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  • Amino acids
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  • 1995-1999  (1,839)
  • 1940-1944  (1,911)
  • 1900-1904
  • 1860-1869  (931)
Year
Keywords
  • 1
    ISSN: 1434-5196
    Keywords: Key words Methadone ; Dihydrocodeine ; Substitution ; Poisoning ; Children ; Schlüsselwörter Methadon ; Dihydrocodein ; Substitution ; Intoxikationen ; Kinder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: 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.
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1248-9204
    Keywords: Contralateral hernia ; Children ; Incidence ; Predisposing disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Surgical and radiologic anatomy 21 (1999), S. 139-141 
    ISSN: 1279-8517
    Keywords: Anatomy ; Human ; Cross-section ; Computer-assisted instruction ; Education ; Medical
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The NPAC visible human viewer (NPAC VHV), graphical interface written in JAVA, freely accessible by the Web, allows the display of anatomic cross-sections of the Visible Human Project developed by the National Library of Medicine. In April 1997, the Medical Media Library of Lyons undertook the construction of a French-language mirror site of the NPAC VHV. The aim of this work is to evaluate first year utilisation of this site. From May 1st, 1997 to April 30th, 1998, the mirror site was consulted 34,752 times. In 45.14% of cases, the request came from France, in 4.42% of cases from Belgium, in 3.98% from Canada and in 2.12% from Switzerland. Other connections came either from a country responsible for fewer than 1% of connections or from unidentified computers. Data analysis showed a peak of connections between 15:00 and 17:00, and an increased number of connections from September to March 1998. The NPAC VHV is housed in 5 sites in the world. It is a software very simple to use. As the figures have no legends, it is more appropriate for group teaching than for self-teaching.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Italian journal of neurological sciences 20 (1999), S. 119-128 
    ISSN: 1126-5442
    Keywords: Key words Learning ; Development ; Memory ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Italian journal of neurological sciences 20 (1999), S. 303-307 
    ISSN: 1126-5442
    Keywords: Key words Lyme disease ; Chronic neuroborreliosis ; Children ; MRI ; Demyelinating disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1438-2199
    Keywords: Amino acids ; RT/PCR ; Protooncogene ; ets-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Marathon ; Endurance exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 17 (1999), S. 369-376 
    ISSN: 1438-2199
    Keywords: Amino acids ; Non-proteinogenic dipeptides ; Dehydrodipeptides ; Diastereoselectivity ; N-Boc-Dehydroamino acids ; Asymmetric hydrogenation ; Chiral rhodium catalysts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 9
    ISSN: 1438-2199
    Keywords: Amino acids ; Polyclonal antibodies ; Phosalone ; Immunodetection ; Hapten synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 10
    ISSN: 1438-2199
    Keywords: Amino acids ; Liver ; Hepatic damage ; Carbon tetrachloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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).
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  • 11
    ISSN: 1438-2199
    Keywords: Amino acids ; Alanine ; Fatty acids ; Glutamine and glutamate synthesis ; Glycerol and lactate metabolism ; Malate-aspartate shuttle ; Rabbit kidney-cortex tubules ; Renal gluconeogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 16 (1999), S. 79-89 
    ISSN: 1438-2199
    Keywords: Amino acids ; Anti-neoplastic amino acids ; Purine and DNA synthesis inhibitors ; PRPP amido transferase and IMP dehydrogenase inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 13
    ISSN: 1438-2199
    Keywords: Amino acids ; Targeting ; Mitochondria ; Chloroplasts ; Cysteine synthase ; Transit peptide ; Transgenic plants ; Processing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 14
    ISSN: 1438-2199
    Keywords: Amino acids ; Non-proteinogenic optically active amino acids ; Dehydroamino acids ; Chiral rhodium catalysts ; Asymmetric hydrogenation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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”.
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  • 15
    ISSN: 1438-2199
    Keywords: Amino acids ; L-Tryptophan ; Serum albumin ; Transport ; L-Tryptophan depletion ; α-Methyl-DL-tryptophan ; Analbuminemic rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 16
    ISSN: 1438-2199
    Keywords: Amino acids ; Tissue protein synthesis ; Stable isotope amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 17
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Kainic acid ; Epilepsy ; Anticonvulsants ; Neuroprotection ; Excitatory amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 16 (1999), S. 191-213 
    ISSN: 1438-2199
    Keywords: Amino acids ; Enzymatic resolution ; Ester hydrolysis ; Proteases ; Lipases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 16 (1999), S. 251-272 
    ISSN: 1438-2199
    Keywords: Amino acids ; Unusual amino acids ; Aspartic acidβ-semialdehyde ; Aspartaldehyde ; 2-Amino-4-oxobutyric acid ; Enantioselective synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Dipeptide derivatives ; Non-proternogenic optically active dipeptide esters ; Dehydrodipeptides ; Chiral rhodium catalysts ; Asymmetric hydrogenation ; Diastereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Phytotoxin AS-I analogues ; FAB ; PD ; ESI mass spectrometry ; 1H,13C and 2D NMR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Diclofenac ; Anti-phlogistics ; Non-proteinogenic amino acids ; Voltaren®. Thionation ; Cyclo-oxygenase inhibitors ; Ulcerogenic gastritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 17 (1999), S. 139-148 
    ISSN: 1438-2199
    Keywords: Amino acids ; Polyamine oxidase ; Polyamines ; Gender ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 17 (1999), S. 195-205 
    ISSN: 1438-2199
    Keywords: Amino acids ; Apis mellifera ; Drones ; Osmolarity ; Age dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Conformational constraint ; Cyclic disulfides ; -Cys-Cys-peptides ; Dipeptide mimetics ; Dithiols ; Glutathione analogues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Polyamine catabolism ; Polyamine oxidase ; Diamine oxidase ; Testosterone ; Mouse kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Allohydroxyproline ; Allothreonine ; Chiral separation ; Chirasil-Val ; Hydroxyproline ; Threonine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    Amino acids 17 (1999), S. 323-334 
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine release ; Cerebellar granule cells ; Celldamaging conditions ; Glutamate receptors ; Veratridine ; Potassium stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 29
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Osmoregulation ; Rat ; Osmolarity sensor protein ENVZ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Protein ; arginine methyltransferase ; Inhibitors ; Ginseng extract ; Arginine derivatives ; Basic amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Hexafluoroacetone ; α-N-Methylamino acids ; α-N-Phosphinoylmethylamino acids ; Pro-Glu-chimeras ; Pro-Tauchimeras
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Perfluorinated compounds ; Surfactants ; Complexing properties ; Carnosine ; β ; Amino acids ; Blood substitutes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    Amino acids 16 (1999), S. 415-423 
