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M Schwarz

Publications and source records attributed to M Schwarz.

At least 217 records · Page 12Linked to original sources

Chromosomal relationships and phylogenetic and clustering analyses on genes Callithrix group argentata (Callitrichidae, Primates).

The karyotypes of three species of marmosets of the Callithrix argentata group (C. argentata, C. humeralifera and C. chrysoleuca) were studied. Comparisons were made among species and with the previously described karyotypes of C. emiliae, C. mauesi (argentata group) and C. jacchus (jacchus group). Two chromosomes rearrangements differentiate the argentata (2n=44) and jacchus (2n=46) groups: fusion or fission and a paracentric invasion. The argentata group is also characterized by the addition of large amounts of distal constitutive heterochromatin (CH) in some chromosomes, while the jacchus group shows mainly centromeric heterochromatin. The five species of the argentata group differ in the amount or location of the distal CH. Interspecific differences were converted to a Basic Data Matrix (BDM), that was submitted to phenetic and cladistic analyses. For cladistic analyses C. jacchus was the outgroup. The results agree with morphological and geographical data.

Animals↗

Protection of rabbit retina from ischemic injury by flupirtine.

PURPOSE: The aim of this study was to determine wether flupirtine can slow down the changes seen in the rabbit retina after ischemia--reperfusion. METHODS: A suction-cup procedure, which raises intraocular pressure, was used to give an ischemic insult to the rabbit retina. Electroretinograms were recorded before ischemia and at different periods after ischemia. In some instances, flupirtine was injected into the eye before ischemia. Immunohistochemistry was used to study the effect of ischemia-reperfusion on the gamma-aminobutyric acid (GABA) immunoreactivity and uptake of serotonin by the retina. The effect of flupirtine and ischemia on retinal adenosine triphosphate (ATP) levels were determined in in vivo and in vitro experiments. RESULTS: Ischemia for 75 minutes causes a change in the nature of normal GABA immunoreactivity and reduction in the b-wave of the electroretinogram. When flupirtine is injected into the vitreous humor at the onset of ischemic insult, the changes in GABA immunoreactivity are reduced and the recovery of the reduced b-wave of the electroretinogram after defined reperfusion times is enhanced significantly. Rat retinas incubated in vitro in physiological solution containing flupirtine caused a significant rise in the tissues' ATP content compared with control samples. However, incubation of the tissue in physiological solution saturated with nitrogen caused a drop in retinal ATP levels. Addition of flupirtine prevented this decrease from taking place. Serotonin injected into the vitreous humor of the rabbit eye is taken up by certain amacrine cells. The amount of serotonin taken up is reduced greatly in retinas, as judged by immunohistochemistry when tissues are subjected to ischemia. Because the ischemia was shown to cause a drop in the tissue ATP level, it is concluded that this is the cause of the reduced uptake of exogenous serotonin. Injection of flupirtine into the vitreous humor during ischemia enhanced the uptake of serotonin. CONCLUSIONS: Combined data show that flupirtine is a neuroprotective agent in retinal ischemia and that one mode of its mechanism of action is to influence ATP levels. Flupirtine may lower the activity of NMDA receptors, thus causing ATP levels to be less affected in the presence of the drug as a secondary effect.

Adenosine Triphosphate↗

[Late outcome and complications of mandibular compression osteosynthesis with intraoral approach--a 10-year study].

Late results and complications following rigid internal fixation of mandibular fractures-a 10 year survey. From 1984 to 1993 541 fractures of the mandible in 332 patients have been treated by rigid internal fixation with the mandibular compression system (MCS). In 0.8% we saw serious complications like pseudarthrosis or osteomyelitis. In a retrospective study 105 patients with 171 fractures of the mandible could be examined 4.1 years after osteosynthesis. In case of preoperative normesthesia of the inferior alveolar nerve in 74.1% of the fractures nomesthesia was still present, 18.1% of the fractures showed hypesthesia and 4.2% showed complete anesthesia. In case of already preoperatively existent hypesthesia in 81.8% of the fractures normesthesia and in 8.2% hyp- or paresthesia were seen. There were no anesthesias seen in this group. 3.6% of the fractures showed mild occlusal disharmonies.

Adult↗

Pretreatment but not posttreatment with GYKI 52466 reduces functional deficits and neuronal damage after global ischemia in rats.

