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Biomedical subjects

S Schwarz

Publications and source records attributed to S Schwarz.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Acute disseminated encephalomyelitis (ADEM)].

Acute disseminated encephalomyelitis (ADEM) is an unusual demyelinating disease of the CNS. We review clinical symptoms, findings from radiological and CSF examinations, and current treatment strategies for ADEM. This disorder is often associated with a precedent infection or vaccination but may also occur spontaneously. The clinical symptoms are highly variable. Analysis of CSF usually reveals lymphocytic pleocytosis and an elevated protein content but may also yield normal results. Magnetic resonance imaging shows solitary or multiple lesions within the CNS. Most patients improve quickly with methylprednisolone. If that fails, immunoglobulin, plasmapheresis, or cytostatic drugs can be employed. Unlike MS, ADEM has a monophasic course and favourable long-term prognosis. Multiphasic courses are very rare. There are no diagnostic criteria to distinguish ADEM reliably from MS during the acute phase. We presume that ADEM is a variant of MS and not an independent disease entity.

Adult↗
PubMed2001

[Value of MRI in intracerebral and subarachnoid hemorrhage].

Intracranial hemorrhage (ICH) accounts for 15% of all strokes. In hyperacute emergency assessment, CT is the diagnostic standard for differentiating between hyperacute ICH and ischemic stroke. At this stage, MRI is considered to be of little value for the diagnosis of ICH or subarachnoidal hemorrhage (SAH). We review the current literature and characterize the role of MRI in the diagnosis of ICH and SAH as well as hyperacute stroke in general: While MRI is considered superior to CT in the diagnosis of subacute and chronic ICH/SAH, in hyperacute ICH this is still a matter of debate. MRI signal characteristics of ICH depend on hemoglobin degradation. Deoxyhemoglobin is the MRI substrate for demonstration of blood due to its paramagnetic properties causing signal loss on susceptibility weighted images (T2*-WI). Preliminary data, however, suggest that the sensitivity of modern stroke MRI protocols is sufficiently high for hyperacute ICH and SAH and may render additional information with regard to the etiology of ICH or SAH. Further interest is focused on perihemorrhagic pathophysiologic processes, which may help to improve therapeutic decision making in patients with ICH.

Cerebral Hemorrhage↗
PubMed2001

Mitotic arrest of female germ cells during prenatal oogenesis. A colcemid-like, non-apoptotic cell death.

The sequence of events and a possible reason for germ cell death during oogenesis in the prenatal ovary were studied in rat and mouse embryos. ED 14-22 rat and ED 14-16 mouse embryos were studied using semithin sections for light microscopy and serial ultrathin sections for electron microscopy. In addition, the rat material was 3H-thymidine labelled for historadioautography and cytospin preparations of freshly obtained gonads were immunohistochemically analysed. During the transition from the proliferating oogonial stage to the meiotic prophase about 16% of the postmitotic oocytes do not pass the initial meiotic checkpoint on ED 18/19 in the rat (ED 15/16 in the mouse). These germ cells first show structural signs of mitosis; the diploid number of 'super-condensed' chromosomes are globally formed and are concentrated in the center of the cell. Although the germ cells show all morphological signs of living cells they never have mitotic spindles; the micro-tubulus-organisation-centres (MTOCs) are found peripherally and become concentrated, forming a single centrosomal body (acentriolar MTOC) as detected by immunohistochemistry for the centrosomal protein MPM2 and gamma-tubulin. EM studies show 25 nm tubule-like profiles within the MTOC bodies. The centrioles frequently lie separate from the MTOC material or are not present at all; the germ cells are apparently arrested in a prophase- or metaphase-like stage when they have reached the postmitotic G2/preleptotenal transition and are unable to enter meiosis. Forty-eight to 72 h after the first mitotically arrested germ cells are found, degeneration is seen in these germ cells. This second event, the germ cell death proper, shows neither criteria of apoptosis (cell shrinkage, marginal condensation of chromatin, DNA fragmentation) nor signs of necrosis (cell swelling, pycnosis, inflammation). Both arrested pro- and metaphase-like stages are found with signs of cell death and phagocytosis. The morphological signs of phagocytosis are found in neighbouring pregranulosa cells. The final heterocytotic bodies contain the remnants of the centrosomal (MTOC) material and DAPI-positive DNA material. The pregranulosa cells are mitotically silent during the phase when mitotic arrest and germ cell degeneration is found. The results suggest the presence of a hypothetical 'anti-spindle' factor, which under normal conditions is necessary for induction of meiotic prophase. The structural events of 'arrested mitosis' is reminiscent of those induced by the antimitotic, tubule-degrading drug colcemid. This type of arrest may inhibit meiosis of more than 33% prenatal germ cells and induce their cell death.