    ISSN: 1438-2199
    Keywords: Amino acids ; SOD-like activity ; Cu (III)-Poly-L-lysine ; Cu(III)-Poly-L-glutamic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Lysine ; Herbicides ; Azotobacter ; Xenobiotics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Trypanothione ; Glutathione ; Benzyloxycarbonyl-reductase ; Hydrocinnamoyl
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    ISSN: 1438-2199
    Keywords: Amino acids ; Serotonin receptor ; Serotonin-3 receptor ; Ion channel ; Ion permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    Amino acids 17 (1999), S. 301-313 
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Transporter ; Rat ; Brain ; Heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    Keywords: Amino acids ; Tyrosine ; Phenylalanine ; Aromatic compounds ; Rumen microorganisms[/klw]
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    Amino acids 17 (1999), S. 357-368 
    ISSN: 1438-2199
    Keywords: Amino acids ; o-Carboranylalanine ; Histidine ; Bacteria ; Fungi ; Oomycota ; Plasmopara
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
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    Amino acids 17 (1999), S. 401-413 
    ISSN: 1438-2199
    Keywords: Amino acids ; Indolylacrylic acid ; Tryptophan ; Indolylacryloylglycine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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
    ISSN: 1437-1596
    Keywords: Key words Poisoning ; Benfuracarb ; Carbofuran ; Human ; Blood ; Urine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract We describe here three cases involving acute fatalities due to benfuracarb ingestion and the forensic toxicological implications. Benfuracarb, a carbamate insecticide and its main metabolite carbofuran, were detected using thin layer chromatography (TLC) and gas chromatography/mass spectrophotometry (GC/MS) after extraction with ethyl acetate and then quantified using gas chromatography (GC) equipped with NPD. The blood levels of benfuracarb and carbofuran were in the range of 0.30∼2.32 μg/ml and 1.45∼1.47 μg/ml, respectively. Benfuracarb was not detected in urine, but carbofuran was detected in the range of 0.53∼2.66 μg/ml.
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  • 42
    ISSN: 1432-1912
    Keywords: Key words Asphyxia ; Nitric oxide ; Electron spin ; resonance ; Adrenocorticotropin ; Resuscitation ; S-Methylisothiourea ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 43
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    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 117-122 
    ISSN: 1432-1912
    Keywords: Key words Ethanol ; Restraint stress ; NMDA receptor complex ; Memantine ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 44
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    Biology and fertility of soils 29 (1999), S. 257-261 
    ISSN: 1432-0789
    Keywords: Key words Alpine nitrogen cycle ; Amino acids ; Kobresia myosuroides ; Organic nitrogen ; Plant-microbe competition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: 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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  • 45
    ISSN: 1432-0975
    Keywords: Key words Otolith ; Chemistry ; ICP-MS ; Stock discrimination ; Epinephelus striatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: 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.
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  • 46
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    Experimental brain research 125 (1999), S. 389-396 
    ISSN: 1432-1106
    Keywords: Key words Neck muscles ; Vibration ; Proprioception ; Sound localization ; Space perception ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of transcutaneous vibration of the posterior neck muscles on the lateralization of dichotic sound was investigated in human subjects. Two-alternative forced-choice (left/right) judgements were made on acoustic stimuli presented with different interaural level differences via headphones during neck-muscle vibration. A shift of the subjective auditory median plane toward the side contralateral of vibration was found, indicating that the sound was perceived as shifted toward the side of vibration. The mean magnitude of the vibration-induced intracranial shift was 1.5 dB. The results demonstrate a neck-proprioceptive influence on sound lateralization and suggest that this proprioceptive input is used for a central-nervous transformation of auditory spatial coordinates onto a body-centered frame of reference.
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  • 47
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    Experimental brain research 125 (1999), S. 435-439 
    ISSN: 1432-1106
    Keywords: Key words Transcranial magnetic stimulation ; Plasticity ; Synchronization ; Motor system ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used focal transcranial magnetic stimulation to examine the effects of 120 synchronized thumb and foot movements on the motor output map of the right abductor pollicis brevis muscle (APB) (experiment 1). To evaluate the performance, the latencies between the onset of the electromyographic activity (EMG) of the two muscles were measured. As control, 120 asynchronous thumb and foot movements were performed (experiment 2). Exclusively in experiment 1, the center of gravity (CoG) of the output map moved medially in the direction of the foot representation area (mean 7 mm, P〈0.05) and returned into its original location within 1 h. In experiment 2, the CoG remained unchanged (mean displacement, 0.68 mm into a lateral direction; not significant). The effect in experiment 1 was independent of an improvement in performance. We conclude that a short-lasting training of synchronous movements induces modulations of motor output maps which probably occur due to interactions between hand and foot representation areas in the motor cortex.
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  • 48
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    Journal of comparative physiology 185 (1999), S. 297-304 
    ISSN: 1432-1351
    Keywords: Key words Odor coding ; Learning ; Enhanced sensitivity ; Rabbit ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The olfactory system is faced with a particular problem – the high dimensionality and inherent unpredictability of the chemical world. Most natural odorants encountered in everyday life are complex mixtures of many different volatiles. This means that from the outset the olfactory system has to contend with a great and often unpredictable diversity of molecules, making it difficult for stable primary features of the chemical world to be mapped onto the sensory surface. One solution to such unpredictability is provided by learning. Learning confers flexibility, enabling individuals of a given species to acquire and make use of the most appropriate information in a particular environment. Two examples of this are presented: learning of maternal odors in neonatal rabbits, including evidence that the sensory surface itself may be influenced by environmental conditions so as to enhance sensitivity to molecules of particular ecological relevance, and cross-cultural human studies suggesting that experience with everyday odors influences not only the way these are evaluated, but also their perceived intensity. It is concluded that an adequate understanding of odor coding and olfactory function will not be possible without taking such experience-dependent factors into account.
