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  • 1995-1999  (1,394)
  • 1980-1984
  • 1975-1979
  • 1999  (1,394)
  • General Chemistry  (750)
  • Industrial Chemistry  (469)
  • Apoptosis  (93)
  • Children  (81)
  • Nuclear reactions
  • Recombinant DNA
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  • 1995-1999  (1,394)
  • 1980-1984
  • 1975-1979
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  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 125 (1999), S. 239-247 
    ISSN: 1432-1106
    Keywords: Key words Precision grip ; Motor development ; Motor control ; Children ; Object manipulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent evidence has shown that the anticipatory control of grip and load force is not innate and develops over several years in childhood. The present study examined the development of grasping behavior by quantifying the relationship between grip force and the vertical acceleration of an object. Children and adults were requested to use a precision grip to lift an instrumented object which varied in size and weight. Grip force, grip force rate and the vertical position and acceleration profiles of the test object were measured or calculated. The results demonstrated the presence of distinct developmental milestones in the maturation of precision grip from 2 to 9 years of age. With 2-year-old children, the peak acceleration was negatively correlated (r=–0.51, n=34, P〈0.01) with peak grip force during lifting. By 3 years of age, peak acceleration and peak grip force during lifting became positively correlated (r=0.28, n=104, P〈0.01) and the correlation continued to strengthen up to 9 years of age. Variations in the temporal coupling of both peak grip force and peak acceleration also decreased with maturation. Furthermore, starting at 4-years-old, children clearly controlled the acceleration and deceleration of the object in a symmetrical pattern and used a single burst of grip force rate to grasp the object with some regularity, suggesting that the emergence of an anticipatory control strategy had already begun.
    Type of Medium: Electronic Resource
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  • 102
    Electronic Resource
    Electronic Resource
    Springer
    European spine journal 8 (1999), S. 439-443 
    ISSN: 1432-0932
    Keywords: Key words Low back pain ; Children ; Clinical examination ; Questionnaire ; Prevalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was undertaken to analyse the prevalence of low back pain (LBP) and confounding factors in primary school children in the city of Antwerp. A total of 392 children aged 9 were included in the study. All children completed a validated three-page questionnaire and they all underwent a specific lumbar spine oriented medical examination during their annual routine medical school control. This examination was performed by the city school doctors. The questionnaire was composed of easy “yes/no” questions and visual analogue scales. Statistical analysis was performed using Student’s t-test and chi-squared test at the significance level P 〈 0.05. The prevalence of LBP was high. No gender difference was found. A total of 142 children (36%) reported having suffered at least one episode of LBP in their lives. Of these, 33 (23%) had sought medical help for LBP from a doctor or physiotherapist. Sixty-four percent of children reporting LBP said that at least one of their parents suffered from or complained of LBP. This was significantly higher than for the children who did not report having suffered LBP. The way in which the school satchel was carried (in the hand, on the back) had no bearing on the incidence of LBP. There was significantly more LBP in children who reported playing video games for more than 2 h per day, but this was not so for television watchers. The visual analogue scales concerning general well-being were all very significantly correlated with self-reported LBP, with children who reported LBP being more tired, less happy, and worse sleepers. Of the 19 clinical parameters taken down during the medical examination, only one was significantly more prevalent in the group of children reporting LBP: pain on palpation at the insertion site on the iliac crest of the ilio-lumbar ligament. From this study we can establish that there are few clinical signs that can help to single out school children with LBP.
    Type of Medium: Electronic Resource
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  • 103
    ISSN: 1432-0983
    Keywords: Key words Fission yeast ; Caspases ; Bcl-2 ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Two pro-apoptotic proteases, caspase-1 and caspase-3, have been expressed as full-length proteins in the fission yeast Schizosaccharomyces pombe. Both proteins autoprocess to generate the corresponding active enzyme and both are lethal to the yeast cell. Lethality is due to catalytic activity since the expression of the inactive mutant forms of both caspases does not result in an obvious phenotype. Caspase-expressing yeast can be rescued by co-expression of the baculovirus protein p35, a known inhibitor of the caspase family. Co-expression of Bcl-2, another anti-apoptotic protein, does not prevent the cell death induced by either caspase. However, Bcl-2 is itself cleaved by both caspase-1 and caspase-3 at two adjacent recognition sites, YEWD31′A and DAGD34′V respectively, immediately downstream from the N-terminal BH4 domain, a region of Bcl-2 which is essential for its anti-apoptotic activity; similar cleavage of Bcl-2 by caspases has been demonstrated in mammalian cells. Hence, key elements of the apoptotic pathway can be reliably reconstituted in fission yeast, opening the way to exploit yeast in order to study the control of apoptosis. Furthermore, the activity of caspase-3, although not caspase-1, can be demonstrated in vitro using chromogenic substrates. This offers the possibility of using caspase-producing strains of yeast to screen for chemical inhibitors either in vivo or in vitro.
    Type of Medium: Electronic Resource
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  • 104
    ISSN: 1432-0851
    Keywords: Key words NK cells ; IL-2 ; Fas ; FasL ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Fas/Fas-ligand (FasL) system seems to play a key role in regulating immunoresponses. Highly purified CD56+CD3− natural killer (NK) cells were found to be resistant to the apoptosis-inducing Fas mAb CH11 in the absence or in the presence of interleukin-2 (IL-2) for up to 3 days. However, NK cells activated with IL-2 for 3 days became apoptotic following combined treatment with CH11 and actinomycin D, suggesting the presence of an intact apoptotic machinery. In contrast, NK cells cultivated in IL-2 for 6 days became sensitive to CH11-induced apoptosis without addition of actinomycin D. At this time, a pronounced up-regulation of the Fas protein on the NK cell membrane was detected. By using reverse transcription/polymerase chain reaction it was found that the anti-apoptotic gene FLIP was strongly expressed in NK cells for up to 6 days of IL-2 stimulation. After day 6, a time-dependent decrease in the expression of FLIP was observed concomitantly with increased sensitivity for Fas-mediated apoptosis. The amount of apoptotic and necrotic NK cells in the presence of IL-2 increased in a time-dependent manner, reaching 40% at day 6 of culture. The amount of apoptotic and necrotic NK cells was reduced in the presence of Fas-Fc protein. In addition, IL-2 stimulated the NK cells to release soluble FasL in a time-dependent manner, whereas membrane FasL did not seem to increase in a similar manner. These results indicate that Fas/FasL interactions are involved in the down-regulation of IL-2-activated human NK cells.
