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Biomedical subjects

M Mayer

Publications and source records attributed to M Mayer.

At least 19 recordsLinked to original sources
PubMed2006

Porcine reproductive and respiratory syndrome virus productively infects monocyte-derived dendritic cells and compromises their antigen-presenting ability.

Dendritic cells (DC) are potent antigen-presenting cells that play an important role in inducing primary antigen-specific immune responses. However, some viruses have evolved to specifically target DC to circumvent the host's immune responses for their persistence in the host. Porcine reproductive and respiratory syndrome virus (PRRSV) causes a persistent infection in susceptible animals. Although it is generally believed that the existence of PRRSV quasispecies is partly responsible for the virus persistence, other mechanisms of immune evasion or immune suppression may also exist. Here, we studied the role of DC in PRRSV persistence and immune suppression. Our results showed that PRRSV underwent a productive replication in pig monocyte-derived DC (Mo-DC) as measured by both immunofluorescence staining of viral nucleocapsid protein and virus titration assays, leading to cell death via both apoptosis and necrosis mechanisms. Additionally, PRRSV infection of Mo-DC resulted in reduced expression of MHC class I, MHC class II, CD14 and CD11b/c. This was in agreement with the impaired mixed lymphocyte reaction of PRRSV-infected Mo-DC compared to that of mock-infected Mo-DC. We also examined the cytokine profiles of PRRSV-infected Mo-DC using a quantitative ELISA method. Results indicated that no apparent change in the levels of IL-10, IL-12 and IFN-gamma was detected. Taken together, our data demonstrate that PRRSV productively infects Mo-DC and impairs the normal antigen presentation ability of Mo-DC by inducing cell death, down-regulating the expression of MHC class I, MHC class II, CD11b/c and CD14 and by inducing minimal Th1 cytokines.

Animals↗
PubMed2006

Role of AMT1;1 in NH4+ acquisition in Arabidopsis thaliana.

AtAMT1;1 was the founding member of the family of AMT/Rh ammonium transporters and accounts for about one third of the total ammonium absorption in the roots of the model plant Arabidopsis. Recent evidence suggested that at least some AMT/Rh proteins are NH3 gas channels. In order to evaluate the transported form of ammonium in AtAMT1;1, the protein was functionally expressed in Xenopus oocytes. AtAMT1;1 elicited NH4+ and methylammonium (MeA+) inward currents that saturated in a voltage-dependent manner with a half maximal concentration of 2.7 +/- 1.6 microM for NH4+ and 5.0 +/- 0.7 microM for the transport analogue methylammonium. AtAMT1;1 was plasma membrane localized and expressed in the root cortex and epidermis, including root hairs. The AtAMT1;1-GFP fusion construct under control of its endogenous promoter revealed additional localization of the protein in the pericycle, in the leaf epidermis, and in mesophyll cells. The functional data and its localization suggest that AtAMT1;1 participates in concentrative NH4+ acquisition in roots, in long-distance transport to the shoots, and in re-uptake of apoplastic NH4+ that derives from photorespiration in shoots.

Arabidopsis↗
PubMed2006

Autosomal-recessive forms of demyelinating Charcot-Marie-Tooth disease.

Autosomal-recessive forms of Charcot-Marie-Tooth (ARCMT) account for less than 10% of the families in the European CMT population but are more frequent in the Mediterranean basin and the Middle East because of more widespread consanguinity. Until now, demyelinating ARCMT was more extensively studied at the genetic level than the axonal form. Since 1999, the number of localized or identified genes responsible for demyelinating ARCMT has greatly increased. Eight genes, EGR2, GDAP1, KIAA1985, MTMR2, MTMR13, NDRG1, PRX, and CTDP1, have been identified and two new loci mapped to chromosomes 10q23 and 12p11-q13. In this review, we will focus on the particular clinical and/or neuropathological features of the phenotype caused by mutations in each of these genes, which might guide molecular diagnosis.

Cataract↗
PubMed2005

Cystic leukoencephalopathy without megalencephaly: a distinct disease entity in 15 children.

OBJECTIVE: To describe a distinctive syndrome of nonprogressive encephalopathy, normo- or microcephaly, and early onset of severe psychomotor impairment in 15 white patients, including two siblings and two first cousins. METHODS AND RESULTS: MRI revealed bilateral cysts in the anterior part of the temporal lobe and white matter abnormalities with pericystic abnormal myelination and symmetric lesions in frontal and occipital periventricular regions. None of the usual inborn errors of metabolism/infectious diseases associated with leukoencephalopathy and bilateral anterior temporal lobe cysts were detected. CONCLUSIONS: These patients' clinical signs and cranial MRI abnormalities are strikingly similar and may represent a distinctive disease with autosomal-recessive inheritance: cystic leukoencephalopathy without megalencephaly.

