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Biomedical subjects

R Janssen

Publications and source records attributed to R Janssen.

At least 19 recordsLinked to original sources
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

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↗
PubMed1992

Thermal influences on nervous system function.

The various effects of temperature change are only partially predictable. Temporal measures relevant to membrane activity, action potentials, synaptic transmission, and evoked potentials are all consistently increased with cooling and decreased by warming. However, the various measures of amplitude at different levels, and even within similar preparations, are contradictory: Some laboratories report increased amplitudes with cooling and others report decreased amplitudes under similar conditions. Emphasis is given to identifying factors that may resolve the differences. These include: (a) the rate of temperature change, (b) sites of cooling, stimulation and recording, (c) stimulus characteristics, and (d) fundamental differences in temperature sensitivities of different neural tissue. Other factors that may affect the ability to predict thermal influences on neural function from existing formulations are: relative ion permeabilities, metabolic ion pumps, the resting potential at the onset of cooling, and an animal's acclimated temperature at sacrifice.

Animals↗
PubMed1992

The role of support in psychoanalysis.

A two-factor theory of clinical psychoanalysis is proposed. In accordance with the predominant position of the structural-adaptational ("classical") approach in psychoanalytic theory, the power of interpretation and insight in clinical psychoanalysis has received ample attention in psychoanalytic literature. There seems, however, to be a growing awareness among analysts that not all the facts of an analytic treatment can be accounted for by this approach alone. A second factor is increasingly recognized: the power of adequate support provided by the analyst and resulting in a specific experience by the analysand. In the application of the developmental ("postclassical") approach of psychoanalytic theory, the importance of this support-experience factor in the treatment of ordinary neurosis by means of ordinary psychoanalysis is emphasized. The relative neglect of this aspect of clinical psychoanalysis may be indicative of the present-day dilemma of how to translate advances in theoretical knowledge of mental development into the therapeutic praxis of psychoanalysis. There may, however, be another important reason. Support and experience are phenomena often occurring on the nonverbal level. In contrast to interpretation and insight, they are usually not voiced, let alone distinctly and loudly expressed. They are the silent power of psychoanalysis.

Humans↗
PubMed1992

Variability of the insulin gene in American blacks with NIDDM. Analysis by single-strand conformational polymorphisms.

Previous studies of the insulin gene--utilized restriction-fragment--length polymorphisms as markers for potential mutations at this locus. This indirect type of analysis could not define the number of variants that might exist within the structural portions and regulatory regions of the gene in non-insulin-dependent diabetes mellitus (NIDDM) patients. New technology has allowed us to examine insulin genes at the single nucleotide level from 100 American black NIDDM patients. Genomic DNA from patients was amplified by the polymerase chain reaction with primers flanking four regions of the gene: 1) the proximal promoter from positions -182 to 42 (including most of exon 1); 2) exon 1 from 14 to 259, which included the rest of exon 1 and all of the 1st intron; 3) exon 2 from 216 to 452; and 4) exon 3 from 1188 to 1433. One of the primers in each reaction was 32P-end labeled and the resulting products denatured into single strands and electrophoresed on nondenaturing sequencing gels such that mobility was a function of composition and size (single-strand conformational polymorphism or SSCP). Under these conditions, single-base changes in fragments up to 245 nucleotides were detected. Analysis of the proximal promoter region revealed several SSCP patterns in individuals. Direct genomic sequencing of DNA representative of these patterns showed the presence of a common C to G change at position -56 and a C deletion at position -90 in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Neurological complications of HIV-1-seropositive internal medicine inpatients in Kinshasa, Zaire.

