Biomedical subjects

P Janssen

Publications and source records attributed to P Janssen.

At least 19 recordsLinked to original sources

PubMed2002

Treatment outcome studies. pitfalls in current methods and practice.

The objective of a treatment outcome study is to investigate the heterogeneity in outcome between patients according to factors other than treatment, such as country, institution or physician. Results of treatment outcome studies have already been extensively presented in the medical literature. However, no clear methodology has emerged to perform treatment outcome studies and various methods have been used. This paper reviews the different types of questions addressed in treatment outcome studies, the different methodologies and the different endpoints used. Statistical techniques are mainly descriptive including tables, estimates of survival curves, but regression models have also been used. Most of the studies use registry data, while only a few use discharge data or data available from clinical trials.

Clinical Trials as Topic↗

PubMed2002

Pharmacological characterization of the 5-HT receptors mediating contraction and relaxation of canine isolated proximal stomach smooth muscle.

1. We aimed to characterize 5-HT receptors mediating contraction and relaxation to 5-HT in dog proximal stomach longitudinal muscle (LM) strips. 2. Of the tryptamine analogues tested, 5-HT was the most potent contractile agent at basal length, while 5-CT was the most potent relaxant of PGF(2alpha)-induced contraction. Neither the contractions to 5-HT, nor the relaxations to 5-CT were influenced by tetrodotoxin, illustrating that action potential propagation is not involved. 3. The 5-HT-induced contraction was antagonized by mesulergine (0.03 to 0.3 microM) and ketanserin (2 - 20 nM), but the antagonism was not of a simple competitive nature, indicating multiple receptor involvement. Ketanserin (3 to 30 nM) and mesulergine (30 nM) competitively antagonized the alpha-Me-5-HT-induced contraction (pK(B): 8.83+/-0.09 and pA(2): 8.25+/-0.06 respectively). These affinity values are in line with literature affinities of ketanserin and mesulergine at 5-HT(2A) receptors in various bioassays. 4. The 5-CT-induced inhibition of PGF(2alpha)-induced contraction was competitively antagonized by mesulergine (pK(B) estimate: 8.52+/-0.12) and by the selective 5-HT(7) receptor antagonist SB-269970 (pK(B) estimate: 9.36+/-0.14). Both pK(B) estimates are in line with literature affinities of these compounds for 5-HT(7) receptors. Mesulergine (30 nM) and SB-269970 (10 nM) shifted the relaxant curve to 5-HT parallel to the right in the presence of ketanserin (0.3 microM) (pA(2) estimates of 8.08+/-0.10 and 8.75+/-0.14 respectively), indicative of 5-HT(7) receptor involvement. 5. It is concluded that 5-HT induces dog proximal stomach (LM) contraction via smooth muscle 5-HT(2A) receptors and relaxation via smooth muscle 5-HT(7) receptors.

Animals↗

PubMed2001

Macaque inferior temporal neurons are selective for three-dimensional boundaries and surfaces.

The lower bank of the superior temporal sulcus (TEs), part of the inferior temporal cortex, contains neurons selective for disparity-defined three-dimensional (3-D) shape. The large majority of these TEs neurons respond to the spatial variation of disparity, i.e., are higher-order disparity selective. To determine whether curved boundaries or curved surfaces by themselves are sufficient to elicit 3-D shape selectivity, we recorded the responses of single higher-order disparity-selective TEs neurons to concave and convex 3-D shapes in which the disparity varied either along the boundary of the shape, or only along its surface. For a majority of neurons, a 3-D boundary was sufficient for 3-D shape selectivity. At least as many neurons responded selectively to 3-D surfaces, and a number of neurons exhibited both surface and boundary selectivity. The second aim of this study was to determine whether TEs neurons can represent differences in second-order disparities along the horizontal axis. The results revealed that TEs neurons can also be selective for horizontal 3-D shapes and can code the direction of curvature (vertical or horizontal). Thus, TEs neurons represent both boundaries and surfaces curved in depth and can signal the direction of curvature along a surface. These results show that TEs neurons use not only boundary but also surface information to encode 3-D shape properties.

Animals↗

PubMed2001

Serum bile acids in liver transplantation--early indicator for acute rejection and monitor for antirejection therapy.

We studied the course of serum bile acids to investigate its reliability in the diagnosis of acute rejection after liver transplantation in relation to pathohistological findings. Serum bile acid concentration, bilirubin and transaminases were measured in 41 patients who underwent liver transplantation. Their course was correlated to liver biopsy. Group I (n = 19) patients were without acute rejection, whereas group II (n = 22) patients showed acute rejection. Bile acid concentrations in group II showed a statistically highly significant (P < or = 0.001) threefold increase 3 days prior to biopsy. Successful antirejection treatment was correlated with a statistically significant (P = 0.008) decrease of serum bile acid 1 day after initiation of therapy. Patients without acute rejection showed a baseline bile acid concentration at the time of biopsy. Bilirubin and transaminases did not show any statistically significant correlation to acute rejection. Infection did not lead to a significant bile acid increase. Our study shows that serum bile acids monitored after liver transplantation can easily be used to detect acute rejection and at the same time they reflect the success of antirejection therapy.

