Leptin signaling in human peripheral blood mononuclear cells, activation of p38 and p42/44 mitogen-activated protein (MAP) kinase and p70 S6 kinase.

The adipocyte-derived hormone leptin plays an important role as a relayer of nutritional status to several organ systems. Evidence is accumulating that leptin plays an important role in the adequate functioning and maintenance of the immune system. Here we show that leptin induces sustained phosphorylation of p38 MAP kinase in human peripheral blood mononuclear cells (PBMCs).

A new phosphospecific cell-based ELISA for p42/p44 mitogen-activated protein kinase (MAPK), p38 MAPK, protein kinase B and cAMP-response-element-binding protein.

Assaying activation of signal transduction is laborious and does not allow the study of large numbers of samples, essential for high-throughput drug screens or for large groups of patients. Using phosphospecific antibodies, we have developed ELISA techniques enabling non-radioactive semi-quantitative assessment of the activation state of p42/p44 mitogen-activated protein kinase (MAPK), p38 MAPK, protein kinase B and the transcription factor cAMP-response-element-binding protein (CREB) in 96-well plates. This assay has been termed PACE (phosphospecific antibody cell-based ELISA) and was used successfully for both adherent and suspension cells.

H pylori colocalises with MUC5AC in the human stomach.

Background: The bacterium Helicobacter pylori is able to adhere to and to colonise the human gastric epithelium, yet the primary gene product responsible as a receptor for its adherence has not been identified.

Aims: To investigate the expression of the gastric mucins MUC5AC and MUC6 in the gastric epithelium in relation to H pylori colonisation in order to examine their possible roles in the binding of H pylori.

Patients: Seventy two consecutive patients suspected of having H pylori infection.

Expression and activation of NF-kappa B in the antrum of the human stomach.

Both in vitro studies and experiments in mice suggest a key role for transcription factor NF-kappa B as a mediator of mucosal inflammation. Experiments in vitro show that NF-kappa B activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. This study examines the expression and activity of NF-kappa B in situ in antral biopsies of 69 consecutive patients with immunohistochemical techniques.

Study of calcium signaling in non-excitable cells.

The fundamental importance of calcium signaling in the control of cellular physiology is widely recognized. A dramatic illustration of this is the fact that a Medline search for review articles containing the word "calcium" in the title reveals 4,629 hits, whereas the whole body of calcium signaling literature (approximately 2 x 10(6) pages) is more than enough to fill a decent-sized library. Most of this literature deals with calcium signaling in excitable cells types (mainly neurons and muscle cells), but non-excitable cell types are capable of calcium signaling as well.

Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2.

For families with a small number of cases of breast and/or ovarian cancer, limited data are available to predict the likelihood of genetic predisposition due to mutations in BRCA1 or BRCA2. In 104 families with three or more affected individuals (average 3.8) seeking counselling at family cancer clinics, mutation analysis was performed in the open reading frame of BRCA1 and BRCA2 by the protein truncation test and mutation-specific assays.

A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families.

We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands.

Hospital adaptation to risk-bearing: managerial implications of changes in purchaser-provider contracting.

A number of countries have adopted contracting reforms in which hospitals are placed at financial risk. This risk has stimulated a number of adaptive strategies to achieve organizational success. This paper presents a model of six forms of contracting relationships and reviews the adaptation strategies observed in three health systems: the USA, England and the Netherlands.

Assembly of polymer/lipid composite films on solids based on hairy rod LB-films.

The present work deals with the assembly of multilayers or rod-like polymers with hydrophobic side chains (called hairy rods) and their potential application as ultrathin polymer cushions for the build-up of self healing supported membranes on various solids (Si/SiO(2)-wafer, gold covered substrates). Three types of hairy rods were studied: Isopentyl cellulose (IPC), phtalocyaniatopolysiloxane with mixed alkane side chains (PCPS) and trimethylsilane cellulose (TMCS). Detailed analysis of the thickness of supported multilayers as a function of the number of deposited monolayers with ellipsometry, near infrared surface plasmon resonance (NIR-SPR), a quartz crystal microbalance (QCM) and reflection interference contrast microscopy (RICM), show that the basic building blocks of hairy rod multilayers are bilayers with the hydrophobic surfaces of the monolayers facing each other.

Treatment of bile duct lesions after laparoscopic cholecystectomy.

From January 1990 to June 1994, 53 patients who sustained bile duct injuries during laparoscopic cholecystectomy were treated at the Amsterdam Academic Medical Centre. There were 16 men and 37 women with a mean age of 47 years. Follow up was established in all patients for a median of 17 months.

Self assembly of covalently anchored phospholipid supported membranes by use of DODA-Suc-NHS-lipids.

