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  • 1995-1999  (1.817)
  • 1940-1944  (1.911)
  • 1900-1904
  • 1860-1869  (499)
Jahr
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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Annals of surgical oncology 6 (1999), S. 279-285 
    ISSN: 1534-4681
    Schlagwort(e): Gemcitabine ; bcl-2 ; Pancreatic cancer ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Gemcitabine is a new nucleoside analogue that produces a clinical response in 30% of patients with unresectable pancreatic carcinoma. The cytotoxic effects of many chemotherapeutic agents occur through induction of programmed cell death (apoptosis), which is controlled by the bcl-2 gene family. We determined whether induction of apoptosis by gemcitabine in pancreatic carcinoma is associated with cellular Bcl-2 content. Methods: Four pancreatic carcinoma cell lines (MIA-PaCa-2, AsPC-1, Panc-1, and Panc-48) were screened by Western blotting for Bcl-2 protein expression. Dose-response relationships for the cytotoxic effects of gemcitabine were determined using methylthiotetrazole assays, and induction of apoptosis was confirmed by fluorescence-activated cell sorting analysis. MIA-PaCa-2 cells transfected with human bcl-2 were also analyzed for gemcitabine-induced apoptosis. Results: Pancreatic cancer cell lines expressed varying amounts of Bcl-2, and the 50% lethal dose for gemcitabine-induced apoptosis was correlated with Bcl-2 content. Furthermore, Bcl-2 overexpression was associated with a significant increase in the 50% lethal dose for gemcitabine-induced apoptosis. Conclusions: Cellular Bcl-2 content was directly correlated with the cytotoxicity of gemcitabine in pancreatic carcinoma. Therefore, routine immunohistochemical analyses may be useful in predicting gemcitabine efficacy, and patients who would likely not benefit could be spared gemcitabine administration. Furthermore, the effectiveness of gemcitabine and other chemotherapeutic agents may be increased by gene therapy-mediated alteration of bcl-2 gene family members.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1434-5196
    Schlagwort(e): Key words Methadone ; Dihydrocodeine ; Substitution ; Poisoning ; Children ; Schlüsselwörter Methadon ; Dihydrocodein ; Substitution ; Intoxikationen ; Kinder
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Rechtswissenschaft
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Es wird über 3 überlebte und 4 tödlich verlaufene akzidentelle Intoxikationen, sechs mit Methadon, eine mit Dihydrocodein, berichtet. Die Intoxikationen betrafen nicht die Substituierten selbst, sondern deren Familienangehörige, Bekannte oder Mit-Patienten. In allen Fällen wurden die Substitutionsmittel weitgehend ungesichert und teilweise vermutlich auch unbeschriftet stehengelassen. Den Substituierten selbst war dabei die Gefahr, die von ihrem Substitutionsmittel ausging, offenbar nicht ausreichend bewußt. Diese Fälle zeigen deutlich, daß qualitätssichernde Maßnahmen bei der immer großzügigeren Substitutionspraxis, insbesondere in Hinblick auf „take-home“-Dosen, notwendig sind.
    Notizen: Abstract A total of seven cases of accidental ingestion of methadone or dihydrocodeine by four children and three adults are reported of which four were fatal. In each case, someone in the environment was taking methadone or dihydrocodeine as a substitute drug for heroin addiction who obviously did not realize the dangers of methadone for non-addicts. Possible preventive measures are the usage of child-proof containers with adequate labels for take-home medications. Furthermore substituted addicts have to be thoroughly indoctrinated concerning the toxicity and hazards of methadone.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1248-9204
    Schlagwort(e): Contralateral hernia ; Children ; Incidence ; Predisposing disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary It is impossible to determine whether or not a child will develop a contralateral hernia after inguinal hernia repair. There exists no risk score for the occurrence of a contralateral hernia. This well-known fact prompted us to perform the underlying study. In a retrospective trial, we reviewed the files of all children operated on for inguinal hernias in our department from January 1986 until December 1994. During this period, we performed 1721 hernia repairs on 1708 children aged 0–16 years. In 96 (5.6%) of these patients, the indication to operate was a contralateral hernia following previous unilateral repair. Comparison of the ages at the time of primary inguinal repair of those children who developed a contralateral hernia (n=96) and those who did not (n=1612) showed a significantly increased incidence of contralateral hernias if the primary operation was performed before the age of two months (p〈0.0001). Diseases predisposing to hernias were found in 38% of all children (prematurity, dystrophia, ventriculo-peritoneal shunt, ascites, asthma). The authors recommend a contralateral exploration for children under the age of two months if they have any predisposing disease.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Italian journal of neurological sciences 20 (1999), S. 119-128 
    ISSN: 1126-5442
    Schlagwort(e): Key words Learning ; Development ; Memory ; Children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Immediate and 15-min delayed recall of semantically related or unrelated word lists was investigated in 144 normally developing children ranging from 5 to 10 years of age. Immediate recall for the related and unrelated lists increased in a parallel fashion as a function of age. The ability to cluster semantically related items during immediate recall also improved with age. However, in no age class recall scores and clustering indexes were significantly associated. Forgetting rate passing from the last immediate to the delayed recall trial increased for the unrelated list but decreased for the related list of words as a function of age. Results of regression analyses revealed that a developmental increase in forgetting on the unrelated list was actually due to the higher number of words recalled in the last immediate trial by older children. As for the related list, instead, the larger reliance on the clustering strategy of recall by older children was responsible for the progressive reduction of forgetting.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Italian journal of neurological sciences 20 (1999), S. 303-307 
    ISSN: 1126-5442
    Schlagwort(e): Key words Lyme disease ; Chronic neuroborreliosis ; Children ; MRI ; Demyelinating disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Lyme disease is a polymorphic and multisystemic disease caused by Borrelia burgdorferi. Neurological manifestations are found in 10%–50% of cases. We present 2 cases followed for 5 and 6 years of chronic relapsing-remitting neuroborreliosis. Diagnosis of neuroborreliosis in these cases was based on serum and cerebrospinal fluid findings. We discuss clinical, neurophysiological, laboratory and instrumental aspects regarding the difficulties of reaching a correct diagnosis. Further studies, especially in the field of immunology, should help identify the mechanisms responsible for the disease becoming chronic. With this knowledge, it may be possible to design immunological therapies for relapses, and to prevent the evolution of the disease.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; RT/PCR ; Protooncogene ; ets-2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Protooncogenes (PO) play a crucial role for brain biology and pathology. Only the concerted action of protooncogenes enables normal brain development. The reliable and sensitive quantification of brain PO is still holding centre stage in neurobiological research. The aim of our study was therefore the determination of PO in minute amounts of brain areas. For this purpose we decided to apply the most sensitive detection principle of competitive reverse transcriptase polymerase chain reaction using capillary electrophoresis and laser-induced fluorescence detection. We selected the PO ets-2 for our studies as this transcription factor was shown to be involved in neurodegenerative disease. As little as 10ng of total RNA each were extracted from 5 different regions of human postmortem brain and used in the assay system. Our results revealed that the ets-2 gene transcript was detectable at the atto-gram level in the brain (54.5 ± 17.7 ag/ 10 ng RNA in the occipital lobe, 34.2 ± 7.5 in temporal lobe, 40.2 ± 15.6 in the frontal lobe, 31.4 ± 15.7 in the cerebellum, and undetectably low in the parietal lobe). This is the first report at this sensitivity level providing neurobiology with a powerful analytical tool.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 16 (1999), S. 71-77 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Taurine ; Marathon ; Endurance exercise
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a Marathon, 42.2km and a 100km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is per formed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 17 (1999), S. 369-376 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Non-proteinogenic dipeptides ; Dehydrodipeptides ; Diastereoselectivity ; N-Boc-Dehydroamino acids ; Asymmetric hydrogenation ; Chiral rhodium catalysts
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary N-Boc protected non-proteinogenic dipeptides with D,L-and L,L-configuration were prepared by catalytic asymmetric hydrogenation of the corresponding dehydrophenylalanyl-(L)-phenylalanine derivatives. The configuration of the new stereogenic centre depends first of all on the catalyst configuration and is less influenced by the substrate configuration. Diastereomeric excesses in the range of 80–96% de could be increased up to 99% by recrystallization. Analytical data of selected new compounds are given.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Polyclonal antibodies ; Phosalone ; Immunodetection ; Hapten synthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Hapten synthesis for the production of specific insecticide phosalone polyclonal antibodies was carried out starting from an intermediate of the phosalone synthesis, 6-chloro-2-benzoxazolone1. Two haptens containing different spacers have been prepared: N-5-carboxypentyl-6-chloro-2-benzoxazolone7 and N-(2-oxo-3-aza-5-carboxypentyl)-6-chloro-2-benzoxazolone12. Each of these two haptens conjugated to bovine serum albumine (BSA) was used to immunize four rabbits. Immunoassays of phosalone were performed with ELISA using solid-phase bound hapten thyroglobulin conjugate and horseradish peroxidase labelled goat antirabbit IgG. The more sensitive response was observed when the antiserum obtained from the rabbit immunized with the hapten-BSA conjugate containing the N-2-oxo-3-aza-5-carboxypentyl spacer was in competition with the same hapten coupled to thyroglobulin. An identical response was obtained under the same conditions when using benzoxazolone instead of phosalone as competitor, showing a good recognition of the specific aromatic part of the organophosphate insecticide phosalone. Reduction of coating conjugate concentration (from 2 to 0.05μg/well) and also the use of heterologous coating protein instead of homologous did improve the sensitivity, resulting in a concentration of phosalone required to inhibit binding by 50% of 2 mg/l and a detection limit of 0.02 mg/l.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Liver ; Hepatic damage ; Carbon tetrachloride
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The aims of the present study were to assess the changes of individual plasma amino acid levels in relation (1) to the severity of liver damage and (2) to the process of liver recovery. Acute liver injury was induced by an intragastric administration of CCl4 diluted in olive oil in doses of 2, 4 and /or 6 g of CCl4 per kg b.w. The control rats received olive oil only. Animals were sacrificed at 16, 24, 48 and 96 hours after treatment. The severity of liver injury was assessed by histological examination, by changes in ALT and AST in the blood plasma and by changes in liver weight. Statistical analysis was carried by ANOVA, p 〈 0.05 was considered significant. The Spearman rank correlation coefficient was used as a measure of the degree of linear relationship between variable and dose. In the period of the development of acute liver damage, i.e. at 16 and 24 hours after treatment, an increase in blood plasma amino acid levels and positive correlations with the dose of CCl4 were observed for most individual amino acids. The only exception was arginine which decreased in a dose dependent manner. At a phase of liver recovery, i.e. at 48 and 96 hours after CCl4 treatment, the concentrations of some individual amino acids decreased below the control values. The negative correlation with the dose of CCl4 occurred for taurine and isoleucine (at 48 hours) and taurine, threonine, valine, methionine, isoleucine and leucine (at 96 hours).
    Materialart: Digitale Medien
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  • 11
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Alanine ; Fatty acids ; Glutamine and glutamate synthesis ; Glycerol and lactate metabolism ; Malate-aspartate shuttle ; Rabbit kidney-cortex tubules ; Renal gluconeogenesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In isolated rabbit renal cortical tubules, glucose synthesis from 1 mM alanine is negligible, while the amino acid is metabolized to glutamine and glutamate. The addition of 0.5 mM octanoate plus 2 mM glycerol induces incorporation of [U-14C]Alnine into glucose and decreases glutamine synthesis, whereas oleate and palmitate in the presence of glycerol are less potent than octanoate. Gluconeogenesis is also significantly accelerated when glycerol is substituted by lactate. In view of an increase in14CO2 fixation and elevation of both cytosolic and mitochondrial NADH/NAD+ ratios, the activation of glucose formation from alanine upon the addition of glycerol and octanoate is likely due to (i) stimulation of pyruvate carboxylation, (ii) increased availability of NADH for glyceraldehyde-3-phosphate dehydrogenase and (iii) elevation of mitochondrial redox state causing a diminished provision of ammonium for glutamine synthesis. The induction of gluconeogenesis in the presence of alanine, glycerol and octanoate is not related to cell volume changes. The results presented in this paper show the importance of free fatty acids and glycerol for regulation of renal gluconeogenesis from alanine. The possible physiological significance of the data is discussed.
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 16 (1999), S. 79-89 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Anti-neoplastic amino acids ; Purine and DNA synthesis inhibitors ; PRPP amido transferase and IMP dehydrogenase inhibitors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 4-Hydroxyproline di- and tri-peptides and N-cbz-hydroxypropylglycinamides were observed to be potent cytotoxic agents against the growth of suspended single cells, L-1210, Tmolt3, and HeLa-S3. The agents were not as potent against the growth of cultured solid tumor cells. Selected derivatives were investigated for their mode of action in Tmolt3 leukemia cells. The compounds selectively inhibited DNA synthesis at 50 and 100smM. The target site of action of the agents appeared to be the purinede novo pathway with marked inhibition of the activities of the two regulatory enzymes of the pathway, i.e. PRPP amido-transferase and IMP dehydrogenase. d[NTP] pools were reduced by the agents consistent with their overall reduction of DNA synthesis. Other marginally inhibited targets of the agents were r-RNA polymerase and TMP-kinase activities. The DNA molecule itself did not appear to be a target of these agents.
    Materialart: Digitale Medien
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  • 13
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Targeting ; Mitochondria ; Chloroplasts ; Cysteine synthase ; Transit peptide ; Transgenic plants ; Processing
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Cysteme synthase, the key enzyme for fixation of inorganic sulfide, catalyses the formation of cysteine from O-acetylserine and inorganic sulfide. Here we report the cloning of cDNAs encoding cysteine synthase isoforms fromArabidopsis thaliana. The isolated cDNA clones encode for a mitochondrial and a plastidic isoform of cysteine synthase (O-acetylserine (thiol)-lyase, EC 4.2.99.8), designated cysteine synthase C (AtCS-C, CSase C) and B (AtCS-B; CSase B), respectively.AtCS-C andAtCS-B, having lengths of 1569-bp and 1421-bp, respectively, encode polypeptides of 430 amino acids (∼45.8 kD) and of 392 amino acids (∼ 41.8 kD), respectively. The deduced amino acid sequences of the mitochondrial and plastidic isoforms exhibit high homology even with respect to the presequences. The predicted presequence of AtCS-C has a N-terminal extension of 33 amino acids when compared to the plastidic isoform. Northern blot analysis showed thatAtCS-C is higher expressed in roots than in leaves whereas the expression ofAtCS-B is stronger in leaves. Furthermore, gene expression of both genes was enhanced by sulfur limitation which in turn led to an increase in enzyme activity in crude extracts of plants. Expression of theAtCS-B gene is regulated by light. The mitochondrial, plastidic and cytosolic (Hesse and Altmann, 1995) isoforms of cysteine synthase ofArabidopsis are able to complement a cysteine synthasedeficient mutant ofEscherichia coli unable to grow on minimal medium without cysteine, indicating synthesis of functional plant proteins in the bacterium. Two lines of evidence proved thatAtCS-C encodes a mitochondrial form of cysteine synthase; first, import ofin vitro translation products derived from AtCS-C in isolated intact mitochondria and second, Western blot analysis of mitochondria isolated from transgenic tobacco plants expressing AtCS-C cDNA/c-myc DNA fusion protein.
    Materialart: Digitale Medien
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  • 14
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Non-proteinogenic optically active amino acids ; Dehydroamino acids ; Chiral rhodium catalysts ; Asymmetric hydrogenation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary (Z)-α-[(Benzyloxy)- or (tert.-butyloxy)carbonylamino]-β (thienyl)-or (furyl)-acrylic acids and their esters were prepared by known methods and hydrogenated to the corresponding optically active alanine derivatives with optical yields in the range of 58–93% ee using the cationic rhodium complex of “PROPRAPHOS”.
    Materialart: Digitale Medien
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  • 15
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; L-Tryptophan ; Serum albumin ; Transport ; L-Tryptophan depletion ; α-Methyl-DL-tryptophan ; Analbuminemic rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The role of serum albumin in the transport of orally administered L-tryptophan (Trp) into rat tissues was examined using analbuminemic and Sprague-Dawley (SD) rats with and without a-methyl-DL-tryptophan (AMT)-induced Trp depletion. Trp was orally administered to rats 16h after AMT or 0.85% NaCl administration, when liver tryptophan 2,3-dioxygenase and protein synthetic activities in AMT-treated rats were similar to those of 0.85% NaCl-treated rats. After oral Trp administration, regardless of the presence or absence of Trp depletion, free serum Trp concentrations were similar in the analbuminemic and SD rats, while total serum Trp concentrations were lower in analbuminemic rats than in SD rats. Although liver, brain, and muscle Trp concentrations after oral Trp administration under Trp depletion were lower in analbuminemic rats than in SD rats, the ratio of the liver Trp concentration in analbuminemic rats to that in SD rats was smaller than that of the brain or muscle Trp concentration. These results suggest that variations in serum albumin levels could affect the transport of orally administered Trp into the liver of rats with Trp depletion.
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 16 (1999), S. 107-111 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Tissue protein synthesis ; Stable isotope amino acids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The tracers L15N-proline and L(1-13C)-leucine were used to explore the synthesis of skin proteins in vivo in rabbits. They orally received a single dose containing an equimolecular mixture of L(1-13C)-leucine and L15N-proline. The changes in the amounts of these tracers in blood and skin were monitored for a total of 8 h. The data showed the appearance of the two tracers in blood within 15 min and their clearance in 8h. They were both rapidly (15 min) incorporated into skin proteins, but more proline was incorporated than leucine. We therefore consider L15N-proline to be a better tracer than L(1-13C)-leucine for studying protein metabolism in the skin.