    Type of Medium: Electronic Resource
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  • 105
    ISSN: 1432-0851
    Keywords: Key words Tumour antigen ; MUC1 ; T cell ; immunosuppression ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The in vitro anti-proliferative properties of various supernatants from MUC1-expressing cell lines and of purified preparations of MUC1 were evaluated. We have observed that supernatants from the MUC1- and MUC3-positive cell line T47D, but not from the MUC1- and MUC4-positive cell line MCF7, were able to inhibit proliferation of cells from various haematopoietic cell lines. Although the activity of T47D supernatants could be abrogated by immunodepletion of MUC1, immunopurified MUC1 from T47D was unable to inhibit cell proliferation. Significantly, supernatants from mouse 3T3 cells transfected with a secreted form of MUC1 or from BHK-21 cells infected with a recombinant vaccinia virus coding for the secreted form of MUC1, as well as preparations of purified MUC1 from bile or urine, were likewise unable to inhibit T cell proliferation. Surprisingly, a crude mixture of bile mucins had a suppressive effect on T cell growth. Our results suggest that other molecules, such as amino sugars or other mucins, which can associate with MUC1, are likely to be responsible for the observed anti-proliferative effects of T47D cells.
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  • 106
    ISSN: 1432-0851
    Keywords: Key words CD95L ; FasL ; Renca ; Apoptosis ; Tumor growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The CD95/CD95 ligand (CD95L) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. In this system, two murine CD95L-transfected renca clones and a control renca clone transfected only with the vector were implanted into the subcapsule of the left kidney of Balb/c and Balb/c nude mice. Both CD95L-expressing and control renca clones formed macroscopic tumors in all of the Balb/c and Balb/c nude hosts 14 days after implantation. Growth of tumors of murine CD95L-transfected renca cells was significantly better than that of control renca cells in Balb/c mice, while the growth advantage of CD95L transfectants was not observed in Balb/c nude mice. Lymphocytes underwent apoptosis mainly in the periphery of the CD95L-expressing tumors but not in control tumors grown in Balb/c mice, while lymphocytes undergoing apoptosis were not observed in CD95L-expressing tumors or in control tumors grown in Balb/c nude mice. Neutrophilic recruitment was rarely observed in CD95L-expressing or control tumors. CD95L expressed on renca cells possibly suppressed immune responses against renca tumors by inducing apoptosis of the infiltrating lymphocytes. However, CD95L-expressing renca cells did not form tumors in the renal subcapsule of allogeneic C3H/HeJ mice.
    Type of Medium: Electronic Resource
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  • 107
    ISSN: 1432-0738
    Keywords: Key words Doxorubicin ; Apoptosis ; Testicular toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To clarify whether apoptosis is involved in doxorubicin (DXR)-induced testicular toxicity and to identify the target germ cell type, adult Sprague-Dawley rats were treated with a single intravenous dose of DXR (8 or 12 mg/kg) and euthanized at 3, 6, 12, 24, and 48 h subsequently. Histologically, germ cell degeneration was first found 6 h after dosing in meiotically dividing spermatocytes and early round spermatids of seminiferous tubules at stage I, and subsequently observed in spermatogonia at stages I–VI showing ultrastructural characteristics of apoptosis. Coincident with the appearance of morphological changes, degenerating germ cells were shown to be undergoing apoptosis as revealed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The frequency of TUNEL-labeled germ cells increased in a stage- and cell type-specific manner, the peak of frequency gradually progressing from stage I of seminiferous tubules to later stages with time after dosing, suggesting that the damaged germ cells, especially spermatogonia, gradually underwent the processes leading to apoptosis. DNA laddering on gel electrophoresis was apparent 24 and 48 h after dosing. The results demonstrate that apoptosis plays an important role in the induction of testicular toxicity caused by DXR with meiotically dividing spermatocytes and type A and intermediate spermatogonia as highly vulnerable target cells.
    Type of Medium: Electronic Resource
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  • 108
    ISSN: 1432-0738
    Keywords: Key words Allylnitrile ; Apoptosis ; Behavioral abnormalities ; Habenula ; Mice brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A single dose of allylnitrile in mice might induce persistent behavioral abnormalities, of which the mechanism is not yet known. The present study was undertaken to explore the relationship between behavioral abnormalities and pathological changes in the brain of mice following exposure to allylnitrile. Exposure to allylnitrile (63, 84, and 112 mg/kg, p.o.) resulted in dose-dependent changes in behavioral abnormalities, including increased locomotor activity, circling, retropulsion, head twitching, and alteration in reflexive behavior, which appeared at day 2 postdosing and were persistent throughout the experimental period (60 days) at the higher dose levels. Allylnitrile produced neuronal retraction including hyperchromasia of the nuclei in the raphe nuclei, cerebral cortex, hypothalamus, hippocampal CA1 and dentate gyrus later than 30 days. No gliosis was observed in these regions. Not all but a significant number of neurons in the hippocampal CA1, medial habenula and raphe nuclei were immunoreactive to CPP32 (Caspase-3) even at day 2. These neurons were also positive to Hoechst 33258 staining, indicating allylnitrile caused apoptotic changes in specific neurons when neuronal behaviors became apparent. These apoptotic changes were persistent even in the area without neuronal contraction such as medial habenula. However, almost all neurons in these areas were also positive to terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL). It is conceivable that allylnitrile caused apoptotic changes in neurons but did not always lead them to cell death immediately. Moreover, even when neuronal contraction resulted in retention of behavioral abnormalities, onset of these abnormalities seems to be associated with the impairment in the habenulo-raphe relay due to activation of apoptotic cascade in neurons.