Animals↗
PubMed2001

Use of antimicrobial agents in veterinary medicine and food animal production.

Antimicrobial resistance is a growing area of concern in both human and veterinary medicine. This review presents an overview of the use of antimicrobial agents in animals for therapeutic, metaphylactic, prophylactic and growth promotion purposes. In addition, factors favouring resistance development and transfer of resistance genes between different bacteria, as well as transfer of resistant bacteria between different hosts, are described with particular reference to the role of animals as a reservoir of resistance genes or resistant bacterial pathogens which may cause diseases in humans.

Animal Diseases↗
PubMed2001

Synthesis and evaluation of diazine containing bioisosteres of (-)-ferruginine as ligands for nicotinic acetylcholine receptors.

In this structure-affinity relationship (SAFIR) study, the bioisosteric potential of diazines in the field of ferruginine-type nAChR ligands was investigated. Novel enantiopure analogues of (-)-Ferruginine (3) such as 6-8 were synthesized utilizing enantiomerically pure N-protected (+)-2-tropanone 9 from the 'chiral pool' as versatile chiral building block and a palladium-catalyzed Stille cross-coupling of the tributylstannyl diazines 12, 14 and 16 with the vinyl triflate 11 of (+)-2-tropanone 9. The structures of the novel diazine analogues 6-8 of (-)-ferruginine (3) were assigned on the basis of spectral data, that of ligand 7 being additionally verified by X-ray crystallography. The bioisosteric replacement of the acetyl moiety as structural part of the lead compound 3 with the pyridazine, pyrimidine and pyrazine nucleus resulted in ligands with high to moderate affinity for the central alpha4beta2 and remarkably low affinity for the alpha7* nAChR subtypes. Among the compounds synthesized and tested, 7 was the most active one with K(i)=3.7 nM (alpha4beta2). Compared with the lead 3, this value represents a 30-fold improvement in the affinity for the alpha4beta2 subtype combined with a substantially improved selectivity ratio between the alpha4beta2 and alpha7* subtypes.

Animals↗
PubMed2001

Loss of Fas (CD95/APO-1) regulatory function is an important step in early MALT-type lymphoma development.

Fas (CD95, APO-1) mutations were found in autoimmune diseases and some lymphomas, suggesting impairment of Fas-mediated cell death signaling that may cause tumor development. Because mucosa-associated lymphoid tissue (MALT)-type lymphoma B cells recognize autoantigens and proliferate in response to antigen and T cell-mediated signals, it is suggestive that autoreactive B cell lymphoma precursor cells may have escaped the Fas-mediated checkpoint that normally operates in healthy individuals. Using different biochemical, molecular, and functional approaches, we analyzed the Fas signaling in malignant B cells from seven MALT-type lymphomas that were additionally characterized for the t(11;18)(q21;q21) and four gastric diffuse large B cell lymphomas (DLBL). All DLBLs and three of seven MALT-type lymphomas were resistant to Fas-mediated apoptosis in vitro. Moreover, four of five MALT-type lymphomas analyzed and one of three DLBLs analyzed showed mutations in Fas mRNA transcripts but no loss of heterozygosity in the Fas promotor region. Alternative mechanisms of resistance to apoptosis, such as decreased expression of Fas or production of soluble Fas were not operative. Therefore, it is suggestive that a subgroup of MALT-type lymphoma B cells, irrespective of t(11;18)(q21;q21), escape the censoring Fas pathway by mutating and inactivating Fas. This identifies a key regulatory step in early MALT-type lymphomagenesis.

Adult↗
PubMed2001

Estrogen sulfamates: a new approach to oral estrogen therapy.

Sulfamate substitution (-O-SO2-NH2) at carbon atom 3 of the steroid skeleton leads to orally active prodrugs of estrogens with much higher systemic, but lower hepatic, estrogenic activity than their parent steroids. This dissociation is achieved by first passage through the liver in erythrocytes, followed by systemic hydrolysis which releases the 'parent' estrogen. In the rat, orally administered tritiated estradiol sulfamate, unlike estradiol, appears in the circulation at high concentrations. At Cmax, approximately one third of the administered dose forms a depot in the circulation (98% in erythrocytes, 2% in plasma). Significant estradiol, estrone and estrone sulfate concentrations were recorded in plasma during depletion of the red blood cell pool. Estradiol sulfamate (J995) has no estrogen receptor affinity per se or estrogenic activity in vitro ( i.e. without hydrolysis). Its oral uterotropic activity in rats is approximately 100 times greater than that of estradiol, however, its hepatotropic activity is only marginally elevated. These functions include bile secretion, the secretion of angiotensinogen, lipoproteins (total and high-density lipoprotein cholesterol) and insulin-like growth factor I (IGF-I). Orally administred estradiol sulfamate led to systemic estrogenic effects without significant hepatic responses, whereas estradiol and other 'conventional' estrogens exerted parallel systemic and hepatic estrogenic effects. Sulfamate technology represents an approach to the use of natural estrogens for fertility control and hormone replacement therapy in both genders. In this context, reduced effects on hemostatic factors, angiotensinogen, bile and IGF-I secretion seem the most important aspects. In addition, blood concentrations of estrogens are less variable than with conventional estrogens.

