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Biomedical subjects

E Janssen

Publications and source records attributed to E Janssen.

At least 19 recordsLinked to original sources
PubMed2003

Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.

In humans, ten Toll-like receptor (TLR) paralogues sense molecular components of microbes, initiating the production of cytokine mediators that create the inflammatory response. Using N-ethyl-N-nitrosourea, we induced a germline mutation called Lps2, which abolishes cytokine responses to double-stranded RNA and severely impairs responses to the endotoxin lipopolysaccharide (LPS), indicating that TLR3 and TLR4 might share a specific, proximal transducer. Here we identify the Lps2 mutation: a distal frameshift error in a Toll/interleukin-1 receptor/resistance (TIR) adaptor protein known as Trif or Ticam-1. Trif(Lps2) homozygotes are markedly resistant to the toxic effects of LPS, and are hypersusceptible to mouse cytomegalovirus, failing to produce type I interferons when infected. Compound homozygosity for mutations at Trif and MyD88 (a cytoplasmic TIR-domain-containing adaptor protein) loci ablates all responses to LPS, indicating that only two signalling pathways emanate from the LPS receptor. However, a Trif-independent cell population is detectable when Trif(Lps2) mutant macrophages are stimulated with LPS. This reveals that an alternative MyD88-dependent 'adaptor X' pathway is present in some, but not all, macrophages, and implies afferent immune specialization.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels.

Transduction of energetic signals into membrane electrical events governs vital cellular functions, ranging from hormone secretion and cytoprotection to appetite control and hair growth. Central to the regulation of such diverse cellular processes are the metabolism sensing ATP-sensitive K+ (K(ATP)) channels. However, the mechanism that communicates metabolic signals and integrates cellular energetics with K(ATP) channel-dependent membrane excitability remains elusive. Here, we identify that the response of K(ATP) channels to metabolic challenge is regulated by adenylate kinase phosphotransfer. Adenylate kinase associates with the K(ATP) channel complex, anchoring cellular phosphotransfer networks and facilitating delivery of mitochondrial signals to the membrane environment. Deletion of the adenylate kinase gene compromised nucleotide exchange at the channel site and impeded communication between mitochondria and K(ATP) channels, rendering cellular metabolic sensing defective. Assigning a signal processing role to adenylate kinase identifies a phosphorelay mechanism essential for efficient coupling of cellular energetics with K(ATP) channels and associated functions.

Adenosine Diphosphate↗
PubMed2001

Allogeneic recombinant soluble MHC class I molecules modify urinary odor cues in rats.

The highly polymorphic genes of the major histocompatibility complex (MHC) determine, in part, the odor cues and behavior of an individual. In animal models, MHC-associated odors that regulate distinct behavior have been identified mainly in urine. However, the underlying mechanism is still not clear. Here, we show that injected recombinant soluble (rs) MHC class I molecules (DA, rsRT1.A(a) and Lewis, rsRT1.A(l)) temporarily alter urine odor of Lewis test rats (RT1.A(l)). This change in urinary signals was observed in behavioral assays using the habituation/dishabituation test and in odor signals analysed by gas chromatography (GC) and mass spectrometry (MS). Gas chromatographic analysis revealed that these altered odor signals are caused by quantitative changes of at least two nitrogen-containing urinary compounds. The results suggest that urinary olfactory cues are directly or indirectly influenced by MHC class I gene products.

Animals↗
PubMed2000

Compromised energetics in the adenylate kinase AK1 gene knockout heart under metabolic stress.

