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Biomedical subjects

Thomas Müller

Publications and source records attributed to Thomas Müller.

At least 127 records · Page 7Linked to original sources
PubMed2002

Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson's disease.

Several lines of evidence indicate that immune mechanisms are involved in the pathogenesis of neurodegenerative disorders. Activated immunocompetent cells and inflammatory cytokines are present in affected brain regions in patients with Alzheimer's (AD) and Parkinson's disease (PD). For AD biochemical and pathological data are supported by genetic studies identifying risk alleles for polymorphisms in regulatory regions of the interleukin-1 alpha (IL-1 alpha-889) and interleukin-1 beta (IL-1 beta-511) gene, respectively. The partially overlapping pathology and inflammatory reaction pattern between AD and PD led us to investigate these polymorphisms in a large sample of 295 German PD patients and 270 healthy controls. We found T in position -511 in the IL-1 beta gene more frequent in patients compared to controls (chi(2)=4.44, P=0.034). For the IL-1 alpha-889 polymorphism no significant difference between patients and controls was observed.

Aged↗
PubMed2002

Kinetics of maternal immunity against rabies in fox cubs (Vulpes vulpes).

BACKGROUND: In previous experiments, it was demonstrated that maternal antibodies (maAb) against rabies in foxes (Vulpes vulpes) were transferred from the vixen to her offspring. However, data was lacking from cubs during the first three weeks post partum. Therefore, this complementary study was initiated. METHODS: Blood samples (n = 281) were collected from 64 cubs (3 to 43 days old) whelped by 19 rabies-immune captive-bred vixens. Sera was collected up to six times from each cub. The samples were analysed by a fluorescence focus inhibition technique (RFFIT), and antibody titres (nAb) were expressed in IU/ml. The obtained data was pooled with previous data sets. Subsequently, a total of 499 serum samples from 249 cubs whelped by 54 rabies-immune vixens were fitted to a non-linear regression model. RESULTS: The disappearance rate of maAb was independent of the vixens' nAb-titre. The maAb-titre of the cubs decreased exponentially with age and the half-life of the maAb was estimated to be 9.34 days. However, maAb of offspring whelped by vixens with high nAb-titres can be detected for longer in RFFIT than that of offspring whelped by vixens with relatively low nAb-titres. At a mean critical age of about 23 days post partum, maAb could no longer be distinguished from unspecific reactions in RFFIT depending on the amount of maAb transferred by the mother. CONCLUSIONS: The amount of maAb cubs receive is directly proportional to the titre of the vixen and decreases exponentially with age below detectable levels in seroneutralisation tests at a relatively early age.

Age Factors↗
PubMed2002

The homeodomain factor lbx1 distinguishes two major programs of neuronal differentiation in the dorsal spinal cord.

Dorsal horn neurons in the spinal cord integrate and relay sensory information. Here, we show that the expression of the homeobox gene Lbx1 distinguishes two major neuronal classes generated in the dorsal spinal cord. The Lbx1(-) (class A) and Lbx1(+) (class B) neurons differ in their dependence on roof plate BMP signals for specification and settle in the deep and superficial dorsal horn, respectively. Lbx1 misexpression blocks the differentiation of class A neurons. Conversely, in Lbx1 mutant mice, class B neurons assume the identity of class A neurons. As a consequence, the morphology and neuronal circuitry of the dorsal horn are aberrant. We conclude that Lbx1 distinguishes two major neuronal classes in the dorsal spinal cord and is an important determinant of their distinct differentiation programs.

Afferent Pathways↗
PubMed2002

Possible strategies toward the elusive tetraaminodisilene.