Administration, Oral↗
PubMed2001

Tetracycline resistance genes in isolates of Pasteurella multocida, Mannheimia haemolytica, Mannheimia glucosida and Mannheimia varigena from bovine and swine respiratory disease: intergeneric spread of the tet(H) plasmid pMHT1.

Tetracycline-resistant isolates of Pasteurella multocida and Mannheimia spp. from respiratory diseases in cattle and swine were investigated for the classes of tet gene and their chromosomal or plasmid location. The 34 isolates comprised eight P. multocida, 23 Mannheimia haemolytica, two Mannheimia varigena and a single Mannheimia glucosida isolate. Identification of the tet genes was achieved by PCR analysis and hybridization with specific probes. Transformation and hybridization experiments served to confirm the plasmid location of tet genes. Selected tet genes and their adjacent regions were sequenced. The tet genes tet(B), tet(G) and tet(H) were detected. The gene tet(H) was present in 26 isolates. The 4.4 kb tet(H)-carrying plasmid pMHT1 was detected in six isolates representing all four species. In the remaining 28 isolates, copies of tet(B), tet(G) and tet(H) were identified as chromosomal. No correlation between the tet gene type and the MIC of tetracycline, or between the number of tet gene copies and the MIC of tetracycline was observed. Tetracycline resistance in P. multocida and Mannheimia spp. is mediated by at least three different tet genes. A new type of tet(H)- carrying plasmid, pMHT1, was identified. The detection of pMHT1 in M. glucosida and M. varigena is the first report of resistance plasmids in isolates of these two species. For the first time, tet(G) genes were detected in members of the family Pasteurellaceae.

Animals↗
PubMed2001

Molecular analysis of tetracycline resistance in Pasteurella aerogenes.

Tetracycline-resistant Pasteurella aerogenes isolates obtained from the intestinal tract of swine were investigated for their tet genes by PCR analysis and hybridization experiments. In contrast to Pasteurella isolates from the respiratory tract, tet(H) genes were detected in the chromosomal DNA of only 2 of the 24 isolates, one of which also carried two copies of a tet(B) gene. All other P. aerogenes isolates carried tet(B) genes, which are the predominant tet genes among Enterobacteriaceae. A single isolate harbored a tet(B) gene as part of a truncated Tn10 element on the 4.8-kb plasmid pPAT2. Comparative analysis of the pPAT2 sequence suggested that the Tn10 relic on plasmid pPAT2 is the result of several illegitimate recombination events. The remaining 21 P. aerogenes isolates carried one or two copies of the tet(B) gene in their chromosomal DNA. In the majority of the cases, these tet(B) genes were associated with copies of Tn10 as confirmed by their SfuI and BamHI hybridization patterns. No correlation between the number of tet gene copies and the MICs of tetracycline, doxycyline and minocycline was observed.

Animals↗
PubMed2001

Influence of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure in patients with acute stroke.

BACKGROUND AND PURPOSE: We undertook this study to evaluate the influence of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with acute stroke. METHODS: A total of 20 ventilated patients of a neurological intensive care unit were examined under a protocol entailing variation of PEEP to 4, 8, 12, and 4 mm Hg; mean arterial blood pressure (MAP), ICP, heart rate, and mean velocity of the middle cerebral arteries (V(m) MCA) were recorded. RESULTS: CPP significantly changed depending on the various PEEP levels. No significant differences in remaining parameters were evident. Three distinct reaction patterns of the parameters monitored were observed: (1) All parameters remained stable through the various PEEP levels (15 patients, 40 examinations). (2) Increase in PEEP resulted in a significant decrease of MAP, while V(m) MCA remained unchanged, indicating an intact cerebral autoregulation. A slight (statistically insignificant) increase in ICP, which was significantly related to the MAP changes, was evident (7 patients, 16 examinations). (3) Increase in PEEP resulted in a decrease of MAP and V(m) MCA; ICP remained unchanged or demonstrated a slight decline (3 patients, 6 examinations). CONCLUSIONS: PEEP increase up to 12 mm Hg does not significantly influence ICP. The observed marked changes in CPP are mediated through the MAP. Thus, PEEP application should be safe, provided that MAP is maintained.