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  • 109
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Kinderdermatologie ; Exanthem ; Kinder ; Key words Pediatric dermatology ; Exanthema ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Unilateral laterothoracic exanthem a (ULE) is a self-limited, probably infectious-allergic skin disease predominately affecting small children. We describe five such cases. The typical unilaterally located or at least unilaterally dominant exanthem usually starts in the axillary region and is characterized by red, partly confluent papules and fine scales. Two of the children presented with atypical manifestations of ULE. Due to its asymptomatic course, therapy is not necessary in the majority of cases.
    Notes: Zusammenfassung 5 Kinder mit der Diagnose eines unilateralen laterothorakalen Exanthems (ULE) werden vorgestellt. Beim ULE handelt es sich um eine selbstlimitierende, vermutlich infektallergische Hauterkrankung, die hauptsächlich im Kleinkindesalter auftritt. Das typischerweise streng einseitig lokalisierte, immer jedoch einseitig dominierende Exanthem geht meist von der Axillarregion aus und zeigt erythematöse, teils konfluierende Papeln. Zwei der fünf Kinder zeigten auch atypische Hautveränderungen eines ULE. Eine Behandlung ist aufgrund seines überwiegend asymptomatischen Verlaufs in der Mehrzahl der Fälle nicht notwendig.
    Type of Medium: Electronic Resource
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  • 110
    Electronic Resource
    Electronic Resource
    Springer
    Child's nervous system 15 (1999), S. 563-570 
    ISSN: 1433-0350
    Keywords: Key words Ependymoma ; Children ; Chemotherapy ; Phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chemotherapy has been used extensively in the management of children with intracranial ependymoma. In this review, we discuss the results of phase II studies and clinical trials conducted in newly diagnosed and recurrent ependymomas. There is little evidence that chemotherapy is effective in this tumour. The response rate to single agents is 11%, with less than 5% complete responses, cisplatin being the most active agent in phase II studies. Combinations may be more effective, although the response rate with high-dose regimens is disappointing. Early results of protocols conducted in infants and young children do not suggest that chemotherapy is beneficial. A more rigorous assessment of chemotherapy is required in order to define its role in patients with intracranial ependymomas. Indeed, it is difficult to justify the use of chemotherapy outside such studies. More large studies, perhaps intergroup, limited to children with ependymomas would be of particular value.
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  • 111
    Electronic Resource
    Electronic Resource
    Springer
    Child's nervous system 15 (1999), S. 342-346 
    ISSN: 1433-0350
    Keywords: Key words Severe neurological disabilities ; Managed and rationed care ; Children ; Questionnaire survey ; Pediatric neurosurgeons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The attitudes of pediatric neurosurgeons to managed and rationed care for children with severe neurological disabilities were surveyed as reflected in responses from International Society for Pediatric Neurosurgery (ISPN) members to a questionnaire. Of 399 ISPN members, 156 (39.1%) responded to the questionnaire. There were 15 questions, which were designed to explore what care is medically indicated, whether all medically indicated care should always be provided, and how this care should be managed or rationed. Most respondents agreed that these patients should receive the same level of medical care as a normally developing child. However, respondents felt that cardiopulmonary resuscitation (CPR) is not indicated if a child is not retrievable. Most respondents also felt that provision of care should be influenced by cost. The responses to the questions from ISPN members were compared with those from Child Neurology Society (CNS) members.
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  • 112
    Electronic Resource
    Electronic Resource
    Springer
    Child's nervous system 15 (1999), S. 468-471 
    ISSN: 1433-0350
    Keywords: Key words Seizures ; Epilepsy ; Children ; EEG ; Computed tomography (CT) ; Saudi Arabia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The clinical patterns, including history, examination, and electroencephalographic (EEG) and computed tomography (CT) findings were examined prospectively in 263 children (153 boys, 110 girls) with newly diagnosed recurrent seizures. The overall mean age was 4.2 years, with a range of 0.05–13 years. The age of onset was within the first year of life in 128 (48.7%) of the patients. Hypoxic-ischemic encephalopathy (14.8%), febrile seizures (9.1%) and developmental delay (4.6%) were the predominant signs in this age group. Consanguinity of the parents was present in 29.7% cases. The main EEG abnormalities were epileptiform activity, which was generalized in 133 (50.6%) and focal in 80 (30.4%). Other abnormalities included slow wave activity in 41 (15.6%) and hypsarrhythmia in 3 (1.1%). The main seizure types were generalized in 60.4% and partial in 32.7%. The types of epileptic syndromes included localization-related (28.1%), generalized (23.2%), undetermined (37.4%) and (special) syndromes 11.4%. The cranial CT findings were normal in 60.5%, and the predominant abnormality was cerebral atrophy in 25.3%. The pattern of seizure types and the peak presentation in early childhood are comparable to those in western reports.
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  • 113
    ISSN: 1433-0350
    Keywords: Key words Cerebrospinal fluid shunt ; Infection ; Colonization ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the efficiency of our management protocol, 33 pediatric cases of bacteria-infected cerebrospinal fluid shunt were reviewed. The causative organism was staphylococcus in 23 patients. In 23 patients, shunt infection was managed according to the protocol. The complexity of the shunt system did not prolong hospitalization. Unchanged but externalized tubings showed persistent colonization despite adequate antibiotics in 10 of 21 patients. Staphylococcal infection was oxacillin-resistant in 7 of 19. The efficiency of an `off-antibiotics' trial was minimal. Further modification of the protocol is expected to enhance efficiency of the management.