In this paper we predict, using quantum mechanical calculations, which diaminosilylenes would dimerize to produce strongly bound tetraaminodisilenes, which so far have proven to be elusive. The central idea is that diaminosilylenes with a small singlet-triplet energy difference would dimerize to strongly bonded disilenes. Calculations at the B3LYP/6-311++G(3df,2p)//MP2/6-31G(d) level of theory showed that the energy difference between the singlet and the triplet states (DeltaE(ST)) of diaminosilylenes (R(2)N)(2)Si: (1) strongly depends on (i) the twist angle varphi between the SiN(2) and the R(2)N planes and (ii) the NSiN bond angle alpha at the divalent silicon. DeltaE(ST) decreases with increased twisting (larger varphi) and with widening of alpha. DeltaE(ST) is reduced from 70.7 kcal mol(-1) for planar (H(2)N)(2)Si: (1a) to DeltaE(ST) = 21.7 kcal mol(-1) when varphi is held at 90 degrees. Likewise, the bicyclic diaminosilylenes 1,4-diaza-7-silabicyclo[2.2.1]hepta-7-ylidene and 1,5-diaza-9-silabicyclo[3.3.1]nona-9-ylidene (4a,b), with the nitrogens in the bridgehead positions (varphi = 90 degrees), have DeltaE(ST) values of 45.1 and 38.3 kcal mol(-1), respectively. When dimerized, these silylenes form strongly bonded disilenes 5 (E(dim) = -32.2 kcal mol(-1) (4a) and -41.3 kcal mol(-1) (4b)) with Si=Si bond lengths of 2.239 A (4a) and 2.278 A (4b) (MP2/6-31G(d)//MP2/6-31G(d)). These theoretical predictions pave the way for the synthesis of the first strongly bonded tetraaminodisilene. Due to the steric requirements, also silyl substitution at nitrogen has a significant effect on DeltaE(ST) and [(H(3)Si)(2)N](2)Si: (1d) is predicted to form a stable Si=Si bonded dimer (E(dim)= -24.1 kcal mol(-1)). However, the larger size of the Me(3)Si substituent prevents the formation of a Si=Si bonded dimer of [(Me(3)Si)(2)N](2)Si: (1e).

Journal Article↗
PubMed2002

Protection against anoikis and down-regulation of cadherin expression by a regulatable beta-catenin protein.

beta-Catenin signaling plays a key role in a variety of cellular contexts during embryonic development and tissue differentiation. Aberrant beta-catenin signaling has also been implicated in promoting human colorectal carcinomas as well as a variety of other cancers. To study the molecular and cellular biological functions of beta-catenin in a controlled fashion, we created a regulatable form of activated beta-catenin by fusion to a modified estrogen receptor (ER) ligand binding domain (G525R). Transfection of tissue culture cells with expression vectors encoding this hybrid protein allows the signal transduction function of beta-catenin to be induced by the synthetic estrogen, 4-hydroxytamoxifen, leading to regulated activation of a beta-catenin-lymphocyte enhancer-binding factor-dependent reporter gene as well as induction of endogenous cyclin D1 expression. The activation of ER-beta-catenin signaling rescues RK3E cells from anoikis and correlates with an increased phosphorylation of mitogen-activated protein kinase. The inhibition of anoikis by ER-beta-catenin can be abolished by a mitogen-activated protein kinase pathway inhibitor, PD98059. Evidence is also provided to show that ER-beta-catenin down-regulates cadherin protein levels. These findings support a key role for activated beta-catenin signaling in processes that contribute to tumor formation and progression.

Animals↗
PubMed2002

Developmental changes in cerebral autoregulatory capacity in the fetal sheep parietal cortex.

We validated laser Doppler flowmetry (LDF) for long-term monitoring and detection of acute changes of local cerebral blood flow (lCBF) in chronically instrumented fetal sheep. Using LDF, we estimated developmental changes of cerebral autoregulation. Single fibre laser probes (0.4 mm in diameter) were implanted in and surface probes were placed on the parietal cerebral cortex at 105 +/- 2 (n = 7) and 120 +/- 2 days gestational age (dGA, n = 7). Basal lCBF was monitored over 5 days followed by a hypercapnic challenge (fetal arterial partial pressure of CO(2), P(a,CO2): 83 +/- 3 mmHg) during which lCBF changes obtained by LDF were compared to those obtained with coloured microspheres (CMSs). Mean arterial blood pressure (MABP) was increased and decreased using phenylephrine and sodium nitroprusside at 110 +/- 2 and 128 +/- 2 dGA. Intracortical and cortical surface laser probes gave stable measurements over 5 days. The lCBF increase during hypercapnia obtained by LDF correlated well with flows obtained using CMS (r = 0.89, P < 0.01). The signals of intracortical and surface laser probes also correlated well (r = 0.91, P < 0.01). Gliosis of 0.35 +/- 0.06 mm around the tip of intracortical probes did not affect the measurements. The range of MABP over which cerebral autoregulation was observed increased from 20-48 mmHg at 110 dGA to 35 to > 95 mmHg at 128 dGA (P < 0.05). Since MABP increased from 33 to 54 mmHg over this period (P < 0.01), the range between the lower limit of cerebral autoregulation and the MABP increased from 13 mmHg at 110 dGA to 19 mmHg at 128 dGA (P < 0.01). LDF is a reliable tool to assess dynamic changes in cerebral perfusion continuously in fetal sheep.