Adult↗
PubMed2001

Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach.

BACKGROUND AND PURPOSE: We undertook this study to evaluate the feasibility of inducing and maintaining moderate hypothermia with the use of endovascular rather than surface cooling. METHODS: Six patients with severe acute ischemic stroke were treated with moderate hypothermia. This was induced and maintained by circulating temperature-adjusted normal saline in a closed-loop system entailing 3 balloons located near the tip of a central line, which dwelled in the inferior vena cava. RESULTS: The mean+/-SD initial temperature of the patients was 37+/-1 degrees C (range, 35.5 degrees C to 38.4 degrees C). The pace of cooling was 1.4+/-0.6 degrees C/h, and target temperature was reached after 3+/-1 hours (range, 2 to 4.5 hours). During hypothermia, the maximal temperature observed was 33.4 degrees C, and the minimal temperature was 32.2 degrees C. Temperature deviations >0.2 degrees C or >0.3 degrees C were observed during 21% or 10% of the hours under hypothermia, respectively. Singultus was the only device-related complication encountered. Pulmonary infection, arterial hypotension, bradycardia, arrhythmia, and thrombocytopenia were the most common side effects. CONCLUSIONS: Induction and maintenance of hypothermia with an intravenous cooling device are feasible. The safety of this approach remains to be evaluated.

Acute Disease↗
PubMed2001

Synthesis and characterization of nanocrystalline silver coating of fly ash cenosphere particles by electroless process.

Electroless nanocrystalline Ag coating of fly ash cenosphere particles utilizing a Sn-Pd catalyst system is demonstrated in this article. The deposition of pure metallic nanocrystalline Ag on the fly ash cenosphere particle surface is confirmed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) analysis. Under the described conditions of electroless coating, average nanocrystalline Ag-coating thickness is observed to be approximately 220 nm, using a focused ion beam technique, which is less than that observed by transmission electron microscopy (TEM) (260-360 nm). TEM observation further reveals that the Ag-coating is made up of 50 nm Ag nanocrystallites, which is comparable with the size of approximately 37 nm obtained from the XRD data. The mechanism of the electroless Ag-coating process is discussed. Ag-coated fly ash particles find applications in manufacturing conducting polymers for electromagnetic interference shielding applications.

Carbon↗
PubMed2001

Studies on modified estrogens: towards the synthesis of novel 14,15-cyclopropa[a]estra-1,3,5(10),8-tetraenes.

To improve the ratio of non-hormonal to hormonal activity, estrogens 3 and 4 were modified at various molecule positions. Isomerization of the 14 alpha,15 alpha-methylene bridge, controlled 3-methoxy group cleavage with respect to the 14 alpha,15 alpha-methylene bridge stereochemistry, reduction of the 8-double bond, and substitution of the oxyfunctionality at C-17 by a methylene and a difluoromethylene moiety were in the focus. As a result of in vivo and in vitro tests, compounds 27 and 29 were selected as potential follow-up candidates of lead 3.

Antioxidants↗
PubMed2000

5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence.

A 1468 bp cDNA coding for the chicken homolog of the human MBD4 G/T mismatch DNA glycosylase was isolated and sequenced. The derived amino acid sequence (416 amino acids) shows 46% identity with the human MBD4 and the conserved catalytic region at the C-terminal end (170 amino acids) has 90% identity. The non-conserved region of the avian protein has no consensus sequence for the methylated DNA binding domain. The recombinant proteins from human and chicken have G/T mismatch as well as 5-methylcytosine (5-MeC) DNA glycosylase activities. When tested by gel shift assays, human recombinant protein with or without the methylated DNA binding domain binds equally well to symmetrically, hemimethylated DNA and non-methylated DNA. However, the enzyme has only 5-MeC DNA glycosylase activity with the hemimethylated DNA. Footprinting of human MBD4 and of an N-terminal deletion mutant with partially depurinated and depyrimidinated substrate reveal a selective binding of the proteins to the modified substrate around the CpG. As for 5-MeC DNA glycosylase purified from chicken embryos, MBD4 does not use oligonucleotides containing mCpA, mCpT or mCpC as substrates. An mCpG within an A+T-rich oligonucleotide is a much better substrate than an A+T-poor sequence. The K:(m) of human MBD4 for hemimethylated DNA is approximately 10(-7) M with a V:(max) of approximately 10(-11) mol/h/microgram protein. Deletion mutations show that G/T mismatch and 5-MeC DNA glycosylase are located in the C-terminal conserved region. In sharp contrast to the 5-MeC DNA glycosylase isolated from the chicken embryo DNA demethylation complex, the two enzymatic activities of MBD4 are strongly inhibited by RNA. In situ hybridization with antisense RNA indicate that MBD4 is only located in dividing cells of differentiating embryonic tissues.