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a deficit in spatial learning and memory occurs. The aim of the present study was to investigate the potential neuroprotective effect of GYKI 52466, an antagonist at the non-N-methyl-D-aspartate receptor, with behavioural and histological measures of global ischemia in rats. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. GYKI 52466 (30 mg/kg i.p.) was administered either 20 min before induction of ischemia or immediately after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. After behavioural testing the animals were sacrificed and the neuronal damaged was assessed. GYKI 52466 reduced the increase in escape latency and in swim distance induced by 4VO when given before ischemia but not when applied after ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was significantly attenuated by pretreatment but not by posttreatment with GYKI 52466. Striatal neuronal damage was not affected by either treatment with GYKI 52466. GYKI 52466 had neuroprotective effects in a rat model of global cerebral ischemia. Pretreatment with GYKI 52466 protected rats against behavioural deficits and hippocampal neuronal damage induced by 4VO.

Animals↗

[Wear behavior of coupled aluminum oxide ceramics-carbon fiber bond as hip acetabulum inlay in a simulated trial].

Hip-simulator studies were carried out to investigate the initial wear between a femoral head made of aluminium oxide ceramic and a CFRP-(carbon fibre-reinforced plastic) inlay in a titanium cup. A load of 2500 N and a frequency of 0.857 Hz were applied. After 200,000 cycles, the centre of the head had moved 9 microns into the liner. After 500,000 cycles, the cup centre had moved inwards by a further micron, and the near radius had increased by 2 microns. After 750,000 cycles the position of the centre of the head remained unchanged, while the mean radius had increased a further 2 microns. After one million cycles any further changes remained below the measuring capability (1 micron) of the system.

Aluminum Oxide↗

Ion channels in the chloroplast envelope membrane.

Isolated chloroplast envelope membranes were fused with azolectin liposomes. Ion transport across the membrane of these liposomes was investigated by the patch-clamp technique and in planar bilayers. Our results show that the chloroplast envelope contains voltage-dependent anion- and cation-selective channels as well as anion- and cation-selective pores with high conductances. At least one of the high-conductance pores could be located in the chloroplast outer envelope membrane. The low-conductance chloride channel and the potassium channel showed complex gating behavior with subconductant states. Potassium channel gating was affected by monovalent and divalent cations as well as by millimolar concentrations of ATP. Low concentrations of Cs+ induced a flickering block. Voltage dependence of the open probability reveals that macroscopic currents of potassium channels are rectified with preferential potassium uptake into the chloroplast. Flux measurements and determinations of the stroma pH of intact chloroplasts confirm the presence of a potassium channel that is regulated by divalent cations (Mg2+) and by ATP. The fully open potassium channel revealed a conductance of lambda approximately equal to 100 pS in asymmetric KCl (250/20 mM KCl), and the fully open chloride channel revealed a conductance of lambda approximately equal to 60 ps in 100 mM Tris/HCl. One high-conductance channel, mainly active at holding potentials > 60 mV, was slightly selective for glutamate anions (PK+/PGlu- approximately equal to 2) and revealed fast voltage-dependent gating. This high-conductance channel had a conductance of lambda approximately equal to 540 pS (in 250/20 mM potassium glutamate) and was closed most of the time. A second type of high-conductance channel, mainly open and active at holding potentials below 30 mV, was slightly selective for cations (PGlu-/PK+ approximately equal to 2) with a conductance of lambda approximately equal to 1.14 nS (in 250/20 mM potassium glutamate).

Adenosine Triphosphate↗

The antioxidant LY 231617 ameliorates functional and morphological sequelae induced by global ischemia in rats.

In this study the effect of LY 231617, an antioxidant, on spatial learning deficit and on neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. LY 231617 (20 mg/kg i.p.) was administered after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. LY 231617 reduced the increase in escape latency and in swim distance induced by 4VO. Neuronal damage in the CAI sector of the hippocampus produced by 4VO was significantly attenuated by LY 231617. The present data demonstrate that posttreatment with LY 231617 exerts a protective effect on hippocampal neuronal damage and deficits in spatial learning induced by 4VO.

Animals↗

Identification of the TS2/18-recognized epitope on the CD2 molecule as a target for suppression of T cell cytokine synthesis.