Animals↗
PubMed2002

Persistent bissilylated arenium ions.

A series of bissilylated arenium ions 1 with different substitution patterns on the aryl ring have been synthesized by hydride abstraction from 2-aryl-substituted 2,6-dimethyl-2,6-disilaheptanes (2) via transient silylium ions. The arenium ions have been identified by their characteristic NMR chemical shifts, (delta(29)Si=19.1-25.6, delta(13)C(ipso) =89.0-102.4, delta(13)C(ortho)=160.9-182.0, delta(13)C(meta)=132.5-146.9, delta(13)C(para)=150.2-169.9) supported by quantum mechanical calculations of structures, energies, and magnetic properties at the B3LYP/6-311G(d,p)//B3LYP/6-31G(d) + DeltaZPVE level of theory. The calculations clearly reveal the charge dispersing and stabilizing effect of the silyl substituents in arenium ions 1. The bissilylated benzenium ion 1a is more stable than the parent benzenium ion (C(6)H(7)(+)) by 37.6 kcalmol(-1). The synthesized arenium ions 1 are stable in solution at room temperature for periods ranging from a few hours to days. This unusual stability is attributed to: 1) the thermodynamic stabilization of the arenium ion by two beta-silyl substituents and 2) the essentially non-nucleophilic reaction conditions (the use of the weakly coordinating [B(C(6)F(5))(4)](-) anion and aromatic hydrocarbons as solvents). Addition of stronger nucleophiles than aromatic hydrocarbons (for example, acetonitrile) results in desilylation of the arenium ion 1 and recovery of the 2-aryl-2,6-disilaheptane moiety.

Journal Article↗
PubMed2002

Budipine provides additional benefit in patients with Parkinson disease receiving a stable optimum dopaminergic drug regimen.

BACKGROUND: The complex pharmacological profile of the antiparkinsonian drug budipine influences neurotransmission beyond the dopaminergic system. Previous studies have demonstrated the therapeutic efficacy of budipine on motor symptoms in insufficiently treated patients with Parkinson disease. OBJECTIVE: To demonstrate the efficacy of 20 mg of budipine, 3 times daily, in addition to a stable, prior, optimum-titrated dopaminergic substitution consisting of a combination of levodopa and a dopa decarboxylase inhibitor, bromocriptine mesylate, and optional selegiline hydrochloride in 99 patients with idiopathic Parkinson disease in a multicenter, double-blind, placebo-controlled trial. RESULTS: Budipine significantly (P<.001) decreased the Columbia University Rating Scale sum score (median, 15.0; 95% confidence interval, 11.3-17.0) compared with placebo (median, 4.3; 95% confidence interval, 3.0-7.5) at study end point. Budipine reduced Columbia University Rating Scale subscores for tremor, rigidity, and akinesia. CONCLUSION: The additional application of budipine provides further therapeutic benefit in subjects with Parkinson disease receiving a stable, prior, optimum-titrated dopaminergic drug regimen because of the hypothetical positive impact of budipine on altered nondopaminergic neurotransmission in patients with Parkinson disease.

Adult↗
PubMed2002

Ethoxylated rapeseed oil derivatives as novel adjuvants for herbicides.

Ethoxylates of rapeseed oil and of methylated rapeseed oil were synthesized and tested as adjuvants for 2,4-D and phenmedipham. Provided they had less than 6 units of ethylene oxide (EO), 1.0 to 10 g litre(-1) ethoxylates in water induced droplet spreading on barley leaves. In an acetone-based medium all derivatives strongly promoted the foliar uptake of 2,4-D, with no clear influence of the ethoxylation degree. In the same medium there was a negative influence of ethoxylate chain length on the foliar uptake of phenmedipham. In a water-based medium, phenmedipham applied with rapeseed oil emulsified with ethoxylated (20 EO) rapeseed oil displayed uptake rates close to a commercial preparation. The same was true for phenmedipham applied with ethoxylated (2 EO) methylated rapeseed oil. In bioassays, phenmedipham prepared with methylated rapeseed oil emulsified with ethoxylated (20 EO) rapeseed oil was as efficacious on barley as a commercial formulation. The same was true for phenmedipham prepared with ethoxylated (2 EO) methylated rapeseed oil. However, neither rapeseed oil nor methylated rapeseed oil emulsified with ethoxylated (2 EO) methylated rapeseed oil conferred good efficacy to phenmedipham. Hence, ethoxylated rapeseed oil derivatives are promising adjuvants or formulants for herbicides.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2002

Neuroleptic malignant-like syndrome after rapid switch from bromocriptine to pergolide.

