that lymphocytes contribute to this process. Bone loss after oral infection was decreased in mice deficient in major histocompatibility complex (MHC) class II-responsive CD4(+) T cells, but no change in bone loss was observed in mice deficient in MHC class I-responsive CD8(+) T cells or NK1(+) T cells. Mice lacking the cytokine gamma interferon or interleukin-6 also demonstrated decreased bone loss. These results suggest that the adaptive immune response, and in particular CD4(+) T cells and the proinflammatory cytokines that they secrete, are important effectors of bone loss consequent to P. gingivalis oral infection. The studies also reinforce the utility of the mouse oral infection model in dissecting the pathobiology of periodontal disease.

Adaptation, Physiological↗

Weekly patterns of drug treatment attendance.

OBJECTIVES: This study examined weekly patterns of drug treatment attendance in relation to date of welfare payment receipt and reason for treatment absence. METHODS: Treatment attendance by Medicaid-eligible pregnant women who were drug dependent was examined by calendar week over a 29-month period. RESULTS: Time series analyses showed that attendance was lower during week 1 than week 4. Drug use was the most frequently reported reason for treatment absence during week 1 (25%) but was not reported as a reason during week 3. CONCLUSIONS: Drug-dependent outpatients had increased absences associated with illicit drug use during the first week of the month when welfare payments were received. The generalizability of the findings is unknown.

Adult↗

Age, geographic, and temporal distribution of fecal shedding of Cryptosporidium parvum oocysts in cow-calf herds.

OBJECTIVE: To evaluate fecal shedding of Cryptosporidium parvum from California cow-calf herds with respect to age, geographic region, temporal effects, and association with watery feces. ANIMALS: Cows and calves from 38 beef cow-calf operations. PROCEDURE: Fecal specimens were collected and examined for C parvum oocysts, using immunofluorescent microscopy. Associations between age, geographic region, month of collection, watery feces, and likelihood of shedding C parvum were evaluated. RESULTS: 3.9% of cattle were shedding C parvum oocysts. Prevalence of shedding among calves ranged from 0 to 13%, and was 0.6% among cattle > or = 12 months old. The odds of shedding C parvum among 2-month-old calves were 41 times greater than among cattle > 4 months old. The odds of shedding C parvum among cattle tested in May were 8.7 times greater than among cattle tested during June, July, or August. The odds of infected individuals having watery feces were 3 to 4 times greater than for noninfected individuals, but the etiologic fraction was only 8 to 9%. CONCLUSIONS AND CLINICAL RELEVANCE: Substantial fecal shedding of C parvum by cow-calf herds was limited to calves 1 to 4 months old, with low prevalence detected in older animals. Risk of contamination of watersheds with C parvum was limited to those periods when young calves were in the herd. Although the odds of having watery feces were greater for animals infected with C parvum than for noninfected animals, the low etiologic fraction suggests that most calves with watery feces were not infected with C parvum.

Age Factors↗

The E7 protein of human papillomavirus type 16 sensitizes primary human keratinocytes to apoptosis.

The 'high risk' human papillomaviruses are associated with the development of anogenital carcinomas and their E6 and E7 genes possess immortalizing and transforming functions in several in vitro culture systems. Recently the E6 gene has also been shown to enhance the apoptosis of human mammary epithelial cells. To determine the apoptotic activity of these oncogenes in the natural host cell, we infected genital keratinocytes with retroviruses expressing either HPV-16 E6, E7, or both the E6 and E7 (E6/7) genes. Apoptosis was quantitated under normal growth conditions or when induced by tumor necrosis factor alpha/cycloheximide or sulfur mustard. In contrast to previous findings with mammary epithelial cells, the E6 gene did not significantly augment either spontaneous or induced apoptosis. E6 also did not suppress apoptosis in normal keratinocytes (despite dramatically reducing their p53 levels), suggesting that p53-independent events mediated this effect. In contrast, E7 increased both spontaneous and induced apoptosis as well as the cellular levels of p53 and p21 protein. Interestingly, co-expression of E6 abrogated E7-facilitated apoptosis by tumor necrosis factor alpha nearly completely, but had only a minor protective effect on sulfur mustard induced apoptosis in these cells, demonstrating at least in part the p53-dependence and -independence of these two apoptotic pathways. Finally, our results indicate that the apoptosis of normal and E7-expressing keratinocytes is differentially affected by E6 expression and that E7, when unaccompanied by E6, sensitizes keratinocytes to apoptosis.