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  • 49
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    Der Nervenarzt 70 (1999), S. 1-10 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Tic-Störung ; Zwangsstörung ; Kinder ; Jugendliche ; Neurobiologie ; Psycho- pharmakologie ; Verhaltenstherapie ; Key words Tic-disorder ; Obsessive-compulsive disorder ; Children ; Adolescents ; Neurobiology ; Psychopharmacology ; Behavior therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: 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.
    Notes: 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.
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  • 50
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    Monatsschrift Kinderheilkunde 147 (1999), S. 328-332 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Asthma bronchiale ; Schulkinder ; Türkische Kinder ; Key words Asthma ; Children ; Turkish children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: 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.
    Notes: 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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  • 51
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    HNO 47 (1999), S. 535-540 
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Hörschäden ; Knalltrauma ; Kinder ; Tinnitus ; Erweiterte Hochtonaudiometrie ; Key words Hearing loss ; Acoustic trauma ; Children ; Tinnitus ; High-frequency audiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: 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).
    Notes: 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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  • 52
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Laryngotracheale Stenose ; Cricotracheale Resektion ; Kinder ; Tracheotomie ; Key words Laryngotracheal stenosis ; Cricotracheal resection ; Tracheostomy ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: 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.
    Notes: 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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  • 53
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    Monatsschrift Kinderheilkunde 147 (1999), S. 122-127 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Körperliche Beschwerden ; CBCL/4 ; 18 ; Kultur-vergleichend ; Kinder ; Jugendliche ; Key words Somatic complaints ; CBCL/4 ; 18 ; Cross-cultural ; Children ; Adolescents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: 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.
    Notes: 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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  • 54
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    Monatsschrift Kinderheilkunde 147 (1999), S. 351-355 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Latexallergie ; Neuogene Blasenentleerungsstörung ; Kinder ; Key words Latex allergy ; Neurogenic bladder dysfunction ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: 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.
    Notes: 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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  • 55
    ISSN: 1437-7799
    Keywords: Key words Desferrioxamine ; Cadmium ; Metallothionein ; Nephrotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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    Pediatric surgery international 15 (1999), S. 32-35 
    ISSN: 1437-9813
    Keywords: Key words Appendicitis ; Ultrasonography ; Children ; Graded compression ultrasonography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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    Pediatric surgery international 15 (1999), S. 50-55 
    ISSN: 1437-9813
    Keywords: Key words Burns ; Inhalation injury ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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    Pediatric surgery international 15 (1999), S. 63-65 
    ISSN: 1437-9813
    Keywords: Key words Actinomycosis ; Antibiotic treatment ; Appendicitis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 59
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    Pediatric surgery international 15 (1999), S. 121-122 
    ISSN: 1437-9813
    Keywords: Key words Ingrowing nails ; Conservative treatment ; Children ; Adolescents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 60
    ISSN: 1437-9813
    Keywords: Key words Congenital diaphragmatic hernia ; Rat ; Glucocorticoid ; Antenatal therapy ; Insulin-like growth factor I and II ; Reverse transcription-polymerase chain reaction (RT-PCR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 61
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    Pediatric surgery international 15 (1999), S. 201-205 
    ISSN: 1437-9813
    Keywords: Key words Esophagus ; Atresia ; Notochord ; Adriamycin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 62
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    Pediatric surgery international 15 (1999), S. 457-460 
    ISSN: 1437-9813
    Keywords: Key words Blunt testicular injury ; Rat ; DNA flowcytometry ; Antisperm antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 63
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    Pediatric surgery international 15 (1999), S. 353-357 
    ISSN: 1437-9813
    Keywords: Key words Testis torsion ; Scrotum ; Appendage ; Cremasteric reflex ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 64
    ISSN: 1437-9813
    Keywords: Key words Ovarian tumor ; Children ; Hypercalcemia ; Small-Cell carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 65
    ISSN: 1437-9813
    Keywords: Key words Unilateral undescended testis ; Rat ; Testicular injury ; DNA flowcytometry ; Anti-sperm antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 66
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    Pediatric surgery international 15 (1999), S. 579-581 
    ISSN: 1437-9813
    Keywords: Key words Hydatid disease ; Pancreas ; Children ; Echinococcosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 67
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    Pediatric surgery international 15 (1999), S. 525-526 
    ISSN: 1437-9813
    Keywords: Key words Central venous catheters ; Children ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 68
    ISSN: 1432-2307
    Keywords: Key words Peroxisomes ; Hepatocellular tumors ; Immunocytochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A significant reduction of catalase activity, a peroxisomal marker enzyme, occurs in human hepatic neoplasias, but no information is available on other peroxisomal proteins. We have studied by means of immunohistochemistry four specific proteins of peroxisomes (catalase and three enzymes of lipid β-oxidation) in human hepatocellular tumors of various differentiation grades from adenoma to anaplastic carcinoma. In all tumors, except the adenomas, the tumor cells contained fewer peroxisomes than extrafocal hepatocytes and the reduction of antigenic sites in the tumor types generally correlated with the degree of tumor dedifferentiation as assessed by classical histopathological criteria. Two poorly differentiated tumors had no detectable peroxisomes at all. There were no major differences in the intensities of the immunocytochemical staining for all four studied peroxisomal antigens in different tumors, suggesting that the neoplastic transformation affects the biogenesis of the entire organelle and not merely the individual peroxisomal enzyme proteins. Some tumors exhibited a distinct peripheral distribution of peroxisomes. In cases with associated liver cirrhosis, the hepatocytes in the adjacent liver showed marked peroxisome proliferation, forming large perinuclear aggregates, occupying occasionally the entire cytoplasm. Taken together, our observations indicate that peroxisomes are significantly altered in both hepatocellular tumors and liver cirrhosis and, thus, could be responsible for some of the metabolic derangements observed in those disease processes.
