Biomedical subjects

R Nagel

Publications and source records attributed to R Nagel.

At least 37 records · Page 2Linked to original sources

PubMed1998

Short-term toxicity of lindane, hexachlorobenzene, and copper sulfate to tubificid sludgeworms (Oligochaeta) in artificial media.

The toxicity of lindane, hexachlorobenzene, and copper sulfate to Tubifex tubifex and Limnodrilus hoffmeisteri was determined using an easily applicable and standardizable 72-h short-term test system. It was designed for the quick assessment of sublethal and lethal effects of sediment-associated chemicals on the worms. An artificial sediment based on the Artificial Soil according to OECD Guideline No. 207 was used as test medium. The data confirm the common view that oligochaetes are highly tolerant of lethal effects. However, sublethal effects were detected at considerably lower concentrations than found for lethal effects. The EC50 values for autotomy (172 mg/kg dry wt sediment) and sediment avoidance (217 mg/kg) for T. tubifex exposed to lindane-contaminated sediment were, for example, more than five times lower than the LC50 value (> 1000 mg/kg). The no-observed-effect concentration for reworking activity (8 mg/kg) was more than 125 times lower than the LC50. Tubificids thus turned out to represent useful test organisms for the assessment of the ecotoxicological hazard potential of chemicals in the sediment compartment, because the sublethal effects not only affect the individual, but can influence the population levels and, consequently, the composition of the benthic community.

Animals↗

PubMed1998

Experimental Results on the Centipede Game in Normal Form: An Investigation on Learning.

We analyze behavior of an experiment on the centipede game played in the reduced normal form. In this game two players decide simultaneously when to split a pie which increases over time. The subjects repeat this game 100 times against randomly chosen opponents. We compare several static models and quantitative learning models, among them a quantal response, model reinforcement models and fictitious play. Furthermore, we structure behavior from period to period according to a simple cognitive process, called learning direction theory. We show that there is a significant difference in behavior from period to period whether a player has decided to split the pie before or after the opponent. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

Matrix metalloproteinases, but not cathepsins B, H, and L or their inhibitors in peripheral blood of patients with rheumatoid arthritis are potentially useful markers of disease activity.

OBJECTIVE: The clinical activity of rheumatoid arthritis (RA) is not reliably reflected by laboratory measures. Proteolytic enzymes involved in the cascade of joint destruction are potentially useful parameters to monitor the extent of joint inflammation in RA. This study compares the validity of two classes of proteolytic enzymes, matrix metalloproteinases (MMP) and lysosomal cysteine proteinases (cathepsin B, H, and L) as well as their respective inhibitors to serve as parameters of RA disease activity. METHODS: The proteolytic activity of cathepsin B, H, and L was determined by fluorometry in sera of 20 patients with active RA and of 20 healthy donors. In addition, the concentrations of cathepsin B and L as well as of cathepsin inhibitors stefin A, stefin B, and cystatin C were measured by ELISA. The plasma concentrations of MMP-1 (collagenase), MMP-3 (stromelysin), tissue inhibitor of metalloproteinases 1 (TIMP-1), and of MMP-1/TIMP-1 complex (MT complex) were analyzed by ELISA as well. RESULTS: A significant increase of MMP-1, MMP-3, and MT complex was observed in RA plasma, compared to normal controls, whereas TIMP-1 concentrations did not differ. In contrast, neither serum activity nor protein concentration of any of the cathepsins or cathepsin inhibitors were elevated in RA. CONCLUSION: Despite ample evidence in the literature that cathepsin activity contributes to the pathogenesis of inflammatory joint disease, this is not reflected by the conditions in peripheral blood. In contrast to the cysteine proteinases, MMP-1 and MMP-3 as well as MT complex are elevated in RA. In the context of findings in the literature, this stresses the importance of MMP as disease activity markers, compared to cysteine proteinases or their inhibitors.

Aged↗

PubMed1998

Immunohistochemical detection of p53 protein in transitional cell carcinoma of the bladder in correlation to DNA ploidy and pathohistological stage and grade.