CD2 mAb can inhibit T cell activation, but the mechanisms involved are still unclear. In this study, we identify the mAb TS2/18, previously reported to bind to an epitope on the distal domain of the CD2 molecule at amino acids 87-99 (1), as a particularly potent inhibitor of T cell cytokine synthesis. Although TS2/18 is comitogenic with the CD2R mAb VIT13, this mAb combination does not induce the secretion of substantial amounts of cytokines. When added to T cells stimulated with the CD2 mAb pair OKT11-VIT13, TS2/18 efficiently blocks the induction of cytokine synthesis induced by that CD2 mAb pair, although it does not interfere with the binding of OKT11. In addition, TS2/18 inhibits the increase in protein tyrosine phosphorylation and the accumulation of phosphatidic acid induced by either OKT11-VIT13 or a cross-linked CD3 mAb. Finally, TS2/18 disrupts CD2 clusters induced by the CD2 mAb pair OKT11-VIT13. We conclude that TS2/18 blocks T cell cytokine synthesis by interfering with early signal transduction, possibly by impairing the formation of signal-transducing molecule complexes on the T cell surface. Together, these data identify the CD2 epitope recognized by the mAb TS2/18 as a candidate epitope for T cell-specific immunosuppressive ligands.

Antibodies, Monoclonal↗

N-methyl-D-aspartate and alpha 2-adrenergic mechanisms are involved in the depressant action of flupirtine on spinal reflexes in rats.

In urethane-chloralose anesthetised rats the muscle relaxant activity of flupirtine was investigated on the monosynaptic Hoffmann reflex recorded from plantar foot muscles and on the polysynaptic flexor reflex recorded from tibialis muscle. Intraperitoneal (i.p.; 2.5-25 mumol/kg) and intrathecal (i.t.; 33-330 nmol) administration of flupirtine depressed the polysynaptic flexor reflex in anesthetised rats in a dose-dependent manner without affecting the monosynaptic Hoffmann reflex. Flupirtine produced a similar pattern on spinal reflexes as NMDA receptor antagonists, such as (-)-2-amino-7-phosphonoheptanoic acid (500 nmol i.t.) and memantine (125 mumol/kg i.p.), the benzodiazepines diazepam (18 mumol/kg i.p.) and midazolam (80 nmol i.t.), and the alpha 2-adrenoceptor agonist tizanidine (2 mumol/kg). In contrast, the GABAA receptor agonist muscimol (21 mumol/kg i.p.; 20 nmol i.t.) and the GABAB receptor agonist baclofen (47 mumol/kg i.p.; 2 nmol i.t.) reduced the magnitude of both the flexor and the Hoffmann reflex, whereas the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 nmol i.t.) depressed the Hoffmann reflex without affecting the flexor reflex. The effect of i.t. injection of flupirtine was prevented by coadministration of the mixed alpha 1/alpha 2-adrenoceptor antagonist yohimbine (10 nmol) and the excitatory amino acid N-methyl-D-aspartate (NMDA; 0.1 nmol), but neither by coadministration of the alpha 1-adrenoceptor antagonist prazosine (10 nmol), the GABAA receptor antagonist bicuculline (1 nmol), the GABAB receptor antagonist phaclofen (100 nmol), the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionic acid (ATPA; 0.1 pmol) nor by pre-treatment with the benzodiazepine receptor antagonist flumazenil (16 mumol/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-2 Receptor Agonists↗

Epiluminescence microscopy. A useful tool for the diagnosis of pigmented skin lesions for formally trained dermatologists.

BACKGROUND AND DESIGN: Epiluminescence microscopy (ELM) is a noninvasive technique that, by employing the optical phenomenon of oil immersion, makes subsurface structures of the skin accessible for in vivo examination and thus provides additional criteria for the clinical diagnosis of pigmented skin lesions. At present, almost all studies about the value and clinical importance of ELM are based on data derived from ELM experts (ie, dermatologists specifically trained in this technique). In the present study, we attempt to determine whether the clinical diagnosis of pigmented skin lesions is significantly improved using ELM and whether ELM-trained individuals and dermatologists not trained in this technique profit equally from this technique. Randomly selected histologically proven pigmented skin lesion specimens, photographed with (ELM) and without oil immersion (surface microscopy) were presented by slide projection to six ELM experts and 13 ELM nonexperts (ie, dermatologists not formally trained in ELM) for diagnosis. To evaluate the diagnostic performance of ELM experts and nonexperts with and without the oil immersion technique (ie, ELM vs surface microscopy), the following parameters were obtained: intraobserver and interobserver agreement by kappa statistics and sensitivity and specificity of diagnostic performance. RESULTS: Our results show that by using the ELM technique the ELM experts reach a substantially better intraobserver agreement than nonexperts (median kappa, 0.56 vs 0.36). The interobserver agreement was markedly increased in the ELM experts group (average gain, 7%) but decreased in the ELM nonexperts group (average loss, 6%). The sensitivity of diagnosis was significantly increased in the ELM experts group (average gain, 10%), but decreased in the nonexperts group (average loss, 10%). Finally, the specificity of diagnosis was excellent in the ELM experts group, both with and without oil immersion (0.91) and was somewhat improved by ELM in the nonexperts group (0.77 vs 0.85). CONCLUSIONS: We conclude that the ELM technique increases sensitivity in formally trained dermatologists, but may decrease the diagnostic ability in dermatologists not formally trained in the ELM technique. Consequently, formal broad-based training in ELM should be offered to the dermatologic community.