    Materialart: Digitale Medien
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  • 17
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Taurine ; Kainic acid ; Epilepsy ; Anticonvulsants ; Neuroprotection ; Excitatory amino acids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Male Sprague-Dawley rats received TAU supplementation (1.5% in drinking water) or TAU deficient diets for 4 weeks to test for a possible neuroprotective role of TAU in KA-induced (10 mg/kg s.c.) seizures. TAU supplementation significantly increased serum and hippocampal TAU levels, but not TAU content in temporal cortex or striatum. TAU deficient diets did not attenuate serum or tissue TAU levels. Dietary TAU supplementation failed to decrease the number or latency of partial or clonic-tonic seizures or wet dog shakes, whereas a TAU deficient diet decreased the number of clonictonic and partial seizures. This study does not support previous observations of an anticonvulsant effect of TAU against KA-induced seizures. KAtreatment decreasedα 2-adrenergic receptor binding sites and TAU content in the temporal cortex across all dietary treatment groups, supporting previous evidence of severe KA-induced damage and neuronal loss in this brain region.
    Materialart: Digitale Medien
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 16 (1999), S. 191-213 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Enzymatic resolution ; Ester hydrolysis ; Proteases ; Lipases
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The present review outlines recent examples of enzyme-based resolution procedures for amino acids via the hydrolysis of their esters. The resolutions have been achieved by using proteases (α-chymotrypsin, subtilisin and other microbial proteases, and sulfhydryl proteases of plant origin) and lipases. Relevant work utilizing yeast and other microbial cells is also included.
    Materialart: Digitale Medien
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 16 (1999), S. 251-272 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Unusual amino acids ; Aspartic acidβ-semialdehyde ; Aspartaldehyde ; 2-Amino-4-oxobutyric acid ; Enantioselective synthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Strategies for the synthesis of optically active aspartaldehyde derivatives are reviewed. Most of them are using the chiral pool: allylglycine or naturally occurring homoserine, aspartic acid or methionme and side chain modifications. This will be developed in the first part. Some other original routes are also displayed in the second part. Different aspects of each strategy are discussed: the nature and number of steps, the problem of protecting groups, the price and availability of starting materials. Some synthetic applications of such interesting chiral synthons are shown in the last part.
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  • 20
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Dipeptide derivatives ; Non-proternogenic optically active dipeptide esters ; Dehydrodipeptides ; Chiral rhodium catalysts ; Asymmetric hydrogenation ; Diastereoselectivity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary N-[(Z)-N-Benzoyl- orN-Boc-(2-fluorophenyl)dehydroalanyl]-(R)-or (S)-phenylalanine esters were synthesized and hydrogenated to give the corresponding dipeptide derivatives with optical yields in the range of 53–87%de using the cationic rhodium complexes of PROPRAPHOS and BPPM. The efficiency of chiral diphosphine ligands as well the effect of the chiral center in the substrate on the catalytic asymmetric induction was studied.
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  • 21
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Phytotoxin AS-I analogues ; FAB ; PD ; ESI mass spectrometry ; 1H,13C and 2D NMR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A series of six tetrapeptides, analogues of AS-I phytotoxin, pathogenic to sunflower, have been synthesized either in solution and/or by solid phase methods and have been tested for phytotoxic activity in various plants and cytotoxic activity in three cancer cell lines. These peptides were identified as model compounds by fast atom bombardment (FAB), plasma desorption (PD), electrospray ionization (ESI) mass spectrometry and by1H,1H-1H,13C and1H-13C NMR. The data presented show that in protected tetrapeptides the molecular ion was easily identified whereas some difficulties appeared with the fully deprotected peptides. NMR spectra are given.
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  • 22
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Diclofenac ; Anti-phlogistics ; Non-proteinogenic amino acids ; Voltaren®. Thionation ; Cyclo-oxygenase inhibitors ; Ulcerogenic gastritis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In search for more potent, particularly less ulcerogenic gastritis that hopefully replace the universal NSAID “Diclofenac”, (2-[(2,6-di-chlorophenyl)amino]-phenylacetic acid, C.A.S. 15307-86-5), twelve new non-proteinogenic amino acid conjugates of the drug, namely that of sarcosine,β-alanine, D-leucine and D-phenylalanine, were synthesized and biologically screened for their anti-inflammatory, analgesic and ulcerogenic activity in rats. “Diclofenac” amino acid esters (IIa-d), were synthesizedvia the corresponding HOSu or HOBt active esters. Alkaline hydrolysis (NaOH) followed by acidification (KHSO4) or thioamide formation (Lawsson's Reagent, C.A.S. 19172-47-5), afforded the corresponding free acids IIIa-d or the thioamides IVa-d respectively. Interestingly, in contrary to the parent “Diclofenac”, the synthesized candidates (except IIId), were entirly nonulcerogenic in rats. Further, they considerably retained a generelized anti-phlogistic activity. The major “Diclofenac” irritating gastric side effect was thus eliminated. Particularly, the sarcosine conjugate IIa and its thiomimic IVa exhibit promising therapeutic perspectives.
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 17 (1999), S. 139-148 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Polyamine oxidase ; Polyamines ; Gender ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Variations in level of polyamines and their related enzymes are frequently observed in response to some treatments which affect in a different way male and female. The possibility of a gender-related difference in the oxidation of polyamines was investigated in rats by measuring the activity of polyamine oxidase, a ubiquitous enzyme of vertebrate tissues, which transforms spermine into spermidine and spermidine into putrescine. The study was carried out on thymus, spleen, kidney and liver of young rats of both sexes, and female rats showed a lower polyamine oxidase activity than male rats in all the tissues. We also found higher values of spermidine acetylation in female than male rats in thymus and liver. Owing to these gender-related differences, a higher spermidine N-acetyltransferase/ polyamine oxidase ratio was found in female than in male rats. A second gender-related difference was a higher spermidine/spermine ratio in female than in male, the only exception being the thymus. These basal differences possibly account for the gender-related differences of polyamine metabolic enzyme activities in response to some treatments, including drugs or hormones.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 17 (1999), S. 195-205 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Apis mellifera ; Drones ; Osmolarity ; Age dependency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In the haemolymph of honeybee drones, concentrations of free amino acids were higher than in worker haemolymph, with different relative proportions of individual amino acids. The overall concentration of free amino acids reached its highest level at the 5th day after adult drone emergence, and after the 9th day only minor changes in the concentration and distribution of free amino acids were observed. This coincides with the age when drones reach sexual maturity and change their feeding behaviour. Levels of essential free amino acids were high during the first 3 days of life and thereafter decreased. Osmolarity was lowest at emergence (334 ± 41 mOsm), increased until the age of 3 days (423 ± 32mOsm) and then stayed generally constant until the 16th day of life. Only 25-day-old drones had significantly higher osmolarity (532 ± 38 mOsm). The overall change in osmolarity during a drone's lifetime was about 40%.
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  • 25
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Conformational constraint ; Cyclic disulfides ; -Cys-Cys-peptides ; Dipeptide mimetics ; Dithiols ; Glutathione analogues
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The glutathione analogue γ-(H-Glu-OH)- -OH (5), containing the 8-membered disulfide ring- replacing the native -Cys-Gly fragment, has been synthesized and characterized together with its reduced dithiol form γ-(H-Glu-OH)-Cys-Cys-OH (6).
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  • 26
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Polyamine catabolism ; Polyamine oxidase ; Diamine oxidase ; Testosterone ; Mouse kidney
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In the present study developmental patterns of renal polyamineoxidizing enzymes polyamine oxidase (PAO) and diamine oxidase (DAO) in male and female ICR mice were demonstrated. The effects of testosterone (10μg/100g body weight) on renal PAO and DAO activities were also studied. The differences between sexes in both PAO and DAO activities were most clearly expressed in the immature kidney. At the age of 20 days PAO and DAO activities were 1.52 fold (p 〈 0.01) and 1.75 (p 〈 0.02) respectively higher in male mouse kidney than in female. Maturational processes reflected in significant increases in polyamine- oxidizing enzyme activities mainly in female mouse kidney, comparable with the gain in the kidney wet weight. Our data show that testosterone is able to influence renal PAO and DAO activities in addition to the well-known stimulation of polyamine biosynthesis. The hormonal effects were sex and age dependent. The influence of testosterone on renal PAO activity was mainly age dependent. The slight stimulation of renal PAO activity observed in 20- and 50-day old mice, 24h after testosterone administration, change with a decrease in the enzyme activity at the age of 70 days. The effects of testosterone on renal DAO activity were mainly sex dependent. Testosterone caused stimulation of DAO activity with a very close magnitude (nearly twice) in female mouse kidney, independently of the age of mice. In contrast, in male mice the hormone treatment resulted in a statistically significant increase in renal DAO activity at the age of 70 days (.1.3 fold, p 〈 0.05) only. It could be suggested that our data indicate the different contribution of renal PAO and DAO in androgen regulation of polyamine levels, depending on sex and the stage of the postnatal development.
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  • 27
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Allohydroxyproline ; Allothreonine ; Chiral separation ; Chirasil-Val ; Hydroxyproline ; Threonine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Experimental conditions for the derivatization and resolution by GLC of all stereoisomers of threonine and 4-hydroxyproline are reported. Threonine was in two steps converted toN,O-bisisobutoxycarbonyl 2,2,2-trifluoroethyl ester derivatives, the second of which was performed under anhydrous conditions. As such the enantiomers could pairwise be separated by capillary gas chromatography on a Chirasil-Val column. SinceL- andD-threonine eluted much earlier than the corresponding allo forms, quantitative determination of the allothreonine content inD- orL-threonine down to the one percent level could be simply accomplished but also enantiomeric impurities could be determined. Unlike for threonine, the corresponding 4-hydroxyproline isomers could not all be resolved asN,O-bisisobutoxycarbonyl 2,2,2-trifluoroethyl esters on this column. Although diastereomers could still be separated, the allo pair cochromatographed and the resolution for theL- andD-isomers was low. Complete separation of the 4-hydroxyproline isomers could be accomplished asN,O-bisprotected isobutyl amides, the formation of which required three derivatization steps. These were used for the determination of allohydroxyproline.
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 17 (1999), S. 323-334 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Taurine release ; Cerebellar granule cells ; Celldamaging conditions ; Glutamate receptors ; Veratridine ; Potassium stimulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The release of taurine from cultured cerebellar granule neurons was studied in different cell-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress and in the presence of free radicals. The effects of both ionotropic and metabotropic glutamate receptor agonists on the release were likewise investigated. The release of [3H]taurine from the glutamatergic granule cells was increased by K+ (50mM) and veratridine (0.1 mM), the effect of veratridine being the greater. Hypoxia and ischemia produced an initial increase in release compared to normoxia but resulted in a diminished response to K. Hypoglycemia, oxidative stress and free radicals enhanced taurine release, and subsequent K− treatment exhibited a correspondingly greater stimulation. A common feature of taurine release in all the bove conditions was a slow response to the stimulus evoked by K+ and particularly to that evoked by veratridine. All ionotropic glutamate receptor agonists potentiated taurine release, but only the action of kainate seemed to be receptor-mediated. Metabotropic receptor agonists of group I slightly stimulated the release. The prolonged taurine release seen in both normoxia and cell-damaging conditions may be of importance in maintaining homeostasis in the cerebellum and reducing excitability for a longer period than other neuroprotective mechanisms.
    Materialart: Digitale Medien
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  • 29
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Taurine ; Osmoregulation ; Rat ; Osmolarity sensor protein ENVZ
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Although the involvement of taurine in osmoregulation is well-documented and widely accepted, no detailed mechanism for this function has been reported so far. We used subtractive hybridization to study mRNA steady state levels of genes up- or downregulated by taurine. Rats were fed taurine 100mg/kg body weight per day for a period of three days and hearts (total ventricular tissue) of experimental animals and controls were pooled and used for mRNA extraction. mRNAs from two groups were used for subtractive hybridization. Clones of the subtractive library were sequenced and the obtained sequences were identified by gen bank assignment. Two clones were found to contain sequences which could be assigned to the osmolarity sensor protein envZ, showing homologies of 61 and 65%. EnvZ is an inner membrane protein in bacteria, important for osmosensing and required for porine gene regulation. It undergoes autophosphorylation and subsequently phosphorylates OmpR, which in turn binds to the porin (outer membrane protein) promoters to regulate the expression of OmpF and OmpC, major outer membrane porines. This is the first report of an osmosensing mechanism in the mammalian system, which was described in bacteria only. Furthermore, we are assigning a tentative role for taurine in the osmoregulatory process by modifying the expression of the osmoregulatory sensor protein ENVZ.
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  • 30
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Protein ; arginine methyltransferase ; Inhibitors ; Ginseng extract ; Arginine derivatives ; Basic amino acids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Protein-arginine N-methyltransferase (protein methylase I) catalyzes methylation of arginyl residues on substrate protein posttranslationally utilizing S-adenosyl-L-methionine as the methyl donor and yields NG-methylarginine residues. Arginyl-fructose and arginyl-fructosyl-glucose from Korean red ginseng were found to inhibit protein methylase I activity in vitro. This inhibitory activity was shown to be due to arginyl moiety in the molecules, rather than that of carbohydrates. Several basic amino acids as well as polyamines were also found to inhibit protein methylase I activity. Interestingly, the intensity of the inhibitory activity was correlated with the number of amino-group in polyamines, thus, in the order of spermine 〉 spermidine 〉 putrescine 〉 agmatine-sulfate, with IC50 at approximately 15 mM, 25 mM, 35 mM, and 50 mM, respectively. On the other hand, neutral amino acids or NaCI did not inhibit the enzyme activity. Lineweaver-Burk plot analysis of the protein methylase I activity in the presence of arginine and spermidine indicated that the inhibition was competitive in nature in respect to protein substrate, with the Ki values of 24.8 mM and 11.5 mM, respectively.
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  • 31
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Hexafluoroacetone ; α-N-Methylamino acids ; α-N-Phosphinoylmethylamino acids ; Pro-Glu-chimeras ; Pro-Tauchimeras
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A new method for the preparation of N-methylamino acids and some of their derivatives starting from hexafluoroacetone protected amino acids is described. The new concept results in saving of steps compared to conventional protection/activation techniques. Protection and deprotection proceed without racemization.
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  • 32
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Perfluorinated compounds ; Surfactants ; Complexing properties ; Carnosine ; β ; Amino acids ; Blood substitutes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The reaction of amines or sodium azide with 3-perfluoroalkyl-3-fluoroprop-2-enoate, followed by hydrogenation, affords perfluoroalkylatedβ-alanine analogues in very good yields. These compounds can be linked via an amide bond to produce peptide analogues such as carnosine or carcinine derivatives, which could have surfactive and complexing properties.
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 16 (1999), S. 415-423 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; SOD-like activity ; Cu (III)-Poly-L-lysine ; Cu(III)-Poly-L-glutamic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The SOD-like activity of Cu(III) -complexes with polypeptides poly-L-lysine and poly-L-glutamic acid respectively was investigated. The Cu(II)-polypeptide complexes were first oxidized by K2IrCl6 to give the corresponding Cu(III) -compounds. The oxidation of Cu(II) and the corresponding Cu(II)/Cu(III) potential was evaluated by cyclic voltammetry (c.v.), UV-Vis and EPR spectroscopic (r.t.) experiments. Spin trapping EPR spectra were also conducted to confirm the formation of the superoxide radical. The SOD-like activity of each Cu(III)-complex was proved using the nitro blue tetrazolium (NBT) method slightly modified.
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  • 34
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Lysine ; Herbicides ; Azotobacter ; Xenobiotics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Production of lysine byAzotobacter chroococcum strain H23 was studied in chemically-defined media amended with different concentrations of alachlor, metolachlor, 2,4-D, 2,4,5-T and 2,3,6-TBA. The presence of 5, 10, and 50μg/ml of alachlor or 2,3,6-TBA significantly decreased quantitative production of lysine. However, the presence 2,4-D or 2,4,5-T at concentrations of 10 and 50μg/ml enhanced the production of lysine. Quantitative production of lysine was not affected as consequence of the addition of metolachlor to the culture medium, showing that the release lysine to the culture media byA. chroococcum was not affected by that herbicide.
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  • 35
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Trypanothione ; Glutathione ; Benzyloxycarbonyl-reductase ; Hydrocinnamoyl
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Kinetic data for alternative substrates of recombinant trypanothione reductase fromTrypanosoma cruzi were measured for a series ofN-substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteineN-substituent was either a variant of the benzyloxycarbonyl group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH2. or NH had relatively minor effects on kcat, but raised the value of Km, 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy group, anN-L-phenylalanyl orN-L-tryptophanyl replacement on the cysteine hardly altered kcat, but increased Km, values by 16.6 and 7.4 fold, respectively. These observations were consistent with the Km, values referring primarily to binding for this series of nonspecific substrates.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 17 (1999), S. 243-255 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Serotonin receptor ; Serotonin-3 receptor ; Ion channel ; Ion permeability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Human 5-HT3 receptors expressed in HEK 293 cells were studied using patch-clamp techniques. The permeability ratios of cations to Na+ were Li+, 1.16; K+, 1.04; Rb+, 1.11; Cs+ 1.11; NMDG+, 0.04; Ca2+, 0.49, and Mg2+, 0.37. The permeability sequence of the alkali metal cations was Li+ 〉 Rb+ = Cs+ 〉 K+ 〉 Na+. Increased external concentrations of Ca2+ or Mg2+ decreased 5-HT-induced currents at all potentials tested in a voltage-independent manner. The single-channel conductance of human 5-HT3 receptors measured by fluctuation analysis of whole-cell currents was 790 ± 100fS. Differences in the basic properties of 5-HT3 receptors between species may explain interspecies differences in pharmacological properties.
