Biomedical subjects

R Janssen

Publications and source records attributed to R Janssen.

At least 55 records · Page 3Linked to original sources

PubMed1995

The pho regulon of Shigella flexneri.

Growth of Escherichia coli K-12 in low-phosphate conditions results in the induction of the synthesis of many proteins, including the outer membrane porin PhoE, alkaline phosphatase, and the Pst system for the transport of phosphate (P1). This response is controlled by a two-component regulatory system of which PhoB and PhoR are the response-regulator and the sensor/kinase, respectively. When Shigella flexneri was starved for P1, neither PhoE nor alkaline phosphatase was produced. However, induction of the synthesis of the PstS protein was observed, indicating that S. flexneri contains a functional PhoB/PhoR regulatory system. Consistent with this notion, the introduction of the E. coli phoA gene in S. flexneri resulted in the induction of alkaline phosphatase synthesis under phosphate limitation. However, introduction of phoE on a plasmid did not lead to the expression of PhoE protein, indicating that S. flexneri PhoB does not recognize the phoE promoter region. The phoB gene was cloned and sequenced and in the deduced amino acid sequence two deviations from that of E. coli PhoB were detected. Site-directed mutagenesis revealed that one of these deviations, i.e. Leu-172, which is Arg in E. coli PhoB, is responsible for the lack of expression of the PhoE protein in S. flexneri.

Alkaline Phosphatase↗

PubMed1994

The effect of a patient charge and a prescription regulation on the use of antihypertension drugs in Limburg, The Netherlands.

On 1 February 1983 a patient charge was introduced for prescription drugs for persons insured under the Dutch Sickness Funds Insurance Act. The charge consisted of a co-payment of NLG 2.50 per prescription item up to a maximum of NLG 125 for each family per calendar year. In the period before the introduction of the charge a prescription regulation was in force. For the majority of drugs this rule directed that each prescription item should be for a dosage of not more than 30 days. The prescription regulation was officially introduced on 1 January 1981 and ceased with the introduction of the charge. The effect of both measures on the use of antihypertension drugs in Limburg was investigated in an interrupted time-series analysis. Both the prescription regulation and the charge appeared to have an effect on the number of prescription items per insurant and the number of units delivered per prescription item. However, neither measure resulted in a reduction in the number of units delivered per insurant or the number of 'defined daily doses' (DDDs) per insurant. These findings suggest that neither measure resulted in a decrease in the inappropriate or appropriate use of antihypertension drugs.

Antihypertensive Agents↗

PubMed1994

WHO Neuropsychiatric AIDS study, cross-sectional phase I. Study design and psychiatric findings.

BACKGROUND: Most available studies on the psychiatric, neuropsychological, and neurological complications of HIV-1 infection and AIDS have been conducted in Western countries, on samples of well-educated, mostly white, homosexual men. Concerns about generalizability of the results of those investigations prompted the WHO to implement the cross-cultural venture called WHO Neuropsychiatric AIDS study. METHODS: This project aims to assess the prevalence and natural history of HIV-1-associated psychiatric, neuropsychological, and neurological abnormalities in representative subject samples enrolled in the five geographic areas predominantly affected by the HIV-1 epidemic. Assessment is made by a data collection instrument including six modules. The intercenter and intracenter reliability in the use of each module has been formally evaluated. The study consists of a cross-sectional phase and a longitudinal follow-up. RESULTS: The cross-sectional phase was completed in five centers. This paper reports on the results of psychiatric assessment, which revealed a significantly higher prevalence of current mental disorders in symptomatic seropositive persons compared with seronegative controls among intravenous drug users in Bangkok and homosexuals/bisexuals in São Paulo. The mean global score on the Montgomery-Asberg Depression Rating Scale was significantly higher in symptomatic seropositive individuals than in matched seronegative controls in all centers. CONCLUSIONS: These results suggest that the significance of the psychopathological complications of symptomatic HIV-1 infection may have been underestimated by previous studies conducted on self-selected samples of well-educated, middle-class, mostly white, homosexual men.

AIDS Dementia Complex↗

PubMed1994

WHO Neuropsychiatric AIDS study, cross-sectional phase II. Neuropsychological and neurological findings.