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  • 114
    Electronic Resource
    Electronic Resource
    Springer
    Child's nervous system 15 (1999), S. 695-710 
    ISSN: 1433-0350
    Keywords: Key words Craniosynostosis ; Blood salvage ; Blood conservation ; Allogeneic blood transfusion ; Children ; History
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the history of surgery, every single step forward in the development of complex surgical techniques has been sustained by the acquisition of more reliable and effective methods for controlling hemostasis. For many years, in fact, uncontrolled hemorrhages, together with infections, represented the most deadly hazard of surgical procedures. In the last century, technical advances in surgical hardware and homologous blood transfusions have been utilized to counteract operative and postoperative anemia and hypovolemia. At the end of this millennium, however, new revelations about the infective and noninfective risks of allogeneic blood transfusions have led to a new acceleration in patients’ and physicians’ demands for autologous transfusions and more efficient blood conservation techniques. Specific surgical protocols, based on the preoperative administration of r-HuEPO, preoperative autologous blood donation, acute preoperative normovolemic hemodilution and intraoperative blood salvage techniques, have been designed by pediatric neurosurgeons to minimize the exposure of patients affected by craniosynostoses to allogeneic blood and blood components even when the surgical procedure is to be realized at an early age. In spite of the evolution expected in this area in the immediate future, the implementation of these blood concentration methodologies may prove to be highly effective only when associated with a concerned attitude of the surgeon toward blood-sparing intraoperative strategies.
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  • 115
    ISSN: 1433-0350
    Keywords: Key words Head injury ; Children ; Traumatic intracerebral haematoma ; Coma scale
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In contrast to the case of extracerebral haematomas, the criteria for operative treatment of traumatic intracerebral haematoma (TIH) are not clear. The purpose of this study was to find factors that would be helpful in reaching a decision for surgical or conservative treatment of TIH. We performed a retrospective analysis of 31 consecutive cases of TIH treated in our department. The following factors were estimated: age, mechanism of injury, initial GCS or CCS score, neurological deficits, coexistence of arterial hypotension and respiratory disturbances, and localisation and size of the haematoma. The outcome was evaluated according to a modified GOS. Treatment was surgical for 20 patients and conservative for 11. Patients with GCS or CCS scores of 3–8 were treated surgically significantly more often than those with higher scores. The other factors did not correlate with type of treatment. It seems, then, that the clinical status of the patient, especially the level of consciousness according to the GCS or CCS score, is the most important predictor of the need for surgery in children with TIH.
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  • 116
    Electronic Resource
    Electronic Resource
    Springer
    Der Radiologe 39 (1999), S. 467-471 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fremdkörper ; Aspiration ; Diagnostik ; Kinder ; Atemwege ; Key words Foreign body ; Aspiration ; Diagnostic imaging ; Children ; Respiratory tract
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Aspiration of foreign bodies is a common cause of respiratory distress in children between the age of 6 months and 3 years. The diagnosis of radiopaque foreign bodies is easy when the whole respiratory tract is depicted. Nonopaque foreign bodies need a more differentiated diagnostic approach. The first step should be plain films in inspiration and expiration. The performance of additional chest radiographs, fluoroscopy and if need be CT or nuclear scans depends on the result of the plain films. The chest radiograph may reveal a variety of findings, the commonest of which is unilateral air trapping. Rarely, atelectasis, recurrent pneumonia at the same localisation and inspiratory obstruction are found. Combinations of the above-mentioned findings are possible. Moreover, the absence of positive radiological findings does not exclude the diagnosis of foreign body aspiration.
    Notes: Zusammenfassung Die Fremdkörperaspiration stellt eine häufige Ursache für Atemnot und respiratorische Insuffizienz bei Säuglingen und Kleinkindern zwischen 6 Monaten und 3 Jahren dar. Röntgendichte Fremdkörper bereiten bei Abbildung des gesamten Respirationstraktes keine diagnostischen Schwierigkeiten. Nicht röntgendichte Fremdkörper erfordern ein differenzierteres Vorgehen, wobei der erste radiologische Schritt in einer konventionellen Thoraxaufnahme in In- und Exspiration bestehen sollte. Zusätzliche Aufnahmen, Durchleuchtungsuntersuchung und gegebenenfalls die Durchführung einer computertomographischen oder szintigraphischen Untersuchung hängen vom Ergebnis der Thoraxaufnahme ab. Häufigstes radiologisches Erscheinungsbild ist die einseitige exspiratorische Ventilstenose mit Überblähung des betroffenen Lungenabschnittes. Seltener finden sich Atelektasen, rezidivierende Pneumonien an identischer Lokalisation und inspiratorische Ventilstenosen. Kombinationsbilder sind möglich, selbst ein unauffälliges Untersuchungsergebnis kann eine Aspiration nicht ausschließen.
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  • 117
    Electronic Resource
    Electronic Resource
    Springer
    Knee surgery, sports traumatology, arthroscopy 7 (1999), S. 243-245 
    ISSN: 1433-7347
    Keywords: Key words Patella ; Fracture ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract Fractures of the patella are relatively rare injuries for children. Fourteen patients with patellar fractures were reviewed. There were 12 boys and two girls with the age ranging between 9 and 15 years and an average of 11.4 years. Sleeve fractures were the most common type of patellar fractures observed (eight cases), followed by transverse fractures (four cases) and comminuted fractures (two cases). All the fractures were treated with open reduction and followed up for 2 to 20 years. Overall results were good in 13 patients, and flexion limitation of the knee was seen in one. Fractures of the patella in children are characterised by sleeve fractures. The prognosis of the patients treated with open reduction is generally good.
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  • 118
    ISSN: 1432-1831
    Keywords: Key words Verocytotoxin ; Verocytotoxin-producing Escherichia coli ; Hemolytic uremic syndrome ; Renal proximal tubular cell ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Verocytotoxin 1 and 2 (VT1 and 2) produced by verocytotoxin-producing Escherichia coli have been considered to play an important role in the pathogenesis of glomerular and tubular damage in the epidemic form of hemolytic uremic syndrome (HUS). VTs are known to be cytotoxic to culture cells by inhibiting cellular protein synthesis. In this in vitro study, the mechanism(s) of tubular damage in HUS and the ability of VT1 to induce apoptosis in normal human renal proximal tubular epithelial cells (HRPTEC) were examined. VT1 markedly reduced cell viability of HRPTEC and rapidly inhibited overall protein synthesis. VT1 directly induced apoptotic cell death in HRPTEC in a dose- and time-dependent fashion, and co-incubation with tumor necrosis factor-α enhanced the VT1-induced apoptosis. These results suggest that apoptosis induced by VT1, possibly in concert with host cytokines, in renal tubular cells may contribute to the tubular damage in HUS.