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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 17 (1999), S. 301-313 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Taurine ; Transporter ; Rat ; Brain ; Heart
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In pro- and eucaryotic life, cellular and subcellular compartments are separated by membranes and the regulated and selective passage of specific molecules across these membranes is a basic and highly conserved principle. We were interested whether taurine, a naturally occuring amino acid, would be able to induce or suppress expression of transporters with the Rationale that taurine was shown to detoxify a series of endogenous toxins and xenobiotics of various chemically non-related structures. For this purpose we used a gene hunting technique, subtractive hybridization, subtracting mRNAs of taurine-treated rat brain and heart from untreated controls. Subtracted mRNAs were then converted to cDNAs, amplified, sequenced and identified by gene bank data. We found five transporter transcripts, the phosphonate transport ATPase PHNC, multidrug transporter homolog MTH104, protein-exportmembrane protein SECD, oligopeptide transporters oppA and oppD, in the brain and two: ABC-transporter BRAF-2 and cation-transport ATPase PACS, in the heart. Homologies of the sequences found were in any case 〉50% thus permitting the identification of transporters with high probability. The biological meaning could be that a naturally occuring amino acid, taurine, modulates complex transport systems. The most prominent finding is the upregulation of a multidrug transporter transcript, explaining a mechanism for the nonselective detoxifying action of taurine.
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  • 38
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Tyrosine ; Phenylalanine ; Aromatic compounds ; Rumen microorganisms[/klw]
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Rumen contents from three fistulated Japanese native goats fed Lucerne hay cubes (Medicago sativa) and concentrate mixture were collected to prepare the suspensions of mixed rumen bacteria (B), mixed protozoa (P) and a combination of the two (BP). Microbial suspensions were anaerobically incubated at 39°C for 12h with or without 1 MM ofl-phenylalanine (Phe). Phe, tyrosine (Tyr) and other related compounds in both supernatant and microbial hydrolysates of the incubations were analyzed by HPLC. Tyr can be produced from Phe not only by rumen bacteria but also by rumen protozoa. The production of Tyr during 12h incubation in B (183.6 μmol/g MN) was 4.3 times higher than that in P. One of the intermediate products between Phe and Tyr seems to bep-hydroxyphenylacetic acid. The rate of the net degradation of Phe incubation in B (76.O μmol/g MN/h) was 2.4 times higher than in P. In the case of all rumen microorganisms, degraded Phe was mainly (〉53%) converted into phenylacetic acid. The production of benzoic acid was higher in P than in B suspensions. Small amount of phenylpyruvic acid was produced from Phe by both rumen bacteria and protozoa, but phenylpropionic acid and phenyllactic acid were produced only by rumen bacteria.
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  • 39
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 17 (1999), S. 357-368 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; o-Carboranylalanine ; Histidine ; Bacteria ; Fungi ; Oomycota ; Plasmopara
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Functionalized polyhedral carboranes, including amino acid analogs, have unique physicochemical properties and are used as experimental anticancer agents. However, our current knowledge on their effect in nonmammalian biological systems is limited. We investigated the activity spectrumin vitro ofo-carboranylalanine (o-Cba), considered to be a highly lipophilic analog of phenylalanine, against representative plant pathogenic bacteria and fungi of various taxonomic position. The antibacterial effect ofo-Cba against some species was comparable to that of the widely used agricultural antibiotic, streptomycin. The sensitivity of individual bacterial species too-Cba within the same genus varied to a greater extent than the average sensitivity of various genera. In general, this carborane-containing amino acid was more toxic to Gram positive bacteria (Bacillus, Corynebacterium, Curtobacterium, Micrococcus, Rhodococcus, and Staphylococcus) than to Gram negative ones (Agrobacterium, Erwinia, Escherichia, Pseudomonas, Rhizobium, and Xanthomonas). Compared to the commercial fungicide, prochloraz,o-Cba was weakly toxic against various fungi (Zygo- and Ascomycota). It was also inferior to the commercial fungicide metalaxyl in inhibiting the vegetative growth of oomyceteous plant pathogens (Pythium irregulare, Phytophthora cryptogea and Plasmopara halstedii). Against the asexual spores of P. halstedii,o-Cba, however, was over a thousandfold more active than tridemorph, a selective zoospore inhibitor fungicide. For all taxonomic groups, the observed antimicrobial effect ofo-Cba could be diminished with histidine, but not with phenylalanine. In studies on healthy and mildew-infected sunflower and tobacco plantso-Cba showed neither fungicidal nor phytotoxic effects at 500ppm. This is the first report on the biological activity spectrum of a carborane-containing amino acid.
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    Amino acids 17 (1999), S. 401-413 
    ISSN: 1438-2199
    Schlagwort(e): Amino acids ; Indolylacrylic acid ; Tryptophan ; Indolylacryloylglycine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In addition to the main catabolic routes of tryptophan (Trp), there exist minor and less thoroughly investigated pathways; one of these leads to indolylacrylic acid (IAcrA). IAcrA is a plant growth hormone, whereas its biological role in animals is still obscure, as is the way and site where it is formed in the organism. A two-stage production is likely: Intestinal microorganisms catabolize Trp to indole derivatives which are then absorbed and converted to IAcrA and its glycine conjugate, indolylacryloylglyeine (IAcrGly). Our finding of IAcrGly in the urine of proven germ-free piglets points to the possibility that Trp can be converted to IAcrA without the intervention of intestinal microorganisms. Seasonal and age variations, influence of light and connection with photodermatoses have been reported. Besides other pathological conditions the differences in IAcrGly excretion relative to normal controls were especially pronounced in some myopathies, namely in boys with Duchenne muscular dystrophy.
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 77 (1999), S. 189-192 
    ISSN: 1432-1440
    Schlagwort(e): Key words Thyroid ; Cell culture ; Retinoids ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Retinoids influence proliferation and differentiation in transformed thyroid cell lines. Retinoids are able to damage cells by destabilizing lysosomal membranes and induce apoptosis in certain cell lines. In normal thyrocytes retinol modulates iodine metabolism. At concentrations higher than 50×10–6 M retinoids are cytotoxic for normal (not transformed) thyroid cells. The mechanism of this cytotoxicity is unknown. We studied the effect of 7–80×10–6 M retinol on porcine follicular thyrocytes in culture. In order to differentiate between membrane-destabilizing effects and apoptosis we investigated cultures after incubation with retinol by light- and electron-microscopy and by labeling of potential nicks in the DNA helix by terminal deoxynucleotidyltransferase-dUTP mediated DNA nick end labeling. We conclude that the observed cytotoxicity is caused mainly by the induction of apoptosis.
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 77 (1999), S. 282-293 
    ISSN: 1432-1440
    Schlagwort(e): Key words Chronic lymphocytic leukemia ; Apoptosis ; Cell growth ; Signaling ; Review
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Chronic lymphocytic leukemia is a malignant disease characterized by clonal expansion of relatively mature B-lymphocytes with a high percentage of cells arrested in the nonproliferative G0/G1 cell cycle phase. Possibly reflecting the clinical heterogeneity observed in patients, various signaling pathways may become affected during the initiation and course of this disease. This review discusses frequent alterations concerning proliferative, differentiation-inducing, and apoptotic pathways elucidated in the recent years that have improved our understanding of this disease.
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  • 43
    ISSN: 1432-1912
    Schlagwort(e): Key words Asphyxia ; Nitric oxide ; Electron spin ; resonance ; Adrenocorticotropin ; Resuscitation ; S-Methylisothiourea ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Anaesthetized rats, endotracheally intubated and mechanically ventilated with room air, were subjected to a 5-min period of asphyxia by turning off the ventilator. The ventilator was then turned back on and, simultaneously, the animals were treated with either the adrenocorticotropin fragment 1–24 [ACTH-(1–24), 160 µg/kg in a volume of 1 ml/kg i.v.] or an equivalent volume of saline. Nitric oxide (NO)-haemoglobin formation was detected ex vivo in arterial blood by electron spin resonance spectrometry; arterial blood pressure, electrocardiogram (ECG) and electroencephalogram (EEG) were monitored for a 60-min observation period, or until prior death. During asphyxia, there was massive formation of NO (red cell concentrations 40–80 µM), associated with a dramatic fall in mean arterial pressure and pulse pressure, marked bradycardia and ECG signs of ischaemic damage, as well as an isoelectric EEG. Treatment with ACTH-(1–24) produced a prompt (within 15 min) and long-lasting drop in NO blood levels, associated with an almost immediate (within 1 min) restoration of cardiovascular function and with a more gradual recovery of EEG, which became normal after 30–40 min; all parameters remained stable throughout the 60-min observation period. In saline-treated rats, on the other hand, there was a further increase in NO blood levels, as detected 3 min after treatment, and all died within 5–8 min. Moreover, pretreatment and treatment with S-methylisothiourea sulphate (SMT, 3 mg/kg i.v.), a relatively specific inhibitor of inducible NO synthase, inhibited NO formation, but did not affect the mortality rate (100% within 5–8 min). The present results provide the first evidence that prolonged asphyxia is associated with high blood concentrations of NO, and that the life-saving effect of melanocortin peptides in severe hypoxic conditions is associated with a complete normalization of NO blood levels. However, the lack of SMT protection in this experimental model seems to rule out the possibility that the ACTH-(1–24)-induced resuscitation is due to an effect on NO overproduction.
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 117-122 
    ISSN: 1432-1912
    Schlagwort(e): Key words Ethanol ; Restraint stress ; NMDA receptor complex ; Memantine ; Drug discrimination ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There is a large body of experimental evidence that both stress and N-methyl-d-aspartate (NMDA) receptor antagonists may alter acute behavioural effects of ethanol. Notably, an uncompetitive, low-affinity NMDA receptor antagonist, memantine, has been recently claimed to possess anti-craving properties in rats with a long-term history of ethanol consumption. The aim of the present study was to assess the effects of restraint stress and memantine on the dose-response curve of ethanol discrimination. Rats were trained to discriminate 1 g/kg ethanol from saline in the two-lever drug discrimination procedure. When ethanol discrimination was acquired, the subjects were exposed to 30-min sessions of acute restraint stress, and different doses of ethanol (0.25, 0.5 or 1 g/kg) or saline were administered. In subsequent experiments the effects of memantine (2.25 or 4.5 mg/kg) on the cueing effects of ethanol were tested. Neither the stress sessions nor memantine influenced the ethanol discrimination dose-response curve. Moreover, the stress did not alter the rate of responding. However, both doses of memantine tended to increase the rate of responding when given in combination with lower doses of ethanol (0.25–0.5 g/kg). In contrast, 4.5 mg/kg memantine decreased the response rate when combined with 1 g/kg ethanol. These results suggest that: (1) pre-exposure to acute restraint stress or memantine does not affect the dose-response curve of ethanol discrimination; (2) memantine given in combination with low doses of ethanol may stimulate operant behaviour in the food-reinforced drug discrimination procedure.
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    Biology and fertility of soils 29 (1999), S. 257-261 
    ISSN: 1432-0789
    Schlagwort(e): Key words Alpine nitrogen cycle ; Amino acids ; Kobresia myosuroides ; Organic nitrogen ; Plant-microbe competition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Geologie und Paläontologie , Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract  Microbes are assumed to possess strong competitive advantages over plants for uptake of nutrients from the soil. The finding that non-mycorrhizal plants can obtain a significant fraction of their N requirement from soil amino acids contradicts this assumption. The amino acid glycine (Gly) has been used as a model amino acid in many recent studies. Our preliminary studies showed that Gly was a poor substrate for microbial growth compared to other amino acids. We tested the hypothesis that the alpine sedge Kobresia myosuroides competes better for Gly than for other amino acids because of decreased microbial demand for this compound. Soil microbial populations that could grow using Gly as a sole carbon source were about 5 times lower than those that could grow on glutamate (Glu). Gly supported a significantly lower population than any of the ten other amino acids tested except serine. In contrast, K. myosuroides took up Gly from hydroponic solution at faster rates than Glu. In plant-soil microcosms, plants competed with soil microbes 3.25 times better for Gly than for Glu. We conclude that the low microbial demand and the rapid plant uptake of Gly relative to other amino acids allow Gly to be an especially important nitrogen source for K. myosuroides.
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  • 46
    ISSN: 1432-0975
    Schlagwort(e): Key words Otolith ; Chemistry ; ICP-MS ; Stock discrimination ; Epinephelus striatus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Geologie und Paläontologie
    Notizen: Abstract  We examined the utility of otolith minor and trace element chemistry, assayed with inductively coupled plasma mass spectrometry (ICP-MS), as a means of delineating population structure in the Nassau grouper (Epinephelus striatus). We characterized the elemental composition of otoliths collected in 1993 from three locations in Exuma Sound, Bahamas and from Glover Reef, Belize in 1995. A single location in Exuma Sound was sampled in 1994 to test temporal variability in otolith composition. Five elements (Ca, Zn, Sr, Ba and Pb) were routinely detected, at levels significantly above background, by solution-based ICP-MS. Results from analysis of variance of elemental data, expressed as a ratio to Ca, indicated that there were no significant differences among the Exuma locations for any element, but significant variability was found between Glover Reef and the pooled Exuma localities for Zn/Ca, Sr/Ca and Ba/Ca ratios. Significant inter-annual differences at one Exuma Sound location was restricted to Ba/Ca ratios. Discriminant function analysis correctly classified 86% and 95% of the Belize and pooled Exuma sites, respectively. Otoliths from Belize were characterized by low Zn/Ca and high Ba/Ca and Pb/Ca ratios compared to otoliths from fish collected in Exuma Sound. Although differences in Ba levels may be related to upwelling at Glover Reef, more data are needed to definitely link otolith composition with regional differences in water chemistry.
    Materialart: Digitale Medien
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 1-8 
    ISSN: 1432-1335
    Schlagwort(e): Key words Cell proliferation ; Apoptosis ; Cell death ; Cultured cells ; Hepatocellular carcinoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There are conflicting results for experiments aimed at determining whether anticancer drug therapy of human hepatocellular carcinoma prolongs the survival rate effectively. The purpose of this study was to assess the effect of low concentrations of doxorubicin, mitomycin C, and ethanol on cell replication (cell number and proliferation), and cell apoptosis of cultured human hepatocellular carcinoma (Hep-G2) cells. After 1 day of exposure doxorubicin inhibited cell replication initially by 72%, but a partial recovery of the cell number was observed. Mitomycin C inhibited to the same extent but without recovery. Ethanol reduced the cell number even further, the maximum inhibition (12 days after exposure) being 96.4%. After 3 days of exposure all three agents stopped cell replication at a level of 2%–4% of the control (P 〈 0.001). Cell apoptosis was activated most strikingly by mitomycin C (5 μg/ml) after 1 day of exposure and by ethanol (150 μl/ml) after 3 days of exposure. Two-way repeated-measures analysis of variance showed statistically significant differences, with ethanol being the most significant followed by mitomycin C doxorubicin, and the control (P 〈 0.01). Thus, a low dose of ethanol combined with an exposure time of up to 3 days appears to be an effective regimen to control growth of human hepatocellular carcinoma cells in vitro. The strong induction of apoptosis by ethanol might be of additional benefit for a local application in vivo.
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  • 48
    ISSN: 1432-1335
    Schlagwort(e): Key words Basic fibroblast growth factor ; Cisplatinum ; Apoptosis ; Bcl-2 ; MCF-7
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Basic fibroblast growth factor (bFGF) is a classical mitogen in fibroblasts and endothelial cells. Our previous studies have demonstrated that bFGF inhibits the growth of MCF-7 human breast cancer cells. The aim of the present study was to examine the effect of bFGF on cis-diamminedichloroplatinum(cisplatin)-induced cytotoxicity in MCF-7 breast cancer cells as compared to normal endothelial cells. MCF-7/NCF cells transduced with a vector expressing the bFGF gene and overexpressing its product, and MCF-7/N2 cells transduced with the backbone vector were incubated with a combination of bFGF and cisplatin for 5 days; results were compared with those obtained with bovine aortic endothelial cells. Cell proliferation was assessed with the sulforhodamine B colorimetric cytotoxicity assay. Apoptosis was quantitatively determined by flow-cytometric analysis for DNA damage and the apoptotic death assay for DNA fragmentation, and qualitatively by electron microscopy. Reverse transcriptase/polymerase chain reaction analysis and an enzyme immunoassay were used to determine the mRNA and protein level, respectively, of the anti-apoptotic bcl-2 gene product. We found that bFGF enhanced cisplatin-induced cytotoxicity in MCF-7 breast cancer sublines. bFGF enhanced proliferation of normal endothelial cells and did not increase cisplatin-induced cytotoxicity. This effect was accompanied by down-regulation of the anti-apoptotic protooncogene bcl-2 and the enhancement of cisplatin-induced apoptosis. We suggest that the improved understanding of the role of bFGF in the differential modulation of the response of breast cancer and normal endothelial cells to chemotherapy may enable active intervention to alter the therapeutic ratio favorably in breast cancer patients.