Clinical Competence↗

Elevated content of p53 protein in the absence of p53 gene mutations as a possible prognostic marker for human renal cell tumors.

p53 tumour suppressor gene expression was estimated immunohistochemically using DO-1 monoclonal antibody (recognising both wild-type and mutant p53 in 88 human renal tumours. Single strand conformation polymorphism (SSCP) analysis of possible mutations within exons 4-8 of the p53 gene was performed in 29 of the tumours (mostly immunostaining-positive cases). Obviously elevated p53 content was detected with DO-1 antibody in chromophobic cell carcinomas and most clear/chromophilic cell tumours (in chromophilic cell populations). In contrast, clear cell carcinomas demonstrated either complete absence of p53 expression or the presence of single immunopositive nuclei. Oncocytomas were completely negative. Additional immunostaining of the positive samples with mutant p53-specific Pab240 monoclonal antibody failed to detect immunopositive material. No p53 mutation was found in any of the samples analysed by SSCP. Our results suggest that the elevated p53 content in human renal cell carcinomas does not result from gene mutation and the p53 gene alterations are probably not an important mechanism in the development of human renal cell carcinomas. Accumulation of the wild-type p53 protein may be a useful prognostic marker indicating neoplastic progression malignancy.

Base Sequence↗

Rapid appearance of beta-amyloid precursor protein immunoreactivity in glial cells following excitotoxic brain injury.

Clinical and experimental data have indicated an up-regulation of amyloid precursor protein (APP) after various types of CNS injury. In the present study the cellular source of lesion-induced APP has been investigated in a neurotoxic CNS model. Quinolinic acid injection into the striatum results in neuronal degeneration, while glial cells survive. APP immunoreactivity was detected in glial cells starting at postoperative day 3 and persisted until day 21, the last time point studied. Double immunocytochemistry identified the majority of APP-immunoreactive cells as glial fibrillary acidic protein-immunoreactive astrocytes. There was no evidence of amyloid fibril deposition during this time. It is concluded that following excitotoxic neuronal degneration APP is mainly produced by reactive astrocytes in the lesioned area.

Amyloid beta-Protein Precursor↗

Arachnoid cysts: does surgery improve epileptic seizures and headaches?

During the period from 1985 to 1992 we treated 43 patients with intracranial arachnoid cysts (ACs). In this retrospective study we assessed the outcome of these patients with regard to non-specific symptoms such as headaches and epileptic seizures. Twelve patients had headaches of obscure origin and a mostly temporal located AC. Six of these 12 underwent surgery. After the operation 4 patients (4/6) had no further headaches, two remained unchanged. The other 6 conservatively treated patients (6/12) had further headaches. Ten of the 43 patients had epileptic seizures. One patient dropped out of the survey. Six of the 9 remaining patients had a temporal AC. Four of these 6 underwent surgery; postoperatively the seizure disease of 3 patients (3/6) declined. One patient was unchanged. Two patients with epileptic seizures and a temporal AC did not undergo surgery and both improved. Three patients with seizures had a convex located AC. Two of these 3 underwent surgery. The first patient improved postoperatively, the second patient remained unchanged. There was a reduction in the seizures of the medically treated patient. It remains ambiguous, whether there is a relationship between epileptic seizures and intracranial ACs without obvious intracranial pressure signs. A review of the literature, however, showed mostly positive results concerning the surgical treatment of ACs under conditions of simultaneous epileptic seizures. However, the results largely depend upon the definition of the decline of the seizures with regard to the postoperative follow-up, therefore we must remain skeptical. Therapy guidelines in the future not only depend on the clarification of the pathophysiology of the ACs, but also on a resonable outcome examination.

Adolescent↗

Role of receptors in human and rodent hepatocarcinogenesis.

The liver is a major target organ in rodent carcinogenicity assays. Amongst the agents that are effective in producing rodent liver tumours are many chemicals which are not mutagenic, but are believed to mediate their effects by promoting the clonal outgrowth of initiated cells. Some of these chemicals, such as dibenzo-p-dioxins and certain PCBs, have been demonstrated to interact with specific cellular receptors and receptor binding appears crucial for their tumourigenic activity. Enzyme-altered foci in rat liver may serve as a sensitive means to estimate the promoting activity of these agents in rodents. Mechanistic considerations are of relevance when extrapolating these data from rodents to humans.