Mutations of p53 gene have been found in a variety of human malignancies; however, the impact of immunohistological detection of p53 expression in the development and progression of TCC of the bladder is still uncertain. In the present study, we investigated the p53 oncoprotein expression and compared the findings to DNA ploidy and pathohistological stage and grade. The study included 147 patients with transitional cell carcinoma of the bladder investigated between February 1981 and September 1994. The average age of the 55 women and 92 men was 67 years (range: 20-71 years). A total of 76 patients (52%) had stage pTa to pT1, 35 (24%) stage pT2, 25 (17%) stage pT3, and 11 (7%) stage pT4 disease. Frozen sections of tumor biopsies obtained by transurethral resection were immunohistochemically stained using the monoclonal antibody clone D0-7 (DAKO), which recognized two different epitopes for mutant and wild-type p53 protein. Tumors expressing p53 in more than 10% of the tumor nuclei were regarded as positive. The DNA ploidy was determined by image analysis. Immunohistochemical detection of p53 expression was found in 84 (57%) of the 147 tumors examined. Positive p53 staining was seen in grade I tumors in 10 to 25%, in grade II tumors 25 to 75%, and in grade III up to 58% of the tumor nuclei. There was a positive correlation between p53 expression and pathological stage (28% in pTa, 73% in pT1-2, and 68% in pT3-4 tumors). There was no appreciable relationship between DNA Ploidy and p53. Although carcinomas with p53 expression had a slight tendency to be more prevalent among higher disease stages and poorly differentiated transitional cell carcinoma, immunohistochemical detection of p53 is not a valuable tool for predicting the outcome of patients with TCC or for identifying subgroups of patients that may be at a higher risk for tumor progression.

Adult↗

PubMed1998

A genetic algorithm-based method for optimizing the performance of a computer-aided diagnosis scheme for detection of clustered microcalcifications in mammograms.

Computer-aided diagnosis (CAD) schemes have the potential of substantially increasing diagnostic accuracy in mammography by providing the advantages of having a second reader. Our laboratory has developed a CAD scheme for detecting clustered microcalcifications in digital mammograms that is being tested clinically at the University of Chicago Hospitals. Our CAD scheme contains a large number of parameters such as filter weights, threshold levels, and region of interest (ROI) sizes. The choice of these parameter values determines the overall performance of the system and thus must be carefully set. Unfortunately, when the number of parameters becomes large, it is very difficult to obtain the optimal performance, especially when the values of the parameters are correlated with each other. In this study, we address the problem of identifying the optimal overall performance by developing an automated method for the determination of the parameter values that maximize the performance of a mammographic CAD scheme. Our method utilizes a genetic algorithm to search through the possible parameter values, and provides the set of parameters that minimize a cost function which measures the performance of the scheme. Using a database of 89 digitized mammograms, our method demonstrated that the sensitivity of our CAD scheme can be increased from 80% to 87% at a false positive rate of 1.0 per image. We estimate the average performance of our CAD scheme on unknown cases by performing jackknife tests; this was previously not feasible when the parameters of the CAD scheme were determined in a nonautomated manner.

Algorithms↗

PubMed1998

Validity of the medical outcomes study depression screener in family practice training centers and community settings.

BACKGROUND AND OBJECTIVES: Screening inventories that identify primary care patients suffering from depression should be brief, correlate with depression diagnoses, and be evaluated in populations with whom the inventories will be used. METHODS: A total of 566 patients from a medical school training center and 457 patients from six community family practice offices completed the Medical Outcomes Study (MOS) depression screener and a questionnaire reporting demographic information and health habits. All subjects scoring above the recommended screener cut-off, and a random sample of those scoring below, were interviewed with the Diagnostic Interview Schedule (DIS). RESULTS: A total of 195 subjects from the training center and 147 from the community sample were called and administered the DIS. About 33% of the training center and 25% of the community sample scored above the cutoff. Of those above the cutoff and administered the DIS, 23% of the training center and 10% of the community sample were diagnosed with either major depression or dysthymia. CONCLUSIONS: The MOS screener was an effective method of identifying depressed subjects in the training center and community settings. However, because of the relatively low prevalence of depression in these settings, a relatively high number are falsely screened positive. Identifying these patients as having subthreshold depressive symptoms and the necessity/efficacy of treatment is controversial, as is the use of screening instruments. The simplified MOS scoring strategy and template used in this study would probably increase its usefulness in the primary care setting.

Chi-Square Distribution↗

PubMed1998

Avirulence and immunogenicity in mice of a bovine mastitis Staphylococcus aureus mutant.

An avirulent mutant, designated RC122, was derived from Staphylococcus aureus bovine mastitis strain RC108 after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. Mutant RC122, which was isolated on the basis of reduced colony size, showed diminished virulence in mice (LD50 of RC122: 3.1 x 10(10) cfu vs LD50 of RC108: 2.3 x 10(7) cfu). Mutant RC122 grew more slowly than its parental strain and showed decreased production of several exoproteins, such as alpha- and beta-hemolysin, DNAse and coagulase. The production of its capsule was induced only under in vivo growth conditions. Clearance studies performed in the mouse kidney revealed that the kinetics of disappearance of the mutant was similar to that of its parental strain. Protection experiments carried out by intraperitoneal administration in mice showed that mutant RC122 conferred a good degree of protection from challenge with homologous and heterologous strains.