Adolescent↗
PubMed2005

[Therapy for organic erectile dysfunction].

Erectile dysfunction is a common disease of men. It is associated with various comorbidities and has a prevalence of about 50% in the 7th decade. Erectile dysfunction often affects the quality of life of the patient and his partner, and it is very important to offer adequate therapy that respects the individual circumstances of each patient. The mandatory diagnostic work-up includes a medical and psychosexual history, a physical examination and routine laboratory tests. Besides psychotherapy, oral pharmacotherapy with oral PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) is the most effective therapy for erectile dysfunction and is superior to centrally acting drugs (yohimbine). In cases of failure or contraindication of oral pharmacotherapy, local pharmacotherapy is the second-line therapy. The third-line options are vacuum erectile devices and penile implants, and these have a high patient satisfaction. New therapeutic strategies such as anti-serotoninergic substrates and growth hormone offer a promising future for the therapy of erectile dysfunction but remain to be evaluated.

Erectile Dysfunction↗
PubMed2005

Influence of operational conditions on the performance of a mesh filter activated sludge process.

Recently, a new type of wastewater treatment system became the focus of scientific research, the mesh filter activated sludge system. It is a modification of the membrane bioreactor where a membrane filtration process serves to separate the sludge from the purified effluent. The difference is that a mesh filter is used instead of the membrane. Due to the much larger pore size of the mesh, the effluent is not of the same excellent quality as with membrane bioreactors. Nevertheless, it still resembles the quality of the now most widely used standard treatment system, where settling tanks are used to retain the activated sludge. At the same time, the new system features all the other advantages of membrane bioreactors including elevated sludge concentrations resulting in decreased volumina of basins and complete substitution of the settling tank. Therefore, this process presents a potential future alternative where a small footprint of the plant is required. However, so far only a few preliminary studies on this innovative process type have been done. In this paper, the effects of suspended solids concentration, flux rate as well as aeration rate on the effluent quality are discussed. Furthermore, the characteristic of the sludge floc was identified as a factor of vital importance. Therefore, another influencing parameter, the food to microorganism (F/M) ratio, which is known to have a significant effect on floc characteristics, was studied. The main result demonstrated that the process was very effective under most of the operation conditions. The suspended solids concentration in the effluent was below 12 mg l(-1), the average COD in the effluent was between 24 and 45 mg l(-1) and the BOD(5) was lower than 5 mg l(-1). High flux rates of up to 150 l m(-2)h(-1) were also achieved.

Bioreactors↗
PubMed2005

A comparison of regression interval mapping and multiple interval mapping for linked QTL.

Regression interval mapping and multiple interval mapping are compared with regard to mapping linked quantitative trait loci (QTL) in inbred-line cross experiments. For that purpose, a simulation study was performed using genetic models with two linked QTL. Data were simulated for F(2) populations of different sizes and with all QTL and marker alleles fixed for alternative alleles in the parental lines. The criteria for comparison are power of QTL identification and the accuracy of the QTL position and effect estimates. Further, the estimates of the relative QTL variance are assessed. There are distinct differences in the QTL position estimates between the two methods. Multiple interval mapping tends to be more powerful as compared to regression interval mapping. Multiple interval mapping further leads to more accurate QTL position and QTL effect estimates. The superiority increased with wider marker intervals and larger population sizes. If QTL are in repulsion, the differences between the two methods are very pronounced. For both methods, the reduction of the marker interval size from 10 to 5 cM increases power and greatly improves QTL parameter estimates. This contrasts with findings in the literature for single QTL scenarios, where a marker density of 10 cM is generally considered as sufficient. The use of standard (asymptotic) statistical theory for the computation of the standard errors of the QTL position and effect estimates proves to give much too optimistic standard errors for regression interval mapping as well as for multiple interval mapping.

Chromosome Mapping↗
PubMed2004

Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations.