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  • 49
    ISSN: 1432-1335
    Schlagwort(e): Keywords Chemosensitivity ; Human gastric carcinoma ; Micrometastasis ; Apoptosis ; Circulating tumor cells ; Fluoropyrimidine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Antimetastatic effects of 5-FU and its derivative, 1-hexylcarbamoyl-5-fluorouracil (HCFU) on human gastric cancer micrometastasis and their mode of action were evaluated, using a spontaneous lung metastasis model (HY-1) in nude mice. Metastases were first detected in the lung from 4 weeks after subcutaneous transplantation, growing intravascularly and forming micrometastases at 100% incidence by 6 weeks after implantation. Lung metastasis in mice bearing subcutaneous tumors was significantly inhibited by HCFU at doses of 100–150 mg kg−1 day−1 without severe toxic side-effects, when orally administered three times per week either from week 4 or week 6 to 9 weeks after implantation. Spontaneous lung metastasis was also inhibited by the administration of 5-FU, but to lesser extent than with HCFU at equimolar low doses. Apoptosis within primary tumors and lung metastatic foci, as detected by the terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling method, was found to be significantly enhanced by HCFU as well as 5-FU administration at doses of more than 100 mg kg−1 day−1 and 50 mg kg−1 day−1 respectively. However, proliferating activity of the metastatic foci, as evaluated by MIB-1 immunostaining, was not significantly suppressed by HCFU or 5-FU treatment. Furthermore, polymerase chain reaction analysis using human specific primers for the β-globin gene, which proved to be capable of detecting 10 tumor cells/ml mouse blood, revealed that circulating tumor cells in the peripheral blood of mice bearing primary tumors were reduced by HCFU or 5-FU administration. These results indicate that circulating tumor cells in blood and micrometastases in the lung are sensitive to these chemotherapeutic agents, and suggest that the anti-metastatic effect of these agents is mediated, at least in part, by enhanced apoptosis rather than by inhibition of cell proliferation.
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  • 50
    ISSN: 1432-1335
    Schlagwort(e): Key wordsIGF ; Apoptosis ; Transformation ; Chemosensitivity ; Signaling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Insulin-like growth factor I (IGF-I) exerts pleiotropic effects on mammalian cells via stimulation of its receptor (IGF-IR), a receptor tyrosine kinase. In vivo, IGF-I acts both as a local tissue growth factor and as a circulating hormone. In oncological research, IGF-I has received increased attention as the activated IGF-I/IGF-IR system displays mitogeneic, transforming, and anti-apoptotic properties in various cell types by stimulating distinct intracellular signaling pathways. Recent data suggest that the anti-apoptotic effect of IGF-I may mediate decreased sensitivity to chemotherapeutic drugs in vitro and in vivo. Thus, targeting the IGF-I/IGF-IR system could serve as an approach to overcome clinical drug resistance in certain tumors.
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  • 51
    ISSN: 1432-1335
    Schlagwort(e): Key words Immunohistochemistry ; DNA repair ; Radiation-inducible response ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Immunohistochemical methods were used to determine abundance and subnuclear distribution of DNA topoisomerase I and the Bax protein in normal and excision-repair-deficient xeroderma pigmentosum (XP) fibroblasts after irradiation of cells with γ rays or UV light, or exposure to the topoisomerase I inhibitor topotecan. DNA topoisomerase I and Bax were monitored using antisera raised against the human proteins. In addition, topoisomerases IIα and IIβ were made visible with specific antibodies. In untreated cells, DNA topoisomerase I was found to occur in the cytoplasm and in nucleoli. Irradiation with γ rays (2–12 Gy) or UV light (0.3–1.2 mW/cm2) changed the staining pattern in nuclei such that a multitude of small topoisomerase-I-rich centers occurred, which were evenly distributed over the karyoplasm. Simultaneously nucleoli disintegrated. Treatment of fibroblasts with topotecan (6–100 μM concentrations) resulted in similar alterations although the changes were much more pronounced. Combinations of topotecan and γ irradiation caused additive effects. We conclude that the increase in the number of topoisomerase-I-positive spots and the high fluorescence intensity of the latter may reflect three biological processes: (i) enhanced transcriptional activity (e.g. of DNA damage response genes), (ii) tagging of damaged DNA sites for repair, or (iii) initiation of apoptosis. In separate assays using normal and XP cells, a dose-dependent increase in protein reacting with Bax antibody was observed in nuclei, following treatment with γ rays or topotecan. In addition, topotecan induced a netlike arrangement of this Bax protein in nuclei. The meshes of the net structure resembled vesicles. DNA staining with 4′,6-diamidino-2-phenylindole dihydrochloride revealed that the vesicle-type structures contained DNA. Upon further incubation with topotecan, cells showing the netlike Bax arrangement eventually died. We conclude that topotecan-induced changes made visible by nuclear Bax protein are associated with apoptosis. XP cells, when treated with topotecan, responded more readily than normal cells with both an increase in nuclear Bax protein and rearrangement of Bax, indicating that UV repair functions may be required to process DNA damage inflicted by topotecan. Monitoring of DNA topoisomerases IIα and IIβ in γ-irradiated cells with antibodies revealed a dramatic increase in the IIα form and a redistribution of the IIβ form representing fragmentation of nucleoli.
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 357-360 
    ISSN: 1432-1335
    Schlagwort(e): Key words Colorectal neoplasms ; Apoptosis ; Chemosensitivity ; p53 gene
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose : The p53 gene is considered one of the most important in the control of apoptosis, and its mutations have a close relationship with chemosensitivity. The aim of this work was to investigate the role of p53 in the apoptosis of colorectal cancer cells in vitro, induced by 5-fluorouracil (5-FU) and hydroxy-camptothecin (HCPT). Methods : A total of 39 colorectal cancer samples from patients were treated in vitro with 5-FU (10 μg/ml), 5-FU (10 μg/ml) + leucovorin (5 μg/ml), HCPT (0.1 μg/ml) and HCPT (0.1 μg/ml) + Salvia mitorrhiza (6 μl), using an in situ terminal deoxynucleotidyltransferase assay to detect chemosensitivity. p53 gene mutations from tumor DNA were detected, after amplification by the polymerase chain reaction of exons 5–8, by non-radioactive single-strand conformation polymorphism. Results : p53 gene mutations were observed in 43.6% (17/39) of colorectal carcinomas, when the terminal deoxynucleotidyltransferase assay was used to detect the tumor apoptotic rate. Cells with mutated p53 had lower chemosensitivity than those without (p 〈 0.01). Conclusion : Routine assessment of p53 status may be helpful in selecting patients with the wild-type p53 gene, who have a predictably better response to chemotherapy.
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  • 53
    ISSN: 1432-1335
    Schlagwort(e): Key words EGF receptor signalling ; Tyrphostin ; Apoptosis ; Colon cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Growth effects of tyrphostins A25 and AG1478 on colorectal tumor cells were studied to explore therapeutic potential. Cell number, DNA synthesis and apoptotic index were measured as growth parameters and cell-death-associated proteins Bcl-2 and Bak and protein phosphorylation were analyzed. Both tyrphostins inhibited DNA synthesis and induced apoptosis in tumor cell cultures with different patterns of activity. A25 displayed strong selectivity for the cell lines expressing high levels of epidermal growth factor (EGF), HT29/HI1 and SW480. Inhibition of DNA synthesis was efficient in all cells except T84, and the apoptotic index increased two- to fivefold. By contrast, AG1478 was highly effective in all cell lines. In addition, it caused cell loss in VACO235 adenoma cells at concentrations lower than those necessary to inhibit BrdU incorporation, reflecting preferential retention of cells actively synthesizing DNA. Induction of apoptosis was more efficient with AG1478 than with A25 (tenfold in VACO235). Insulin-like growth factor (IGF1) did not rescue cells exposed to A25 or to high concentrations of AG1478, but was effective with suboptimal amounts of AG1478. Both compounds inhibited phosphorylation of the EGF receptor as well as additional proteins. AG1478 induced expression of Bak and down-regulated Bcl-2. In summary, tyrphostins may provide alternatives for colorectal tumor treatment. Their broader range of activities and the lower susceptibility to interactions with IGF1 can be an advantage over receptor antibodies.
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  • 54
    ISSN: 1432-1335
    Schlagwort(e): Key words Experimental pancreatic cancer ; Hormonal therapy ; Bombesin antagonist ; Somatostatin analog ; LH-RH antagonist ; EGF receptor ; Apoptosis ; AgNOR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Reduction in receptors for epidermal growth factor (EGF) in cancers appears to be one of the principal mechanisms through which peptide hormone analogs can inhibit tumor growth. In this study, hamsters with nitrosamine-induced pancreatic cancers were treated for 8 weeks with bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, somatostatin analog RC-160 or the luteinizing hormone-releasing hormone antagonist Cetrorelix, using sustained delivery systems releasing 20, 35 and 20 μg analog/ day respectively. To establish the pattern of changes in the number and affinity of EGF receptors on tumors, groups of animals were sacrificed at regular intervals during therapy. Chronic treatment with RC-3095 or Cetrorelix resulted in an early (day 10) and sustained reduction (71% or 69% respectively) in EGF receptors on pancreatic tumors. In contrast, RC-160 decreased receptor concentration by 60% only after 20 days. Among the histological characteristics of proliferation, the decrease in argyrophilic nucleolar organizer regions, but not apoptotic and mitotic indices, showed a correlation with the fall in EGF receptors. The concentration of the receptors returned to the control level 4 days after cessation of chronic treatment with RC-3095. The effect of single injections of RC-3095, RC-160 and Cetrorelix on EGF receptors was also investigated. RC-160 decreased the number of EGF receptors on pancreatic cancers by 31% 3 h after administration, but the receptors had returned to normal level at 6 h. RC-3095 and Cetrorelix caused a 67% and 59% decline, respectively, in EGF receptors only 6 h after injection and the concentration of receptors remained low for 24 h. Thus, the pattern of down-regulation of EGF receptors in pancreatic cancers appears to depend on the peptide used for therapy. Since the antitumor effect may be the result of the fall in EGF receptors in cancers, information on the time course of changes in these receptors during treatment with these analogs may lead to an improvement in therapeutic regimens.
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    Der Nervenarzt 70 (1999), S. 1-10 
    ISSN: 1433-0407
    Schlagwort(e): Schlüsselwörter Tic-Störung ; Zwangsstörung ; Kinder ; Jugendliche ; Neurobiologie ; Psycho- pharmakologie ; Verhaltenstherapie ; Key words Tic-disorder ; Obsessive-compulsive disorder ; Children ; Adolescents ; Neurobiology ; Psychopharmacology ; Behavior therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary In children and adolescents motor/vocal tics and obsessive-compulsive behavior are known to be closely related. Thereby, a continuum of symptoms ranging from single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to clinically relevant obsessions and compulsions could be described. As neurobiological substrates dysfunctions in corresponding cortico-striato-thalamo-cortical circuits (sensorimotor circuit in tic symptomatology, orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both disturbances behavioral therapy can be used to improve control mechanisms to counterregulate tics and obsessive-compulsive behavior, respectively, and psychopharmacological agents can be administerd to compensate dysbalances in neurotransmitter systems. In case of a mixed symptomatologic picture it is necessary to include interventions for both pols of the symptom-continuum in the therapeutic programme to achieve extensive improvement as a basis for a further positive development of the patient.
    Notizen: Zusammenfassung Motorische/vokale Tics und zwanghafte Verhaltensweisen kommen bei Kindern und Jugendlichen häufig gemeinsam vor; dabei kann ein Symptomkontinuum von solitär auftretenden Tics über ein Mischbild von Tics und Ritualen/zwanghaften Gedanken und/oder Handlungen bis hin zu eindeutigen Zwangsphänomenen beschrieben werden. Neurobiologisch können diesem Symptomkontinuum unterschiedlich ausgebreitete Dysfunktionen entsprechender kortiko-striato-pallido-thalamo-kortikaler Regulationssysteme zugrunde liegen. Therapeutisch lassen sich bei beiden Verhaltensauffälligkeiten mittels verhaltenstherapeutischer Techniken Steuerungs- und Kontrollmöglichkeiten zur Gegenregulation der Auffälligkeiten verbessern sowie durch Einsatz von Psychopharmaka Dysbalancen von Neurotransmittersystemen ausgleichen. Bei einem Mischbild von Tics und Zwängen sind therapeutische Interventionen für beide Zielbereiche erforderlich. Nur so können umfassende Verbesserungen erreicht und günstige Entwicklungsbedingungen für die betroffenen Kinder und Jugendlichen eröffnet werden.
    Materialart: Digitale Medien
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  • 56
    ISSN: 1433-0474
    Schlagwort(e): Schlüsselwörter Ataxia teleangiectatica ; Immunfunktionsstörung ; Lymphozytensubpopulationen ; Apoptose ; CD45RO ; CD45RA ; Key words Ataxia teleangiectasia ; Immunodeficiency ; Lymphocyte subset ; Apoptosis ; CD45RO ; CD45RA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Background: Can a characterisation of the lymphocyte subset in patients with ataxia teleangiectasia offer an explanation for the cellular defect of their immunfunction? Methods: In ten patients with ataxia teleangiectasia and a corresponding control group of individuals of similar age and sex, immunophenotyping was carried out by means of flow cytometric analysis and the use of monoclonal antibodies. Results: Patients with ataxia teleangiectasia showed a reduction of the number of T-cells with a decrease in the T-helper cell subset (CD3: 990/µl, p〈0.0005 and CD4: 568/µl, p〈0.0005). The number of B-cells was low (CD19: 39/µl, p〈0.005). Moreover, there was an increase in highly activated T-lymphocytes which can be seen from a higher percentage of the HLA-DR- and CD45RO-expression in patients with ataxia teleangiectasia compared to the individuals of the control group (HLA-DR: 57%, p〈0.0005 and CD45RO: 82%, p〈0.001). At the same time, the expression of CD95 (Fas/AP01) was clearly increased (CD95: 74%, p〈0.001). Interpretation: The lymphocyte subset of the patients suffering from ataxia teleangiectasia shows a significant decrease of the B- and T-cell subsets. The reduced number of T-helper cells – caused by a CD45RA-cell loss – leads to a change in the relation „RA/RO”. It is possible that there is a link between the imbalance of „RA/RO”, the increase of highly activated T-lymphocytes and the higher expression of CD95 (Fas/APO1).
    Notizen: Zusammenfassung Fragestellung: Können durch eine Charakterisierung der Lymphozytensubpopulationen bei Patienten mit Ataxia teleangiectatica Rückschlüsse auf den zellulären Defekt der Immunfunktionsstörung gezogen werden? Methodik: Mit Hilfe der Durchflußzytometrie und des Einsatzes monoklonaler Antikörper führten wir eine Immunophänotypisierung bei jeweils 10 Patienten mit Ataxia teleangiectatica und eines bezüglich des Alters und des Geschlechts gleichverteilten Kontrollkollektivs durch. Ergebnisse: Die Patienten mit Ataxia teleangiectatica zeigten verminderte T-Zell-Zahlen mit Abnahme der T-Helferzell-Subpopulationen (CD3: 990/µl, p〈0,0005 und CD4: 568/µl, p〈0,0005). Auch die B-Zell-Zahl war erniedrigt (CD19: 39/µl, p〈0,005). Die T-Lymphozyten befanden sich darüber hinaus vermehrt im aktivierten Zustand, erkennbar an einer prozentual erhöhten HLA-DR- und CD45RO-Expression (HLA-DR: 57%, p〈0,0005 und CD45RO: 82%, p〈0,001) sowie an einer Verschiebung der Relation „RA/RO” zugunsten der „RO”-Expression. Gleichzeitig war die Expression von CD95 (Fas/APO1) deutlich gesteigert (CD95: 74%, p〈0,001). Schlußfolgerung: Die Veränderungen der Lymphozytensubpopulationen zeigen bei den Patienten mit Ataxia teleangiectatica eine verminderte B- und T-Zell-Zahl. Die CD4-Lymphopenie – verursacht durch einen CD45RA-Zellverlust – bedingt eine Verschiebung der Relation „RA/RO”. Möglicherweise besteht ein Zusammenhang zwischen der Störung der Homöostase „RA/RO” und dem erhöhten Aktivierungsgrad der Zellen sowie der vermehrten CD95(Fas/APO1)-Expression.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 328-332 
    ISSN: 1433-0474
    Schlagwort(e): Schlüsselwörter Asthma bronchiale ; Schulkinder ; Türkische Kinder ; Key words Asthma ; Children ; Turkish children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Objectives: In Germany 4.2% (in Munich 8.6%) of all children under 15 years of age are of Turkish origin, representing the largest ethnic minority in this age group. However, very little is known about the prevalence, severity and management of asthma and other atopic diseases in Turkish children living in Germany. Methods: In a cross-sectional survery the prevalence, severity and treatment of asthma and other atopic diseases was assessed in 7,445 schoolchildren aged 9 to 11 years, living in Munich, southern Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin-prick tests and cold-air hyperventilation challenge. Results: Of those returning the questionnaires (n = 6490/87%), 5,030 (77.5%) were of German and 451 (7%) of Turkish origin. Turkish children showed a significantly lower prevalence of asthma (5.3% versus 9.4%, P 〈 0.05) than their German peers. Furthermore, Turkish children with asthma were less frequently free of symptoms (10.5% versus 34.6%, P 〈 0.05), reported more severe symptoms (41.2% versus 10.9%, P 〈 0.05) and more hospital admissions (55.6% versus 21.6%, P 〈 0.05) due to asthma than German children. Conclusions: The results of this study indicate that despite the lower prevalence of asthma and allergy in the Turkish population living in Germany, asthma is a major health problem for Turkish children. Furthermore, these findings suggest inadequate management of asthma in Turkish children.