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  • 119
    Electronic Resource
    Electronic Resource
    Springer
    Medical microbiology and immunology 187 (1999), S. 221-226 
    ISSN: 1432-1831
    Keywords: Key wordsToxoplasma gondii ; Apoptosis ; Actinomycin D ; HL-60 ; Intracellular survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intracellular microorganisms have to rely on the integrity of their host cells to persist. We, therefore, investigated the effect of infections with different Toxoplasma gondii strains on apoptosis of human-derived HL-60 cells at the single cell level. Infection with either mouse-avirulent (NTE strain) or virulent parasites (RH strain) did not induce apoptosis of HL-60 cells as compared to uninfected controls. In contrast, treatment with actinomycin D (act D) led to apoptosis in 15–25% of the cells. However, concomitant infection with T. gondii clearly abrogated act D-induced apoptosis. This was especially apparent in those host cells that were actually infected; in these parasite-positive cells the rate of apoptosis decreased by 82.8±4.3% (mean±SEM, P=0.017, Student's t-test) and 91.7±3.4% (P=0.024) after infection with either the NTE or the RH strain, respectively. Inhibition of host cell apoptosis was similarly observed in cells which had been invaded by UV-irradiated, non-replicating parasites (P=0.001, Student's t-test). However, incubation with heat-killed parasites or T. gondii lysates did not abrogate act D-induced apoptosis. In conclusion, inhibition of apoptosis by living, but not necessarily replicating T. gondii may facilitate parasite survival and persistence within its host cell.
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  • 120
    ISSN: 1432-2307
    Keywords: Key words Proliferation ; Apoptosis ; Ki-67 antigen ; Prognosis ; Retinoblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The balance between proliferation and cell death is the major determinant of tumour growth. We analysed the proliferative and apoptotic indices (PI and AI, respectively) of 33 children with retinoblastoma. PI and AI were assessed by immunohistochemistry for Ki-67 antigen and TUNEL staining, respectively. The mean PI was 21.0±21.1%, and higher PI was associated with more advanced tumour stage (P〈0.0001) and poor clinical outcome (P〈0.05). Patients in whom amplified N-myc oncogene was found (n=6) determined by the multiplex polymerase chain reaction tended to have a higher PI (37.6±27.2%) than those without amplified N-myc (n=27; PI=17.3±18.1). A PI value of over 40% was clearly associated with an unfavourable prognosis. The AI, however, did not correlate with any of the other variables analysed. The findings suggest that proliferation, but not apoptosis, is of critical significance in retinoblastoma biology. PI, as determined by the Ki-67 antigen labelling index, seems to be a relevant histopathological parameter that can predict the clinical outcome of retinoblastoma.
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  • 121
    ISSN: 1432-0878
    Keywords: Key words Adenosine ; Nucleosides ; Neurotoxicity ; Embryogenesis ; Apoptosis ; Chick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Previous work has shown that nucleosides produce apoptosis in sympathetic ganglion (SG) cells in vitro. The present study examined the effects of nucleosides on the development of the chick embryo in vivo with special attention to the SG and the optic tectum of the central nervous system. In the presence of an adenosine deaminase inhibitor, adenosine and 2’-deoxyadenosine (2’-dAdo) produced different toxicity patterns: both adenosine and 2’-dAdo were toxic to E3 embryos, but only 2’-dAdo was toxic at later stages (E6 1/2, E11). Dosage experiments on E6 1/2 embryos showed that adenosine was less toxic than 2’-dAdo and that 2’-dAdo in sublethal doses was teratogenic. We also examined the effects of 2’-dAdo on embryonic chicken SG and optic tectum in vivo to determine whether sublethal doses of 2’-dAdo produced cell death in these centers on E6 1/2 and 10. In the E6 1/2 SG, 2’-dAdo produced significant neuron loss (83%) and a decrease in SG volume (65%); however, at E10, there was only minor cell loss (7%) and no significant change in SG volume. In the optic tectum at E6 1/2, cell loss was confined mainly to the tectal ventricular zone, but there was little sign of cell loss in this organ at E10. Since cell production is vigorous in the SG and optic tectum at E6 1/2 but relatively low at E10, 2’-dAdo appears to work by stopping cell proliferation. The ineffectiveness of 2’-dAdo at E10 may result from the lethality of 2’-dAdo to the embryo at low concentrations (30 µM) in vivo, well below the apoptosis-inducing concentrations employed in vitro (100–300 µM). These data extend previous findings showing that purine and pyrimidine metabolism plays an important role in development.
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  • 122
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    Personal and ubiquitous computing 3 (1999), S. 81-89 
    ISSN: 1617-4917
    Keywords: Child-centred participatory design ; Children ; Collaboration ; Education ; Handheld computing ; Learning environments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Computers are becoming an important tool in learning environments; however, children's access to computer technology is often limited. Computers are commonly placed at the back of the classroom or in a separate computer room. At home, if computers are available, they are often found in a home-office or another communal area. In both cases, the physical location of the computers is separate from many places where children's activities and learning occur. Flexible access to technology will provide tools to help children construct knowledge throughout their daily activities. The growth of handheld computers provides the potential to integrate computer technology into the many facers of children's lives. This paper investigates issues surrounding the design of handheld computers for children's use in learning environments. It focuses on child-centred design, engaging children as active participants in the design of handheld technologies. Two central issues are addressed: mobility and sharability.
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  • 123
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    Personal and ubiquitous computing 3 (1999), S. 137-140 
    ISSN: 1617-4917
    Keywords: Children ; Product concept design ; Social aspects of fun ; User study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract This paper describes two explorative user studies conducted in a research project called Maypole. The purpose of the first user study was to understand how children thought communication with personal technologies could be fun. The second study focused on what children thought was fun in taking and editing digital images. In both studies, children aged 7–12 were given existing personal technologies to use in their own environment for one week. After that, a focus group was held with the children in order to discuss what they thought was fun in using the technologies. The results of the two user studies illustrate how fun in using personal technologies could relate to a user's social behaviour, and not only to human-computer interaction. Therefore, designers are encouraged to explore further the social aspects of fun in their creations. Moreover, the two studies illustrate some methodological problems in studying a user's experience of fun, which refer to a need for more public research on methods.