Neuroleptic malignant-like syndrome (NMLS) occurred after rapid switch from bromocriptine to pergolide in a Parkinsonian patient. Although the underlying mechanisms are as yet obscure, we hypothesize that differences in dopamine receptor affinities between bromocriptine and pergolide may be involved. Long-term treatment with bromocriptine may thus have induced plastic changes in intracellular signal processing in the nigrostriatal system, which resulted in reduced dopaminergic efficacy of pergolide. We recommend vigilant outpatient supervision during performance of rapid switchover from one dopamine agonist to another in advanced Parkinson's disease or in subjects with predisposing factors for onset of a neuroleptic malignant syndrome.

Bromocriptine↗
PubMed2002

Apomorphine delays simple reaction time in Parkinsonian patients.

BACKGROUND: Parkinsonian patients have difficulty in the preparation and execution of movements, which translate into delayed performance of simple reaction time (SRT) paradigms. OBJECTIVE: To examine short-term effects of an acute subcutaneous injection of the dopamine agonist apomorphine on the results of a SRT task. METHODS: We studied a SRT paradigm in 26 non-fluctuating idiopathic Parkinsonian patients, before and 30, 60, 90 min after administration of apomorphine. RESULTS: The reaction time (RT) was significantly delayed after apomorphine injection. We found no significant change in movement time (MT). CONCLUSION: Delay of RT and the lack of response of MT to apomorphine administration may result from the sedative effects of apomorphine, overstimulation of postsynaptic dopaminergic receptors with subsequent inhibition of prefrontal cholinergic neurotransmission, and at least partial binding of apomorphine to presynaptic dopaminergic autoreceptors, which cause inhibition of locomotor activity. We suggest that future studies testing the capacity for reaction in Parkinsonian patients should consider the exact timing of the delivery of dopamine substituting drugs prior to the test.

Adult↗
PubMed2002

Arterial and ductus venosus Doppler in fetuses with absent or reverse end-diastolic flow in the umbilical artery: correlation with short-term perinatal outcome.

BACKGROUND: High perinatal morbidity and mortality rates have been reported in association with absent or reverse end-diastolic flow velocities in the umbilical artery. Doppler of fetal venous blood flow might be a helpful instrument for predicting fetal outcome. However, clinical data addressing this issue are rare. Thus, the aim of this study was to evaluate arterial and ductus venosus blood flow velocities as a predictor of short-term outcome in fetuses with umbilical absent or reverse end-diastolic flow velocities. METHODS: Thirty-five high-risk single pregnancies complicated by umbilical absent or reverse end-diastolic flow velocities were monitored by serial measurement of the pulsatility index of the umbilical artery, middle cerebral artery, and ductus venosus waveforms over a period of 1-75 days. RESULTS: The mean observation period between first detection of an umbilical absent or reverse end-diastolic flow velocity and delivery was 8.9 days. A significant correlation was found between parameters of short-term perinatal outcome (art. pH, art. base excess, development of intraventricular hemorrhage, mortality) and end-diastolic flow velocity waveform or pulsatility index of the ductus venosus waveform, but not with arterial Doppler parameters. Gestational age proved to be the best predictor for duration of assisted ventilation and development of respiratory distress syndrome. CONCLUSIONS: Our results indicate that in high-risk pregnancies with umbilical absent or reverse end-diastolic flow velocities, determination of blood flow velocities in the ductus venosus is a useful additional parameter for prediction of fetal outcome and for timing delivery.

Blood Flow Velocity↗
PubMed2002

HSP-25 and HSP-90 stabilize Na,K-ATPase in cytoskeletal fractions of ischemic rat renal cortex.