Animals↗

PubMed1997

Involvement of recA and recF in the induced precise excision of Tn10 in Escherichia coli.

It has been shown that the increased frequency of precise excision of Tn10 observed after UV or mitomycin C (MMC) treatment or with uvrD- mutants is recA-dependent. Previous work has also shown that expression of SOS genes is required for UV- or MMC-induced Tn10 precise excision. In order to determine if the increased excision of Tn10 in uvrD- mutants requires only expression of recA, or expression of other SOS genes, or both, we studied the precise excision of Tn10 in lexA3 (Ind-, SOS non-inducible) and lexA3 recAo98 (operator constitutive recA) mutants. The results of these experiments indicate that the induced excision of Tn10 in the uvrD- null mutant depends on the expression of recA rather than on any of the other genes repressed by LexA. The effect of a null recF mutation on the excision of Tn10 in a uvrD- mutant was also investigated and found to abolish the increased frequencies of this process. Similarly, the recF mutation was found to decrease markedly the increased precise excision of Tn10 induced by MMC in a uvrD+ isogenic strain. These observations indicate that recA and recF are involved in the increased frequencies of Tn10 excision exhibited by uvrD- mutants or after MMC treatment. It remains to be determined whether these two genes participate in these two induction processes in the same biochemical pathways.

Adenosine Triphosphatases↗

PubMed1997

The sae locus of Staphylococcus aureus controls exoprotein synthesis at the transcriptional level.

Agr and sar are known regulatory loci of Staphylococcus aureus that control the production of several extracellular and cell-wall-associated proteins. A pleiotropic insertional mutation in S. aureus, designated sae, that leads to the production of drastically diminished levels of alpha- and beta-hemolysins and coagulase and slightly reduced levels of protein A has been described. The study of the expression of the genes coding for these exoproteins in the sae::Tn551 mutant (carried out in this work by Northern blot analyses) revealed that the genes for alpha- and beta-hemolysins (hla and hlb) and coagulase (coa) are not transcribed and that the gene for protein A (spa) is transcribed at a somewhat reduced level. These results indicate that the sae locus regulates these exoprotein genes at the transcriptional level. Northern blot analyses also show that the sae mutation does not affect the expression of agr or sar regulatory loci. An sae::Tn551 agr::tetM double mutant has been phenotypically characterized as producing reduced or null levels of alpha-, beta-, and delta-hemolysins, coagulase, and high levels of protein A. Northern blot analyses carried out in this work with the double mutant revealed that hla, hlb, hld, and coa genes are not transcribed, while spa is transcribed at high levels. The fact that coa is not expressed in the sae agr mutant, as in the sae parental strain, while spa is expressed at the high levels characteristic of the agr parental strain, suggests that sae and agr interact in a complex way in the control of the expression of the genes of several exoproteins.

Bacterial Proteins↗

PubMed1997

Toxicity of binary chemical mixtures: effects on reproduction of zebrafish (Brachydanio rerio).

A complete life-cycle test with zebrafish was carried outwith different concentrations of the binary mixture 3,4-dichloroaniline andlindane under flow-through conditions. Length and weight of fish of theF1-generation were reduced, even in the lowest test concentrationof 2 microg/L 3,4-dichloroaniline and 40 microg/L lindane. The same effects werefound in the early life stage test for the F2-generation. In themixture of 100 microg/L 3,4-dichloroaniline and 40 microg/L lindane, fish whichwere exposed for their whole life time stopped spawning, irreversibly; thefish population will become extinct. In an additional experiment, fish wereexposed to the same xenobiotic concentrations after reaching maturity. Inthis case, egg production was reduced. Cessation of egg production occurs ina concentration of 200 microg/L 3,4-dichloroaniline and 40 microg/L lindane.Nevertheless, effects on spawning are influenced by duration of exposure andthe life stages of exposure.

Aniline Compounds↗

PubMed1997

Field trials of a vaccine against bovine mastitis. 1. Evaluation in heifers.