Rapid exchange of high energy carrying molecules between intracellular compartments is essential in sustaining cellular energetic homeostasis. Adenylate kinase (AK)-catalyzed transfer of adenine nucleotide beta- and gamma-phosphoryls has been implicated in intracellular energy communication and nucleotide metabolism. To demonstrate the significance of this reaction in cardiac energetics, phosphotransfer dynamics were determined by [(18)O]phosphoryl oxygen analysis using( 31)P NMR and mass spectrometry. In hearts with a null mutation of the AK1 gene, which encodes the major AK isoform, total AK activity and beta-phosphoryl transfer was reduced by 94% and 36%, respectively. This was associated with up-regulation of phosphoryl flux through remaining minor AK isoforms and the glycolytic phosphotransfer enzyme, 3-phosphoglycerate kinase. In the absence of metabolic stress, deletion of AK1 did not translate into gross abnormalities in nucleotide levels, gamma-ATP turnover rate or creatine kinase-catalyzed phosphotransfer. However, under hypoxia AK1-deficient hearts, compared with the wild type, had a blunted AK-catalyzed phosphotransfer response, lowered intracellular ATP levels, increased P(i)/ATP ratio, and suppressed generation of adenosine. Thus, although lack of AK1 phosphotransfer can be compensated in the absence of metabolic challenge, under hypoxia AK1-knockout hearts display compromised energetics and impaired cardioprotective signaling. This study, therefore, provides first direct evidence that AK1 is essential in maintaining myocardial energetic homeostasis, in particular under metabolic stress.

Adenosine Triphosphate↗
PubMed2000

Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement.

Efficient cellular energy homeostasis is a critical determinant of muscle performance, providing evolutionary advantages responsible for species survival. Phosphotransfer reactions, which couple ATP production and utilization, are thought to play a central role in this process. Here, we provide evidence that genetic disruption of AK1-catalyzed ss-phosphoryl transfer in mice decreases the potential of myofibers to sustain nucleotide ratios despite up-regulation of high-energy phosphoryl flux through glycolytic, guanylate and creatine kinase phosphotransfer pathways. A maintained contractile performance of AK1-deficient muscles was associated with higher ATP turnover rate and larger amounts of ATP consumed per contraction. Metabolic stress further aggravated the energetic cost in AK1(-/-) muscles. Thus, AK1-catalyzed phosphotransfer is essential in the maintenance of cellular energetic economy, enabling skeletal muscle to perform at the lowest metabolic cost.

Adenine↗
PubMed2000

The dual control model of male sexual response: a theoretical approach to centrally mediated erectile dysfunction.

A theoretical model of dual control of male sexual response is considered, based on the balancing of central excitation and inhibition, with individuals varying in their propensity for both sexual excitation and inhibition of sexual response. A questionnaire method for measuring propensities for sexual excitation and inhibition has been developed (SIS/SES questionnaire), resulting in one excitation factor (SES) and two inhibition factors (SIS1 and SIS2). Evidence for the existence of both inhibitory and excitatory tone is discussed. The first inhibition factor (SIS1) may be related to level of inhibitory tone and is associated with fear of performance failure. The second inhibition factor (SIS2) may be related to external threats (e.g. from within the sexual relationship). The implications for the treatment of centrally mediated erectile dysfunction are discussed, with predictions that high SIS2 individuals will respond to psychological treatment, whereas high SIS1 individuals will respond better to pharmacological methods of treatment.

Animals↗
PubMed2000

Effects of fragrance on female sexual arousal and mood across the menstrual cycle.

The effects of fragrance on sexual response in women were investigated using subjective and physiological measures of sexual arousal and of mood. Responses were obtained from female participants in three different fragrance conditions (female fragrance, male fragrance, and a "blank" or neutral substance), as they viewed erotic and sexually neutral films, and fantasized about sexual situations. Each woman was tested twice: during the midfollicular and periovulatory phases of her menstrual cycle. Menstrual cycle phase effects were apparent; self-report data indicated greater sexual arousal and more positive mood during the periovulatory than during the follicular phase. Results demonstrated a positive effect of the male fragrance on genital arousal during erotic fantasy, but this finding was apparent only during the follicular phase testing session. This effect did not appear to be mediated by any effects of fragrance on mood.

Adult↗
PubMed1999

How does the major histocompatibility complex influence behavior?

The major histocompatibility complex (MHC) encodes highly polymorphic cell surface glycoproteins that form the basis of immunological individuality. It has been postulated that MHC besides its role in immune defence also determines behavior through formation of specific odor cues. In addition several studies have implicated MHC disassortative odor and mating preferences in mice, rats, and humans. Further leading studies have suggested that mice and humans prefer to mate with MHC dissimilar individuals. Although the latter remains controversial, MHC dependent mating preferences provide a potentially important selective factor driving the polymorphisms of the MHC genes. Here we review some of the available data and hypotheses on the influence of the MHC on behavior and discuss its molecular and chemical basis.

