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Biomedical subjects

R Janssen

Publications and source records attributed to R Janssen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Simple mental addition in children with and without mild mental retardation.

The speeded performance on simple mental addition problems of 6- and 7-year-old children with and without mild mental retardation is modeled from a person perspective and an item perspective. On the person side, it was found that a single cognitive dimension spanned the performance differences between the two ability groups. However, a discontinuity, or "jump," was observed in the performance of the normal ability group on the easier items. On the item side, the addition problems were almost perfectly ordered in difficulty according to their problem size. Differences in difficulty were explained by factors related to the difficulty of executing nonretrieval strategies. All findings were interpreted within the framework of Siegler's (e.g., R. S. Siegler & C. Shipley, 1995) model of children's strategy choices in arithmetic. Models from item response theory were used to test the hypotheses.

Case-Control Studies↗
PubMed1999

Validating marker-based incidence estimates in repeatedly screened populations.

Disease incidence (new cases of disease per person per year) is usually measured by using longitudinal data. However, several recent proposals for measuring the incidence of human immunodeficiency virus (HIV) rely on cross-sectional data only. These methods assume each person is only sampled once; however, in some instances, it is necessary to consider these cross-sectional methods when individuals are represented more than once in the survey sample. We derive an extension of the cross-sectional incidence estimator that is valid for data from repeatedly screened populations and show under what conditions our new estimator reduces to the old estimator. An example involving estimation of HIV incidence among repeat blood donors is presented.

Biometry↗
PubMed1998

Calpain regulates actin remodeling during cell spreading.

Previous studies suggest that the Ca2+-dependent proteases, calpains, participate in remodeling of the actin cytoskeleton during wound healing and are active during cell migration. To directly test the role that calpains play in cell spreading, several NIH-3T3- derived clonal cell lines were isolated that overexpress the biological inhibitor of calpains, calpastatin. These cells stably overexpress calpastatin two- to eightfold relative to controls and differ from both parental and control cell lines in morphology, spreading, cytoskeletal structure, and biochemical characteristics. Morphologic characteristics of the mutant cells include failure to extend lamellipodia, as well as abnormal filopodia, extensions, and retractions. Whereas wild-type cells extend lamellae within 30 min after plating, all of the calpastatin-overexpressing cell lines fail to spread and assemble actin-rich processes. The cells genetically altered to overexpress calpastatin display decreased calpain activity as measured in situ or in vitro. The ERM protein ezrin, but not radixin or moesin, is markedly increased due to calpain inhibition. To confirm that inhibition of calpain activity is related to the defect in spreading, pharmacological inhibitors of calpain were also analyzed. The cell permeant inhibitors calpeptin and MDL 28, 170 cause immediate inhibition of spreading. Failure of the intimately related processes of filopodia formation and lamellar extension indicate that calpain is intimately involved in actin remodeling and cell spreading.

3T3 Cells↗
PubMed1998

Industrial hygiene aspects of a sampling survey at a bleached-kraft pulp mill in British Columbia.

To validate exposure estimates used to investigate correlations between exposure and cancer risk, 1678 personal measurements were collected for 46 job titles during 73 day shifts at a bleached-kraft pulp mill. Measurements included shift-long average and short-term exposures to carbon monoxide, chlorine dioxide (ClO2), and hydrogen sulfide; and shift-long average exposures to calcium oxide and wood dust (WD). Overall results indicate low levels of exposure with a few noteworthy exceptions. Although ClO2 was the exclusive bleaching agent, 77 area samples indicated that chlorine (Cl2), not ClO2 was present in all areas apart from the chemical preparation area (chem-prep) and during a pulp spill. The highest shift-long exposures to Cl2 were measured in the chip yard and are attributed to uncontrolled stack emissions. Finally, WD samples collected from several laborers significantly exceeded regulatory limits, with the highest exposures measured in the steam and recovery area. For short-term exposures to ClO2 in chem-prep, 12 of 17 data-logging electro-chemical sensor sample results showed at least one peak that exceeded the short-term exposure limit of 0.3 ppm. The use of data-logging equipment quantified short-term exposures that previously had been characterized only anecdotally. The peaks were correlated with tasks and upset conditions and, given their transient nature, these exceedances could not have been detected using shift-long average-based sampling devices. Since the respiratory effects of significant short-term exposures to irritant gases such as Cl2 and ClO2 are well-documented, data-logging instruments are necessary to characterize exposures in the pulp and paper industry.