    Notizen: Zusammenfassung Fragestellung: Türkische Kinder stellen in der Bundesrepublik Deutschland mit 4,2% und in München mit 8,6% den größten Anteil nicht-deutscher Kinder in der Altersgruppe bis 15 Jahren. Wenig ist jedoch bisher über Häufigkeit, Symptome und Behandlung von Asthma bronchiale und anderer atopischer Erkrankungen der türkischen Minderheit in Deutschland bekannt. Methodik: In einer Querschnittstudie wurde bei 7445 Schulkindern im Alter von 9 bis 11 Jahren im Großraum München die Häufigkeit, der Schweregrad und die Behandlung des Asthma bronchiale und anderer atopischer Erkrankungen untersucht. Fragebögen wurden von den Eltern ausgefüllt, Lungenfunktionsuntersuchungen und Hautpricktests wurden bei den Kindern durchgeführt. Ergebnisse: Von denen, die die zugeschickten Fragebögen ausfüllten (n = 6490/87%), waren 5030 (77,5%) deutscher und 451 (7%) türkischer Nationalität. Die türkischen Kinder zeigten eine niedrigere Prävalenz von Asthma bronchiale (5,3% versus 9,4%, p 〈 0,05) und Neurodermitis (1,6% versus 12,9%, p 〈 0,001) im Vergleich zu den deutschen Kindern. Signifikante Unterschiede bestanden zwischen türkischen und deutschen Kindern in Art der Symptome und der Krankheitswahrnehmung. Türkische Kinder mit Asthma bronchiale waren seltener beschwerdefrei (10,5% versus 34,6%, p 〈 0,05) berichteten von schwereren Symptomen (41,2% versus 10,9%, p 〈 0,05) und von einer größeren Anzahl von Krankenhausaufenthalten (55,6% versus 21,6%, p 〈 0,05) aufgrund von Asthma bronchiale. Schlußfolgerung: Die Ergebnisse der Studie legen den Schluß nahe, daß Asthma bronchiale trotz der niedrigeren Prävalenz in der türkischen Bevölkerungsgruppe ein erhebliches Gesundheitsproblem bei türkischen Schulkindern darstellt. Die höhere Anzahl von Fehltagen in der Schule und die deutlich höhere Anzahl von Klinikaufenthalten aufgrund von Asthma bronchiale sprechen für eine mangelhafte präventive Behandlung dieser Erkrankung bei türkischen Kindern.
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    HNO 47 (1999), S. 535-540 
    ISSN: 1433-0458
    Schlagwort(e): Schlüsselwörter Hörschäden ; Knalltrauma ; Kinder ; Tinnitus ; Erweiterte Hochtonaudiometrie ; Key words Hearing loss ; Acoustic trauma ; Children ; Tinnitus ; High-frequency audiometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary The study presents an analysis of 20 cases of acute acoustic trauma caused by toy pistols. The problem generally involves boys within the age range from 6 to 11 years. Half of the incidents involved attacks with toy pistols used as weapons. Auditory damage appeared in two types, each of which had a notch in the audiogram at the frequency range between 10 and 14 kHz. In children, a shot close to one ear can damage both ears. Great differences in the severity of tinnitus were apparent. The most severe cases of tinnitus were observed in the children with no or minor premanent auditory damage. Children experiencing long periods of uninterrupted tinnitus suffer significantly. This is not only detrimental to family-life but also to the performance of the children at school. The total expenses of treatment for these 20 cases were estimated to be approximately 80,000 DM (40.000 Euro).
    Notizen: Zusammenfassung Im Rahmen einer Studie wurden 20 Fälle von Knalltraumata durch Kinderpistolen erfaßt und ausgewertet. Die Problematik betrifft fast nur männliche Personen und schwerpunktmäßig den Altersbereich von 6–11 Jahren. Die Hälfte der Vorfälle waren Angriffe, bei denen die Kinderpistole als Waffe eingesetzt wurde, 2 Typen von Hörschäden sind festzustellen, die jedoch beide durch eine Senke im Bereich von 10–14 kHz charakterisiert sind. Bei Kindern kann der Schuß in eines der Ohren auch das andere Ohr schädigen. Sehr große Unterschiede bestehen im Auftreten von Tinnitus. Die Fälle mit starkem Tinnitus haben keine oder nur geringe bleibende Hörschäden. Die von Knalltraumata betroffenen Kinder leiden oft sehr stark unter langanhaltendem Tinnitus. Dabei wird nicht nur das Leben der Familien beeinträchtigt, sondern auch die schulischen Leistungen der Kinder leiden teilweise sehr stark darunter. Für die Therapie dieser 20 Fälle entstanden Gesamtkosten von ca. 80.000,- DM
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  • 59
    ISSN: 1433-0458
    Schlagwort(e): Schlüsselwörter Laryngotracheale Stenose ; Cricotracheale Resektion ; Kinder ; Tracheotomie ; Key words Laryngotracheal stenosis ; Cricotracheal resection ; Tracheostomy ; Children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Approximately 90% of infants and children with severe acquired laryngotracheal stenoses are tracheotomy dependent and therefore impaired in their physical and speech developments. In addition, tracheotomized infants can be endangered by the cannula due to the possible crusting of secretions or its dislocation. Thus, early repair of a stenosis is mandatory. Within the last 10 years, we successfully operated on 18 children with severe laryngotracheal stenoses. Ten children were treated with a modified Cotton technique. This paper reports our results of cricotracheal resection performed in 8 children since 1994 (age distribution: 7 months through age 15 years). Four children had Cotton grade II stenoses, three had grade III stenoses and one grade IV stenoses. In 3 patients a tracheotomy had been performed at another institution. Since their tracheostomas were too far caudal, they could not be included in the primary resection. All 8 children have been successfully decannulated. Five children without tracheotomies could be extubated uneventfully on the 5th postoperative day. All three primarily tracheotomized children needed further endotracheal stenting with T-tubes because of stomal and suprastomal collapse. Two of these latter children additionally required a tracheoplasty with rib cartilage grafts in order to stabilize the suprastomal trachea prior to decannulation. No patient experienced injuries to the recurrent laryngeal nerves or insufficiencies of the anastomosis. All children’s voices were not impaired. This is the third report in literature of cricotracheal resections in infants and children, indicating that this effective, one-stage procedure is superior to laryngotracheal reconstruction with rib cartilage.
    Notizen: Zusammenfassung Kinder mit schweren, erworbenen subglottischen laryngotrachealen Stenosen sind zu 90% tracheotomiert und daher in ihrer körperlichen und sprachlichen Entwicklung beeinträchtigt. Zusätzlich sind mit einer Trachealkanüle versorgte Kinder, insbesondere Kleinkinder, gefährdet, so daß die chirurgische Beseitigung der Stenose dringend geboten ist. Wir haben innerhalb der vergangenen 10 Jahre 18 Kinder mit einer schweren subglottischen laryngotrachealen Stenose operiert; 10 Kinder, über die kürzlich berichtet wurde, konnten mit der modifizierten Cotton-Technik erfolgreich dekanüliert werden. Über 8 Kinder (Alter 7 Monate bis 15 Jahre, 4mal Stenose II. Grades, 3mal Stenose III. Grades, einmal Stenose IV. Grades), die wir mit cricotrachealer Resektion (CTR) und thyrotrachealer Anastomose operierten, wird in der vorliegenden Arbeit berichtet. 3 Kinder waren anderenorts bereits tracheotomiert. Da die Stomata zu weit kaudal lagen, konnten sie nicht in die Resektion einbezogen werden. Alle 8 Kinder konnten inzwischen dekanüliert werden und sind beschwerdefrei: Die 5 nicht tracheotomierten Kinder konnten problemlos am 5. postoperativen Tag extubiert werden. Die zuvor tracheotomierten Kinder konnten erst nach endotrachealer Schienung (2mal nach zusätzlicher Trachealplastik mit Rippenknorpel bei suprastomaler Tracheomalazie) dekanüliert werden. Bei keinem der Kinder trat eine Recurrensparese auf. Die Stimme bei allen Kindern ist unbeeinträchtigt. Die CTR, über die bei kindlichen laryngotrachealen Stenosen mit dieser Arbeit in der Literatur zum 3. Mal berichtet wird, ist eine sehr effektive, einzeitige, komplikationsarme Operationsmethode, deren Resultate für Atmung und Stimme günstiger sind, als mit der Erweiterungsplastik nach Cotton.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 122-127 
    ISSN: 1433-0474
    Schlagwort(e): Schlüsselwörter Körperliche Beschwerden ; CBCL/4 ; 18 ; Kultur-vergleichend ; Kinder ; Jugendliche ; Key words Somatic complaints ; CBCL/4 ; 18 ; Cross-cultural ; Children ; Adolescents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Question: What is the frequency of parent-reported somatic complaints of children in Germany and the Netherlands dependent on their age, sex and the education of their parents. Methods: 4876 CBCL (Child Behaviour Checklist) of children aged 4 through 17 years from the general population were analysed. Results: Dutch children were scored higher by their parents than German children. Moreover somatic complaints increased with age and girls were scored higher. The frequencies of somatic complaints varied from 2% for ’problems with eyes’ to 15% for ’headaches’. The presence of one somatic complaint increased the likelihood of concomitant somatic complaints. Conclusion: Somatic complaints of children without any known cause are often seen. Some symptoms are often reported together. More, especially causal studies on the somatic symptoms of children are recommended.
    Notizen: Zusammenfassung Fragestellung: Wie verhält sich die Häufigkeit körperlicher Beschwerden bei Kindern in Deutschland und den Niederlanden nach Laieneinschätzung, gibt es Unterschiede abhängig vom Alter und Geschlecht der Kinder und des Ausbildungsniveaus der Eltern? Methode: 2757 deutsche und 2119 niederländische CBCL (child behavior checklist) über Kinder und Jugendliche im Alter zwischen 4 und 17 Jahren aus repräsentativen Studien wurden mit Hilfe von Varianzanalysen ausgewertet. Ergebnisse: Niederländische Eltern beschrieben mehr körperliche Beschwerden als deutsche. Die Ausprägung auf der Symptomskala stieg mit zunehmendem Alter und zeigte höhere Werte für Mädchen. Die Häufigkeit der Beschwerden variiert von 2% für „Augenbeschwerden” bis zu 15% für „Kopfschmerzen”. Bei Anwesenheit eines körperlichen Symptoms stieg die Frequenz zusätzlicher Beschwerden. Schlußfolgerung: Körperliche Beschwerden bei Kindern treten häufig ohne bekannte Ursache auf, bestimmte Beschwerden werden häufig gleichzeitig beschrieben, wobei die Koinzidenz nicht umkehrbar ist. Weitere, besonders ursächliche Studien auf dem Gebiet der körperlichen Beschwerden bei Kindern sind auch hinsichtlich steigender Kosten im Gesundheitswesen empfehlenswert.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 351-355 
    ISSN: 1433-0474
    Schlagwort(e): Schlüsselwörter Latexallergie ; Neuogene Blasenentleerungsstörung ; Kinder ; Key words Latex allergy ; Neurogenic bladder dysfunction ; Children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Objectives: The risk to suffer from natural latex allergy is increased in children with congenital neurogenic bladder dysfunction. We, therefore, evaluated whether or not a serologic screening for detection of sensitization to latex is reasonable in these children. Patients and Methods: 40 children aged from 6 months to 17 years were examined by specific questionnaire-based patient histories, and by determination of total serum immunoglobuline E (total IgE) and natural latex-specific serum immunoglobulin E (latex-IgE) by solid-phase immunoassays. Results: 5 children had a history of allergic reaction to rubber containing materials. In 10 children, latex-IgE was elevated 〉 0.35 kU/l, 6 out of these 10 children without a history of allergic reactions to rubber containing materials. There was a positive correlation of elevated latex-IgE values and the number of former surgical procedures (p 〈 0.006), while no correlation was found between elevated latex-IgE values and clean intermittent catheterization (p = 0.408). Conclusion: Compared to questionnaire-based patient histories, serologic screening examination including determination of latex-IgE values may better identify children at risk to suffer from sensitization to natural latex.
    Notizen: Zusammenfassung Fragestellung: Naturlatexallergien kommen bei Kindern mit angeborener neurogener Blasenentleerungsstörung gehäuft vor. Es wurde deshalb untersucht, ob bei dieser Patientengruppe ein serologisches Screening zur Erfassung einer Sensibilisierung gegenüber Naturlatex sinnvoll ist. Patienten und Methode: Untersucht wurden 40 Kinder im Alter von 6 Monaten bis 17 Jahren. Die Untersuchung umfaßte eine gezielte Anamneseerhebung durch Fragebogen sowie die Bestimmung des Gesamtimmunglobulin E (Gesamt-IgE) und des naturlatexspezifischen Immunglobulin E (Latex-IgE) im Serum durch Festphasenimmunoassays. Ergebnisse: 5 Kinder hatten anamnestisch Zeichen einer allergischen Reaktion nach Gummikontakt. 10 Kinder wiesen im Serum erhöhte Werte des Latex-IgE auf, wobei 6 dieser Kinder bisher noch keine Zeichen einer Latexallergie hatten. Pathologische Werte für das Latex-IgE korrelierten statistisch signifikant mit der Anzahl operativer Eingriffe (p 〈 0,0006), nicht aber mit einem durchgeführten sauber intermittierenden Einmalkatheterismus (p = 0,408). Schlußfolgerung: Im Vergleich zur alleinigen fragebogengestützen Anamneseerhebung können durch ein serologisches Screening mit Bestimmung des Latex-IgE mehr Kinder entdeckt werden, die durch eine Sensibilisierung gegenüber Naturlatex gefährdet sind.
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  • 62
    ISSN: 1437-7799
    Schlagwort(e): Key words Desferrioxamine ; Cadmium ; Metallothionein ; Nephrotoxicity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. Desferrioxamine (DFO) a chelating agent, is used to treat metal toxicity caused by iron and aluminum in patients on hemodialysis. We hypothesized that DFO could also be used to treat cadrium-induced nephropathy. Animal experiments were therefore performed to explore whether DFO removed cadmium (Cd) from the kidneys of rats with a Cd burden. Methods. Rats received subcutaneous injections of Cd chloride (3 mg Cd/kg per day, days 0–7) followed by DFO (50 mg/kg per day, days 8–14). Levels of Cd were determined in liver, kidneys, and plasma. Enzymes assays and histopathological examination were performed in kidneys. Results. In liver, Cd injections elevated Cd levels; subsequent injections of DFO lowered the Cd levels compared with levels after injections of Cd alone. In kidneys, Cd injections increased levels of total Cd and Cd bound to cellular membranes (Mem-Cd), and decreased leucine aminopeptidase (LAP) activity (a marker of renal injury); subsequent injections of DFO elevated levels of total Cd and Mem-Cd, and lowered LAP activity compared with fundings after the injection of Cd alone. After the injections of Cd alone and DFO following Cd the renal levels of Cd were below the critical concentration required to cause renal injury, since no histopathological changes were observed in the kidney. Conclusion. DFO administration to Cd-burdened rats removed Cd from the liver, but led to accumulation of Cd in the kidneys, particularly in the cellular membranes. These results suggest that if DFO is given long-term to Cd-burdened patients, the Cd level in kidneys, particularly in renal cellular membranes, could reach concentrations that could cause manifest renal injury.
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 32-35 
    ISSN: 1437-9813
    Schlagwort(e): Key words Appendicitis ; Ultrasonography ; Children ; Graded compression ultrasonography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The diagnosis of acute appendicitis in childhood is frequently difficult. In some situations the need to operate is clear, but in others the decisions may be much “tougher” because the clinical findings are equivocal. This is a retrospective study of a consecutive series of 253 children presenting with “acute abdominal pain? appendicitis” who had graded compression ultrasonography (GCUS) because the clinical scenario did not warrant immediate laparotomy. This represents 30% of all cases seen in the study period. The aim of the study was to examine the role of GCUS and a clinical scoring system (the Alvarado score) in patients in whom the diagnosis is uncertain.
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 50-55 
    ISSN: 1437-9813
    Schlagwort(e): Key words Burns ; Inhalation injury ; Children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Survival from serious burns in children has improved substantially in recent years. Mortality is predominantly determined by the total body surface area burned and the often unrecognised inhalation injury. A retrospective review of 4,451 consecutive children with thermal injuries over a 10-year period was undertaken to determine the incidence, clinical presentation, and pathology of inhalation injury and its contribution to morbidity and mortality. Inhalation burns were diagnosed clinically and confirmed endoscopically and post-mortem in 97 (2.2%) children; 77 sustained fire burns (mean age 4 years) and 20 hot-water burns (mean age 18 months). The Moylan classification stratified them into upper-airway burns in 59 children, major–airway burns in 29, and parenchymal burns in 44. Major-airway burns were always seen in conjunction with either upper-airway or parenchymal injury. Stridor and acute progressive respiratory distress were the two main symptoms, the onset of which was occasionally delayed for up to 72 h. Endoscopy was most helpful in confirming the diagnosis and determining airway management. Endotracheal intubation was needed in more than 50% of children, usually for less than 5 days, and was converted to tracheostomy in only 6. Persistent laryngeal and tracheal damage was identified in 4. Secondary pneumonia occurred in 41.5% of children with fire burns and 55% with hot-water burns. Extensive surface burns, parenchymal injury, and secondary pneumonia all contributed to the significant mortality. Post-mortem findings corroborated clinical and endoscopic evidence. This study suggests that inhalation burns were often not recognised, could present late, and usually had significant consequences. Early clinical diagnosis, supported by endoscopic findings and appropriate management, is essential if the high morbidity and mortality amongst these children is to be improved.