A vaccine was developed against bovine mastitis based on inactivated, highly encapsulated Staphylococcus aureus cells; a crude extract of Staph. aureus exopolysaccharides; and inactivated, unencapsulated Staph, aureus and Streptococcus spp. cells. This vaccine was tested on 30 heifers during a 7-mo period. The 30 heifers were randomly assigned to three groups of 10 heifers each. The prepartum group received two injections of the vaccine at 8 and 4 wk before calving, and the postpartum group received two injections at 1 and 5 wk after calving. The control group received two injections of a placebo at 8 and 4 wk before calving. The vaccine or the placebo was administered subcutaneously in the brachiocephalicus muscle of the neck. The frequencies of intramammary infections caused by Staph. aureus were reduced from 18.8% for heifers in the control group to 6.7 and 6.0% for heifers in the prepartum and postpartum groups, respectively. This protective effect was maintained for at least 6 mo. The relative risk of mastitis caused by Staph. aureus was 0.31 and 0.28 for heifers in the prepartum and postpartum groups, respectively, compared with that for heifers in the control group. The results of the trial indicated the effectiveness of the vaccine in decreasing the incidence of intrammammary infections caused by Staph. aureus. A slight but nonsignificant increase occurred in fat production in the milk of vaccinated cows. The vaccine had no observable effect on somatic cell count or streptococcal infections.

Animals↗

PubMed1997

Field trials of a vaccine against bovine mastitis. 2. Evaluation in two commercial dairy herds.

A vaccine against bovine mastitis was developed. The vaccine was based on inactivated, highly encapsulated Staphylococcus aureus cells; a crude extract of Staph. aureus exopolysaccharides; and inactivated unencapsulated Staph. aureus and Streptococcus spp. cells. In this study, the vaccine was evaluated in 164 cows from two commercial dairies (A and B) during a 4-mo period. Two doses of the vaccine were administered subcutaneously to 82 cows in the brachiocephalicus muscle of the neck within a 4-wk interval. The results of this trial revealed significantly fewer intramammary infections caused by Staph. aureus at various levels of severity (clinical, subclinical, and latent) in cows that were vaccinated. The odds ratios of all types of intrammammary infections caused by Staph. aureus for dairies A and B, which were determined by a logistic model, were 1.84 and 1.89, respectively, for quarters of vaccinated cows and quarters of control cows. The colony counts for Staph. aureus in milk from infected quarters of vaccinated cows were significantly lower than those in milk from infected quarters of control cows. Also, the somatic cell counts per milliliter in milk from vaccinated cows were significantly decreased when the initial somatic cell count was < 500,000 cells/ml at the start of the trial. The vaccine had no observable effect on fat production in milk or on streptococcal infections.

Animals↗

PubMed1997

Telephone counseling for patients with minor depression: preliminary findings in a family practice setting.

BACKGROUND: Depression is a frequently occurring condition in family practice patients, but time limitations may hamper the physician's ability to it treat effectively. Referrals to mental health professionals are frequently resisted by patients. The need for more effective treatment strategies led to the development and evaluation of a telephone-based, problem-solving intervention. METHODS: Patients in a family practice residency practice were evaluated through the Medical Outcomes Study Depression Screening Scale and the Diagnostic Interview Schedule to identify those with subthreshold or minor depression. Twenty-nine subjects were randomly assigned to either a treatment or comparison group. Initial scores on the Hamilton Depression Rating Scale were equivalent for the groups and were in the mildly depressed range. Six problem-solving therapy sessions were conducted over the telephone by graduate student therapists supervised by a psychiatrist. RESULTS: Treatment group subjects had significantly lower post-intervention scores on the Hamilton Depression Rating Scale compared with their pre-intervention scores (P < .05). Scores did not differ significantly over time in the comparison group. Post-intervention, treatment group subjects also had lower Beck Depression Inventory scores than did the comparison group (P < .02), as well as more positive scores for social health (P < .002), mental health (P < .05), and self-esteem (P < .05) on the Duke Health Profile. CONCLUSIONS: The findings indicate that brief, telephone-based treatment for minor depression in family practice settings may be an efficient and effective method to decrease symptoms of depression and improve functioning. Nurses in these settings with appropriate training and supervision may also be able to provide this treatment.

Counseling↗

PubMed1996

Depressive symptoms: associations with health perceptions and health behaviors.

The association of depressive symptoms with health behaviors and perceptions was determined for 876 patients seeing family physicians. Correlational analyses revealed stress, pain, and overall health status were moderately related to depression for males and females. Smoking was positively related to depressive symptoms in women (r = .19, P < 0.01), and drinking was inversely related to depressive symptoms in men (r = -.16, P < .01). Multiple regression analyses indicated stress, poor health, smoking, and drinking were significant predictors of depressive symptoms in women; stress, poor health, and drinking were significant in men. Health perceptions appear to be better predictors of depressive symptoms than reported health behaviors.

Adolescent↗

PubMed1996

[Preoperative staging of bladder carcinomas with Gd-DTPA-supported dynamic magnetic resonance tomography. Comparison with plain and Gd-DTPA-supported spin-echo sequences].