BACKGROUND: The neuropsychological and neurological complications of HIV-1 infection and AIDS were explored within the cross-sectional phase of the WHO Neuropsychiatric AIDS Study. Special attention was devoted to the controversial issue of the prevalence and clinical significance of subtle cognitive deficits in asymptomatic seropositive subjects. METHODS: A neuropsychological test battery validated for cross-cultural use, a structured interview for the diagnosis of dementia, a rating scale of functioning in daily living activities, and a neurological module were administered to representative samples of seropositive subjects and to matched seronegative controls living in the five geographic areas predominantly affected by the HIV-1 epidemic. Data are available for five centers. RESULTS: The prevalence of global neuropsychological impairment was significantly increased in asymptomatic seropositive subjects compared with controls in only two centers. A significant effect of education on neuropsychological performance was observed among asymptomatic seropositive individuals. In the two African centers, low-education, but not high-education, asymptomatic seropositive persons had an impaired performance. The frequency of impaired functioning in daily living activities and of neurologic abnormalities was higher in symptomatic, but not in asymptomatic, seropositive subjects compared with controls in all centers. CONCLUSIONS: These data suggest that the risk of subtle cognitive deficits may be increased in asymptomatic stages of HIV-1 infection. However, these deficits are not associated with neurologic changes and do not seem to affect subjects' social functioning.

AIDS Dementia Complex↗

PubMed1994

Immunogenicity of a mycobacterial T-cell epitope expressed in outer membrane protein PhoE of Escherichia coli.

The outer membrane protein PhoE of Escherichia coli can be used for the expression of foreign antigenic determinants. Previously, a T-cell epitope of the 65 kDa heat shock protein (hsp65) of Mycobacterium tuberculosis, comprising amino acids 180 to 188, was expressed in PhoE. The hybrid protein induced proliferation of epitope-specific T-cell clones in vitro. In this report, the potential of the hybrid protein to induce an in vivo T-cell response against the 180-188 T-cell epitope was assessed. Popliteal lymph node cells, isolated from rats immunized with PhoE containing the hsp65 epitope, showed high proliferative responses to a synthetic peptide consisting of amino acids 180 to 188 of hsp65, indicating that the epitope is immunogenic in the PhoE-associated conformation.

Animals↗

PubMed1994

The ototoxicity of 3,3'-iminodipropionitrile: functional and morphological evidence of cochlear damage.

Previous reports have suggested that IDPN may be ototoxic (Wolff et al., 1977; Crofton and Knight, 1991). The purpose of this research was to investigate the ototoxicity of IDPN using behavioral, physiological and morphological approaches. Three groups of adult rats were exposed to IDPN (0-400 mg/kg/day) for three consecutive days. In the first group, at 9-10 weeks post-exposure, thresholds for hearing of 5.3- and 38-kHz filtered clicks were measured electrophysiologically and brainstem auditory evoked responses (BAERs) were also recorded to a suprathreshold broadband click stimulus. A second set of animals was tested at 9 weeks for behavioral hearing thresholds (0.5- to 40-kHz tones) and at 11-12 weeks post-exposure for BAER thresholds (5- to 80-kHz filtered clicks). A third group of animals was exposed (as above), and killed at 12-14 weeks post-exposure for histological assessment. Kanamycin sulfate was used as a positive control for high-frequency selective hearing loss. Surface preparations of the organ of Corti were prepared in order to assess hair cells, and mid-modiolar sections of the cochlea were used to examine Rosenthal's canal and the stria vascularis. Functional data demonstrate a broad-spectrum hearing loss ranging from 0.5 kHz (30 dB deficit) to 80 kHz (40 dB deficit), as compared to a hearing deficit in kanamycin-exposed animals that was only apparent at frequencies greater than 5 kHz. Surface preparations revealed IDPN-induced hair cell loss in all turns of the organ of Corti, with a basal-to-apical gradient (more damage in the basal turns) at the lower dosages. At higher dosages there was complete destruction of the organ of Corti. There was also a dosage-related loss of spiral ganglion cells in all turns of the cochlea, again with a basal-to-apical gradient at the lower dosages. These data demonstrate that IDPN exposure in the rat results in extensive hearing loss and loss of neural structures in the cochlea.