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  • 124
    ISSN: 1615-2573
    Keywords: Endomyocardial biopsy ; Dilated cardiomyopathy ; Children ; Ultrastructure ; Basal lamina layering of capillary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We analyzed the electron-microscopic features of endomyocardial biopsy from pediatric patients with dilated cardiomyopathy (DCM). The specimens examined were taken from the right ventricle of ten patients aged from 2 to 15 years (mean 9.7 years). Biopsy specimens from eight patients with congenital heart disease (tetralogy of Fallot), aged from 3 to 12 (mean 7.3 years), and ten adult patients with DCM, aged from 32 to 60 (mean 45 years), were also examined. Patients considered to have endocardial fibroelastosis, arrhythmogenic right ventricular cardiomyopathy, specific cardiomyopathy, or coronary heart disease were excluded from this study. Specimens from pediatric patients with DCM showed various degrees of ultrastructural abnormalities of myocytes, including myofibrillar fragmentation, mitochondrial abnormalities, and intracellular edema. The ultrastructurally determined contractility failure index based on the severity of myocardial degeneration at the electronmicroscopic level was 4.9 ± 1.1. This value was significantly higher than that in patients with tetralogy of Fallot (0.9 ± 0.6,P 〈 0.001) but was not significantly different from that in adult patients with DCM (6.1 ± 2.6). The index of pediatric patients with DCM who died within 3 years was high (6.0 ± 0.8). Basal lamina layering of a capillary (BLL) in the myocardium was revealed in 1 of the 10 (10%) pediatric patients with DCM and in 6 of the 10 (60%) adult patients with DCM (P 〈 0.05). No BLL was noted in the patients with tetralogy of Fallot. These findings may be related to the pathogenesis of DCM in children and adults.
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  • 125
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    European journal of trauma 25 (1999), S. 254-266 
    ISSN: 1615-3146
    Keywords: Unterarmfraktur ; Kind ; Konservative/operative Therapie ; Forearm fractures ; Children ; Conservative/operative treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Forearm fractures rank among the most frequent injuries of children and adolescents. At our department, during a 5-year's period a total of 783 forearm fractures have been treated. The patient's age ranged between 1 and 17 years, with an average of 10.2 years. The vast majority were isolated forearm lesions without concomitant injuries, and the gender ratio of males to females was nearly 3 : 2. With 58.1% the left extremity was involved more frequently than the right one (40.4%), in 12 children (1.5%) fractures of both forearms were diagnosed simultaneously. Predominantly isolated radius fractures (59.1%) were seen, followed by complete forearm fractures (36.7%). Greenstick fractures occurred as frequent as 38.2%. With 78.7% the distal forearm was the most common location, followed by the middle and proximal shaft with 14.3% and 7.0%, respectively. Treatment was predominantly non-operative, only in 2.6% open reduction internal fixation (ORIF) became necessary. Therefore, majority treatment was outpatient and complications occurred very rarely. The data presented confirm the outstanding spontaneous correction capacity of the distal forearm in children in contrast to fractures located more proximally. Therefore, patients suffering from shaft fractures of the middle third have been invited to follow-up examinations revealing 44.4% excellent and good results, respectively. Fair and unsatisfying results have been found in 5.6% each. It could be demonstrated, that residual angulations of the middle third often overtax the organism's spontaneous correction capacity, at least as far as children aged 10 years and older are concerned. Therefore, in middle shaft forearm fractures in children generally should be reduced anatomically. If anatomical reposition and redression cannot be achieved conservatively, operative stabilization is indicated. We consider closed reduction and elastic stable intramedullary nailing (ESIN) the treatment of choice. In cases of higher degree open fractures or nerve lesions, revision with open reduction internal fixation (ORIF) using plates or external fixation are recommended, respectively.
    Notes: Zusammenfassung Unterarmfrakturen gehören zu den häufigsten Verletzungen im Kindes- and Jugendalter. In einem Zeitraum von fünf Jahren wurden insgesamt 783 Kinder and Jugendliche im Alter von einem bis zu 17 Jahren mit Unterarmfrakturen behandelt. Der Altersdurchschnitt lag bei 10,2 Jahren. Es handelte sich vorwiegend um isolierte Verletzungen, and das Verhältnis von Jungen zu Mädchen lag bei 3 : 2. Der linke Arm war mit 58,1% häufiger betroffen als der rechte (40,4%), zwölf Kinder (1,5%) hatten doppelseitige Frakturen. Zum größten Ted (59,1%) handelte es sich um isolierte Radiusfrakturen, gefolgt von den kompletten Unterarmfrakturen (36,7%). In 38,2% der Fälle lagen Grünholzfrakturen vor. Die Frakturen des distalen Schaftdrittels wurden mit 78,7% am haufigsten gesehen, gefolgt von Brüchen des mittleren (14,3%) and proximalen (7,0%) Drittels. Die Therapie erfolgte vorwiegend konservativ, die osteosynthetische Versorgung wurde nur in 2,6% der Fälle erforderlich. Somit konnte die Behandlung meist ambulant erfolgen, and Komplikationen waren außerordentlich selten. Das gute Spontankorrekturpotential kindlicher Unterarmfrakturen des distalen Drittels gegenüber weiter proximal gelegenen Frakturen bestätigte sich in der vorliegenden Untersuchung. Daher wurden die Patienten mit Frakturen des mittleren Drittels — soweit erreichbar - embestellt and eingehend nachuntersucht. Hierbei fanden sich in jeweils 44,4% der Fälle sehr gute and gute funktionelle Ergebnisse. Befriedigende and schlechte Behandlungsresultate wiesen je 5,6% der Patienten auf. Es zeigte sich, daß belassene Achsfehlstellungen im mittleren Drittel vor allem nach Erreichen des zehnten Lebensjahres die spontane Korrekturfähigkeit im Rahmen des weiteren Wachstums häufig überfordern and mit einem Ausgleich der Fehlstellung daher nicht regelhaft gerechnet werden darf. Daher sollten Unterarmfrakturen des mittleren Schaftdrittels bei Kindern anatomiegerecht reponiert werden. Gelingen Reposition oder Retention auf konservativem Wege nicht, ist die Indikation zur osteosynthetischen Versorgung gegeben. Hier empfiehlt sich, außer bei höhergradig offenen Frakturen oder Nervenschäden, als Therapie der ersten Wahl die geschlossene Reposition in Narkose mit elastisch-stabiler Markraumschienung (ESM). Dieses Osteosyntheseverfahren birgt gleichzeitig die Vorteile des kleineren operativen Traumas mit Verkürzung von Ruhigstellung (Gipsbehandlung) and Krankenhausaufenthalt. Schlüsselwörter: Unterarmfraktur - Kind - Konservative/operative Therapie