Animals↗
PubMed1998

Purified truncated recombinant HLA-B7 molecules abrogate cell function in alloreactive cytotoxic T lymphocytes by apoptosis induction.

BACKGROUND: Soluble MHC class I molecules are ubiquitous in human body fluids, including serum, urine, sweat, and cerebrospinal fluid. However, their biological function has remained unresolved. Membrane-derived human soluble MHC molecules (soluble human leukocyte antigen; sHLA) have been shown to induce apoptosis in alloreactive cytotoxic T lymphocytes (CTL). Here we report the efficacy of recombinant soluble HLA-B7 (rsHLA-B7) to modulate T-cell function. METHODS: Primers of HLA-B7 were designed to allow amplification of a cDNA lacking the transmembrane and cytoplasmic domains yielding a truncated gene. rsHLA-B7 molecules were expressed in the human myeloma cell line 721.221 and purified by affinity chromatography using the BB7.7 mouse monoclonal antibody. CTL were generated from peripheral blood lymphocytes derived from healthy blood donors by stimulation with irradiated Epstein Barr virus-transformed HLA-B7-positive B cells. CTL were preincubated with rsHLA-B7, and cytotoxicity and apoptosis were tested according to standard procedure. RESULTS: A total of 2 x 10(6) cells/ml secreted 10 microg/ml rsHLA-B7 as determined by a conformation-dependent ELISA, suggesting that rsHLA-B7 do not require the transmembrane and cytoplasmic regions for proper folding. After purification by affinity chromatography, rsHLA-B7 induced apoptosis in anti-HLA-B7 CTL, but not in anti-HLA-A2-specific, CTL. As a consequence, allorecognition of target cells by the CTL was significantly blocked. CONCLUSION: Recombinant sHLA are sufficient binding cues for T cells, which efficiently induce apoptosis and block allorecognition of target cells by CTL. Thus, recombinant sHLA molecules may become a valuable new modality for specific immunological therapeutic intervention.

Animals↗
PubMed1998

[Histopathological findings in the proprioception of the shoulder joint].

Purpose of this study was the evaluation of distribution and morphology of mechanoreceptors in the glenohumeral joint capsule and rotator cuff in comparison to the coracoacromial ligament by means of specific immunfluorescence microscopy. The complemente joint capsules, rotator cuffs and coracoacromial ligaments of three fresh cadaver shoulder were harvesed. Serial cryostate sections were taken and alternately incubated with antiserum against neurofilament, lamin or myelin of peripheral nerves. The antibody-reaction was visualized with fluorescin lg-G. The nerve endings were photographed and computer-aided 3-dimensional reconstructions were performed. Three types of corpuscular and free nerve endings of different morphology were found in different distributions: whereas the Ruffini corpuscles were much more frequent in the coracoacromial ligament and rotator cuff, Pacini endings were predominantly found in the joint capsule. Generally corpuscular nerve endings were more frequent in the coracoacromial ligament and the rotator cuff than in the antero-inferior capsule and the number of corpuscles increased from medial to lateral within the anterior and inferior parts of the capsule. The dense ligamentous tissue was almost aneural whereas the periarticular fatty or loose connective tissue contained nerve fibres and nerve endings. In view of the results of other experimental and clinical studies the high frequency of Ruffini and Pacini endings in the rotator cuff and coracoacromial ligament suggest, that both are involved in the neurosensory control of glenohumeral stability and subacromial impingement. In contrast our findings in the joint capsule do not clearly prove, that those joint receptors predominantly maintain joint stability.

Acromioclavicular Joint↗
PubMed1998

Asking for the indicator function of bioassays evaluating soil contamination: are bioassay results reasonable surrogates of effects on soil microflora?

In evaluating the biological effect of solid materials like soil a bacterial contact assay often shows higher sensitivity than elutriate testing. Results of the Bacillus cereus contact assay for some environmental important toxicants are presented in this article. A comparison with another heterotrophic soil bacterium, Arthrobacter globiformis, shows comparable sensitivity. In a bioassay approach organisms at the level of individuals or populations are exposed to soil material to determine the significance of contaminants. An investigation that incorporates community level processes in comparison with toxicity test results provides a better understanding of the indicator function of bioassays. Comparison of soil bioassays (aqueous and solid phase) with ecological parameters demonstrates the problems in predicting ecological effects of soil contamination.