PURPOSE: Evaluation of dynamic Gd-DTPA enhanced MR imaging in the staging of bladder cancer. METHODS: We studied 40 patients with histologically proven bladder cancer. All patients were examined with routine T1- and T2-weighted MRI and late Gd-DTPA enhanced T1-weighted MRI. Additionally, a dynamic study was performed with 10 subsequent short FLASH-2-D gradient echo sequences without delay immediately after bolus injection of Gd-DTPA. Signal intensities of the tumour and of the surrounding tissue as well as image contrast parameters were quantified. RESULTS: The dynamic study showed a higher accuracy in the evaluation of stage pTa to pT2 cancer compared to spin echo MRI (63% and 46%, respectively) and no difference regarding the sensitivity (87.5%). However, overstaging was a problem with both modalities. The contrast-to-noise ratio of bladder tumour and muscle was equal or significant higher with the dynamic study compared to spin echo MRI. A higher signal-to-contrast ratio of bladder tumour and bladder muscle was calculated for the dynamic study compared with the spin-echo MRI (p < 0.01; Mann-Whitney U test). CONCLUSION: Dynamic Gd-DTPA enhanced MRI is recommended to be used additionally in the preoperative staging of bladder neoplasms.

Adult↗

PubMed1996

Phenotypic characterization and virulence of a sae- agr- mutant of Staphylococcus aureus.

A sae::Tn551 agr::tetM double mutant was constructed and characterized. The production of several exoproteins (e.g., beta-hemolysin, DNase, and proteases) by this mutant was determined and found to be lower than the already diminished production of either isogenic single mutant sae- or agr-. The double mutant also showed, like the agr- mutant, null production of alpha- and delta-hemolysins and diminished levels of lipase. The reduced levels of many exoproteins in the double mutant as compared with their already diminished levels in either single mutant suggest that there is an additive or synergistic interaction between the two mutations involved, sae- and agr-. However, inactivation of both loci, sae and agr, had a different effect on the two exoproteins that are up regulated in the agr- mutant; thus, coagulase dropped to levels close to the null levels of the sae- parental strain, while extracellular protein A displayed the high levels characteristic of the agr- single mutant. The virulence of the sae- agr- double mutant, determined by intraperitoneal injection in mice, was found to be significantly diminished as compared with that of the sae+ agr+ parental strain or the sae- agr+ single mutant.

Animals↗

PubMed1996

In vivo expression of exoprotein synthesis with a Sae mutant of Staphylococcus aureus.

The expression of exoprotein synthesis of Staphylococcus aureus Sae mutant RC121 and its parental strain was studied under in vivo growth conditions. Cultures of both strains were inoculated into dialysis sacs implanted in sheep peritoneum. Results indicated that similar to in vitro grown mutant cells, Sae mutant RC121 shows diminished synthesis of alpha- and beta-hemolysin, coagulase, DNase and protein A. However, in vitro and in vivo grown mutant cultures showed different exoprotein profiles in SDS-PAGE; some bands from in vivo mutant cultures were diminished or missing and others appeared as more concentrated, when compared with the pattern of the in vivo grown parental strain, while all the exoprotein bands from the in vitro cultures of the mutant were diminished or missing as compared to the in vitro grown parental strain. The virulence of the Sae mutant, assayed by intraperitoneal injection in mice, was lower than that of the parental strain after both in vivo and in vitro growth conditions.

Animals↗

PubMed1995

Enzymological differences of AChE and diazinon hepatic metabolism: correlation of in vitro data with the selective toxicity of diazinon to fish species.

The in vitro hepatic metabolism of diazinon, as well as the sensitivity of the brain acetylcholine esterase, to diazoxon inhibitory action have been studied in order to explain the different toxicity of diazinon to Oncorhynchus mykiss (rainbow trout), Poecilia reticulata (guppy), Brachydanio rerio (zebra fish) and Cyprinus carpio (carp). In spite of a very sensitive acetylcholine esterase the carp is very resistant to diazinon toxicity because of its very low rate of bioactivation and relatively high activity of detoxicating enzymes. The trout is very sensitive towards diazinon in spite of its low activity of bioactivation, because of its lack of detoxicating enzymes and a very sensitive acetylcholine esterase. Diazinon is very toxic for the guppy, because this fish combines a relatively sensitive acetylcholine esterase with a high rate of bioactivation. The zebra fish has the most insensitive acetylcholine esterase, associated with a limited activation rate, thus resulting a rather resistant species. The results obtained indicate that diazinon toxicity differences among the fish species studied can largely be explained in relation to metabolic balances in the liver and with the features of the target enzyme.

Acetylcholinesterase↗