Acoustic Stimulation↗

PubMed1994

Influence of amino acids of a carrier protein flanking an inserted T cell determinant on T cell stimulation.

CD4+ helper T cells recognize antigen in association with MHC class II molecules. To investigate the role of the context of a minimal T cell epitope on presentation and recognition in association with MHC class II molecules, an epitope of the 65 kDa heat shock protein of Mycobacterium tuberculosis was inserted at four different sites in the outer membrane protein PhoE of Escherichia coli. Only some of the constructs could stimulate the epitope-specific T cell clone A2b in vitro. One non-stimulatory construct could be made stimulatory by denaturation, suggesting that the protein conformation prevents correct presentation of the epitope. Other non-stimulatory constructs did not become stimulatory with denaturation. One of these constructs could be made stimulatory by substitution of either one of the two amino acids directly preceding the minimal epitope in the recombinant protein. In synthetic peptides the presence of these upstream residues did not interfere with T cell recognition, suggesting that these residues influence processing of the recombinant protein. Flanking amino acids also influenced induction of a T cell response against the inserted epitope in vivo. These results demonstrate that insertion of minimal T cell epitopes in carrier proteins for the design of vaccines might fail because of the inhibiting effects of flanking residues.

Amino Acid Sequence↗

PubMed1994

Psychoanalytic supportive psychotherapy.

Psychoanalytic Supportive Psychotherapy (PSP) is described as a distinct psychotherapeutic method rooted in the psychoanalytic frame of reference. It is argued (a) that PSP is psychotherapy and indeed a therapeutic modality on its own, (b) that it is supportive, and (c) that it is psychoanalytic. PSP is characterized by a therapeutic relationship determined predominantly by its primary relationship aspect, a therapeutic technique consisting in the main of supportive interventions, a therapeutic process that consists essentially of growing by experience, and a therapeutic goal residing in the first place in structure building. Like psychoanalysis proper, but in a substantially different way, it aims at structural personality change and can provide lasting results. As far as therapy is concerned, psychoanalysis is no longer a unimodal discipline. The psychoanalytic therapies include at least three treatment modalities: psychoanalysis proper, interpretive psychotherapy, and psychoanalytic supportive psychotherapy. Enlarging the number of therapeutic methods based on psychoanalytic theory represents a new approach to the widening scope of indications for psychoanalysis.

Humans↗

PubMed1994

PhoE protein as a carrier for foreign epitopes.

Outer membrane protein PhoE of E. coli appears to be a suitable carrier for the expression of foreign antigenic determinants at the bacterial cell-surface. Insertion of stretches of amino acids in the cell-surface exposed regions of PhoE does not interfere with the biogenesis of the protein. Dependent on the cell-surface exposed loop used for insertion and the character of the inserted amino acids up to 50 amino acids could be inserted. Both B-cell epitopes and T-cell epitopes remain antigenic and immunogenic in the PhoE-associated conformation. However, flanking amino acids can interfere with the antigenicity and immunogenicity of T-cell epitopes inserted in PhoE. Because E. coli PhoE can be expressed in attenuated Salmonella and Shigella strains, it seems to be a suitable vaccine carrier candidate.

Amino Acid Sequence↗

PubMed1994

Reforming health care in The Netherlands.

Health reforms in The Netherlands have been introduced into a very different environment but with similar aims: efficient, effective, high quality care that addresses the needs of individual patients. Anne-Marie te Maarssen and Richard Janssen outline progress so far.

Economic Competition↗

PubMed1993

Use of the enterobacterial outer membrane protein PhoE in the development of new vaccines and DNA probes.