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 63-65 
    ISSN: 1437-9813
    Schlagwort(e): Key words Actinomycosis ; Antibiotic treatment ; Appendicitis ; Children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Abdominal actinomycosis (AMC) is a rare infection in children. The appendix is the most common intra-abdominal organ involved. It presents as an undifferentiated mass, forming abscesses and fistulas in the right lower quadrant. The case of a 15-year-old girl with a AMC of the appendix detected by the pathologist after routine appendectomy is discussed. Long-term antibiotic treatment and follow-up by ultrasound and laboratory controls are necessary.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 121-122 
    ISSN: 1437-9813
    Schlagwort(e): Key words Ingrowing nails ; Conservative treatment ; Children ; Adolescents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ingrowing nails are not uncommon in children, and even so receive little attention in the pediatric surgery literature. The purpose of the present study was to demonstrate our modification of the conservative treatment of ingrowing nails. Our technique of local treatment combined with patient education for better foot and toe care was successfully used and well tolerated by 19 out of 20 young patients with ingrown toenails.
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  • 67
    ISSN: 1437-9813
    Schlagwort(e): Key words Congenital diaphragmatic hernia ; Rat ; Glucocorticoid ; Antenatal therapy ; Insulin-like growth factor I and II ; Reverse transcription-polymerase chain reaction (RT-PCR)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There is increasing evidence to suggest that insulin-like growth factors (IGF) I and II play a crucial role in fetal lung development. Expression of IGF-I and II has been demonstrated to be predominant during fetal life and decreases prior to birth. Antenatal glucocorticoids are reported to improve lung immaturity. The aim of this study was to investigate the effect of antenatal glucocorticoid administration on IGF-I and II expression in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats. A CDH model was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5 of gestation (term = 22 days). Dexamethasone (0.25 mg/kg) was given intraperitoneally on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21. The fetuses were divided into three groups: I, normal controls; II, nitrofen-induced CDH; and III, nitrogen-induced CDH with antenatal dexamethasone treatment. mRNA was extracted from whole lung and a reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the relative amounts of IGF I and II mRNA. Levels of mRNA were expressed as a ratio of the band density divided by that of β-actin, a housekeeping gene known to be expressed at a constant level. Immunohistochemistry using anti-rat IGF I and II antibody was also performed in each group. Levels of IGF I mRNA were significantly increased in group II (0.50 ± 0.08) compared to group I (0.34 ± 0.10) or group III (0.32 ± 0.06) (P 〈 0.05). Levels of IGF II mRNA were also significantly increased in group II (0.95 ± 0.20) compared to group I (0.42 ± 0.07) or group III (0.31 ± 0.09) (P 〈 0.05). Strong IGF I and II expression was observed in the hypoplastic CDH lung (group II), mainly in the bronchiolar epithelium. IGF I and II expression in group I and III lungs was either absent or weak. The finding of significant reductions in IGF I and II mRNA and protein levels in dexamethasone-treated CDH lung suggest that dexamethasone may accelerate the fetal stage of lung development.
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 201-205 
    ISSN: 1437-9813
    Schlagwort(e): Key words Esophagus ; Atresia ; Notochord ; Adriamycin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Esophageal atresia (EA) is often accompanied by vertebral defects and other anomalies. The adriamycin rat model of EA has disclosed the embryology of the malformation and shown that the vertebrae and notochord are also abnormal. This study describes the nature of notochord malformations in rat embryos exposed to adriamycin. Time-mated rats received either 1.75 mg/kg adriamycin or vehicle i.p. on gestational days (E) 6 to 9; E-12, E-12.5, and E-13 embryos were harvested, embedded in paraffin, and serially sectioned at 3 μm in transverse plane from the head to the stomach for subsequent PAS staining. The findings in both groups were compared at the three endpoints. Control embryos had neither tracheoesophageal nor notochord malformations. On day 12, only 11/36 adriamycin embryos were normal; 7/36 had abnormal notochords, 11/36 had EA, and 7/36 had both. The corresponding figures for 12.5 days were 12/27, 0/27, 7/27, and 8/27 and those for the day 13 7/23, 5/23, 3/23, and 8/23. The malformed notochords were thickened, bifurcated, or trifurcated in the sagittal plane. The simultaneous presence of notochord and esophageal malformations suggests a direct link between both defects, but our observation of isolated occurrence of both shows that they reflect two expressions of the profound disturbance of embryonic para-axial organization responsible for the cluster of malformations rather than a cause-effect association.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 457-460 
    ISSN: 1437-9813
    Schlagwort(e): Key words Blunt testicular injury ; Rat ; DNA flowcytometry ; Antisperm antibodies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Injury to the testis breaching the tunica albuginea is known to affect fertility. Blunt testicular trauma with an intact tunica albuginea has been reported to have no effect on contralateral testicular histology and Johnsen testicular maturation score. However, sensitive techniques like DNA flowcytometry have not been utilized so far to evaluate contralateral testicular germ-cell changes. Sixty-four male Wistar rats aged 20 days were randomized into groups I (control), II (unilateral blunt testicular trauma, UBTT), III (UBTT and excision of ipsilateral testis at 6 h), and IV (UBTT and cyclosporine for 30 days). Fertility, DNA flowcytometry of contralateral testicular tissue, and anti-sperm antibodies (ASA) were evaluated. Fertility and haploid-cell percentage of the contralateral testis were significantly decreased compared to controls in early adulthood (100 days). Around 150 days of age, as ASA decreased significantly, fertility and contralateral testicular haploid-cell population recovered and were comparable to the controls. Excision of the traumatized testicle around 6 h after injury or administration of cyclosporine for 30 days protected fertility and the contralateral testis. In contrast to group II rats, ELISA for ASA was negative in group III and IV rats. UBTT affects the contralateral testis and fertility. ASA mediate this damage. Orchidectomy performed around 6 h after trauma or short-term cyclosporine therapy prevents the damage.
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  • 70
    Digitale Medien
    Digitale Medien
    Springer
    Clinical and experimental nephrology 3 (1999), S. 254-260 
    ISSN: 1437-7799
    Schlagwort(e): Key words Low density lipoprotein ; Apoptosis ; Malondialdehyde ; TGFβ1 ; Unilateral ureteral obstruction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. To test the hypothesis that oxidized low density lipoprotein (oLDL) is involved in the renal injury of obstructive nephropathy, male Sprague-Dawley rats weighing 125–150 g were used. Methods. Three days after arrival, the rats were randomly assigned to undergo: (1) sham operation, (2) left unilateral ureteral obstruction (UUO), or (3) reversal of the unilateral ureteral obstruction (R-UUO). Seven days after the reversal operation or 10 days after the sham or UUO procedure, all animals were killed by exsanguination under anesthesia, with blood taken from the abdominal aorta. LDL was prepared by gradient ultracentrifugation and used immedi-ately after isolation. Rat mesangial cells were utilized with an LDL concentration of 100 μg/ml/protein in the media. After 72 h, cell survival was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) method. Cell survival was determined by comparing the optical density between the control wells and the experimental wells. In order to investigate the mechanisms of injury and repair of obstructive nephropathy, data for kidney apoptosis, malondialdehyde (MDA), and transforming growth factor β1 (TGFβ1) mRNA were obtained in the sham-operated, UUO, and R-UUO groups. Results. Our results showed that LDL malondialdehyde during UUO was increased 87% over baseline values (P 〈 0.005). With R-UUO, the oxidized LDL dropped 23% from the peak values during UUO (P 〈 0.005), but was still different from that of the baseline values (P 〈 0.025). Rat mesangial cell survival, after 72 h exposure to oLDL, inversely correlated to oLDL cytotoxicity and showed a 14% drop during UUO compared with sham-operated animals (P 〈 0.01). Cell survival increased 11% after R-UUO (P 〈 0.02) and was not different from control values (P = NS). The apoptotic counts by the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling) technique showed significant increases during UUO and a noticeable reduction after R-UUO. Conclusion. Our data support the proposition that UUO stimulates oxidation of LDL. The cytotoxicity of oLDL plays a significant role in the injury of UUO. A decrease in cytotoxicity was associated with the repair in R-UUO. Our observations that apoptosis follows this same pattern, point to the importance of apoptosis in the injury and repair of obstructive nephropathy. Future studies to interrupt these processes of injury may lead to novel treatment modalities in reversing the injury and hastening the repair of obstructive nephropathy.
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 243-247 
    ISSN: 1437-9813
    Schlagwort(e): Key words Wilms' tumo ; Apoptosis ; Bcl-2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Wilms' tumor (WT) usually has a good outcome, although a poor prognosis is often related to more advanced stages and anaplastic features. Apoptosis occurs with variable frequency in malignant tumors, and may have a role in reducing their growth rate. The bcl-2 proto-oncogene inhibits apoptosis, and the consequent increase in the number of cells may play a role in the development of tumors. The aim of this study was to analyze the role of apoptosis and bcl-2 expression in WT. Twenty-six resected WT specimens were studied; 12 patients had stage I tumor, 4 stage II, 5 stage III, 3 stage IV, and 2 stage V. Twenty-three tumors were classified as favorable histology (FH) and 3 as unfavorable (UH). The mean follow-up was 34 months; 22 patients were alive and 4 were dead (2 with FH: 1 stage III and 1 stage IV, and 2 with UH stages 4). Apoptosis was detected by the in-situ end-labelling technique; bcl-2 expression was detected by immunohistochemistry. An apoptotic index (AI) was calculated as the ratio of apoptotic to normal cells in each specimen. The AI was lower in higher tumor stages, with a significant difference between stages I and IV (P 〈 0.05). In cases with UH, Al was lower than in tumors with FH (P 〈 0.01). The AI was also lower in patients who died than in those who survived (P 〈 0.01). In all specimens no correlation between AI and bcl-2 expression was observed. Progression to advanced stages of WT and a poor prognosis f anaplastic tumors may be linked with disruption of the mechanisms that control apoptosis. Bcl-2 does not play a role as a regulator of apoptosis in WT, other oncogenes and tumor-suppression genes may be more involved in inhibiting apoptosis in WT.
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 353-357 
    ISSN: 1437-9813
    Schlagwort(e): Key words Testis torsion ; Scrotum ; Appendage ; Cremasteric reflex ; Children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A total of 543 boys suffering from acute scrotal pain underwent emergency surgery between 1986 and 1996. Of these, 91 had a testicular torsion (TT) (16.8%) and 250 had an appendage torsion (AT) (46%). The cause varied with patient age, with most TTs in newborns and boys of 15 years and most ATs in 10–11-year-olds; 21.5% were operated upon within 6 h of the onset of pain and 69.2% within 24 h. Most stayed in hospital for less than 24 h. Pre-surgical examination identified no criterion for excluding TT. We therefore believe that all children complaining of acute scrotal pain should undergo surgery. As release of an inflamed AT reduces pain, three-fourths of the children benefited directly from surgery.
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  • 73
    ISSN: 1437-9813
    Schlagwort(e): Key words Ovarian tumor ; Children ; Hypercalcemia ; Small-Cell carcinoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Tumors of the ovary in girls represent about 80% of pediatric genital tumors; approximately 30% of these tumors are malignant. The risk of malignancy increases with decreasing age. The most frequent finding is a teratoma; other tumors are rare. Small-cell carcinoma (SCCO) of the ovary is extremely rare, occurring mostly in young women. We present an 8-year-old girl with a SCCO of the hypercalcemic type. The findings and treatment are discussed with emphasis on the poor prognosis in these patients, even in stage 1 disease. The current literature is reviewed.
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  • 74
    ISSN: 1437-773X
    Schlagwort(e): Key words Epithelial rest of Malassez ; Cell ; cell interaction ; Extracellular matrix ; In vitro ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The present study investigated how cell plating density and extracellular matrix protein influence cell survival of epithelial rests of Malassez (ERM) in vitro. ERM cells were plated on culture dishes coated with laminin (LM), type IV collagen (type IV), or fibronectin (FN), or on noncoated dishes, (Non) at a cell density of 2 × 104–1 × 105/ml in a nonserum culture medium. XTT assays were performed to calculate the number of cells attached on the substrata after 6, 24, 48, and 72 h. Mean cell numbers were calculated, and significant differences were determined using ANOVA. When epithelial cells were cultured on various matrices at a cell density of less than 2 × 104/ml, the cells did not grow and then fell into apoptotic cell death, which was confirmed by transmission electron microscopy. The cell number was significantly increased in cells plated on FN compared to those on Non at a cell density of 4 × 104/ml–8 × 104/ml. These results suggest that both extracellular matrix proteins and cell–cell interactions may contribute to prevent apoptosis of ERM in vitro. Cell–cell interactions may be a more important factor than exogenous extracellular matrix proteins for the survival of ERM cells in vitro.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    Journal of infection and chemotherapy 5 (1999), S. 139-143 
    ISSN: 1437-7780
    Schlagwort(e): Key words Fas ; ADR ; Bladder cancer ; Synergy ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Fas and Fas ligand play an important role in cytotoxic T lymphocyte-mediated cytotoxicity. Like Fas ligand, anti-Fas monoclonal antibody (mAb) induces apoptosis of cells expressing Fas and mimics tumor necrosis factor-α (TNF-α) in its cytotoxic activity, but not in regard to other TNF-α-mediated activities. Since combination treatment with TNF-α and some anticancer chemotherapeutic agents results in synergistic cytotoxicity against various cancer cells, anti-Fas mAb may also synergize with anticancer agents in exerting cytotoxicity. The present study examined this hypothesis using bladder cancer cells. Cytotoxicity was examined by a 1-day microculture tetrazolium dye assay. Treatment of T24 cells with anti-Fas mAb in combination with mitomycin C, methotrexate, or 5-fluorouracil did not overcome their resistance to these agents. However, combination treatment with anti-Fas mAb and adriamycin (ADR) resulted in a synergistic cytotoxic effect on T24 cells, three other bladder cancer lines, and fresh bladder cancer cells derived from four patients. Treatment with ADR enhanced the expression of Fas on T24 cells. The expression of P-glycoprotein was not affected by the antibody-mediated sensitization. This study showed that combination treatment of bladder cancer cells with anti-Fas mAb and ADR can overcome their resistance and that the upregulation of Fas expression by ADR may play a role in the enhanced cytotoxicity.
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  • 76
    ISSN: 1437-773X
    Schlagwort(e): Key words Hepatocellular carcinoma ; Apoptosis ; Fas protein ; Bcl-2 protein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Because the induction of apoptosis in cancer cells is very important in clinical management, it is useful to examine the association with the Fas–Fas ligand pathway and Bcl-2 protein family in apoptosis. We morphologically examined the expression of Fas and Bcl-2 proteins and induction of apoptosis by anti-Fas in four human hepatocellular carcinoma cell lines, PLC/PRF/5, Huh-6, and Huh-7, as well as OCUH-16, which was originally established in our university. Fas protein was expressed in 96% of OCUH-16 cells in cytoplasm, 24% of PLC/PRF/5 cells, 20% of Huh-6 cells, and no Huh-7 cells. Bcl-2 protein was expressed in 43%–72% of cells in cytoplasm and nuclei of the four lines examined. Administration of anti-Fas induced apoptosis in about 40% of OCUH-16 cells, but did not induce apoptosis in the other three cell lines. In conclusion, an original cell line, OCUH-16 cells, expressed Fas and Bcl-2 proteins and underwent apoptosis following treatment with anti-Fas, but the other three cell lines examined did not undergo apoptosis. OCUH-16 cells are thus very useful for the study of apoptosis and molecules related to apoptosis at the levels of cell-surface receptors and intracytoplasmic regulation of apoptosis.
    Materialart: Digitale Medien
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  • 77
    ISSN: 1437-9813
    Schlagwort(e): Key words Unilateral undescended testis ; Rat ; Testicular injury ; DNA flowcytometry ; Anti-sperm antibody
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study was designed to evaluate whether creation of a unilateral undescended testis (U/L UDT) in rats by direct fixation of the testis can lead to changes in the contralateral (C/L) descended testis, and if so, whether this inherent problem of the model could be eliminated by anchoring the divided gubernaculum to indirectly fix the testis. Thirty male newborn rats were divided into three groups of 10 each and the procedure done on the 2nd day of life to create U/L UDT according to the group allocated: group I: sham-operated; group II: anchoring the gubernaculum after gubernaculectomy; group III: Direct suture fixation of the testis. Fertility, C/L testicular weight (TW), Johnsen score, seminiferous tubular diameter (STD), DNA flowcytometry, and serum anti-sperm antibodies (ASA) were studied. Fertility, C/L TW, Johnsen score, STD, and haploid cell population were significantly reduced in group III compared to group II, while significantly higher titers of ASA were found in group III. Gubernaculectomy and anchoring the gubernaculum to the anterior abdominal wall is a better technique of creation of experimental UDT, as direct fixation of the testis is potentially detrimental to the C/L normal, descended testis.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 579-581 
    ISSN: 1437-9813
    Schlagwort(e): Key words Hydatid disease ; Pancreas ; Children ; Echinococcosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Primary hydatid disease of the pancreas is rare. The authors report a 3-year-old girl who had a cystic mass in the head of the pancreas with no other viscera involved. At laparatomy the entire endocyst was totally extracted from the surrounding pancreatic parenchyma. The postoperative course was uneventful. She is currently disease-free with a follow-up of 5 years. Only four other pediatric cases have been reported in the English literature.