Arthrobacter↗
PubMed1997

Inflammatory infiltrate and interleukin-8 expression in the synovium of psoriatic arthritis--an immunohistochemical and mRNA analysis.

Psoriatic arthritis is an inflammatory arthropathy that ultimately can lead to joint destruction. In this study, we investigated the immunophenotypes of the inflammatory cells and the expression of interleukin-8 (IL-8), which is the hallmark chemoattractant cytokine of psoriasis in synovial membranes from patients exhibiting active psoriatic synovitis (n = 9). The tissue samples were examined by immunohistochemistry, Western blot analysis and in situ hybridisation. The inflammatory infiltrate consisted predominantly of CD3+ T lymphocytes, with a higher proportion of CD4+ than CD8+ T lymphocytes in six cases. CD3+ T lymphocytes were focally distributed near small blood vessels and the enlarged synovial intima. CD1+ interdigitating reticulum cells were not detected. CD22+ B lymphocytes and plasma cells were found in small aggregates without KiM4+ follicular dendritic cells. KiM8+ macrophages were located in the synovial intima and were distributed in a diffuse pattern near the synovial lining cells. CD15+ neutrophil granulocytes were detected in four cases. They were preferentially located in the vicinity of blood vessels and the synovial intima. IL-8 was found at a high level in the synovial lining cells and to a lesser extent in cells located in the perivascular areas. Immunofluorescence double staining showed IL-8 to be expressed in KiM8+ multinucleated giant cells, KiM8+ macrophages and CD3+ T lymphocytes. IL-8 receptor A was demonstrated in the synovial lining and in macrophages and lymphocytes. IL-8 was detected by immunoblot analysis of the synovial tissue at 8.4 kD. Employing in situ hybridisation, IL-8 mRNA was strongly and preferentially expressed in the synovial intima, as well as in macrophages and lymphocytes. The immunophenotype of the psoriatic arthritis inflammatory cells shows great similarity to the inflammatory infiltrate found in the synovial tissue of patients with rheumatoid arthritis. The preferential expression of IL-8 and IL-8 mRNA in the enlarged synovial intima and in lymphocytes and macrophages suggests that IL-8 exerts its action through activated mononuclear cells and T lymphocytes. It seems to play a role in regulating leucocyte traffic into the enlarged synovial intima and may contribute to the aggressive synovitis of patients with psoriatic arthritis.

Adult↗
PubMed1997

Chronic renal failure and sexual functioning: clinical status versus objectively assessed sexual response.

BACKGROUND: Sexual dysfunctions are common among patients with chronic renal failure. The prevalence was assessed in a population of 281 patients (20-60 years), and it was attempted to determine whether their mode of treatment (haemodialysis, peritoneal dialysis, or kidney transplantation), or biochemical and endocrine variables and neuropathy affect sexual functioning. Patients with rheumatoid arthritis served as a comparison group. METHODS: Assessment included clinical history, physical and laboratory examinations, questionnaires measuring erotosexual dysfunctions, and a psychophysiological test procedure. The latter is a laboratory method which measures, in a waking state, subjective and physiological sexual arousal. RESULTS: Men on haemodialysis or peritoneal dialysis suffered significantly more often from 'Hypoactive Sexual Desire Disorder', 'Sexual Aversion Disorder' and 'Inhibited Male Orgasm' than men with kidney transplantation or rheumatoid arthritis. Interestingly, the prevalence of 'Male Erectile Disorder' did not differ significantly between the four groups and ranged between 17 and 43%. Of the women, transplanted patients suffered significantly less from 'Hypoactive Sexual Desire Disorder' than the other three groups; the prevalence of other sexual dysfunctions did not differ between the groups. Although 'Male Erectile Disorder' and 'Female Sexual Arousal Disorder' had a relatively high prevalence there were no differences in the four groups of patients in genital responses during psychophysiological testing. Genital responses during psychophysiological assessment had no relationship to the duration of renal replacement treatment, biochemical/endocrine variables, or the presence/ absence of neuropathy. CONCLUSION: The prevalence of sexual dysfunction was high. Sexual dysfunction in men on haemodialysis or peritoneal dialysis was not so much due to erectile failure but largely to loss of sexual interest, subjectively ascribed to fatigue. The latter was also found in women on haemodialysis or peritoneal dialysis.