Acute Disease↗

PubMed2001

Genetic polymorphisms of microsomal and soluble epoxide hydrolase and the risk of Parkinson's disease.

Oxidative stress is hypothesized to play a major role in the destruction of dopaminergic neurons, which is associated with Parkinson's disease. Epoxides are potentially reactive intermediates formed through the oxidative metabolism of both exogenous and endogenous substances that contribute to cytotoxic damage mediated by oxidative stress. The microsomal (EPHX1) and soluble (EPHX2) epoxide hydrolases function to regulate the oxidation status of a wide range of xenobiotic- and lipid-derived substrates; therefore, interindividual variation in these pathways may mitigate epoxide-related cellular injury. In this investigation, we examined the potential association between the risk of Parkinson's disease and genetic variation within the EPHX1 and EPHX2 genes. Fluorescent 5' nuclease-based assays were developed to identify the allelic status of individuals with respect to specific single nucleotide polymorphisms in exons 3 and 4 of the EPHX1 gene and exons 8 and 13 of the EPHX2 gene. EPHX1 and EPHX2 genotype data were obtained from 133 idiopathic Parkinson's disease patients and 212 control subjects matched on age, gender and ethnicity. No statistically significant differences were found in the distribution of the reference and variant alleles between Parkinson's disease and control subjects, or when results were stratified by gender. Therefore, common polymorphisms within EPHX1 and EPHX2 do not appear to be important risk factors for Parkinson's disease.

Adult↗

PubMed2001

Solubilization and purification of the human ETB endothelin receptor produced by high-level fermentation in Pichia pastoris.

In the present report, the successful solubilization and purification of the ETB receptor heterologously produced in the methylotrophic yeast P. pastoris is described for the first time. In comparison to the baculovirus system where successful production, solubilization and purification have already been reported, handling and up-scaling of recombinant P. pastoris cells was much easier and less time consuming. Recombinant P. pastoris clones producing two different ETB receptor constructs were grown in a fermenter to a density of about 360 g/l. After induction with methanol, a production level of maximally 45 pmol/mg was obtained, a value which is in the range of that reported for baculovirus-infected insect cells. A method for the large-scale preparation of membranes was established. Solubilization of the recombinant ETB receptor was achieved with the detergent n-dodecyl-/beta-D-maltopyranoside. The stability of the solubilized and ligand-bound receptor was examined in detail. Subsequently, two purification methods for two different receptor constructs were tested and a large-scale procedure for isolation of recombinant receptor was established. In general, the purification methods described herein will be adaptable to other G protein-coupled receptors heterologously produced in heterologous expression systems including P. pastoris.

Binding Sites↗

PubMed2000

Genome sequences and great expectations.

To assess how automatic function assignment will contribute to genome annotation in the next five years, we have performed an analysis of 31 available genome sequences. An emerging pattern is that function can be predicted for almost two-thirds of the 73,500 genes that were analyzed. Despite progress in computational biology, there will always be a great need for large-scale experimental determination of protein function.

Animals↗

PubMed2000

Induction of labour: a continuous quality improvement and peer review program to improve the quality of care.

This article describes a program developed to improve the process of planned induction of labour and to reduce the rates of inappropriate induction. The setting is a tertiary-care maternity hospital in urban Vancouver, BC, in which 7000 deliveries take place annually. Approximately 65% of these can be considered primary care; the remainder are secondary- or tertiary-level cases. Continuous quality improvement (CQI) methods were used by a multidisciplinary team, which included nursing staff, physicians, health records personnel and a CQI facilitator. Interventions included the development of a new induction-booking process, clear criteria for induction, feedback to caregivers about changes and a peer review system to oversee and maintain improvement. The overall induction rate for the institution decreased, and this change has been maintained.

British Columbia↗

PubMed2000

Selectivity for 3D shape that reveals distinct areas within macaque inferior temporal cortex.

The anterior part of the macaque inferior temporal cortex, area TE, occupies a large portion of the temporal lobe and is critical for object recognition. Thus far, no relation between anatomical subdivisions of TE and neuronal selectivity has been described. Here, we present evidence that neurons selective for three-dimensional (3D) shape are concentrated in the lower bank of the superior temporal sulcus, whereas neurons in lateral TE are generally unselective for 3D shape, though equally selective for 2D shape. These findings reveal that TE consists of at least two distinct areas, one of which processes a specific object property.