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  • 79
    ISSN: 1437-7772
    Schlagwort(e): Key words Ovarian cancer ; Apoptosis ; IL-6 ; CDDP ; Taxol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background. Apoptosis is a cascade of events that is regulated by many factors. We studied the effects of interleukin-6 (IL-6) on chemotherapy-induced apoptosis in three human ovarian cancer cell lines (JV, GG, and NF). Methods. Cells were treated with the anticancer drugs cis-diamminedichloroplatinum (II) (CDDP) and paclitaxel (Taxol; Bristol-Myers Squibb Pharmacessticals, Noble Park, Australia) over a period of 72 h. The treatments were repeated in combination with human recombinant IL-6 or anti-IL-6 monoclonal antibody (anti-IL-6 mAb). The induction of cell death was examined by morphology and by internucleosomal DNA fragmentation. Results. Reduced cytotoxicity and fewer apoptotic cells were observed after treatment with CDDP or Taxol combined with IL-6 compared with treatment with CDDP or Taxol alone. However, treatment with CDDP or Taxol combined with anti-IL-6 mAb enhanced the cytotoxic effects of the drugs and increased the number of apoptotic cells. These findings indicated that apoptosis caused by CDDP or Taxol was influenced negatively by high doses of IL-6. Conclusion. The use of CDDP or Taxol combined with anti-IL-6 mAb may have therapeutic value for patients with ovarian cancer.
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  • 80
    Digitale Medien
    Digitale Medien
    Springer
    Pediatric surgery international 15 (1999), S. 525-526 
    ISSN: 1437-9813
    Schlagwort(e): Key words Central venous catheters ; Children ; Complications
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The insertion of central venous catheters has become an established practice in the management of children with different types of malignancies for the administration of chemotherapeutic agents, antibiotics, blood and blood products, as well as drawing blood for various investigations. A commonly encountered problem is that despite the catheter being patent it may be impossible to draw blood from it. We believe this is related to the cut of the catheter tip. To overcome this problem, a technique for cutting the tip of the catheter is described.
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  • 81
    ISSN: 1432-2307
    Schlagwort(e): Key words Pyruvate kinase isoenzymes ; N-Nitrosomorpholine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The expression of the pyruvate kinase (PK) isoenzymes L and M2 was analysed in the livers of rats treated with the hepatocarcinogenic agent N-nitrosomorpholine (NNM) in the drinking water. In control animals L-PK expression was restricted to liver parenchymal cells, whereas M2-PK was detected in bile duct epithelial, blood vessel wall, endothelial and Kupffer cells. In rats treated with NNM proliferating oval cells were consistently L-PK negative and M2-PK positive, while the ductal cells of cholangiofibroses were clearly L-PK positive and coexpressed M2-PK. However, no morphological differentiation of ductal cells into hepatocyte-like cells was observed. In the clear and acidophilic cell foci storing glycogen in excess strong staining for L-PK was observed. In glycogen-poor foci induced by NNM a shift from L-PK to M2-PK expression takes place.
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  • 82
    ISSN: 1432-2307
    Schlagwort(e): Key words Anencephaly ; Thymic hyperplasia ; CD99 ; Apoptosis ; Aggregation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In a significant proportion of cases, anencephaly is associated with thymic enlargement, suggesting a possibility that anencephalic fetuses have a functional disturbance in thymocyte differentiation and development. In this report, we demonstrated that CD99 expression was consistently reduced in cortical thymocytes of all anencephalic fetuses. In addition, the CD99-dependent aggregation of immature cortical thymocytes was almost completely impaired and apoptosis of thymocytes was markedly reduced in several cases. These results are in agreement with previous findings that CD99 regulates the aggregation and apoptosis of various types of cells. These data strongly suggest that functional disturbance of thymocytes and thymic hyperplasia are related to the reduced expression of CD99 molecule in anencephalic fetuses.
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  • 83
    ISSN: 1432-2307
    Schlagwort(e): Key words Medullary thyroid carcinoma ; Basement membrane ; Laminin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Medullary thyroid carcinoma (MTC) originates from C cells, which secrete calcitonin (CT), their specific marker. C cells are located in contact with the basement membrane (BM) of the thyroid follicles, which is partly made up of the laminin-2 isoform synthesized by thyrocytes. During oncogenesis, proliferation of the C cells, invading the centre of the follicles, leads to a break in their normal contact with the BM. As specific interactions of cells with BM components, especially laminins, are important for proliferation and differentiation, we investigated the relationships of normal and neoplastic C cells with laminin in the Wag/Rij rat model of human MTC. Immunocytochemical studies showed a progressive loss of the laminin layer underlying the hyperplastic C cell nodules around the large dedifferentiated tumours. The α2, β1 and γ1 chains of the laminin-2 isoform were synthesized and secreted by rat MTC 6–23 cell cultures and the tumours induced by subcutaneous injection of these cells. In situ hybridization combined with anti-CT immunocytochemistry showed a low expression of α2 mRNA on differentiated C cells and thyrocytes, but an overexpression on immunonegative spontaneous MTC and induced intrathyroid tumours. The high level of α2 gene expression, together with tumour dedifferentiation, suggests a relationship with malignancy.
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  • 84
    Digitale Medien
    Digitale Medien
    Springer
    Urological research 27 (1999), S. 41-47 
    ISSN: 1434-0879
    Schlagwort(e): Key words Ureter ; Histology ; Polyuria ; Diabetes mellitus ; Nephrectomy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The influence of increased functional load on the macroscopical and histological appearance of the ureter was investigated. Sixty rats were divided into five groups: (1) sucrose-fed rats with non-osmotic polyuria; (2) diabetic rats with osmotic polyuria; (3) uninephrectomized rats; (4) sham-operated control rats; and (5) control rats. The 24-hour urinary volume was measured on days 7, 14 and 21. Growth of the kidney, ureter and bladder was investigated and the histological appearance of the ureter was further evaluated. Diabetic and sucrose-fed rats had comparable polyuria with a seven-fold increase in urinary output. The urinary volume for the remaining kidney was doubled in uninephrectomized rats. After 3 weeks, diabetic rats had increased weight of the kidney, ureter and bladder, sucrose-fed rats had increased weight of the bladder, whereas uninephrectomized rats had increased weight of the kidney and ureter. The cross-sectional area (CSA) of the ureter wall from control rats increased from the proximal to the distal portion. The size of the whole ureter from diabetic rats was dramatically increased, the CSA of the wall of the distal ureter portion being four times that of the controls. The CSA of the ureter wall from sucrose-fed rats was increased only in the distal portion, whereas the ureter from uninephrectomized rats was increased only in the proximal portion. The results demonstrate the importance of differentiating between different portions of the rat ureter when examining histological sections of this organ. Moreover, polyuria per se is shown to induce growth of the bladder and of the adjacent distal part of the ureter, whereas uninephrectomy and diabetes caused growth of the kidney and the upper parts of the ureter, in addition to the growth induced by polyuria.
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  • 85
    ISSN: 1434-0879
    Schlagwort(e): Key words Nonbacterial prostatitis ; Animal model ; Partial urethral obstruction ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The pathogenesis of nonbacterial prostatitis (NBP) is not understood mainly due to the lack of appropriate experimental models. We developed a new experimental model of NBP by inducing a partial obstruction of the urethra (PUO) in the rat. Male Wistar rats aged 12 weeks were used. PUO was produced by a nylon ligature on the urethra over a rubber tube. The tube was slipped out after the ligature had been tied. Two rats were examined histologically 6 h, 1 day, 3 days and 7 days after PUO. In another group, two rats were killed at 1, 3 and 7 days after the release of the PUO that had been left in place for 3 days. On day 3, another eight rats with PUO and eight control rats had 2 ml of urine in the bladder replaced by the same volume of lucifer yellow (LY; 10 μg/ml, MW 500), microperoxidase (MP; 20 μg/ml, MW 1900), horseradish peroxidase (HRP; 10 μg/ml, MW 40 000), or saline as control, respectively. Lymphocytic infiltration and interstitial edema were noted in the prostate following PUO, being most prominent on day 3. After the release of the PUO, these inflammatory changes gradually disappeared. Only LY was noted within the prostatic stroma of the rats 2 h after bladder instillation. Intraprostatic urinary reflux may be an etiologic factor in NBP. The present study showed that lower urinary tract obstruction caused NBP in the rat. Penetration of prostatic tissue by low-molecular-weight substances in the urine may trigger NBP.
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    Urological research 27 (1999), S. 476-482 
    ISSN: 1434-0879
    Schlagwort(e): Key words Urinary bladder ; Enterocystoplasty ; Cecocystoplasty ; Innervation ; Nerve growth ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Incorporation of bowel into the bladder (enterocystoplasty) has been widely used to increase bladder capacity. It has been reported by others that the response of smooth muscle from the cystoplastic segment of the intestine shifts from that of the intestine (relaxation to α-agonists and ATP) to that of the bladder (contraction to α-agonists and ATP). This suggests a functional integration of the intestinal muscle into the bladder; the mechanisms are unknown. The aims of the present study were (1) to elucidate if there are signs of bladder nerves sprouting across the anastomosis into the intestinal segment, and (2) to study what happens with the intrinsic innervation of the intestinal segment. As a model, we used cecocystoplasty in rats. The bladder was opened and a patch of cecum with intact vascular supply was anastomosed to the bladder. After two to 11 months the rats were sacrificed and the bladders mounted as wholemounts and stained for acetylcholinesterase-containing nerves, or embedded in paraffin for histology. A pronounced degeneration of the myenteric plexus was found in the cecal segments. In some areas, this had proceeded to the extent that the ganglia were isolated ovoid lumps of cells with no apparent connection to other ganglia. Areas lacking ganglia and nerve trunks but still with muscle could be found in all specimens. Abundant axon bundles were demonstrated sprouting from the cut bladder nerves close to the anastomosis. The bundles spread out in a fan-like pattern or were organized as fewer thicker nerves. There were many nerve bundles entering the cecal segment where they branched and the diameter decreased till they no longer became visible. Some nerves reached surviving lumps of myenteric ganglion cells. The results show that the bladder nerves sprout into the anastomosed cecal segment. It is reasonable to assume that these nerves are responsible for the changes in receptor pharmacological properties of the cecal smooth muscle towards that of bladder muscle.
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  • 87
    Digitale Medien
    Digitale Medien
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 3 (1999), S. 210-212 
    ISSN: 1434-3940
    Schlagwort(e): Schlüsselwörter Plattenepithelkarzinom ; Tumorneoangiogenese ; Apoptose ; Key words Squamous cell carcinoma ; Tumor neoangiogenesis ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Paclitaxel and docetaxel are potent drugs that are effective in the treatment of malignant tumors. The cytotoxic action of these drugs is not fully understood, but it appears to be mediated mainly through mitotic arrest and subsequent apoptosis. Because no information is available on the antiangiogenesis action of docetaxel, the investigations were performed to determine whether inhibition of neoangiogenesis plays a role in docetaxel’s antitumor efficacy. Four different mouse tumors, two squamous cell carcinomas (SCC-IV; SCC-VII) and two adenocarcinomas (MCA-4; MCA-29) were assayed for angiogenic activity using the in vivo i.c. angiogenesis assay. Tumor cells (5 × 105) were injected i.c. into the skin flap over the abdominal wall, and the number of new blood vessels at the tumor cell injection site was determined 2, 4, 6, 8, 10 and 12 days later. The mice were treated with docetaxel (Taxotere – 31.3 mg/kg i.v.) 1 or 4 days after tumor cell injection. The number of new blood vessels increased with time. Docetaxel reduced the number of newly formed blood vessels in MCAs, but not in SCCs. The reduction was associated with slower tumor growth. In a separate set of experiments we observed that docetaxel’s inhibitory effect on the two MCAs was histologically associated with massive tumor cell destruction by means of both apoptosis and necrosis. This was not observed for the two SCCs. Since no reduction in blood vessels occurred in tumors unresponsive to docetaxel, the inhibition of neoangiogenesis in docetaxel-responsive tumors was likely the result of a decrease in angiogenic stimuli due to docetaxel’s destruction of tumor cells.
    Notizen: Die zytotoxische Aktivität der Taxane Paclitaxel und Docetaxel ist zum jetzigen Zeitpunkt noch nicht vollständig erklärt. Diese, zur Behandlung maligner Tumoren eingesetzten antineoplastischen Chemotherapeutika, scheinen jedoch weitgehend über die Blockierung der Mitose und die nachfolgende Induktion der Apoptose zu wirken. Über eine evtl. Hemmung der Neoangiogenese, wie sie kürzlich für Paclitaxel beschrieben wurde, liegen für Docetaxel noch keine Studienergebnisse vor. Es wurde deshalb untersucht, ob die therapeutische Aktivität von Docetaxel zur Hemmung der Neoangiogenese im Tumor beitragen kann. 4 murine Tumoren, 2 Plattenepithelkarzinome (SCC-VII; SCC-IV) und 2 Adenokarzinome (MCA-4; MCA-29), wurden in einem quantitativen intrakutanen In-vivo-Angiogenese-Assay experimentell untersucht. 5 · 10 5 Tumorzellen wurden in einen Abdominallappen der Maus injiziert. Die Anzahl neuformierter Blutgefäße und das Tumorwachstum wurden im 2tägigen Intervall über einen Zeitraum von zwischen 10 und 14 Tagen bestimmt. 2 Behandlungsgruppen wurde am 1. oder 4. Tag nach der Tumorzellinokulation Docetaxel (Taxotere – 31,3 mg/kg) i.v. injiziert. Die Plattenepithelkarzinome waren gegenüber der Therapie mit Docetaxel nicht sensibel, während die Adenokarzinome mit einer Abnahme der Gefäßzahl und einer Reduktion des Tumorvolumens reagierten. Histologisch zeigten die Adenokarzinome außerdem eine massive Tumorzelldestruktion durch Apoptose und Nekrose. Da die gegenüber Docetaxel nichtsensiblen Tumoren (Plattenepithelkarzinome) nicht mit einer Abnahme der Gefäßzahl reagierten, ist der beschriebene Effekt in den Adenokarzinomen am ehesten als indirekte Wirkung von Docetaxel zu werten. Die Tumorzelldestruktion führte in den betroffenen Tumoren zu einer verminderten Freisetzung endothelialer Mitogene wie VEGF und bFGF und zur Hemmung der Tumorneoangiogenese.
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    Urological research 27 (1999), S. 174-179 
    ISSN: 1434-0879
    Schlagwort(e): Key words Apoptosis ; Ischemia-reperfusion ; Blood flow ; Ischemia ; Prostate ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The mechanisms involved in the castration-induced involution of the ventral prostate (VP) are not fully understood. It was recently reported that castration decreases blood flow in the VP in rats and that this occurs before the apoptotic involution of the organ. However, it is unknown whether a decrease in blood flow may trigger apoptosis in the VP, and this was therefore examined in this study. The right iliac artery was clamped for 1 h in adult male rats. After 24 h of reperfusion, the VPs were frozen or fixed. In situ end-labeling (ISEL) was used to identify apoptotic cells, and testosterone repressed prostatic message-2 (TRPM-2) was measured. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was used to identify proliferating cells. Clamping the right iliac artery reduced blood flow in the right VP to 0.17 of that in the contralateral lobe. This relative ischemia resulted in a threefold increase in the volume density of apoptotic epithelial cells on the treated side, but left cell proliferation unaffected. Testosterone substitution did not change this pattern. This study suggests that a transient period of relative ischemia may induce apoptosis in the rat ventral prostate. This may be of importance for the understanding of castration-induced prostatic involution.
    Materialart: Digitale Medien
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  • 89
    ISSN: 1434-0879
    Schlagwort(e): Keywords Ischemia-reperfusion ; Heat shock ; HSP70 ; Kidney ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ischemia-reperfusion injury in the kidney is known to cause induction of the inducible form of the 70 kDa heat shock protein HSP70i (or HSP72). However, knowledge of the expressional regulation of the two coding genes for HSP70i –HSP70-1 gene and HSP70-2 gene – is very limited. We investigated the time course of HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in the renal cortex after different periods of unilateral warm renal ischemia (10–60 min) and reperfusion (up to 60 min) in 10-week-old male Wistar rats. Immediately after ischemia there was a significant induction of both HSP70i genes. While HSP70-1 expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSP70-2 mRNA – which was generally expressed at a far lower level than HSP70-1 mRNA – was strongly induced (3-fold) during reperfusion only after brief periods (10 min) of ischemia. Cellular ATP levels rapidly dropped to 5% with ischemia and the pattern of recovery during reperfusion significantly depended on the duration of the ischemic period, thus showing a good relation with the heat shock (protein) gene expression. We conclude that HSP70-2 is the more sensitive gene with a lower activation threshold by mild injury, while the HSP70-1 gene mediates the major response of heat shock protein induction after severe injury.
    Materialart: Digitale Medien
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  • 90
    ISSN: 1434-0879
    Schlagwort(e): Keywords Testicular neoplasms ; Embryonal cell ; carcinoma ; Apoptosis ; Lymphocytes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Disorders in the regulation of apoptotic cell death may contribute to cancer. Furthermore, lymphocytes are supposed to play a role in counteracting tumorigenesis by inducing apoptosis in different human tumors. In this study, for the first time, tumor cell and lymphocyte apoptosis were investigated systematically in human embryonal cell carcinoma. DNA fragmentation and DNA condensation were measured simultaneously on double-fluorescence-labeled testis tumor sections using immunofluorescence microscopy. Different apoptotic indices (AIs), based either on biochemical (DNA fragmentation) or morphological criteria (DNA condensation) alone or on a combination of both, were determined in different histological regions in and around the tumor. Using morphological criteria alone, 40–75% of all apoptotic cells were not detected. Based on previous observations this finding might be related to subsets of apoptotic cells which induce the process of DNA condensation without activation of processes responsible for DNA fragmentation. Moreover, the AIs of tumor cells and lymphocytes were highest in the tumor region, compared with regions around the tumor and distant from it; these findings are discussed in the context of the Fas/FasL system.