Because little was known about the prevalence of neurological complications of human immunodeficiency virus type 1 (HIV-1) infection in Africa, we conducted a cross-sectional study among consecutive admissions to the internal medicine wards of Mama Yemo Hospital in Kinshasa, Zaire. Of the 196 patients studied, 104 (53%) were HIV-1 seropositive, of whom 50 (48%) had stage 3 and 49 (47%) had stage 4 HIV-1 infection according to the provisional WHO staging criteria for HIV infection. Neuropsychiatric abnormalities were present in 43 (41%) of 104 HIV-1-seropositive patients. Of the HIV-1-seropositive patients, 9 (8.7%; 95% confidence interval, 4-16%) were diagnosed as having possible HIV-1-associated dementia complex, 1 (1%) as having possible HIV-1 myelopathy, and 3 (2.7%) as having possible HIV-1-associated minor cognitive/motor disorder. Definitive diagnoses could not be made because there were no facilities for neuroimaging and neuropathology. Meningitis caused by cryptococcus was diagnosed in six (5.6%) and by Mycobacterium avium in two (2%) of the HIV-1 seropositive patients. Acute onset hemiplegia, believed to be due to stroke, was present in four (4%) of the HIV-1-seropositive patients. The prevalence of other central nervous system opportunistic infections and mass lesions, especially toxoplasmic encephalitis, could not be assessed. In this population of Zairian inpatients, the prevalence of neurological complications of HIV-1 infection was similar to that observed in industrialized countries among patients with advanced HIV disease.

Adult↗
PubMed1991

Glutamate neurotoxicity in the developing rat cochlea: physiological and morphological approaches.

The neurotoxic effects of exogenous glutamate were studied in the rat cochlea. Glutamate-treated rats (4 g/kg/day i.p., postnatal days 2-9) exhibited electrophysiologically-measured elevations in high frequency thresholds usually associated with hair cell loss in the basal region of the cochlea. While surface preparations of the organ of Corti revealed no loss of hair cells, there was a dramatic and selective reduction of neurons in the basal, high frequency-related portion of the spiral ganglion. This sensitivity of developing spiral ganglion cells to the neurotoxicity of glutamate is consistent with the hypothesis that glutamate or a structurally related substance is a neurotransmitter at afferent synapses of cochlear hair cells.

Acoustic Stimulation↗
PubMed1991

The World Health Organization's cross-cultural study on neuropsychiatric aspects of infection with the human immunodeficiency virus 1 (HIV-1). Preparation and pilot phase.

The WHO launched a multicentre study to explore the nature and prevalence of HIV-1-associated neurological, psychiatric, and neuropsychological abnormalities in persons living in different geographical and sociocultural contexts. The study is being conducted in Brazil, Germany, Kenya, Thailand, the United States of America, and Zaire. A comprehensive instrument for the collection of neuropsychiatric data (including a battery of neuropsychological tests suitable for cross-cultural use) has been developed, and the feasibility of the recruitment and assessment procedure designed for the main phase has now been demonstrated.

Attention↗
PubMed1991

HTLV-I-associated myelopathy associated with blood transfusion in the United States: epidemiologic and molecular evidence linking donor and recipient.

Six months after receiving 58 units of blood components, a 65-year-old white man from New York City, with no other risk factors for human T-lymphotropic virus type I (HTLV-I) infection, developed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Investigation of blood donors identified a 25-year-old white Hispanic woman from Florida whose platelets had been given to the patient and who was seropositive for the virus on a serum specimen obtained 2 years after the donation. She was born in Cuba and had had 2 sexual relationships with men who either had been born in or had resided in the Caribbean. Polymerase chain reaction (PCR) studies of peripheral blood mononuclear cells indicated that both donor and recipient were infected with HTLV-I. Molecular studies of a 595-nucleotide sequence in the 5' envelope region of HTLV-I indicated that the viruses from donor and recipient were identical in each of 32 positions in which published HTLV-I sequences demonstrate molecular heterogeneity; the donor and recipient viruses were also identical in 2 additional positions in which they differed from all published sequences. Transfusion-associated HAM/TSP has occurred in the United States, but additional cases should be prevented by screening blood donations for HTLV-I. Molecular studies of HTLV-I may prove useful in defining the genetic heterogeneity of HTLV-I isolates in the United States and in studying transmission of this virus.

Adult↗
PubMed1991

Aspects of the analytic relationship.