Air Pollutants, Occupational↗
PubMed1998

An epitope delivery system for use with recombinant mycobacteria.

We have developed a novel epitope delivery system based on the insertion of peptides within a permissive loop of a bacterial superoxide dismutase molecule. This system allowed high-level expression of heterologous peptides in two mycobacterial vaccine strains, Mycobacterium bovis bacille Calmette-Guérin (BCG) and Mycobacterium vaccae. The broader application of the system was analyzed by preparation of constructs containing peptide epitopes from a range of infectious agents and allergens. We report detailed characterization of the immunogenicity of one such construct, in which an epitope from the Der p1 house dust mite allergen was expressed in M. vaccae. The construct was able to stimulate T-cell hybridomas specific for Der p1, and it induced peptide-specific gamma interferon responses when used to immunize naive mice. This novel expression system demonstrates new possibilities for the use of mycobacteria as vaccine delivery vehicles.

Amino Acid Sequence↗
PubMed1997

Presence of human immunodeficiency virus (HIV) type 1 subtype A infection in a New York community with high HIV prevalence: a sentinel site for monitoring HIV genetic diversity in North America. Centers for Disease Control and Prevention-Bronx Lebanon HIV Serosurvey Team.

To determine whether US residents are infected with subtypes of human immunodeficiency virus (HIV) type 1 other than subtype B (Western), the predominant North American subtype with a unique GPGR genetic sequence in the V3 loop, viruses from 22 HIV-infected adults were serotyped and subtyped. Twenty patients had subtype B (Western), of whom 15 had serotype B (Western), 3 had serotype A/C, 1 had serotype B (Thai), and 1 had a nontypeable serotype. Two had subtype A, both serotype A/C. Both subtype A-infected patients, only 1 of whom had been outside the United States, reported sex with persons traveling abroad, suggesting possible acquisition in the United States. Because US residents are infected with non-subtype B (Western) strains, US surveillance for HIV-1 diversity is needed to elucidate subtype-specific transmission patterns and pathogenesis and to guide evaluation and development of HIV diagnostic tests and vaccines.

Adolescent↗
PubMed1997

Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae.

A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-gamma) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-gamma. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.

Administration, Oral↗
PubMed1996

Performance characteristics of a rapid HIV antibody assay in a hospital with a high prevalence of HIV infection. CDC-Bronx-Lebanon HIV Serosurvey Team.

BACKGROUND: The delay between collection of blood samples and availability of test results may be as long as 3 weeks and is one barrier to the acceptance of voluntary testing for human immunodeficiency virus (HIV) infection. Serologic tests that provide results rapidly could overcome this barrier, but the accuracy and reliability of rapid tests have not been well characterized in the United States. OBJECTIVE: To evaluate, in a "real world" setting, the performance characteristics of a rapid HIV assay that reduces the need for patients to return for counseling after the test. DESIGN: Testing of HIV antibodies by rapid and nonrapid assays and survey about risk behaviors for HIV. SETTING: A hospital in Bronx, New York, with a high prevalence of HIV-seropositive patients. PATIENTS: 837 patients who were not known to be infected with HIV, had not been admitted for conditions related to the acquired immunodeficiency syndrome, and agreed to participate in HIV testing and an interview. MEASUREMENTS: Sensitivity and specificity of a rapid HIV antibody assay based on comparisons with nonrapid assay and Western blot assay. RESULTS: According to nonrapid assays, 5.4% of patients were infected with HIV. The rapid assay was highly accurate in this sample overall: its sensitivity was 1.00, its specificity was 0.991, its positive predictive value was 0.865, and its negative predictive value was 1.00. The assay was also highly accurate in various subgroups. CONCLUSIONS: Accurate, rapid tests for HIV infection may enhance testing programs by preventing the need for delayed counseling of seronegative patients and by providing preliminary results to seropositive patients. These preliminary results may encourage patients to return for confirmatory test results and to adopt risk-reducing behaviors sooner.

Adolescent↗
PubMed1996

Absence of human immunodeficiency virus type 2 infection among patients in a hospital serving a New York community at high risk for infection. Centers for Disease Control and Prevention/Bronx-Lebanon Hospital Center HIV Serosurvey Team.