Animals↗

PubMed2000

Three-dimensional shape coding in inferior temporal cortex.

Neurons in the rostral lower bank of the superior temporal sulcus (TEs), part of the inferior temporal cortex, respond selectively to three-dimensional (3D) shapes. We have investigated how these neurons represent disparity-defined 3D structure. Most neurons were selective for either first-order (disparity gradients) or second-order (disparity curvature) disparities. The latter selectivity proved remarkably vulnerable to disparity discontinuities, such as sharp edges or steps in disparity. The majority of the neurons remained selective for small disparity variations within the stimulus. 3D shape selectivity was preserved when the frontoparallel position or the stimulus size was altered. Thus, in TEs, 3D shape is coded by first- and second-order disparity-selective neurons, which are highly sensitive to spatial variations of disparity.

Action Potentials↗

PubMed2000

Metastatic breast cancer presenting with diabetes insipidus.

We present a case of acute-onset diabetes insipidus in a 60-year-old woman who had been treated for breast cancer. MR images showed a thickened and enhancing pituitary stalk and an asymmetrical hypophysis. The clinical diagnosis of a pituitary metastasis of the breast carcinoma was made.

Bone Neoplasms↗

PubMed2000

The human ET(B) endothelin receptor heterologously produced in the methylotrophic yeast Pichia pastoris shows high-affinity binding and induction of stacked membranes.

The human endothelin B receptor (ET(B) receptor) was produced in the methylotrophic yeast Pichia pastoris under transcriptional control of the highly inducible alcohol oxidase 1 (AOX1) gene promoter. In the expression plasmids pPIC9KFlagET(B)Bio and pPIC9KFlag deltaGPET(B)Bio the ET(B) receptor coding region was fused in frame to the Saccharomyces cerevisiae alpha-factor prepropeptide and the FLAG-tag. In both constructs, the receptor was also fused to a biotinylation domain. Additionally, in pPIC9KFlag deltaGPET(B)Bio the putative N-glycosylation site and a protease site have been deleted by site directed mutagenesis. Crude membranes prepared from recombinant P. pastoris revealed specific and saturable binding of [125I]ET-1 with a K(D) of about 42 pM. Receptor levels of 60 pmol/mg and 35 pmol/mg for the Flag deltaGPET(B)Bio and the FlagET(B)Bio construct, respectively, were determined. The pharmacological profile for ET-1, ET-2 and ET-3 were as expected for a subtype B endothelin (ET) receptor. Immunoblot analysis showed an apparent molecular mass of 55 kDa for the Kex2-processed and about 74 kDa for the Kex2-unprocessed receptor. Contrary to the Flag deltaGPET(B)Bio construct, the FlagET(B)Bio construct was not correctly processed by the internal Kex2 endopeptidase. As was detected by ultrastructural analysis of recombinant yeast cells, high-level production of the receptor resulted in the formation of stacked membranes.

Amino Acid Sequence↗

PubMed1999

Macaque inferior temporal neurons are selective for disparity-defined three-dimensional shapes.

Real-world objects are three-dimensional (3D). Yet, it is unknown whether the neurons of the inferior temporal cortex, which is critical for object recognition, are selective for the 3D shape of objects. We tested for such selectivity by comparing responses to stereo-defined curved 3D shapes derived from identical pairs of monocular images. More than one-third of macaque inferior temporal neurons were selective for 3D shape. In the vast majority of those neurons, this selectivity depended on the global binocular disparity gradient and not on the local disparity. Thus, inferior temporal cortex processes not only two-dimensional but also 3D shape information.

Animals↗

PubMed1999

Vaginal sonography and gender preference for sonographer.

PURPOSE: The invasive nature of vaginal sonography, recently introduced as an improved diagnostic method for imaging the contents of the pregnant uterus, has provoked discussion about patient preference for female sonographers. This study examined whether patients had a gender preference for the sonographer who would conduct such an examination. METHODS: Over 3 months, a written survey was given to pregnant women to complete anonymously while waiting for their scheduled sonographic examination. The survey covered gender preference for the sonographer and education, ethnicity, and previous experience with the procedure. Surveys were turned in by 1,002 pregnant women. RESULTS: Of the women whose survey responses were analyzed, 62% preferred a female sonographer. The principal reason given for this preference was comfort with the same gender. The majority of respondents were 25-40 years old, married, white, and multiparous. The level of education varied widely. CONCLUSIONS: These findings point to a need to seek consumer input when new technology is introduced, to provide women with choices where possible, and to ensure that they have access to information about those choices.