Apoptosis↗

In situ measurement of dihedral angles at liquid grain boundary inclusions.

This work describes experimental aspects of the measurement of relative interfacial energies from the equilibrium dihedral angles of small liquid inclusions or precipitates at interfaces in solids using in situ transmission electron microscopy. We demonstrate how limitations such as faceting, free surfaces, and projection errors can be handled to minimize experimental errors.

Alloys↗

Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons.

Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on both developing and mature DA neurons. In vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct injection of NTN into the substantia nigra protects mature DA neurons from cell death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of intact adult animals induces behavioral and biochemical changes associated with functional upregulation of nigral DA neurons. The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results suggest that NTN is an endogenous trophic factor for midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRalpha1.

3,4-Dihydroxyphenylacetic Acid↗

Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.

BACKGROUND: Tuberculosis is a common complication of HIV-1 infection, especially in developing countries. Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals. METHODS: We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged 16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival. FINDINGS: Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants who received rifampicin and pyrazinamide compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tuberculosis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time. INTERPRETATION: Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.

AIDS-Related Opportunistic Infections↗

Filling the gut activates paradoxical sleep in suckling rats.

Recent studies with rat pups suggest that suckling and sleeping are coordinated through milk-related events in the gut. Our experiments revealed that suckling rats respond to milk in the upper gastrointestinal tract by displaying more paradoxical sleep (PS) as the volume increases to 4% of the pup's body weight. Conversely, gastric loads larger than 4% reduced PS as a function of the volume. We also discovered that filling the stomach with warm non-nutritive paraffin is as effective as an equivalent volume of warm milk for enhancing PS. Although the temperature of the gut load did not appear to play a major role in the amount of PS displayed, increasing ambient temperature from 22 degrees C to 32 degrees C increased PS significantly. Moreover, a gut load of milk (4% body weight) was more effective than the same volume of water or no load for enhancing PS. Gut loads that stay in the stomach and warm ambient temperature appear to work in an additive manner to enhance PS. The electrophysiological data together with the stomach volume data and behavioral observations of nipple attachment revealed that milk-related stimuli along the gastrointestinal tract, especially gastric distension, alter sleep patterns in predictable ways that permit us to distinguish postingestive satiety from a deprivation state and nimiety in suckling rats.

Analysis of Variance↗

High-level expression of murine terminal deoxynucleotidyl transferase in Escherichia coli grown at low temperature and overexpressing argU tRNA.

Terminal deoxynucleotidyl transferase (TdT) is a highly conserved vertebrate enzyme that possesses the unique ability to catalyze the random addition of deoxynucleoside 5'-triphosphates onto the 3'-hydroxyl group of a single-stranded DNA. It plays an important role in the generation of immunoglobin and T-cell receptor diversity. TdT is usually obtained from animal thymus gland or produced in a baculovirus system, but both procedures are rather tedious, and proteolysis occurs during purification. Attempts to overexpress TdT in bacteria have been unsuccessful or have yielded an enzyme with a lower specific activity. A dearth of TdT has thus hampered detailed structural and functional studies. In the present study, we report that by lowering growth temperature and overexpressing a rare arginyl tRNA, it is possible to boost the production in Escherichia coli of murine TdT with minimal proteolysis and high specific activity.

Animals↗

Accuracy of CLOtest after Helicobacter pylori therapy.