BACKGROUND: Although human immunodeficiency virus type 2 (HIV-2) infection among United States residents is considered rare, there are US populations at high risk. Few studies have surveyed these populations with a high likelihood of infection, that is, those with high percentages of persons from HIV-2-endemic areas and high prevalences of behaviors that would allow for transmission. STUDY DESIGN AND METHODS: Patients (n = 832) enrolled in a confidential HIV serosurvey at a hospital that serves a community with a relatively high percentage of West African immigrants, drug injectors, and persons who practice high-risk sexual activity were evaluated. Sera were tested for HIV type 1 (HIV-1) and HIV-2 by rapid enzyme immunoassays, standard enzyme immunoassays and Western blots. RESULTS: Eight of 832 patients were weakly reactive to HIV-2 on rapid assay, but none was confirmed to be infected when tested by standard immunoassay and Western blot. Five of these eight were reactive to HIV-1. CONCLUSION: Weak reactivity to HIV-2 antibody on the rapid assay is best explained by cross-reactivity with HIV-1 antibody; thus, even in this population at high risk for infection, false-positive reactions are more likely than true infections. The finding that HIV-2 is absent in this population at potentially high risk for infection corroborates the findings of other studies that HIV-2 infection is rare among US residents. These results support previous recommendations that, in settings other than blood collection facilities, HIV-2 testing should be selectively offered to persons with epidemiologic risk factors.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Quaternary structure of a carrier protein influences antigenicity and immunogenicity of an inserted T cell determinant.

To study the influence of the quaternary structure of the outer membrane protein PhoE of Escherichia coli on the presentation of an inserted T cell epitope, an epitope comprising amino acid residues 72-85 of myelin basic protein (MBP) was inserted at different sites in PhoE. This sequence is the critical T cell epitope in experimental autoimmune encephalomyelitis (EAE) in Lewis rats. The antigenicity and immunogenicity of two different conformational forms of the chimeric PhoE constructs, i.e. the denatured monomeric form and the native trimeric form, were studied. It appeared that the monomeric form, but not the native trimeric form of such PhoE constructs induced proliferation of the MBP72-85-specific T cell line Z1a. This conformational discrepancy was independent of the site in PhoE in which the epitope was inserted. Immunization with the monomeric form of PhoE constructs resulted in the priming of MBP72-85-specific T cells. In contrast, the trimeric form of these constructs was much less efficient in priming such cells. The differences between the monomeric and trimeric forms were most apparent when induction of EAE was studied. The monomeric form was encephalitogenic while the trimeric form was not. Furthermore, the antigen fine specificity, Vbeta usage and encephalitogenicity of T cells triggered by immunization with a monomeric PhoE construct appeared to be the same as those of T cell line Z1a, which was obtained after immunization with MBP, indicating that similar cells are triggered by immunization with the epitope either in PhoE or in its native context.

Allergens↗
PubMed1996

The Young Men's Survey: methods for estimating HIV seroprevalence and risk factors among young men who have sex with men.

Traditional sampling methods are unsuitable for determining the levels of human immunodeficiency virus type I infection and related behavioral risk factors among young men who have sex with men. Most surveys of this hard-to-reach population have used nonprobability samples of young men in clinical or public settings. While these studies have revealed high rates of HIV infection and risk behaviors, their findings are not generalizable to broader populations of young men who have sex with men. To better understand the epidemiology of HIV within this population, the Centers for Disease Control and Prevention, in collaboration with state and local health departments, has developed a venue-based probability survey of young men who have sex with men. Conducted in seven metropolitan areas in the United States, the Young Men's Survey combines outreach techniques with standard methods of sample surveys to enumerate, sample, and estimate prevalence outcomes of a population of young men who frequent public venues and who have sex with other men. Venues where young men who have sex with men are sampled include dance clubs, bars, and street locations. At sampled venues, young men are enumerated, consecutively approached, and offered enrollment if they are determined eligible. Young men who agree to participate in the Young Men's Survey are interviewed, counseled, and tested for human immunodeficiency virus, hepatitis B, and syphilis in vans parked near sampled venues. The Young Men's Survey provides data on the locations and times at which demographic and behavioral subgroups of young men who have sex with men may be targeted for prevention activities. Behaviors and psychosocial factors associated with human immunodeficiency virus infection can be used to design culturally relevant and age-specific prevention activities for young men who have sex with men.