Educational Status↗

PubMed1999

Amplified-fragment length polymorphism analysis versus macro-restriction fragment analysis for molecular typing of Streptococcus pneumoniae isolates.

Forty-eight pneumococci were genotyped by on-line laser fluorescence amplified-fragment length polymorphism (AFLP) and pulsed-field gel electrophoresis (PFGE) analysis of chromosomal restriction fragments. Overall, the data generated by the two methods corresponded well. However, with AFLP, clusters were delineated at a higher similarity level, and isolate differentiation was more pronounced. AFLP and PFGE were equally efficient for assessing intraserotype diversity. We conclude that AFLP is a useful alternative to PFGE.

Algorithms↗

PubMed1999

Conservative management of spontaneous abortions. Women's experiences.

OBJECTIVE: To describe women's experiences with expectant management of spontaneous abortions. DESIGN: Descriptive survey using questionnaires with fixed-choice and open-ended questions. The latter were analyzed for themes, using qualitative methods. SETTING: Urban and suburban private primary care family practices. PARTICIPANTS: A convenience sample of family practice patients (59 of 80 eligible) pregnant for less than 12 weeks who had spontaneous abortions without surgery. Response rate was 84.7%; 50 questionnaires were received from the 59 women. METHOD: Women were asked about their physical experiences, including amount of pain and bleeding; emotional effects; their satisfaction with medical care; and their suggestions for improving care. MAIN FINDINGS: The mean worst pain experienced during a spontaneous abortion on an 11-point scale was 5.9. Bleeding varied, but was often very heavy. Satisfaction rate was 92.9% with family physician care and 84.6% with hospital care. Women described the emotional effect of "natural" spontaneous abortions and made recommendations for improving care. CONCLUSIONS: A better understanding of the physical and emotional experiences of the women in this study might help physicians better prepare and support patients coping with expectant management of spontaneous abortions.

Abortion, Spontaneous↗

PubMed1999

Reducing surgery in management of spontaneous abortions. Family physicians can make a difference.

OBJECTIVE: To test the effectiveness of physician and patient education in reducing the rate of surgery in management of spontaneous abortions in family practice. DESIGN: A before-after intervention trial. SETTING: Urban and suburban family doctors' practices in greater Vancouver, BC. PARTICIPANTS: Family practice patients (56 physicians contributed 417 patients) who had spontaneous abortions between June 1997 and August 1998. INTERVENTIONS: Seminars for doctors and educational pamphlets for patients. MAIN OUTCOME MEASURES: Rate of surgeries, and rates of referrals and complications. RESULTS: In the 2 years before the intervention, the rate of surgery was 45.8% (n = 299); after, it was 32.2% (n = 118). No transfusions were required. Before the intervention, 17% of women had hemorrhages; after, 13%. Rates of infection were 3.7% and 0.8%, respectively. Rates of referral to gynecologists were 54.0% and 40.2%, respectively. CONCLUSIONS: Patients of family doctors who attended seminars and agreed to join the study had significantly reduced rates of surgery after spontaneous abortions. Rates of referral for these patients were also lower, and there was no increase in complications.

Abortion, Spontaneous↗

PubMed1998

Scarcity or complete lack of single rhamnose residues interspersed within the homogalacturonan regions of citrus pectin.

Commercial citrus pectin containing galacturonic acid and rhamnose in a ratio of approximately 40:1 was saponified and then exhaustively digested with endopolygalacturonase (EPG). The products were separated by ultrafiltration into low-molecular-weight (LMW) and high-molecular-weight (HMW) fractions. The LMW fraction accounted for 80% of the starting material, but for only 10% of the total rhamnose. The molar ratio of galacturonic acid to rhamnose of the LMW fraction was 236, suggesting that very few small Rha-containing oligomers were generated by the EPG digestion. No distinct Rha-containing oligomers were found by various chromatographic analyses of the LMW fraction. The HMW fraction, which only accounted for 10% by weight of the starting pectin, contained more than 85% of the rhamnose. The ratio of GalA to Rha in the HMW fraction was 1.7:1 and partial acid hydrolysis of this fraction produced a series of oligomers consisting of GalA-Rha repeating units, suggesting that it contained rhamnogalacturonan, which has a backbone composed of GalA-Rha disaccharide repeating units. The HMW fraction also contained large amounts of arabinose and galactose, which probably originated from side chains linked to some of the rhamnose residues. We propose that commercial citrus pectin is composed of two regions: the predominant region consists of chains of uninterrupted 1,4-linked alpha-D-GalA residues with between 60-70% of the residues methyl esterified; and the other region consists of rhamnogalacturonan with a backbone composed of GalA-Rha disaccharide repeating units and neutral sugar side chains.

Carbohydrate Sequence↗