    Materialart: Digitale Medien
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  • 91
    ISSN: 1432-0533
    Schlagwort(e): Key words c-Jun ; Jun B ; Jun D ; Apoptosis ; Colchicine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The expression of members of the Jun family of transcription factors was examined by immunohistochemistry, Western blotting, in situ hybridization and Northern blotting in the developing and adult rat brain following colchicine administration. Apoptotic cells, as revealed by their typical morphology and positive staining with the method of in situ end-labeling of nuclear DNA fragmentation, were restricted to granule cells of the dentate gyrus and olfactory bulb, and a few cells in the upper layers of the entorhinal cortex in adult rats, whereas widespread apoptosis occurred in developing rats after colchicine administration. No modifications in the expression of Jun D and Jun B, except for a generalized and moderate Jun B expression in glial cells, were observed in colchicine-treated rats. Generalized and strong c-jun mRNA induction and c-Jun/AP-1 (Ab-1) protein expression was observed in the cerebral neocortex, entorhinal and piriform cortices, CA1 and CA3 areas of the hippocampus and granule cell layer of the dentate gyrus in adult treated rats, thus indicating a generalized c-Jun response to colchicine administration. In contrast, c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) immunoreactivity was restricted to apoptotic cells in colchicine-treated adult and developing brains. Western blots of hippocampal homogenates and total brain homogenates in adult and developing rats, respectively, demonstrated a band of 39 kDa for the c-Jun/AP-1 (Ab-1) antibody in control animals, the intensity of which increased in colchicine-treated rats. However, a band of 37 kDa, the intensity of which also increased following colchicine administration, was observed for the c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) antibodies. Selective c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) expression was also observed in apoptotic cells of the SH-SY5Y neuroblastoma line after the addition of colchicine to the culture medium. Taken together, the present in vivo and in vitro results indicate a generalized c-Jun response to colchicine in sensitive cells, whereas the antibodies c-Jun/AP-1 (N) and c-Jun/AP-1 (Ab-2) recognize vulnerable cells dying via apoptosis.
    Materialart: Digitale Medien
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 97 (1999), S. 192-195 
    ISSN: 1432-0533
    Schlagwort(e): Key words Neuronal vacuolation ; Rottweiler dog ; Bcl-2 ; Bax ; c-Jun ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Neuronal vacuolation, involving the cerebellar roof nuclei, Purkinje cells, selected nuclei of the brain stem, thalamus, Clarke’s column, anterior and posterior horns of the spinal cord, visceral autonomic ganglia and myenteric plexus, as well as axonal degeneration of the white matter of the brain stem, cerebellar pedunculi, dorsolateral columns of the spinal cord and ventral roots of the spinal cord, were observed in two young Rottweiler dogs which were clinically afflicted with hind limb weakness progressing to paraparesia, ataxia, intention tremor, and difficulty in swallowing and barking. The absence of modifications in Bcl-2 and Bax immunoreactivity, a lack of strong c-Jun/AP-1 (N) immunoreactivity in vacuolated cells, and the absence of DNA breaks, as seen with the method of in situ end-labeling of nuclear DNA fragmentation, all suggest that there is no involvement of the apoptotic pathway in vacuolated cells in this new neurodegenerative disorder.
    Materialart: Digitale Medien
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  • 93
    ISSN: 1432-0533
    Schlagwort(e): Key words Glucocorticosteroids ; Apoptosis ; Guillain-Barré syndrome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Lipocortin-1 exerts a potent immunosuppressive effect on pathogenic T cells. In multiple sclerosis and experimental autoimmune encephalomyelitis levels of lipocortins are raised, suggesting their involvement in the recovery from an immunological insult or in neural regeneration. To further understand the role of lipocortins in the peripheral nervous system we have characterized lipocortin-1 levels and cellular distribution of lipocortin-1 immunoreactivity in sciatic nerves of rats with experimental autoimmune neuritis (EAN), a model of human Guillain-Barré syndrome. EAN was induced actively by immunization with bovine peripheral myelin (active EAN) or by adoptive-transfer (AT-EAN) of P2-specific T cells. Cellular infiltrates in serial and semithin cryosections were characterized by immunohistochemistry. In parallel, lipocortin-1 levels in tissue extracts were quantified by a sandwich-ELISA. Only weak lipocortin-1 immunoreactivity was found in nerves of control animals injected with non-pathogenic T cells. The majority of macrophages and lymphocytes in EAN lesions exhibited lipocortin-1 immunoreactivity. Some very heavily stained cells showed a distribution and morphology similar to ED-2-positive macrophages which were abundant during early stages of EAN. Lipocortin-1 expression in T cells and macrophages was proven by immunocytochemical studies in semithin serial sections. In tissue extracts, lipocortin-1 levels increased from 0.24 ± 0.14 μg/mg protein in controls receiving non-pathogenic T cells to a maximum of 0.55 ± 0.1 μg/mg protein in AT-EAN at the peak of disease, and then slowly decreased during clinical recovery but still remained elevated. In dose-response studies in AT-EAN, highest values of lipocortin-1 (0.71 ± 0.23 μg/mg protein) were recorded after transfer of 2 × 107 T cells. Increased levels of lipocortin-1 were also measured in active EAN but occurred during the recovery phase (0.65 ± 0.27 μg/mg protein). By analogy with other immune-mediated disorders, increased lipocortin-1 expression in the inflamed sciatic nerve in EAN may exert immunoregulatory functions in-situ and contribute to the termination of the autoimmune response.
    Materialart: Digitale Medien
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 199 (1999), S. 265-280 
    ISSN: 1432-0568
    Schlagwort(e): Key words Cat ; Rat ; Immunocytochemistry ; NADPH-diaphorase ; Thalamus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  To gain insight into the cellular organisation of the zona incerta, we have examined the chemoarchitectonic properties of this ”uncertain zone”. The brains of Sprague-Dawley rats and common cats were processed for immunocytochemistry or NADPH-diaphorase histochemistry using standard methods. For the immunocytochemistry, antibodies to γ-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD), parvalbumin, calbindin, tyrosine hydroxylase, somatostatin, serotonin and glutamate were used. Two general patterns of distribution in the zona incerta were seen. First, labelled cells were restricted largely to one of the cytoarchitectonically defined sectors of the zona incerta. For instance, GABA, GAD and parvalbumin-immunoreactive cells were found principally within the ventral sector, NADPH-diaphorase and glutamate-immunoreactive cells within the dorsal sector and tyrosine hydroxylase- and somatostatin-immunoreactive cells within the rostral sector. Second, labelled cells were scattered somewhat across all incertal sectors, with no clear region of concentration. This pattern included the calbindin- and serotonin-immunoreactive cell groups. These results indicate that the zona incerta is made up of many neurochemically distinct cell groups, some of which respect the well-defined cytoarchitectonic boundaries of the nucleus, whilst others do not. This rich neurochemical diversity in the zona incerta suggests that this nucleus may have differential effects on the different structures that it projects to.
    Materialart: Digitale Medien
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  • 95
    ISSN: 1432-0533
    Schlagwort(e): Key words Immediate early gene ; Heat shock protein ; Cerebral ischemia ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The neuroprotective role of the expression of heat shock protein (HSP) and immediate early gene remains unclear. Using immunoelectron microscopy, we examined the ultrastructural integrity of the neurons with expression of c-Fos, c-Jun and HSP70 in gerbils after transient cerebral ischemia and repefusion. Induction of c-Fos and c-Jun was observed in the CA3 region resistant to ischemia, while HSP70 was expressed not only in the CA3 but also in the vulnerable CA1 region. With immunoelectron microscopy, the expression of c-Fos/c-Jun and HSP70 was observed in the neurons which retained neuronal integrity except for mitochondrial swelling and polyribosomal disaggregation. In contrast, the CA1 neurons without immunoreaction for HSP70 showed cytoplasmic vacuoles and parallel stacking of rough endoplasmic reticulum, the features associated with the process of delayed neuronal death. These findings suggested that c-Fos and c-Jun were induced selectively in reversibly damaged neurons, whereas HSP70 was up-regulated even in neurons with irreversible damage, but was more preferentially and intensely expressed in neurons with reversible damage.
    Materialart: Digitale Medien
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  • 96
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 97 (1999), S. 5-12 
    ISSN: 1432-0533
    Schlagwort(e): Key words Creutzfeldt-Jakob disease ; Apoptosis ; Cell death ; Prion protein ; In situ end-labeling of nuclear DNA fragmentation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The method of in situ end-labeling of nuclear DNA fragmentation was used in the study of ten patients (two biopsies, eight autopsies) with sporadic Creutzfeldt-Jakob disease (CJD). All the patients had the typical morphological lesions including neuron loss, spongiform change and astrocytosis. Four of them also showed prion protein (PrP) deposits in the cerebral cortex, and two of them kuru-like plaques in the cerebellum. A few cells with DNA breaks were found in the two biopsy cases; one of them, suffering from a panencephalopathic form of the disease, showed positive nuclei not only in the cerebral cortex but also in the subcortical white matter. Variable numbers of positive nuclei were observed in the gray and white matter in the eight autopsy cases, in which, although the distribution of positive cells roughly correlated with the distribution of neuron loss, no clear relationship was found as regards the distribution and degree of cell labeling and the degree of neuron loss. Furthermore, large numbers of positive cells were concentrated in a particular area, whereas a few cells were seen in a neighboring equally affected area. Positive glial cells in the plexiform layer of the CA1 area of the hippocampus, and in the frontal white matter were frequently encountered. Staining of the cytoplasm in a minority of cells was interpreted as the result of nuclear DNA leakage. None of the stained cells had the typical morphology of apoptosis; most particularly, peripheral chromatin condensation and formation of apoptotic bodies were not seen in any case. PrP deposits did not result in an increase of nuclear DNA breaks either within the area or in adjacent regions. Although positive cells were also observed in autopsy cases of controls which were processed in the same way, positive labeling as a whole was higher in CJD than in age-matched controls. These results show that brain nuclear DNA is vulnerable in CJD, and suggest that increased DNA vulnerability has a role in cell death and neuron loss. Since nuclear shrinkage and positive nuclear staining with the method of in situ end-labeling of nuclear DNA fragmentation are not exclusive to apoptosis, further information is needed to categorize cell death in CJD as apoptosis. Necrosis or other forms of cell death, as well as increased DNA vulnerability to agonal changes of the individuals, and to postmortem delay in the fixation of the tissues, may account for additional positive staining in cases examined at autopsy.
    Materialart: Digitale Medien
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  • 97
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 200 (1999), S. 203-214 
    ISSN: 1432-0568
    Schlagwort(e): Key words Extracellular material ; Cell proliferation ; Apoptosis ; Anoikis ; Tenascin ; Laminin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Extracellular material molecules play a key role in the regulation of morphogenesis and differentiation of a large number of organs including the central nervous system. However, the role of the neural basement membrane in the growth of different parts of the neural tube has yet to been delineated. Here, the structural and compositional modifications of the basement membrane (BM) of rhombencephalic tectoria lamina anlage (RTLA) have been examined during the process of RTLA epithelial attenuation. Between stages 10 to 11– the presumptive RTLA epithelium showed a structure, thickness and cell-proliferating capacity similar to those observed in other zones of the rhombencephalic walls. Moreover, the rhombencephalic vesicles were surrounded by a continuous BM that was heterogeneous both ultrastructurally and with regard to ruthenium red, laminin and tenascin distribution. After stage 11, the RTLA epithelium underwent a rapid process of attenuation and change to a stratified flattened epithelium. During this remodelling process, apoptosis and inhibition of both PCNA expression and 3H-thymidine uptake occurred in the RTLA epithelium. The BM of the RTLA underwent a process of degration at the beginning of the remodelling, and apoptosis and cell proliferation inhibition of RTLA epithelium were also observed. The loss of the biochemical signals encoded within the BM could lead to cell shape changes, cell proliferation inhibition and to the anoikis type of cell death. Our findings support the idea that the BM surrounding the neural tube plays a key role in controlling both the structure and growth of the CNS during the early developmental stages.
    Materialart: Digitale Medien
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  • 98
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 200 (1999), S. 239-252 
    ISSN: 1432-0568
    Schlagwort(e): Key words Somite explant culture ; Sonic hedgehog protein ; Myogenic induction ; Primary fiber type diversity ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Primary skeletal muscle fibers first form in the segmented portions of paraxial mesoderm called somites. Although the neural tube and notochord are recognized as crucial in patterning myogenic cell lineages during avian and mammalian somitic myogenesis, the source, identities, and actions of the signals governing this process remain controversial. It has been shown that signals emanating from the ventral neural tube and/or notochord alone or Shh alone serve to activate MyoD expression in somites. However, beyond a role in initiating MyoD expression, little is known about the effects of Shh on primary muscle fiber formation in somites of higher vertebrates. The studies reported here investigate how the ventral neural tube promotes myogenesis and compare the effects of the ventral neural tube with those of purified Shh protein on fiber formation in somites. We show that purified Shh protein mimics actions of the ventral neural tube on somites including initiation of muscle fiber formation, enhancement of numbers of primary muscle fibers, and particularly, the formation of primary fibers that express slow myosin. There is a marked increase in slow myosin expression in fibers in response to Shh as somites mature. The effects of ventral neural tube on fiber formation can be blocked by disrupting the Shh signaling pathway by increasing the activity of somitic cyclic AMP-dependent protein kinase A. Furthermore, it was demonstrated that apoptosis is a dominant fate of somite cells, but not somitic muscle fibers, when cultured in the absence of the neural tube, and that application of Shh protein to somites reduced apoptosis. The block to apoptosis by Shh is a manifestation of the maturity of the somite with a progressive increase in the block as somites are displaced rostrally from somite III forward. We conclude that purified Shh protein in mimicking the effects of the ventral neural tube on segmented mesoderm can exert pleiotropic effects during primary myogenesis, including: control of the proliferative expansion of myogenic progenitor cells, antagonism of cell death pathways within the precursors to muscle fibers, and during the crucial process of primary myogenesis, can exert an effect on diversification of muscle fiber types.
    Materialart: Digitale Medien
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  • 99
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 200 (1999), S. 521-531 
    ISSN: 1432-0568
    Schlagwort(e): Key words Development ; Internal capsule ; Nucleus basalis ; Rat ; Thalamus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  This study defines several features of the early connections of the developmentally transient perireticular thalamic nucleus of rats. The neocortex of developing rats was injected with either DiI, biotinylated dextran, WGA-HRP (wheatgerm agglutinin conjugated-horseradish peroxidase), fluorescent latex beads or cholera toxin subunit B (CTB) and their brains were processed for tracer detection with standard methods. In general, tracer injections into various regions of the developing neocortex revealed no labelled neurones within the perireticular nucleus, although some of these tracers (WGA-HRP, dextran) labelled many of the amoeboid microglial cells that are found within this nucleus. There were, however, many retrogradely labelled neurones in a region adjacent to the perireticular nucleus, within the nucleus basalis of the basal forebrain (medial edge of globus pallidus). Their identity was confirmed as neurones of the nucleus basalis since they were all were similar in morphology and somal size to neurones that were immunoreactive to NGFr (nerve growth factor receptor), an antigen found only among neurones of the nucleus basalis and basal forebrain. Moreover, double labelling experiments revealed that most, if not all, of the cortically labelled neurones were NGFr-immunoreactive also. Thus, in conclusion, our results suggest that the perireticular nucleus does not project to the neocortex; the only neurones in the general vicinity of the perireticular nucleus that have a cortical projection form part of the nucleus basalis.
    Materialart: Digitale Medien
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  • 100
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 200 (1999), S. 533-540 
    ISSN: 1432-0568
    Schlagwort(e): Key words Coronary vasculogenesis ; Angiogenesis ; Coronary artery ; Development ; Rat ; Embryonic heart
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The aim of this work was to address spatiotemporal and morphologic patterns of coronary artery development in rats, based on immunohistochemical and ultrastructural studies of hearts at different stages of prenatal development. Griffonia simplicifolia I lectin and α-smooth muscle antibody were used to demonstrate endothelial cells and/or their precursors and smooth muscle cells, respectively. Ultrastructural examination was performed on ED14–16 hearts to study the morphology of the developing coronary arteries in different regions of the truncus arteriosus and adjacent myocardium. On ED14 endothelial-like cells present within the mesenchyme surrounding the outflow tract penetrated the aortic wall and the truncoconal proximal myocardium. On ED15 these penetrating cells formed vascular clusters, which were the first signs of presumptive vascular channels. Development of the coronary artery proceeded by coalescence of discontinous vascular clusters, formation of the lumen (vascular channels) and establishing a connection of the proximal part with the aorta. The second layer of cells around vascular channels (embryonic media) consisted of mesenchymal cells that were attracted to the immature vessel and were first seen on ED15. At this time no lumenized connection of the coronary artery with the aorta has been seen. After the lumenized connection of the coronary artery with the aorta had been established perivascular cells of the media started to differentiate into vascular smooth muscle, as was shown by α-smooth muscle actin-staining. Further development and differentiation of the media and adventitia proceeded distally (towards the apex).
    Materialart: Digitale Medien
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