Adult↗
PubMed1997

An in vivo comparison of two circumferential penile strain gauges: the introduction of a new calibration method.

This study assessed the comparability of two types of penile strain gauges using both a circular and a newly developed oval calibration device. A group of 25 sexually functional participants placed both an electromechanical and an indium/gallium-in-rubber strain gauge on the penis and viewed an erotic film. The electromechanical gauge as calibrated on the circular device resulted in greater penile circumference changes than the indium/gallium-in-rubber gauge. Mean circumference changes were not different for the two strain gauges when the oval calibration device was used. The use of an oval calibration device improves ecological validity of calibration of penile strain gauges. Standard inclusion of this method in studies on male sexual response will increase comparability of research findings.

Adult↗
PubMed1996

Intrusiveness of rheumatoid arthritis on sexuality in male and female patients living with a spouse.

OBJECTIVE: To determine whether physical disability, pain, depressive mood, and criticism by the spouse are differentially related to intrusiveness of rheumatoid arthritis (RA) on sexuality in male and female patients. METHODS: Physical and psychological aspects of health were assessed in 102 male and 118 female RA patients who were living with a spouse. Patients were classified into 3 levels of intrusiveness of RA on sexuality. The data were analyzed by means of analysis of covariance and multiple regression analysis. RESULTS: Greater intrusiveness of RA on sexuality was related to greater physical disability, pain, and depression in male and female RA patients. Female patients, compared with male patients, appeared to have lower levels of mobility and self-care. Male and female patients did not differ in their level of intrusiveness of RA on sexuality. CONCLUSION: Physical disability, pain, and, to a lesser extent, depression were found to contribute to intrusiveness of RA on sexuality. It is suggested that differences in sexual motivation between men and women might have been influential in the absence of gender differences in intrusiveness.

Activities of Daily Living↗
PubMed1994

Validation of a psychophysiological waking erectile assessment (WEA) for the diagnosis of male erectile disorder.

OBJECTIVE: The aim of the present study was to evaluate a psychophysiological waking erectile assessment (WEA). WEA was designed to elicit penile responses using visual and vibrotactile stimuli and cognitive tasks (distraction and monitoring of erections). METHODS: One hundred consecutive patients with erectile dysfunction and a control group of 50 sexually functional males were examined. Clinical decision analysis, including a receiver operating characteristic (ROC) analysis, was used to determine the accuracy of WEA in predicting independent diagnostic classifications. RESULTS: Fifty percent of the patients were independently diagnosed as having pure psychogenic impotence. In 45 percent of the patients an organic factor was found. Discrimination was best in three (out of 7) WEA conditions in which film was combined with vibration. This combination of conditions resulted in a test sensitivity of 81 percent, and predictive values positive (the probability of "no organic involvement" given a penile response greater than 12 mm) ranging from 66 to 95 percent. About one third of the patients with pure psychogenic erectile dysfunction had an average response of more than 30 mm to the three conditions combining vibration and film. None of the patients with organic involvement exceeded this 30 mm criterion. Thus, the predictive value positive reached its maximum of 100 percent. CONCLUSIONS: The results suggest that WEA is an appropriate initial screening procedure, and that it is of particular value in the detection of psychogenic cases.

Decision Support Techniques↗
PubMed1994

A self psychological approach to treating the mentally ill, chemical abusing and addicted (MICAA) patient.

There is a growing population of mentally ill, chemical abusing and addicted (MICAA) patients being admitted to inpatient psychiatric units. This article proposes a self psychological approach for this population and discusses how this model addresses the underlying intrapersonal and interpersonal reasons for chemical abuse. A synopsis of self psychology is presented and applied to both addiction and MICAA patients. A self psychological treatment approach is reviewed, including specific nursing interventions.

Diagnosis, Dual (Psychiatry)↗