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  • 69
    ISSN: 1432-2307
    Keywords: Key words p21 ; p53 ; Colon ; Immunohistochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The WAF1/CIP1 gene product, p21, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the p53 pathway. The expression of p21 in human neoplasms is heterogeneous, and may be related to p53 functional status. We evaluated p21 immunoreactivity in 103 colorectal carcinomas (CC) in relation to the p53 gene and protein alterations and clinico-pathologic parameters. High p21 expression (more than 10% reactive cells) was seen in 39% of cases. p21 staining was heterogeneous and often detected in clusters of tumour cells; in some tumours p21 staining was more pronounced in superficial areas. No relation was seen between p21 immunoreactivity and site of the tumours (right vs left), TNM stage and grade. p21 expression was related to p53 status as evaluated with IHC or with SSCP analyses, low p21 expression usually being associated with p53 protein overexpression (P=0.048) and p53 gene alteration (P=0.005). The strongest associations were seen when the combined p53/p21 immunophenotype was compared with p53 gene alterations (P=0.0002). These data support the hypothesis that p21 expression in CC is mainly related to p53 functional status, suggesting that p21 expression could be an interesting adjunct in the evaluation of the functional status of the p53 pathway in CC.
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  • 70
    ISSN: 1432-2307
    Keywords: Key words Pyruvate kinase isoenzymes ; N-Nitrosomorpholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 71
    ISSN: 1432-2307
    Keywords: Key words Medullary thyroid carcinoma ; Basement membrane ; Laminin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 72
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    Urological research 27 (1999), S. 41-47 
    ISSN: 1434-0879
    Keywords: Key words Ureter ; Histology ; Polyuria ; Diabetes mellitus ; Nephrectomy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 73
    ISSN: 1434-0879
    Keywords: Key words Nonbacterial prostatitis ; Animal model ; Partial urethral obstruction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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  • 74
    ISSN: 1434-0879
    Keywords: Key words Alpha-1-microglobulin ; Calcium oxalate ; Crystallization ; ELISA ; Human ; Urine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the past few years, alpha-1-microglobulin (α1m) has been copurified from human urine with bikunin, a potent inhibitor of calcium oxalate (CaOx) crystallization in vitro. In this study, we have purified α1m without bikunin contamination and investigated its possible role in CaOx crystallization by in vitro and in vivo studies. Alpha-1m was purified with an anti-α1m antibodies CNBr-activated sepharose column. Two molecular species of α1m of respectively 30 and 60 kDa were purified. For each protein, two blots of 30 and 60 kDa cross-reacted with anti-α1m antibodies, suggesting that these two forms were derived one from the other. Both protein species inhibited CaOx crystallization in a dose-dependent manner in two in vitro tests. In the first test, the presence of α1m of 30 kDa (8 μg/ml) in a medium containing 0.76 mM CaCl2 (with 45Ca) and 0.76 mM Ox(NH4)2 inhibited CaOx crystallization by 38% as estimated by supernatant radioactivity after 1 h of agitation. In the second test, CaOx kinetics were examined for 3 to 10 min in a turbidimetric model at 620 nm. The presence of α1m of 30 kDa in a medium containing 4 mM CaCl2 and 0.5 mM Na2Ox inhibited CaOx crystallization by 41.5%, as estimated by the slope modification of turbidimetric curve. Alpha-1m can be considered as another inhibitor of urinary CaOx crystal formation, as shown by the present in vitro studies. Using an ELISA assay, we found that urinary α1m concentration was significantly lower in 31 CaOx stone formers than in 18 healthy subjects (2.95 ± 0.29 vs 5.34 ± 1.08 mg/l respectively, P = 0.01). The decreased concentration of α1m in CaOx stone formers could be responsible in these patients, at least in part, for an increased risk of CaOx crystalluria.
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  • 75
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    Urological research 27 (1999), S. 476-482 
    ISSN: 1434-0879
    Keywords: Key words Urinary bladder ; Enterocystoplasty ; Cecocystoplasty ; Innervation ; Nerve growth ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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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    Urological research 27 (1999), S. 174-179 
    ISSN: 1434-0879
    Keywords: Key words Apoptosis ; Ischemia-reperfusion ; Blood flow ; Ischemia ; Prostate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 77
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    Anatomy and embryology 199 (1999), S. 265-280 
    ISSN: 1432-0568
    Keywords: Key words Cat ; Rat ; Immunocytochemistry ; NADPH-diaphorase ; Thalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 78
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    Anatomy and embryology 199 (1999), S. 45-56 
    ISSN: 1432-0568
    Keywords: Key words Skin ; Proteoglycan ; Development ; Human ; Fetal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The extracellular matrix of human fetal skin differs substantially from that of adult skin. Fetal skin contains sparse amounts of fibrillar collagen enmeshed in a highly hydrated amorphous matrix composed of hyaluronan and sulfated proteoglycans. Both fetal and adult skin contain two major interstitial proteoglycans that are extracted by chaotrophic agents and detergents. These are the large chondroitin sulfate proteoglycan versican and the small dermatan sulfate proteoglycan decorin. For this study, proteoglycans extracted from fetal and adult skin were compared on Western blots to determine the relative amounts of versican. Decorin present in the same samples provided an internal standard for these studies. Fetal skin differed from adult skin in that it contained a significantly higher proportion of versican than did adult skin. Immunohistochemical studies compared early-fetal with mid-fetal skin and found that versican was a significant component of the interstitial extracellular matrix at both of these stages of skin development. However, by the mid-fetal period, interstitial versican became restricted to the upper half of the dermis, although versican also continued to be highly expressed around hair follicles, glands, and vasculature in the lower half of the dermis. Fetal skin extracts differed from an adult skin extract by the presence of a 66-kDa protein immunologically related to versican and by the absence of a 17-kDa core protein of a proteoglycan related to decorin. Both of these molecular species may represent degradation products of their respective proteoglycans. Monoclonal antibodies which detect epitopes in native chondroitin sulfate glycosaminoglycan chains recognized versican extracted from fetal skin. However, the tissue distribution of these antigens did not entirely conform to that for versican core protein, suggesting that versican in different regions of the skin may be substituted with glycosaminoglycan chains with different microchemistries. The results of these studies indicate that human fetal skin is structurally different from adult skin in terms of both the distribution and the composition of the large, aggregating chondroitin sulfate proteoglycan versican.