BACKGROUND: We recently designed an in vitro system based on differential Triton-extractability of Na,K-ATPase from the cytoskeletal protein fraction isolated from rat renal cortex after renal ischemia. In the present study, we hypothesized that heat shock protein (HSP)-70, HSP-25 and HSP-90 work synergistically to stabilize the cytoskeletal anchorage of Na,K-ATPase. METHODS: Cellular proteins were fractionated by differential centrifugation into cytoskeletal pellets (I-PEL) obtained early (exhibiting abnormally high Triton extractability of Na,K-ATPase) and non-cytoskeletal supernatants (R-SUP) obtained late (exhibiting high abundance of HSP) after renal ischemia. For assessment of the role of HSP-70, HSP-25 and HSP-90 upon in vitro re-compartmentalization, I-PEL was either incubated in R-SUP with/without HSP antibodies, or in buffer with/without HSPs at different titers and combinations. Effects were evaluated by changes of Triton extractability of Na,K-ATPase after co-incubation. RESULTS: R-SUP was shown to contain significant amounts of HSP-70, HSP-25 and HSP-90. Incubation of I-PEL in R-SUP reduced Triton extractability of Na,K-ATPase. Addition of antibodies against each HSP significantly abolished these effects of R-SUP. Incubation of I-PEL with purified HSP-70, HSP-25 or HSP-90 each partly reproduced the effects of R-SUP, whereas the combination of all three HSP demonstrated a strong and more than additive effect on the cytoskeletal stabilization of Na,K-ATPase. CONCLUSIONS: The molecular mechanisms responsible for postischemic re-compartmentalization of Na,K-ATPase in rat renal cortex likely involves interactions between HSP-70, HSP-25 and HSP-90, stress proteins known to be induced in the ischemic kidney.

Acute Kidney Injury↗
PubMed2002

Kinetics of gene expression profiling in Swiss 3T3 cells exposed to aqueous extracts of cigarette smoke.

Previous studies from different laboratories have demonstrated that cigarette smoke (CS) harbours a strong oxidative stress potential, which broadly impacts exposed cells. Many of these studies have been devoted to identifying differentially expressed genes in exposed cells. Emerging DNA microarray techniques provide a sophisticated tool to characterize gene expression on a more comprehensive basis. Here, we report on kinetic studies performed to characterize gene expression profiles in Swiss 3T3 cells exposed to aqueous extracts of CS ('smoke-bubbled phosphate-buffered saline') up to 24 h through glass chips containing 513 different cDNA probes. The results obtained display a distinct expression pattern of up regulated and repressed genes, which was most evident after 4-8 h of exposure. The CS-related stress response involves mainly antioxidant response genes coding for, e.g. haem oxygenase-1 (HO-1), metallothionein 1/2 (MT1/2) and heat shock proteins (HSPs); genes coding for transcription factors, e.g. JunB and CAAT/enhancer binding protein (C/EBP); cell cycle-related genes, e.g. gadd34 and gadd45; and notably, genes described as mediators of an inflammatory/immune-regulatory response, e.g. st2, kc and id3. From a kinetic perspective, the stress response is characterized by the synchronized up regulation of antioxidant pathways, e.g. as reflected by the co-ordinated expression of ho-1 and ferritin. This expression pattern is obviously orchestrated by stress-responsive transcription factors, as exemplified by the early and strong expression of junB and c/ebp. Interestingly, among the 10 most up regulated genes are five which are known to counteract stress brought about by peroxynitrite. Altogether, these results demonstrate that CS induces a distinct signature of differential gene expression in exposed cells.

3T3 Cells↗
PubMed2002

Renal function in meningomyelocele: risk factors, chronic renal failure, renal replacement therapy and transplantation.

PURPOSE OF REVIEW: This review is on renal function in patients with spina bifida. Risk factors for renal injury as well specific issues concerning the treatment of chronic renal failure, renal replacement therapy and kidney transplantation are discussed. Relevant work published earlier than 2000 is also considered because of a lack of recent literature. RECENT FINDINGS: Data from adult and paediatric surveys show renal damage to be the single most prevalent cause of morbidity and mortality; even in children, 30-40% exhibit evidence of renal damage. Additional factors such as chronic infection and stone formation will then render the kidney more vulnerable to progressive loss of renal mass and subsequent chronic renal failure. As in other patients with renal insufficiency, the control of hypertension, preferably with angiotensin-converting enzyme inhibitors, and adequate nutrition are mainstays of nephrological care. The modality of dialysis in these patients is complicated by ventriculoperitoneal shunts or urinary stomata in peritoneal dialysis, or difficult vascular access in haemodialysis. Renal transplantation is now considered the optimal treatment for end-stage renal disease in all age groups. Although more prone to complications, recent data on patients with meningomyelocele or severely abnormal lower urinary tracts demonstrate excellent patient and graft outcomes. SUMMARY: The common goal in caring for these patients must be the prevention of progressive renal damage. However, once kidney failure has occurred, good and safe techniques for renal replacement therapy are available to bridge the time to transplantation, which is undoubtedly the best treatment for these patients.

Child↗