Animals↗

Engineering of human cholinesterases explains and predicts diverse consequences of administration of various drugs and poisons.

The acetylcholine hydrolyzing enzyme, acetylcholinesterase, primarily functions in nerve conduction, yet it appears in several guises, due to tissue-specific expression, alternative mRNA splicing and variable aggregation modes. The closely related enzyme, butyrylcholinesterase, most likely serves as a scavenger of toxins to protect acetylcholine binding proteins. One or both of the cholinesterases probably also plays a non-catalytic role(s) as a surface element on cells to direct intercellular interactions. The two enzymes are subject to inhibition by a wide variety of synthetic (e.g., organophosphorus and carbamate insecticides) and natural (e.g., glycoalkaloids) anticholinesterases that can compromise these functions. Butyrylcholinesterase may function, as well, to degrade several drugs of interest, notably aspirin, cocaine and cocaine-like local anesthetics. The widespread occurrence of butyrylcholinesterase mutants with modified activity further complicates this picture, in ways that are only now being dissected through the use of site-directed mutagenesis and heterologous expression of recombinant cholinesterases.

Carbamates↗

Successive organophosphate inhibition and oxime reactivation reveals distinct responses of recombinant human cholinesterase variants.

To explore the molecular basis of the biochemical differences among acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and their alternative splicing and allelic variants, we investigated the acylation phase of cholinesterase catalysis, using phosphorylation as an analogous reaction. Rate constants for organophosphate (DFP) inactivation, as well as for oxime (PAM)-promoted reactivation, were calculated for antibody-immobilized human cholinesterases produced in Xenopus oocytes from natural and site-directed variants of the corresponding DNA constructs. BuChE displayed inactivation and reactivation rates 200- and 25-fold higher than either product of 3'-variable AChE DNAs, consistent with a putative in vivo function for BuChE as a detoxifier that protects AChE from inactivation. Chimeric substitution of active site gorge-lining residues in BuChE with the more anionic and aromatic residues of AChE, reduced inactivation 60-fold but reactivation only 4-fold, and the rate-limiting step of its catalysis appeared to be deacylation. In contrast, a positive charge at the acyl-binding site of BuChE decreased inactivation 8-fold and reactivation 30-fold. Finally, substitution of Asp70 by glycine, as in the natural 'atypical' BuChE variant, did not change the inactivation rate yet reduced reactivation 4-fold. Thus, a combination of electrostatic active site charges with aromatic residue differences at the gorge lining can explain the biochemical distinction between AChE and BuChE. Also, gorge-lining residues, including Asp70, appear to affect the deacylation step of catalysis by BuChE. Individuals carrying the 'atypical' BuChE allele may hence be unresponsive to oxime reactivation therapy following organophosphate poisoning.

Acetylcholinesterase↗

Role of cell proliferation at early stages of hepatocarcinogenesis.

Hepatocarcinogenesis in rodents is characterized by the early appearance of foci of enzyme-altered (initiated) cells which are believed to represent precursors on the way to malignancy. Proliferation of cells within enzyme-altered liver foci is generally increased as compared to surrounding normal hepatocytes. This may be mediated by changes in the rates of cell division and/or cell death (apoptosis). Cell proliferation is controlled by complex signaling networks and may be modulated by xenobiotics. In mouse--but not rat or human--liver, mutation of the Ha-ras gene appears to represent a critical genetic alteration which may confer a selective growth advantage to the mutated cells. Exogenous tumor-promoting agents may stimulate cell division and depress apoptosis of preneoplastic hepatocytes, thereby increasing the probability of cancer. By means of histochemical methods, data on the frequencies of both cell division and cell death can be collected separately and utilized for estimation of promoter efficacy. In addition, quantitative stereology may be applied to the analysis of the size distribution of enzyme-altered foci and used for modeling of hepatocarcinogenesis.

Animals↗

Influence of flupirtine on human lower limb reflexes.

The influence of a single oral dose (400 mg) of flupirtine on lower limb reflexes was investigated in normal human subjects using H-reflex testing, flexor reflex testing and dynamic posturography. Flupirtine did not significantly change the latency of the H-reflex or the Hmax/Mmax ratio. Both, the first (F1) and the second (F2) components of the flexor reflex were significantly depressed. Flupirtine significantly decreased the size of the ML response following fast transient platform movements rotating toe-up around the ankle joint. We conclude that flupirtine acts on polysynaptic spinal pathways. In addition to its well known analgesic effect flupirtine might have a muscle relaxant effect.

Adult↗