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  • 79
    ISSN: 1432-0533
    Keywords: Key words Amantadine ; Human ; N-methyl-d-aspartate ; Phencyclidine ; Postmortem brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Low doses of N-methyl-d-aspartate (NMDA)-type glutamate receptor antagonists induce morphological alterations in neurons of the cingulate gyrus and retrosplenial cortex of the rat. Neuronal cell death may result at higher doses. These effects are a major concern with regard to the introduction of new NMDA receptor antagonists into clinical trials. Amantadine is an uncompetitive NMDA receptor antagonist, which has been in clinical use for many years. In the present study we have looked for possible morphological alterations like necrosis in postmortem human brain tissue of patients previously treated with amantadine. Formalin-fixed tissue samples were taken from the hippocampus, cingulate gyrus, and retrosplenial cortex of 8 patients on previous amantadine medication and of 11 controls. Histopathological examination of sections was performed blind. All brains except one revealed either nonspecific age-related or cerebrovascular changes or other neurodegenerative disorders including Alzheimer’s, Parkinson’s or Lewy body disease. In conclusion, histopathological examination of the hippocampus, retrosplenial cortex, and cingulate gyrus of human brain did not reveal changes suggested to be specific for previous amantadine treatment.
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  • 80
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    Anatomy and embryology 200 (1999), S. 521-531 
    ISSN: 1432-0568
    Keywords: Key words Development ; Internal capsule ; Nucleus basalis ; Rat ; Thalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 81
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    Anatomy and embryology 200 (1999), S. 533-540 
    ISSN: 1432-0568
    Keywords: Key words Coronary vasculogenesis ; Angiogenesis ; Coronary artery ; Development ; Rat ; Embryonic heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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).
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  • 82
    ISSN: 1432-0568
    Keywords: Key words Morphogenesis ; Histochemistry ; Lectins ; Carbohydrates ; Salivary glands ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The developmental expression of salivary glycoconjugates was investigated in the rat submandibular and sublingual glands by conventional and lectin histochemistry. By the time of the first differentiation of secretory structures, in spite of similar morphological features, a different histochemical reactivity was detected, accounting for a relevant content of neutral glycoconjugates in the submandibular gland and the occurrence of both neutral and acidic glycoconjugates in the sublingual one. The use of lectins allowed the main changes of secretory components to be noted around gestational day 18. DBA and WGA lectins seemed to act as pre- and post-natal development markers while Con A lectin was indicative of post-natal differentiation. Taken together, data from lectin histochemistry indicated the transitional occurrence of glycoconjugates, probably involved in temporally restricted functions, as well as the co-existence of different secretory components that might also reflect maturational changes of single products.
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  • 83
    ISSN: 1432-0533
    Keywords: Key words Purkinje cell ; Cerebellum ; Development ; Inositol 1 ; 4 ; 5-triphosphate type 1 receptor ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemical analyses were carried out on the Purkinje cells from 21 autopsied fetal and early postnatal normal cerebella using a monoclonal antibody against the inositol 1, 4, 5-triphosphate type 1 receptor (IP3R1) as a cytochemical marker of Purkinje cells. In normal adult cerebella used as positive controls, the cell bodies, axons, and dendrites, including spiny branchlets of the Purkinje cells, were specifically stained by the antibody. In the fetal cerebella examined, the IP3R1 immunoreactivity was first detected in the soma of multilayered cells just beneath the molecular layer at 16 weeks of gestation. The IP3R1 immunoreactivity gradually increased in area of positive staining from soma to dendrites and spiny branchlets, and the dendritic outgrowth rapidly progressed during 6 months after birth. The Purkinje cell maturation was more advanced in the vermis than in the hemisphere, more in the posterior lobe than in the anterior lobe, and more at the bottom of the folia than at the top. Partial absence of the Purkinje cells in the cerebellar cortex was observed in three cases. Heterotopias including Purkinje cells were often noted in the cerebellar white matter in five cases.
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  • 84
    ISSN: 1432-0533
    Keywords: Key words Clomethiazole ; Rat ; Spinal cord-injury ; Neuroprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clomethiazole (CMZ) has a neuroprotective effect in experimental focal and global forebrain ischemia. This neuroprotective effect may depend on its ability to enhance GABA receptor activity. We have studied the effect of pretreatment with CMZ on motor function recovery and nerve cell damage after spinal cord injury (SCI). Rats were randomized and 30 min before SCI they received a single intraperitoneal dose of CMZ (150 mg/kg) or saline. The spinal cord was injured with a 50 g (4.5 g/mm2) load, applied over the exposed dura, through a curved rectangular plate (2.2 × 5.0 mm) for 5 min at T8–9. The animals became paraplegic 1 day after injury. The rats were evaluated for recovery of hind limb motor function. All animals recovered to some extent over the observation period of 12 weeks. However, hind limb motor function was significantly better in the animals pretreated with CMZ. At 12 weeks the rats were killed and perfused/fixed for morphological investigations. Microtubule-associated protein 2 (MAP2) immunostaining was used to stain neurons and dendrites and Luxol-fast blue to stain myelinated tracts of the white matter. The injured segment of the spinal cord showed severe atrophy, distortion, cavitation and necrosis of grey and white matter. Compared to uninjured controls the transverse sectional area was reduced to 32.7 ± 4% in untreated animals but only to 38.5% ± 4.1 in CMZ-treated animals. MAP2 staining showed that, compared to uninjured controls, grey matter was reduced to 7.4 ± 2.7% in saline-treated injured animals and to 22.7 ± 5.4% in CMZ-treated rats. Our results thus show that in this model CMZ improves hind limb motor function and attenuates the morphological damage to the spinal cord.