Adolescent↗
PubMed1995

Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis.

We undertook this study to determine the incidence proportion of and risk factors for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia, central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis. A historical cohort of 487 consecutive inpatients with AIDS treated by San Francisco General Hospital inpatient and outpatient services entered the study. We abstracted all available records for demographic information, diagnoses, and dates of death and estimated the incidence proportion of AIDS patients diagnosed with major CNS complications using the Kaplan-Meier method. We used the Cox proportional hazards model to analyze the effect of demographic factors on the hazard (risk per unit time) of diagnosis with these CNS conditions. The estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18. Corresponding proportions were 0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal meningitis. Only HIV dementia was independently associated with increasing age at AIDS diagnosis (relative hazard [RH] of 2.75 for ages 41-50 [95% confidence interval, 1.08-6.98]; RH of 4.73 for ages > 50 [95% confidence interval, 1.41-15.87]) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19-3.47). HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about equally common complications in patients with AIDS, but only HIV dementia is associated with increasing age at AIDS diagnosis and injection drug use.

AIDS Dementia Complex↗
PubMed1995

Intracellular processing and presentation of T cell epitopes, expressed by recombinant Escherichia coli and Salmonella typhimurium, to human T cells.

Vaccines based on recombinant attenuated bacteria represent a potentially safe and effective immunization strategy. A carrier system was developed to analyze in vitro whether foreign T cell epitopes, inserted in the outer membrane protein PhoE of Escherichia coli and expressed by recombinant bacteria, are efficiently processed and presented via human leukocyte antigen (HLA) class I and II molecules by bacterial infected human macrophages. A well-defined HLA-B27-restricted cytotoxic T cell (CTL) epitope and an HLA-DR53 restricted T helper (Th) epitope of the fusion protein of measles virus were genetically inserted in a surface-exposed region of PhoE, and the chimeric proteins were expressed in E. coli and Salmonella typhimurium. Macrophages infected with both recombinant bacteria presented the Th epitope to the specific CD4+ T cell clone, but failed to present the CTL epitope to the specific CD8+ T cell clone. Presentation of the Th epitope by the infected macrophages was inhibited by cytochalasin D, indicating that phagocytic processing of intact bacteria within infected macrophages was essential for antigen presentation via HLA class II. Presentation of the Th epitope to the CD4+ T cell clone by infected macrophages was blocked by brefeldin A and cycloheximide, indicating the requirement of nascent HLA class II molecules for presentation. The efficiency of macrophages to process and present the inserted Th epitope was similar for both the recombinant E. coli and S. typhimurium strains.

Amino Acid Sequence↗
PubMed1995

Species identification of cyst and root-knot nematodes from potato by electrophoresis of individual females.

To carry out rapid and reliable species identification of Globodera and Meloidogyne specimens, two electrophoretic methods were modified and adapted for an automated electrophoresis system (PhastSystem, Pharmacia). Proteins of individual Globodera cysts were identified using isoelectric focusing and a sensitive silver stain. Proteins of young single Meloidogyne females were separated using polyacrylamide gradient gels and stained for the isozymes esterase and malate dehydrogenase.

Animals↗
PubMed1995

Induction of the phoE promoter upon invasion of Salmonella typhimurium into eukaryotic cells.

Live attenuated Salmonella typhimurium strains expressing foreign antigens can be used for vaccination purposes. Due to deleterious effects of constitutive, high-level expression of the heterologous antigens, there is often strong selection pressure against plasmids encoding these antigens, resulting in rapid segregation in vivo. In vivo-inducible promoters may be a good alternative for constitutive promoters. The outer membrane protein PhoE of Escherichia coli is being used as a carrier for foreign antigenic determinants. Here we studied whether its expression from a plasmid is induced in S. typhimurium upon invasion of eukaryotic cells. This appeared to be the case. Furthermore, a S. typhimurium phoE mutant was constructed and the effects of the mutation on invasion, intracellular survival and virulence were studied. Survival in HEp-2 cells or in the macrophage-like cell line J744 was not, or only slightly, affected. Furthermore, the mutant appeared to be as virulent for mice as the wild-type strain.

Cell Line↗