In this article the analysand-analyst relationship is investigated from the classical and from the post-classical point of view. This leads to the distinction of four fundamental aspects of the analytic relationship: the realistic relationship, the working relationship, the transference relationship, and the primary relationship. Similarities and differences between these various aspects of the analytic relationship are discussed. Examples of confusion about the aspects are given. Disagreement about the issue is mentioned. Emphasis is laid on one of the four aspects: the primary relationship. Its importance in ordinary psychoanalysis has not received the attention it deserves.

Countertransference↗
PubMed1990

Nationwide survey of HTLV-I-associated myelopathy in Japan: association with blood transfusion.

To study the epidemiology of human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Japan, we conducted two nationwide surveys between October 1986 and March 1989. A total of 710 patients with HAM (definite HAM, 589; probable HAM, 121) were reported. Of the 589 patients with definite HAM, 69% were residents of the areas with the highest prevalence HTLV-I in Japan. To determine the importance of blood transfusion in the pathogenesis of HAM/TSP, we performed a case-control study in the Kagoshima district in southern Japan. Significantly more patients with HAM reported a history of blood transfusion (26/129, or 20%) than did subjects in a health survey of the general population (41/1,290, or 3%; odds ratio = 7.7, p less than 0.001) or than did hospitalized neurological patients (6/119, or 5%; odds ratio = 4.8, p less than 0.001). Furthermore, the cumulative percentages of the intervals between blood transfusion and the onset of the symptoms of HAM fit a lognormal curve, suggesting that transfusion was an important common exposure. Blood transfusion probably transmitted HTLV-I to the patients with transfusion-associated HAM because there was a significant decrease in the number of patients with the transfusion-associated HAM who received blood after implementation of nationwide screening of blood donors in 1986 (p = 0.004). In the first 2 years, screening the blood supply in Japan appears to have decreased the number of reported patients with HAM by 16%.

Humans↗
PubMed1990

Trimethyltin effects on auditory function and cochlear morphology.

Trimethyltin (TMT) is a neurotoxicant known to alter auditory function. The present study was designed to compare TMT-induced auditory dysfunction using behavioral, electrophysiological, and anatomical techniques. Adult male Long-Evans hooded rats (n = 9-12/group) were acutely exposed to saline, 3, 5, or 7 mg/kg TMT. Auditory thresholds were determined 11 weeks postdosing for 5- and 40-kHz tones using reflex modification of the auditory startle response (ASR). Brainstem auditory evoked response (BAER) thresholds were determined for 5-, 40-, and 80-kHz tonal stimuli 9 weeks postdosing. Cochlear histology was assessed at 13 weeks postdosing. Functional endpoints demonstrated a high-frequency hearing loss. ASR thresholds for 40-kHz tones were elevated 25-35 dB in all dosage groups. BAER thresholds for 40- and 80-kHz tones were elevated 30-50 dB in the 5 and 7 mg/kg groups. Organ of Corti surface preparations revealed a pattern of damage suggesting classical ototoxicity. That is, outer hair cells died preferentially in regions associated with high-frequency hearing, in a dosage-dependent manner from base to apex. These data demonstrate the utility of the ASR and BAER in detecting functional alterations in audition and indicate that TMT-induced high-frequency hearing loss is associated with cochlear damage.

Animals↗
PubMed1990

Neuropsychological effects of early HIV-1 infection: assessment and methodology.

Studies of neuropsychological performance early in the course of human immunodeficiency virus-type 1, infection are reviewed. The studies differed on reporting the presence and severity of neuropsychological changes, and comparisons among studies are hampered by variations in the study populations, sample sizes, assessment methods, approaches to data analysis, and definitions of thresholds for abnormality. Recommendations that would facilitate comparisons among future studies include using markers for disease state, applying longitudinal designs, using common instruments for assessing neuropsychological status, selecting appropriate controls, controlling for co-factors, reporting raw scores as well as presumed indices of impairment, and relating impairment on neuropsychological tests to affected individuals' daily activities, if possible.

AIDS Dementia Complex↗