We present a novel preparation method for the self assembly of covalently anchored phospholipid supported membranes. The surface is gold covered by cysteamine. Vesicles containing DMPC and activated DODA-Suc-NHS-lipids assembled on this surface.

Spectinomycin interacts specifically with the residues G1064 and C1192 in 16S rRNA, thereby potentially freezing this molecule into an inactive conformation.

The upper stem of helix 34, consisting of the base-paired sequences C1063G1064U1065 and A1191C1192G1193, is suggested to be involved in the binding of spectinomycin. In E. coli 16S rRNA, each of the three mutations at position C1192 confers resistance to spectinomycin.

Vitamin E in extrapyramidal disorders.

In this article the effect of vitamin E on two extrapyramidal disorders, tardive dyskinesia and Parkinson's disease, is reviewed. After a brief description of the symptoms, the current hypotheses for the pathogenesis of these diseases are described. A summary of the clinical research that has been done to establish the effectiveness of vitamin E is given.

The use of hypoglycaemic and cardiovascular drugs in 582 patients with diabetes mellitus. Description and quality assessment.

The medication of 582 patients taking insulin or oral hypoglycaemic agents has been analysed. A characterization is given of the patients and their antidiabetic medication. Subsequently, a description of the use of cardiovascular drugs, in comparison with an age-matched control group, is presented.

A drug use review study in patients with obstructive lung disease. Assessment of the quality of drug therapy.

This study presents the results of an analysis of the pharmacy records of 778 patients with asthma or chronic obstructive lung diseases. The high percentage of patients taking oral corticosteroids was striking. Inhaled beta-agonists for use as needed have been prescribed to only a minority of patients using these agents.

Circadian rhythm and diurnal excursion of plasma cortisol in diabetic pregnant women.

The effect of type I and II diabetes in pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol was studied in the second and third trimesters and post partum. Cosignor analysis demonstrated persistence during gestation of the significant circadian rhythm of the nonpregnant state. As previously reported in control pregnancies, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased during gestation while the relative excursion of cortisol (expressed as the percent deviation from the 24-hour mean) was blunted.

Comparison of cefixime and co-trimoxazole in acute uncomplicated urinary tract infection. A double-blind general practice study.

Five hundred and twenty-eight patients with presumptive acute uncomplicated urinary tract infection (UTI) were randomly assigned to receive cefixime 400 mg once daily, cefixime 200 mg twice daily or co-trimoxazole 2 tablets twice a day for 10 days; 477 completed at least 5 days of therapy. Of the patients 342 (65%) had positive baseline urine cultures, yielding 353 pathogens. A microbiological response was determined for 280 pathogens (79%), eradication being observed in over 94% of isolates; 153 pathogens (43%) were sensitive to both cefixime and co-trimoxazole and eradication was observed in over 96% of cases.

A model for the slow control system during monocular fixation.

A method has been developed to compare the behaviour of the oculomotor control system during steady fixation and during reactions on small stimulus movements. No difference between the two conditions was found, and the reactions on small steps (1-5') and step/ramps (2-10'/sec), during normal and stabilized vision, have been used to develop a model for the slow control system during fixation. The model consists of a position channel, which integrates the retinal error, and a velocity channel, that uses both the retinal velocity and an efferent copy of the eye velocity.

Qualitative and quantitative assessment of the circadian rhythm of cortisol in pregnancy.

The effect of pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol and urinary free corticoids was examined in a sequential study during the second and third trimester and 6 to 12 weeks post partum. Hourly blood samples from six subjects and 8-hour urine collections from eight subjects were obtained around the clock. While the circadian rhythm was maintained during gestation, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased.

On the relativity of pitch.

The way we interpret a given set of sensory stimuli can depend very strongly on our choice of cues. The resulting ambiguity is particularly familiar in visual perception, and underlies many well-known visual illusions. It is shown that comparable ambiguities exist in the field of hearing, particularly pitch perception.

Detection of vertical disparties.

Psychometric curves determined for the detection of differences between vertical disparities as a function of the reference disparity for three presentation times (20 msec, 160 msec and 2 sec) and for two eccentricites of the stimulus (0.5 degree and 4 degrees) are presented. The results show that the detectability of disparity differences first increases and then decreases when the reference disparity is increased from zero.

The effect of presentation time on detection and diplopia thresholds for vertical disparities.

Detection and diplopia thresholds for vertical disparities are found to decrease when the presentation time of the stimulus with disparity is increased between 20 msec and 2 sec. This result supports the following notions previously put forward in literature; (a) the human visual system embodies detection processes which reveal vertical disparities; there is no sensory fusion mechanism in this system that gradually conceals vertical disparities: (b) the detection of vertical disparity in tachistoscopically presented stimuli is not based upon the initial appearance of the stimulus with disparity.