Mutations in LMNA, the gene that encodes nuclear lamins A and C, cause up to eight different diseases collectively referred to as "laminopathies." These diseases affect striated muscle, adipose tissue, peripheral nerve, and bone, or cause features of premature aging. We investigated the consequences of LMNA mutations on nuclear architecture in skin fibroblasts from 13 patients with different laminopathies. Western-blotting showed that none of the mutations examined led to a decrease in cellular levels of lamin A or C. Regardless of the disease, we observed honeycomb nuclear structures and nuclear envelope blebs in cells examined by immunofluorescence microscopy. Concentrated foci of lamin A/C in the nucleoplasm were also observed. Only mutations in the head and tail domains of lamins A and C significantly altered the nuclear architecture of patient fibroblasts. These results confirm that mutations in lamins A and C may lead to a weakening of a structural support network in the nuclear envelope in fibroblasts and that nuclear architecture changes depend upon the location of the mutation in different domains of lamin A/C.

Adolescent↗
PubMed2004

[Congenital myasthenic syndromes due to mutations in the rapsyn gene].

Congenital myasthenic syndromes (CMS) are genetic diseases characterized by dysfunctional neuromuscular transmission and usually start during the neonatal period. Most are due to postsynaptic abnormalities, specifically to mutations in the acetylcholine receptor (AChR) genes. In 2002, the group of A Engel reported the first cases of CMS with mutations in the gene coding rapsyn, a postsynaptic molecule which stabilizes AChR aggregates at the neuromuscular junction. Since this first publication, more than 30 other cases, including six in France, have been reported. Study of these published cases allows us to distinguish three classes of phenotypes: 1) severe neonatal cases; 2) more benign cases, starting during infancy; 3) cases with facial malformations, involving Jewish patients originating from the Near-East. Comparison of the observations of other groups with our own has led us to the following conclusions: the N88K mutation is frequent (homozygous in 50% of cases); besides the N88K mutation, the second mutation varies considerably; heterozygous allelic cases (N88K + another mutation) are severe; there is probably a founder effect in the European population. There is phenotypic variability in the homozygous N88K cases, with benign cases and severe cases of early expression. A Engel and colleagues report that the seven cases of benign CMS with facial malformation, previously described in the Jewish population of Iraq and Iran, were caused by mutation in the promoter region of the rapsyn gene.

Alleles↗
PubMed2004

Parasuicide online: Can suicide websites trigger suicidal behaviour in predisposed adolescents?

The present case report describes a 17-year-old female who explicitly visited suicide web forums, where she researched reliable suicide methods, contacted an anonymous user and purchased substances for the implementation of suicide. The risk of Internet use by vulnerable youth is discussed. Psychiatric exploration should include questions of manner and frequency of media use. The application of media guidelines for suicide prevention is demanded for websites, as are accessible self-help sites for suicidal persons targeted to youthful users.

Adolescent↗
PubMed2003

Risperidone-associated steatohepatitis and excessive weight-gain.

We report on a 17-year-old girl who developed steatohepatitis and marked weight gain during risperidone treatment for paranoid psychosis. Viral, metabolic, and other causes of liver disease were excluded. Although the exact mechanism of antipsychotic associated weight gain is unclear, the impact of risperidone on the serotonergic system and on neuropeptide Y, a stimulator of food intake, might be implicated in the development of obesity. Additionally, weight gain-related hyperleptinemia could be a link between overweight and hepatotoxicity via cytokines. Physicians should routinely monitor body weight, liver function, fasting blood glucose, and lipid profiles in children and adolescents at the beginning of risperidone therapy. Additionally, patients complaining about weight gain should be monitored more carefully during the maintenance phase.

Adolescent↗
PubMed2002

Treatment of cluster headache with topiramate: effects and side-effects in five patients.

We report on clinical experience with topiramate in the prophylactic treatment of three patients with chronic and two patients with episodic, otherwise therapy-resistant, cluster headache. Patients were treated with daily doses of 75-200 mg topiramate. Topiramate was effective in three patients but proved ineffective and also caused intolerable side-effects in two patients. Topiramate may have prophylactic properties for treating cluster headache at lower doses than needed in epilepsy therapy, but its clinical value is limited due to central nervous system side-effects.

Adult↗
PubMed2002

Impaired response to insulin associated with protein kinase C in chronic fructose-induced hypertension.