PhoE protein is a major outer membrane protein of Escherichia coli. The polypeptide spans the membrane 16 times, thereby exposing 8 regions at the cell surface. Insertions in these regions did not affect the biogenesis of the protein. Therefore, we considered the possibility of using PhoE as a vector for the exposure of foreign antigenic determinants at the cell surface, with the ultimate goal of constructing new (live oral) vaccines. Via recombinant DNA techniques, B-cell epitopes of VP1 protein of foot-and-mouth-disease virus were inserted in the exposed regions of PhoE. The inserted epitopes were antigenic and immunogenic in the PhoE-associated conformation. Guinea pigs, immunized with such a hybrid protein were protected against viral challenge. Similarly, a T-cell epitope of the 65 kDa heat-shock protein of Mycobacterium tuberculosis remained antigenic and immunogenic in the PhoE-associated conformation, although recognition by the cells of the immune system was dependent on the amino acids, flanking the epitope. When the amino acid sequences of the PhoE proteins of different members of the family of Enterobacteriaceae are compared, the cell surface-exposed regions are hypervariable. Therefore, we considered the possibility that the DNA segments encoding these regions are species-specific. By using synthetic oligonucleotides corresponding to such DNA segments, primer couples for the specific detection and identification of different enterobacterial species, including Salmonella, by polymerase chain reactions have been developed.

Amino Acid Sequence↗

PubMed1993

Evaluation of two new neuropsychological tests designed to minimize cultural bias in the assessment of HIV-1 seropositive persons: a WHO study.

In the course of the preparatory work for the WHO cross-cultural study on the neuropsychiatric aspects of HIV-I infection, two new neuropsychological tests (the WHO/UCLA Auditory Verbal Learning Test and the Color Trails 1 & 2) were developed. The evaluation of these tests was performed at four sites, two in developed and two in developing countries. The data obtained suggest that the tests are more culture fair than others currently used to assess the same functional domains, that they are sensitive to HIV-1-associated cognitive impairment, and that this sensitivity "holds" across different cultures.

Journal Article↗

PubMed1992

Glutamate neurotoxicity in the developing rat cochlea is antagonized by kynurenic acid and MK-801.

Glutamate (Glu) is neurotoxic in the neonatal rat cochlea, producing hearing impairment which is largely due to the death of spiral ganglion cells, whereas the receptor hair cells are spared. Dendritic processes of the spiral ganglion are postsynaptic to the primary afferent synapse of the auditory system. The experiments reported here were designed to test whether this apparent excitotoxicity can be blocked by Glu antagonists. The broad-spectrum antagonist kynurenic acid (KYNA) was coadministered with Glu initially to determine whether the high-frequency hearing deficit caused by Glu may be mediated by excitatory amino acid receptors. Subsequently, the N-methyl-D-aspartate (NMDA)-specific receptor blocker MK-801 was used to test whether NMDA receptors may be involved in the effect. Both antagonists partially blocked the high-frequency hearing impairment caused by Glu. The blocker-alone control groups exhibited mid-frequency effects of unknown origin. The significant antagonism of Glu-induced impairment is consistent with the hypothesis that Glu or a similar excitatory amino acid is an important afferent transmitter in the cochlea.

Animals↗

PubMed1992

Equity in the finance of health care: some international comparisons.

This paper presents the results of a ten-country comparative study of health care financing systems and their progressivity characteristics. It distinguishes between the tax-financed systems of Denmark, Portugal and the U.K., the social insurance systems of France, the Netherlands and Spain, and the predominantly private systems of Switzerland and the U.S. It concludes that tax-financed systems tend to be proportional or mildly progressive, that social insurance systems are regressive and that private systems are even more regressive. Out-of-pocket payments are in most countries an especially regressive means of raising health care revenues.

Cross-Cultural Comparison↗

PubMed1992

Equity in the delivery of health care: some international comparisons.

This paper presents the results of an eight-country comparative study of equity in the delivery of health care. Equity is taken to mean that persons in equal need of health care should be treated the same, irrespective of their income. Two methods are used to investigate inequity: an index of inequity based on standardized expenditure shares, and a regression-based test. The results suggest that inequity exists in most of the eight countries, but there is no simple one-to-one correspondence between a country's delivery system and the degree to which persons in equal need are treated the same.

Cross-Cultural Comparison↗

PubMed1992

Time prices and the demand for GP services.