BACKGROUND: The accuracy of rapid urease testing after Helicobacter pylori therapy has not been widely studied and might be diminished because of decreased numbers of organisms. We assessed CLOtest results after therapy in two randomized, double-blind trials. METHODS: A total of 233 patients (in two separate studies) with true-positive baseline CLOtests (by histology or culture) received 2 weeks of omeprazole/amoxicillin, omeprazole, or amoxicillin. In study 1, patients received an additional 2 weeks of omeprazole therapy (20 mg/day) or placebo; no additional therapy was given in study 2. Endoscopy was repeated 4 weeks after completion of therapy in both studies. A diagnosis of cure required at least two negative endoscopic biopsy tests (histology, culture, CLOtest) and no positive tests. RESULTS: After therapy, 178 patients (76%) remained positive for H. pylori by histology and/or culture for both studies combined. Post-therapy CLOtest sensitivity was 86% and specificity was 95%. Sensitivity was poorer in patients after dual therapy than after monotherapy in both study 1 (68% vs. 89%; p = 0.03) and study 2 (75% vs. 94%; p = 0.03). CONCLUSIONS: CLOtest sensitivity after therapy was lower than expected in our large group of patients with baseline true-positive CLOtests. In addition, sensitivity was lower after the use of more effective therapy (i.e., dual therapy as compared with monotherapy). Although most patients with unsuccessful treatment will be identified with the CLOtest alone, a negative result should not be taken as diagnostic of eradication.

Amoxicillin↗

The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents.

Neuronal nicotinic acetylcholine receptors (NAChRs) are pentameric ligand-gated ion channel receptors which exist as different functional subunit combinations which apparently subserve different physiological functions as indicated by molecular biological and pharmacological techniques. It is possible to design and synthesize novel compounds that have greater selective affinities and efficacies than nicotine for different NAChRs, which should translate into different behavioral profiles and therapeutic potentials. Examples of NAChR agonists studied are nicotine, SIB-1508Y, SIB-1553A and epibatidine. These compounds have different degrees of selectivity for human recombinant NAChRs, different neurotransmitter release profiles in vitro and in vivo and differential behavioral profiles. Preclinical studies suggest that SIB-1508Y is a candidate for the treatment of the motor and cognitive deficits of Parkinson's disease, whereas SIB-1553A appears to have potential as a candidate for the treatment of Alzheimer's disease. Epibatidine has a strong analgesic profile, however the ratio between pharmacological activity and undesirable effects is so low that it is difficult to envisage the use of this compound therapeutically. Nicotine has a broad profile of pharmacological activity, for instance demonstrating activity in models for cognition and analgesia. As for epibatidine, the adverse effects of nicotine severely limits its therapeutic use in humans. The discovery of subtype-selective NAChR agonists such as SIB-1508Y and SIB-1553A provides a new class of neuropsychopharmacological agents with better therapeutic ratios than nonspecific agents such as nicotine.

Animals↗

Kidney transplants from living donors: how donation affects family dynamics.

Living donors continue to provide the optimum outcome for kidney transplant recipients, yet information is limited on how donation can affect the donor and his or her family. Questionnaires returned by 524 donors whose donor nephrectomies took place between August 1, 1985 and December 31, 1996 at the University of Minnesota were analyzed to determine if perioperative complications influence their quality of life, among other emotional and lifestyle areas. Results showed that donors have a higher quality of life than the general population, confirming they have an increased self-worth and positive self-esteem. An overwhelming 96% would donate again. However, donation was self-reported as more stressful when complications were experienced (P = .003) and when donors were female (P = .041). Relatives other than immediate family members (extended relatives) were more likely to be among the 4% who said they would not donate again. Available support, financial impact, and relationship changes as a result of donation also were revealed. Relevant results from this larger study are discussed as they relate to how the renal donor and transplant family are affected.

Adolescent↗