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  • 85
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    Anatomy and embryology 200 (1999), S. 413-417 
    ISSN: 1432-0568
    Keywords: Key words Receptor cell ; Axon ; Vomeronasal organ ; Regeneration ; Rat ; HRP-WGA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chemosensory neurons in the vomeronasal epithelium (vomeronasal neurons) regenerate following experimentally induced degeneration. Transection of the vomeronasal nerves leads to retrograde degeneration of vomeronasal neurons followed by replacement of the cell population. The projection of the axons of regenerated vomeronasal neurons was examined by horseradish peroxidase(HRP) histochemistry and electron microscopy. HRP-wheat germ agglutinin (WGA) was placed on the surface of the vomeronasal organ of the rat. Dense distribution of HRP-labeled fibers was observed in the vomeronasal nerve and glomerular layers in the accessory olfactory bulb (AOB) of the intact rat. At one week after transection, HRP-labeled fibers were not found in the AOB, and no labeled fibers could be observed on the medial surface of the olfactory bulb where the vomeronasal nerve traversed. Three weeks after transection, labeled fiber bundles were observed on the medial surface of the olfactory bulb in all animals. No labeled fibers were detected in the AOB. From 12 to 32 weeks after transection, projection of HRP-labeled fibers was identified in the AOB in 8 out of 26 rats (the incidence of projection was 30%). But the number of projection fibers on the operated side was much smaller than on the control side. Electron microscopy confirmed that the HRP-labeled terminals make synaptic contacts with neurons in the AOB.
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  • 86
    ISSN: 1432-069X
    Keywords: Key words Chronic diabetic wounds ; Human ; fibroblasts ; Wound healing ; Cell culture ; Proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with diabetes mellitus experience impaired wound healing often resulting in chronic foot ulcers. Hospital discharge data indicate that 6–20% of all diabetic individuals hospitalized (mostly with type 2 diabetes) have a lower extremity ulcer. Maintaining glucose levels at acceptable levels (below 10 mmol/l) is considered to be an important part of the clinical treatment, but the exact mechanism by which diabetes delays wound repair is not yet known. We studied this phenomenon by determining the potential of fibroblasts isolated from the ulcer sites of four patients with non-insulin-dependent diabetes mellitus to proliferate in vitro. Controls were fibroblasts isolated from normal skin of the upper leg of five healthy age-matched volunteers and of six non-insulin-dependent diabetes patients. Proliferative capacity was analysed by evaluation of plates after trypsinization and [3H]thymidine incorporation. Fibroblast morphology was studied by light and transmission electron microscopy. Diabetic ulcer fibroblasts, measured by [3H]thymidine incorporation, proliferated significantly more slowly than the nonlesional control fibroblasts (P 〈 0.00047) and age-matched control fibroblasts (P 〈 0.00003). After culturing the fibroblasts for a prolonged period in high-glucose (27.5 mM) and low-glucose (5.5 mM, i.e. physiological) medium, this difference in proliferation rate between diabetic ulcer fibroblasts and nonlesional diabetic fibroblasts remained (P 〈 0.0001 for high-glucose and P 〈 0.0009 for low-glucose on day 7). Fibroblast proliferation in all three groups was slightly lower in high-glucose than in low-glucose medium, although not significantly at any time-point. Light microscopy showed diabetic ulcer fibroblasts to be large and widely spread. Transmission electron microscopy of cultured diabetic ulcer fibroblasts and nonlesional diabetic skin fibroblasts revealed a large dilated endoplasmic reticulum, a lack of microtubular structures and multiple lamellar and vesicular bodies. These results show a diminished proliferative capacity and abnormal morphology of fibroblasts derived from diabetic ulcers of non-insulin-dependent diabetes patients.
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  • 87
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    Archives of dermatological research 291 (1999), S. 247-252 
    ISSN: 1432-069X
    Keywords: Key words T cell activation ; Nickel ; Human ; Interferon-gamma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Contact hypersensitivity to nickel is the most common form of allergic contact dermatitis. To gain insight into the induction of this frequent disease, T cell reactivity towards nickel was investigated in “nonallergic” individuals defined as those with no skin manifestations and a negative patch test towards NiSO4. Surprisingly, we found that nickel induced proliferation of peripheral blood mononuclear cells (PBMC) from 16 of 18 adult individuals tested. This activation was specific, and no stimulation of PBMC was observed using control stimulants at equimolar concentrations. Furthermore, the NiSO4-induced activation required the presence of professional antigen-presenting cells. To describe the functional capacity of the nickel-inducible T cells, cytokine release was investigated in both nickel-allergic and nonallergic individuals. The T cells from both groups released interferon-γ but no interleukin-4 upon stimulation with nickel, suggesting that the functional capacities of these cell populations were similar in nickel-allergic and nonallergic individuals. Thus, at this level, no qualitative differences could be demonstrated between T cells obtained from nickel-allergic and nonallergic individuals.
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  • 88
    ISSN: 1432-069X
    Keywords: Key words ORS cells ; Melanocytes ; Human ; Organotypic cultures ; Melanosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Because outer root sheath (ORS) cells are valuable substitutes for interfollicular epidermal keratinocytes, we wanted to determine whether epidermal equivalents generated from ORS cells and containing cultured melanocytes can serve as an in vitro model for skin pigmentation. In such epidermal equivalents prepared with ORS cells and melanocytes from donors of phototypes II, III and VI, a stratified epithelium resembling normal epidermis developed within 14 days, as documented by histological, ultrastructural (e.g. basement membrane-like structure, keratohyalin granules, keratinosomes) and immunohistochemical (e.g. keratins, integrins, gp80, involucrin, filaggrin) criteria. The melanocytes were localized in the basal layer and accounted for 10% of the total cell number. Heavily pigmented melanocytes from black donors contained regular melanosomes in all stages of maturation, whereas melanocytes derived from white donors contained predominantly melanosomes of stages I and II. Melanosome-laden dendrites were readily detected extending from the heavily pigmented melanocytes, while they were less conspicuous in melanocytes from white donors. The extent of melanosome transfer was independent of the racial origin of the ORS cells. Melanosomes could also be transferred “through racial barriers”. Melanosomes, mainly of stages III and IV, were detected in the ORS cells, being distributed either as single or compound melanosomes, again irrespective of the racial origin of the ORS cells. In conclusion, pigmented epidermal equivalents generated from ORS cells offer practical advantages over other in vitro pigmentation models: (1) the ORS cells are easily and repeatedly available from any donor regardless of age; (2) primary cultures of ORS cells are free of contaminating melanocytes, a bias if using interfollicular epidermal keratinocytes; (3) a high degree of epidermal differentiation is maintained for 3 weeks in fully defined medium, enabling labelling and stimulation experiments to be performed and compounds interfering with melanin pigmentation to be tested.