Amino Acid Sequence↗
PubMed2000

Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats.

Membrane currents evoked by repeated noxious heat stimuli (43-47 degrees C) of 3 s duration were investigated in acutely dissociated dorsal root ganglion (DRG) neurones of adult rats. The heat stimuli generated by a fast solution exchanger had a rise time of 114 +/- 6 ms and a fall time of 146 +/- 13 ms. When heat stimuli were applied to heat-sensitive small (< or = 32.5 microm) DRG neurones, an inward membrane current (I(heat)) with a mean peak of 2430 +/- 550 pA was observed (n = 19). This current started to activate and deactivate with no significant latency with respect to the heat stimulus. The peak of I(heat) was reached with a rise time of 625 +/- 115 ms. When the heat stimulus was switched off I(heat) deactivated with a fall time of 263 +/- 17 ms. During constant heat stimulation I(heat) decreased with time constants of 4-5 s (inactivation). At the end of a 3 s heat stimulus the peak current was reduced by 44 +/- 5 % (n = 19). Current-voltage curves revealed outward rectifying properties of I(heat) and a reversal potential of -6.3 +/- 2.2 mV (n = 6). Inactivation was observed at all membrane potentials investigated (-80 to 60 mV); however, inactivation was more pronounced for inward currents (37 +/- 5 %) than for outward currents (23 +/- 6 %, P < 0.05). When neurones were investigated with repeated heat stimuli (3 to 5 times) of the same temperature, the peak current relative to the first I(heat) declined by 48 +/- 6 % at the 3rd stimulus (n = 19) and by 54 +/- 18 % at the 5th stimulus (n = 4; tachyphylaxis). In the absence of extracellular Ca2+ (buffered with 10 mM EGTA) inactivation (by 53 +/- 6 %) and tachyphylaxis (by 42 +/- 7 % across three stimuli) were still observed (n = 8). The same was true when intracellular Ca2+ was buffered by 10 mM BAPTA (inactivation by 49 +/- 4 %, tachyphylaxis by 52 +/- 7 % across three stimuli; n = 13). Thus, inactivation and tachyphylaxis were mainly independent of intra- and extracellular Ca2+. These results indicate that inactivation and tachyphylaxis of heat-evoked inward currents can be observed in vitro, similar to adaptation and suppression of action potential discharges elicited by comparably fast heat stimuli in vivo. Whereas the voltage dependence of I(heat) resembles that of capsaicin-induced membrane currents (I(Caps)), the independence of inactivation and tachyphylaxis of I(heat) from calcium is in clear contrast to I(Caps). A similar difference in calcium dependence of inactivation has been reported between heat-evoked and capsaicin-induced currents through the cloned capsaicin receptor channel VR1. Thus, the properties of I(heat) and of VR1 largely account for the adaptation and suppression of heat-evoked nociceptor discharges.

Animals↗
PubMed2000

Three-dimensional analysis of object properties during active electrolocation in mormyrid weakly electric fishes (Gnathonemus petersii).

Weakly electric fishes are nocturnal and orientate in the absence of vision by using their electrical sense. This enables them not only to navigate but also to perceive and recognize objects in complete darkness. They create an electric field around their bodies by producing electric signals with specialized electric organs. Objects within this field alter the electric current at electroreceptor organs, which are distributed over almost the entire body surface. During active electrolocation, fishes detect, localize and analyse objects by monitoring their self-produced electric signals. We investigated the ability of the mormyrid Gnathonemus petersii to perceive objects three-dimensionally in space. Within a range of about 12 cm, G. petersii can perceive the distance of objects. Depth perception is independent of object size, shape and material. The mechanism for distance determination through electrolocation involves calculating the ratio between two parameters (maximal slope and maximal amplitude) of the electrical image which each object projects onto the fish's skin. During active electrolocation, electric fishes cannot only locate objects in space but in addition can determine the three-dimensional shape of an object. Up to certain limits, objects are spontaneously categorized according to their shapes, but not according to their sizes or the materials of which they are made.

Animals↗