This paper analyzes the effects of time prices on the demand for general practitioner (GP) services. Where data on earnings per unit of time was not available, an alternative method was used to impute the value of time. Separate elasticities were estimated using interactive dummy variables for individual employment status. Furthermore, a distinction was made between patient-initiated and physician-initiated visits to a GP. The results show that the probability of a patient-initiated visit is negatively influenced by the time required, for 4 of the 6 employment status categories defined. For a subsample, time was valued on the basis of earnings per time unit. The resulting time price was found to have a significant negative impact on the probability of a patient-initiated visit to a GP. However neither time nor time prices have any effect on the probability of a physician-initiated visit. It can therefore be concluded that time prices are a relevant factor in the determination of demand for GP services, particularly if it is the patient who is making the decision. Ignoring time prices could result in the mis-specification of demand equations, obtaining biased results from statistical analyses and wrongly assessing policy implications.

Adolescent↗

PubMed1992

Mapping the human liver/islet glucose transporter (GLUT2) gene within a genetic linkage map of chromosome 3q using a (CA)n dinucleotide repeat polymorphism and characterization of the polymorphism in three racial groups.

The human liver/islet glucose transporter (GLUT2), a candidate gene for diabetes, has been incorporated into a genetic linkage map for chromosome 3q using a (CA)n dinucleotide repeat polymorphism adjacent to the 3'-end of exon 4a. We have found a total of nine alleles ranging in length from 153 to 169 nucleotides in three racial groups and have determined the precise structure of the variable region for four of the alleles by DNA sequencing. Five alleles were found to be common to the American Black, Caucasian, and Pima Indian racial groups studied. One allele (169 bp) was unique to American Blacks, and another rare allele (153 bp) was found only in the Caucasian population studied. Observed heterozygosity of the polymorphism in the Caucasian (CEPH) reference pedigree collection is 60%, for American Blacks 71%, and for Pima Indians 53%. An independent study recently identified the same dinucleotide repeat and found six alleles in a Caucasian population (Froguel et al., 1991), a result that we confirm; however, our sequencing data indicate a different molecular structure for the polymorphism for some of the alleles. We have constructed a new genetic linkage map of chromosome 3q uniquely placing the GLUT2 gene between flanking markers D3S26 and D3S43. The genetic map consists of 23 loci (25 RFLPs and 2 (CA)n dinucleotide repeat markers) with 14 markers uniquely localized with odds of at least 1000:1. Three genes (FTHL4, TF, GLUT2) are integrated into the map, which spans a sex-average distance of 147.3 cM, 103.8 cM in males and 227.0 cM in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

PubMed1992

A polymorphic (CA)n repeat element maps the human glucokinase gene (GCK) to chromosome 7p.

A compound imperfect dinucleotide repeat element, [CA]4TTTGT[CT]7[CA]9AA[CA]4CCACATA[CA]3, was found approximately 10 kb 3' to the human glucokinase gene (GCK) from analysis of contiguous genomic DNA obtained from a bacteriophage lambda chromosome walk. Direct human genomic sequencing revealed the source of polymorphism to be variable numbers of CT and CA repeats. Altogether six alleles that range in length from +10 to -15 nucleotides compared to the most common (Z) allele have been identified. Alleles Z, Z + 2, and Z + 4 were present in American Blacks, Pima Indians, and Caucasians, with somewhat varied frequencies among the groups. Two alleles, Z + 10 and Z - 15, appear to be unique to American Blacks, while a Z + 6 allele was observed only in the Caucasian population studied. Observed heterozygosity of the polymorphism in the CEPH reference pedigree collection is 44% and the PIC 0.44. The polymorphism is assayed by PCR amplification and resolution of 32P-end-labeled products (ranging in length from 180 to 205 bp) on denaturing polyacrylamide sequencing gels. Using the PCR assay, the human glucokinase gene was physically localized to chromosome 7 in a panel of rodent/human somatic cell lines. Genetic analysis in CEPH pedigrees placed the dinucleotide repeat element, and thereby the human glucokinase gene, on chromosome 7p between TCRG and a RFLP locus D7S57. The glucokinase dinucleotide repeat genetic marker can now be used to assess the role of the glucokinase gene in diabetes by population association studies. In addition, this repeat marker and others flanking it on chromosome 7 can be used in linkage studies with families segregating the disorder.

Alleles↗