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  • 89
    ISSN: 1432-0584
    Keywords: Key words Hypergammaglobulinemia ; Polyclonal ; Acute myeloid leukemia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Polyclonal hypergammaglobulinemia (PHG) associated with hematological malignancies is a rare occurrence. We reviewed our series of 47 children with AML in order to define the prevalence of PHG and its prognostic value in achieving complete remission (CR) after induction treatment. Patients were stratified by immunoglobulin levels into two groups: with PHG and without PHG. CR reached after induction chemotherapy was considered a positive response. Conditional exact tests were used for the statistical analysis; conditional maximum likelihood estimates of the odds ratio (OR) were obtained. Significance levels (p) were determined from two-tailed tests. Twenty-two of 38 (57.9%) evaluable children showed PHG. Children with PHG and AML were more likely to be in CR after first induction treatment (OR=6.25, p=0.021), independent of sex, age at diagnosis, white blood cell count, percentage of blasts in the bone marrow, FAB phenotype, and treatment protocol. Infections seemed to positively influence early treatment response (p=0.038). PHG and infections were not statistically associated (p=0.16). PHG may result from the uncontrolled stimulation of B lymphocytes by cytokines. Infections or transfusions may act as triggers for the immune system, leading to the antileukemic effect seen in patients with AML and PHG going into spontaneous remission. It could be that this activation caused the larger number of CRs observed in our series. Clarification of why PHG exerts a positive influence on children with AML could help us to understand the ways by which the organism is able to control a malignant disease.
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  • 90
    ISSN: 1432-0584
    Keywords: Key words Thrombopoietin ; Interleukin-11 ; Interleukin-6 ; Thrombocytopenia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and IL-6 in 90 different samples from 67 pediatric patients with thrombocytopenia (TP). The cytokine levels were determined by enzyme-linked immunosorbent assays (ELISA), and the biological activity of TPO was measured using a cell line transfected with human c-mpl. In patients with impaired megakaryocytopoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP, or TP with absent radii, we found TPO levels which were highly elevated compared with normal values (mean=261 AU/ml, n=52, vs. 22 AU/ml in healthy controls). In contrast, patients suffering from idiopathic thrombocytopenic purpura (mean=16 AU/ml, n=31) or platelet function defects (mean=23 AU/ml, n=7) demonstrated normal TPO levels. The biological activity tested in the bioassay correlated well with the ELISA data. However, sera of some patients with amegakaryocytic TP demonstrated a remarkably higher biological activity of TPO than expected from the ELISA data. Within the different groups there was no correlation between platelet counts and TPO levels. Only 27% of all samples had elevated levels of IL-11 (mean=450 pg/ml, n=20). Elevated IL-6 serum levels were detected in only 13% of all samples analyzed (mean=42 pg/ml, n=12). We conclude that megakaryocytopoiesis is regulated mainly by TPO, that it is dependent on the platelet and the megakaryocytic mass, and that IL-11 plays an additional role in supporting the platelet production. IL-6 does not appear to be up-regulated in children with thrombocytopenia.
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  • 91
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 208 (1999), S. 50-56 
    ISSN: 1431-4630
    Keywords: Key words Flavor enhancer ; Savory flavoring ; Taste ; Amino acids ; Partial least squares regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Enzymatically hydrolyzed vegetable protein was produced from soy protein using hydrolysis times of 0–20 h. The development of sensory properties and the pattern of protein degradation was followed. Around two-thirds of the final amount of free amino acids and degree of hydrolysis (DH) were achieved during the first 4 h of hydrolysis. Between 6 h and 10 h of hydrolysis the bouillon-like tastes increased significantly (P〈0.001). In this time interval the amount of free amino acids exceeded 40% of the total amino acids and the DH exceeded 50% of the theoretically possible (100%). Using partial least squares regression with standardisation of free amino acid data according to their taste threshold values showed that free glutamic acid, aspartic acid and lysine correlated with the bouillon-like tastes. By standardisation of free amino acid data with respect to their SD the specificity of the enzymes for amino acid side-chains could be seen.
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  • 92
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 208 (1999), S. 355-361 
    ISSN: 1431-4630
    Keywords: Key words Flavor enhancer ; Taste ; Amino acids ; Carbohydrates ; Maillard reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Hydrolyzed vegetable protein produced using hydrochloric acid (HVP) or proteolytic enzymes (EVP) was given a maturation period of up to 6 weeks at 30  °C. The maturation resulted in a darker color for both hydrolysates, but the sensory profiles were not altered to any great extent. For both hydrolysates a decrease in the amount of free amino acids or an increase in the amount of bound amino acids was seen, and for EVP, a decrease in the amount of free monosaccharides was likewise observed. In HVP the mono- and polysaccharides were destroyed during hydrolysis. The changes in amino acids could be due to, for example, a reversible binding to either a monosaccharide in EVP or a degradation product of carbohydrates in HVP, leading to the first stage of the Maillard reaction. These early reactions did not proceed to any flavor-giving Maillard reaction compounds. Maturation can therefore not be used to enhance the flavor of protein hydrolysates under the applied production conditions.
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  • 93
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 208 (1999), S. 183-188 
    ISSN: 1431-4630
    Keywords: Key words Sulphadimidine ; Fermented sausage ; Carbon-14-labelling ; Rat ; Bound residues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Sulphadimidine (SDM), a drug frequently administered to pigs, is partially converted into other compounds by processing meat to produce raw, fermented sausage. With the aid of 14C-labelled SDM, evidence was obtained that part of the radioactive matter was covalently bound to the matrix. Part of these bound residues could be released in vitro by 4 M HCl at 21  °C or by 0.024 M HCl at 37  °C. Female rats were also able to release bound SDM residues and to excrete these in their urine, in amounts approaching those obtained by treatment with 4 M HCl. Both the parent compound and its main metabolite, N 4-acetyl-SDM, were observed in the urine of rats.