A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations in rats. Our hypothesis was that an increase in protein kinase C (PKC) activation, reported in the acute period of fructose overload, and an impaired vessel's response to vasoactive substances contribute to maintain elevated blood pressure levels in the chronic period. The aims of this study were to investigate in this animal model of hypertension: (1) if the increase in PKC activation was also found in the chronic stage; (2) the involvement of nitric oxide and insulin in the vessel's response; and plasma atrial natriuretic factor and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the effects of: PKC-stimulator 12,13-phorbol dibutyrate, phenylephrine, insulin, nitric oxide synthase-inhibitor NG-nitro-L-arginine methyl esther (L-NAME) and PKC-inhibitor Calphostin C on aortic rings responses of Sprague-Dawley rats: fructose-fed and control. The fructose-fed group showed higher contractility to 12,13-phorbol dibutyrate than the control group in aortic rings pre-incubated with insulin, and this difference disappeared with L-NAME. The response to phenylephrine in rings pre-incubated with Calphostin C was decreased in the fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates than controls. In conclusion, chronic fructose feeding seems to develop an impaired response to insulin, dependent on nitric oxide, suggesting a PKC alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric oxide, would behave as compensatory mechanisms in response to high blood pressure.

Animals↗
PubMed2002

Regulation of cyclooxygenase activity and progesterone production in the rat corpus luteum by inducible nitric oxide synthase.

This study explores interactions between the nitric oxide synthase (NOS) and the cyclooxygenase (COX) pathways in the regulation of progesterone production in early corpus luteum cells of rats. Nitric oxide (NO), prostaglandin E (PGE) and progesterone production was analysed in luteal cells of the rat corpus luteum exposed to inhibitors of non-specific NOS, inhibitors of inducible NOS (iNOS) and inhibitors of COX. Equine chorionic gonadotrophin (eCG)/hCG-primed rat corpus luteum cells produced NO, PGE and progesterone in a linear manner during 66 h of culture. Exposure of the cells to the non-specific NOS inhibitor, N(omega)-nitro-L-arginine (0.15 mmol l(-1)) for 48 h reduced NO, PGE and progesterone production to 21, 32 and 60% of that of the controls, respectively (P < 0.05 to P < 0.01). Another non-specific NOS inhibitor, N(omega)-methyl-L-arginine, produced similar inhibitions. Exposure of the cultured cells to S-ethylisothiourea (1 mmol l(-1)), a selective inhibitor of iNOS, suppressed the production of NO by 63%, PGE by 69% and progesterone by 48%. These findings indicate that production of PGE is regulated partly by iNOS, and that progesterone is probably regulated indirectly by the secondary changes in PGE. The addition of arachidonic acid to N(omega)-methyl-L-arginine-treated cells resulted in a significant increase in PGE and progesterone production (273 and 186%, respectively) without stimulating NO production. In contrast to the regulation exerted by the NO system on COX activity, the COX system does not modulate NO production in this model. This notion stems from the observation that the COX inhibitors acetylsalicylic acid (5 mmol l(-1)) and indomethacin (5 micromol l(-1)) suppressed PGE by 86 and 89%, respectively, and progesterone by 34 and 57%, respectively, but failed to inhibit NO production. The results from the present study indicate that iNOS-mediated NO production is involved in stimulating PGE synthesis in rat luteal cells, which may upregulate progesterone production.

Animals↗
PubMed2002

Clinical neurokinesiology of spastic gait.

Locomotor control requires a spatiotemporal coordination of passive and active forces across the movement system. Both anticipatory and reactive strategies operate in locomotor control. Mammalian locomotion is based on a rhythmic, "pacemaker" activity of spinal stepping generators. Reflex modification of the gait cycle is task-, context- and especially phase-dependent. In spasticity, together with disturbed supraspinal control, the phase-dependent reflex modulation of the gait cycle is severely impaired and there is altered modulation and timing of muscle activation and relaxation during voluntary movement. There is also a poor correlation between EMG activity and tension development in the spastic muscle. The tension increases without sufficient muscle activation and disconnection and dyscoordination between muscle activation, tension development and motor performance develops. The pattern of muscle activation and the development of increased muscle tone in patients with spasticity may be dramatically different in active movement from that observed in clinical testing of the passive muscles. Strategies used in the functional treatment of spasticity should be aimed at training and activating residual motor function, suppression of pathological and unfavourable movement and postural patterns and preventing secondary complications. In the 1990s a number of new specific instrumental methods and technical equipment supporting gait rehabilitation in patients with CNS lesions were developed: rhythmic auditory stimulation and other types of rhythmic stimulation, partial body support, usually with treadmill walking, complex orthotic support of bipedal locomotion, multichannel functional electrical stimulation, usually with programmable computer control, and advanced gait trainers. In therapy of spastic gait, the functional goals should be clearly determined from the kinesiological point of view of the impairment, and the impact on disability and handicap should be considered and a multidisciplinary approach is essential. (Ref. 139.)

Central Nervous System Diseases↗