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  • 126
    ISSN: 1619-7089
    Keywords: Key words:Helicobacter pylori ; Carbon-14 urea breath test ; Biokinetics ; Dosimetry ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The long-term biokinetics and dosimetry of carbon-14 were studied in nine adults and eight children undergoing carbon-14 urea breath test for Helicobacter pylori (HP) infection. The elimination of 14C via exhaled air and urine was measured with the liquid scintillation counting technique and with accelerator mass spectrometry. After the subjects had been given 110 kBq 14C-urea (children: 55 kBq) orally, samples of exhaled air were taken up to 180 days after administration and samples of urine were collected up to 40 days. Sixteen of the subjects were found to be HP-negative. In these subjects a total of 91.1%±3.9% (mean of adults and children ± standard error of the mean) of the administered 14C activity was recovered. The majority of the administered activity, 88.3%±6.2% in adults and 87.7%±5.0% in children, was excreted via the urine within 72 h after administration. A smaller fraction was exhaled. In adults 4.6%±0.6% of the activity was exhaled within 20 days and in children 2.6%±0.3%. Uncertainties in the biokinetic results are mainly due to assumptions concerning endogenous CO2 production and urinary excretion rate and are estimated to be less than 30%. The absorbed dose to various organs and the effective dose were calculated using the ICRP model for urea and CO2. The urinary bladder received the highest absorbed dose: in adults, 0.15±0.01 mGy/MBq and in children of various ages (7–14 years), 0.14–0.36 mGy/MBq. The findings indicate that an investigation with 14C-urea gives an effective dose to adults of 2.1±0.1 µSv (for 110 kBq) and to children of 0.9–2.5 µSv (for 55 kBq). From a radiation protection point of view, there is thus no reason for restrictions on even repeated screening investigations with 14C-urea in whole families, including children.
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  • 127
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    International journal of anthropology 14 (1999), S. 55-59 
    ISSN: 1824-3096
    Keywords: Ascaris ; Nutrition ; I.Q. ; Children ; Egypt
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract It was estimated that about 1.3 billion persons all over the world were infected with Ascaris Lumbricoides (A.L.), Especially children in tropical and subtropical countries. AIM To investigate the effects of A.L. infection on the nutritional status and the intellectual level in a sample of Egyptian primary school children from rural Giza province. SUBJECTS AND METHODS A sample of 637 children (329 boys and 308 girls) aged 6–12 years, have been subjected to some anthropometric measurements including body weight, body height, arm circumference, head circumference and triceps skinfold thickness. In addition, the I.Q. was determined using “Draw-a-man” test. Blood hemoglobin concentration was also determined using a spectrophotometric method. All the children were then subjected to stools and urine examinations, and peri-anal swab. Only 242 children were included for further study, of whom 45 boys and 38 girls were found infected with A.L. solely, and 81 boys and 78 girls of about the same age free of parasitic infections were taken as control. RESULTS Children infected with A.L. has significantly lower body weight, height, and arm circumference but insignificantly lower skinfold thickness and head circumference as comparedto the control group. Infected children had significantly lower hemoglobin concentration and I.Q. than the controls. CONCLUSIONS Selected anthropometric measurements, biochemical and intellectual tests from a useful complementary battery for reliable and informative investigation of the effects of parasitic infection on child nutrition and health. A.L. was found to have a significant effect on the physical and intellectual status of the rural Egyptian children of age 6–12 years.
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  • 128
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    European journal of applied physiology 79 (1999), S. 504-511 
    ISSN: 1439-6327
    Keywords: Key words Co-activation ; Children ; Knee ; Electromyography ; Isokinetic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Determining the mechanisms of co-activation around the knee joint with respect to age and sex is important in terms of our greater understanding of strength development. The purpose of this study was to examine the effects of age, sex and muscle action on moment of force and electromyographic (EMG) activity of the agonist and antagonist muscle groups during isokinetic eccentric and concentric knee extension and flexion. The study comprised nine pubertal boys [mean age 12.6 (SD 0.5) years], nine girls [12.7 (SD 0.5) years] nine adult men [23.1 (SD 2.1) years] and nine adult women [23.7 (SD 3.1) years] who performed maximal isometric eccentric and concentric efforts of knee extensors and flexors on a dynamometer at 30° · s−1. The moment of force and surface EMG activity of vastus lateralis and biceps femoris muscles were recorded. The moment of force:agonist averaged EMG (aEMG) ratios were calculated. The antagonist aEMG values were expressed as a percentage of the aEMG activity of the same muscle, at the same angle, angular velocity and muscle action when the muscle was acting as agonist. Three-way analysis of variance (ANOVA) designs indicated no significant effects of age or sex on moment:aEMG ratios. Eccentric ratios were significantly higher than the corresponding concentric ones (P 〈 0.05). The results also indicated no significant effect of age and sex on the aEMG of the vastus lateralis and biceps femoris muscles when acting as antagonists. The antagonist aEMG was significantly greater during concentric agonist efforts compared with the corresponding eccentric ones (P 〈 0.05). These findings would suggest that the moment exerted per unit of agonist EMG and the antagonist activity are similar in children compared with adults and are not sex dependent. Future comparisons between eccentric and concentric moments of force and agonist ENG should take into consideration the antagonist effects, irrespective of age or sex.