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  • 94
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    Cancer chemotherapy and pharmacology 44 (1999), S. 203-209 
    ISSN: 1432-0843
    Keywords: Key words Vincristine ; Pharmacokinetics ; Repetitive dosing ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We studied vincristine disposition after 169 weekly i.v. bolus injections in 32 children with acute lymphoblastic leukemia, non-Hodgkin lymphoma, or Wilms' tumor. The aim of the study was to determine intrapatient and interpatient variability in vincristine disposition and demographic, clinical, and biochemical characteristics influencing this variability. Methods: Vincristine plasma concentrations were measured by a high-performance liquid chromatography assay with electrochemical detection. A limited sampling strategy was used based on a bayesian parameter estimation algorithm that is part of the ADAPT II software package. A two-compartment, first-order model was fitted to the data, and pharmacokinetic parameters were calculated from the model using the ADAPT II software. For statistical analysis, analysis of variance (ANOVA), t test, simple and multiple regression analysis, and non-parametric or robust equivalents were used. Results: Results showed a large intrapatient and interpatient variability in distribution half-life, elimination half-life, total body clearance, apparent volume of distribution at steady state, and area under the concentration–time curve. Intrapatient variability was significantly smaller than interpatient variability for all these parameters except distribution half-life. The diagnosis or treatment protocol turned out to be the most predictive characteristic; leukemia and non-Hodgkin lymphoma patients had a significantly higher total body clearance than Wilms' tumor patients. Conclusions: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable.
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  • 95
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    Immunogenetics 49 (1999), S. 438-445 
    ISSN: 1432-1211
    Keywords: Key words PA28 ; Proteasome ; Gene structure ; Evolution ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Two proteasome activators PA28α and β, which have been implicated in antigen processing for loading class I MHC molecules, are synthesized in response to Ifn-γ. The human genes encoding these activators (PSME1 and PSME2, respectively) were analyzed by sequencing. Each gene comprised 11 exons, consistent with gene duplication during vertebrate evolution. The intron/exon organization of both genes was highly conserved, the major difference being the absence of the exon encoding the lysine and glutamic acid-rich 'KEKE' motif in PA28β. Two other genes of relevance to the immune system were located close to those for PA28 at 14q11.2 including ISGF3G, a protein involved in transcription after IFNα signalling. These sequences were also characterized.
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  • 96
    ISSN: 1432-1211
    Keywords: Key words Class II MHC sequence ; Rat ; Cloning ; RT-PCR ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 97
    ISSN: 1432-1211
    Keywords: Key words NK cells ; Human ; Surface molecule ; Lectin superfamily ; NK gene complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Natural killer (NK) cells constitute the third major population of lymphocytes. They possess the inherent capacity to kill various tumor and virally infected cells and mediate the rejection of bone-marrow grafts in lethally irradiated animals. A large family of NK cell receptors belong to the C-type lectin superfamily and are localized to the NK gene complex on Chromosome (Chr) 6 in the mouse and Chr 12 in the human. Genes in the NK gene complex encode type II receptors and examples include the families of NKR-P1, Ly-49, and NKG2 receptors. Examples of other C-type lectin-like NK cell receptors that occur as individual genes are CD94, CD69, and AICL. Here we report the molecular characterization and chromosomal mapping of a human lectin-like transcript (LLT1) expressed on NK, T, and B cells and localized to the NK gene complex within 100 kilobases of CD69. The cDNA encodes a predicted protein of 191 amino acid residues with a transmembrane domain near the N-terminus and an extracellular domain of 132 amino acid residues with similarity to the carbohydrate recognition domain of C-type lectins. The predicted protein of LLT1 shows 59 and 56% similarity to AICL and CD69, respectively. The predicted protein does not contain any intracellular ITIM motifs, suggesting that LLT1 may be involved in mediating activation signals.
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  • 98
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    European journal of pediatrics 158 (1999), S. 519-522 
    ISSN: 1432-1076
    Keywords: Key words Pulmonary function test ; Adjustment ; Children ; Prediction equations ; Population specific
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fitting adequate prediction equations for pulmonary function test (PFT) parameters is crucial in the analysis of lung function tests and their interpretation. Our work aimed at studying the necessity of building population specific prediction equations, rather than using prediction equations built-in in commercial equipment. We used as an example results of studies carried out among Israeli schoolchildren. Second to sixth grade children (7–13 years old), 1064 boys and 1211 girls, were studied in Tel-Aviv. PFT (forced vital capacity, forced expiratory volume in 1st second, peak expiratory flow, forced expiratory flow in 50% volume, forced expiratory flow in 75% volume) performed by these children were adjusted for height, weight and age, for each sex separately, by a multiple regression procedure. Predicted PFT parameters of 300 boys and 301 girls aged 7–13 years, living along the southern shore of Israel, were calculated using the equations built for the same aged Tel-Aviv children as well as the prediction equations built-in in the spirometer used. The ratios between the observed PFT parameters in the southern children and their expected values, using the Israeli population specific equations, were around 1.00. Using the built-in equations resulted in ratios around 0.90. Conclusion The development of population specific prediction equations for PFT parameters is necessary. Such equations should be used both in clinical assessment to minimize misclassification (healthy/sick child) and in epidemiological studies.
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  • 99
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    European journal of pediatrics 158 (1999), S. 550-552 
    ISSN: 1432-1076
    Keywords: Key wordsShigella ; Toxic encephalopathy ; Children ; Brain oedema ; Shiga toxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 6-year-old girl is described who died following rapid neurological deterioration, ending in lethal cerebral oedema. Despite the absence of severe intestinal and metabolic derangement, Shigella was cultured from the stool. Toxic encephalopathy is responsible for death following this rare complication of childhood shigellosis in developed countries. The pathophysiology is unknown. Conclusion Lethal toxic encephalopathy can be caused by Shigella despite the absence of severe intestinal and metabolic derangement. If shigelllosis is suspected, headache may be a first significant sign for the development of toxic encephalopathy. Early recognition and rapid measures to prevent brain oedema may improve outcome.
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  • 100
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    Experimental brain research 128 (1999), S. 539-542 
    ISSN: 1432-1106
    Keywords: Key words Silent period ; Transcranial magnetic stimulation ; Motor cortex ; Epidural recordings ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50–200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357±62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability.
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