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    European journal of applied physiology 80 (1999), S. 118-124 
    ISSN: 1439-6327
    Keywords: Key words Exercise ; Children ; Ventilation ; Gas exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purposes of this investigation were to quantify the noise component of child breath-by-breath data, investigate the major determinants of the breath-to-breath noise, and to characterise the noise statistically. Twenty-four healthy children (12 males and 12 females) of mean (SD) age 13.1 (0.3) years completed 25 min of steady-state cycle ergometry at an exercise intensity of 50 W. Ventilatory and gas exchange variables were computed breath-by-breath. The mean (SD) oxygen consumption (V˙O2) ranged from 0.72 (0.16) to 0.92 (0.26) l · min−1; mean (SD) carbon dioxide production (V˙CO2) ranged from 0.67 (0.20) l · min−1 to 0.85 (0.16) l · min−1; and mean (SD) minute ventilation ranged from 17.81 (3.54) l · min−1 to 24.97 (5.63) l · min−1. The majority of the breath-to-breath noise distributions differed significantly from Gaussian distributions with equivalent mean and SD parameters. The values of the normalised autocorrelation functions indicated a negligible breath-to-breath correlation. Tidal volume accounted for the majority of the V˙O2 (43%) and V˙CO2 (49%) variance. The breath-to-breath noise can be explained in terms of variations in the breathing pattern, although the large noise magnitude, together with the relatively small attainable response amplitudes in children reduces the certainty with which ventilatory and gas exchange kinetics can be measured.
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  • 130
    ISSN: 1573-7284
    Keywords: Asthma ; Atopic diseases ; Children ; Epidemiology ; Socio-economic status ; Tobacco smoke
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A cross-sectional survey of a cohort study was carried out between June and December 1994 in Valencia, Spain (population in 1994: 764,293 inhabitants). Two hundred sixty public and private schools randomly selected from the total of schools in Valencia were invited to participate; 3948 children aged 6–7 years cooperated in our study after informed consent was obtained from parents and school director. The survey in Valencia is part of the International Study of Asthma and Allergy in Childhood (ISAAC). Prevalences for asthma, rhinitis and atopic dermatitis were determined and contrasted with socioeconomic status (SES) among children. No statistically significant associations were established between the prevalences of asthma, rhinitis and atopic dermatitis, and SES. However, atopic dermatitis was found to be common among upper class children (21.5 per 100 children). Likewise, significant associations were observed between the severity of atopy (2 or 3 atopic manifestations) and SES (p=0.000), being greater for lower strata (4.5 per 100 children); for the three SES level significant differences were established (p = 0.008) regarding passive exposure to tobacco smoke in the home.
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  • 131
    ISSN: 1573-7284
    Keywords: Children ; Clinical characteristics ; Lower respiratory tract infections ; Nosocomial infections ; Respiratory syncytial virus ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper has analyzed respiratory syncytial virus lower respiratory tract infections in 201 hospitalized children. In children with wheezing, erythrocyte sedimentation rate (ESR) was significantly higher in those with pneumonia than with syndroma pertussis, while the white blood cell (WBC) count was significantly lower in patients with bronchitis than in those with bronchiolitis and syndroma pertussis. Bronchodilatators were applied in 75.6% and corticosteroids in 20% of patients. Ten patients were ventilated. Fatal disease outcome was observed in one infant. Twelve consecutive-year study of respiratory syncytial virus (RSV) infections showed that 27.3% of these diseases were bronchiolitis and pneumonia.
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  • 132
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    Pharmacy world & science 21 (1999), S. 168-172 
    ISSN: 1573-739X
    Keywords: Adenoidectomy ; Children ; Day‐case surgery ; Home care ; Pain medication ; Postoperative pain ; Tonsillectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The aim of this study was to describe how parents manage their child's postoperative pain at home following day‐case surgery. The incidence of pain, different analgesics used and problems related to administering medications were the main interests of the study. A postal questionnaire was sent to the parents of 275 children who were under 8 years of age and had undergone an ear, nose and throat (ENT) day‐case operation. The questionnaire was sent to the parents a week after discharge from hospital. Altogether, the parents of 227 children answered the questionnaire (response rate 83%). The study was divided into two phases (preintervention and postintervention), and incorporated a training program for doctors and nurses between these two phases. The training program aimed to improve the treatment practices of postoperative pain in children. Seventy‐eight per cent of the children in the preintervention study and 75% in the postintervention study experienced at least mild pain after discharge. The training program for doctors and nurses affected the home treatment practices of postoperative pain. The proportion of parents treating their children increased from 68% to 80% after the training program (p=0.028). Many parents faced problems while treating their children; for example, 19% (n=30) of the children refused to take their medicine, and suppositories were regarded to be an especially unpleasant dosage form. However, no serious adverse effects were reported. We conclude that due to the pain experienced at home by the great majority of children following day‐case ENT operations, parents need information on how to manage their child's pain. A training program for doctors and nurses can improve the treatment of children's pain even at home. Since some children dislike suppositories, it would be worth considering the use of small tablets or mixtures instead.
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  • 133
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    Child psychiatry & human development 29 (1999), S. 261-276 
    ISSN: 1573-3327
    Keywords: Children ; Obsessive-Compulsive ; Rituals ; Fear
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study examined the relationship between ritualistic, compulsive-like behaviors and normative fears and phobias in 61 children ranging from 1 to 7 years of age. Parents reported on their children's ritualistic habits, and perfectionistic behaviors that reflect what we have previously called “compulsive-like” behaviors. Parents also reported on their children's fears and phobias. Results indicated that various aspects of children's ritualistic and compulsive-like behaviors are correlated with children's fears and phobias. Developmental differences existed such that younger children's (〈 4 years) repetitive, compulsive-like behaviors were related to “prepotent” fears such as stranger and separation anxieties, whereas the compulsive-like behaviors of older children (〉 4 years) were correlated with more specific, “contextual” fears such as fears of contamination, death, and fears often associated with concerns of the inner city such as burglars, assault, etc. These findings are discussed in terms of the phenomenologic and possible neurobiological continuities between normative and pathologic rituals, fears and phobias.
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  • 134
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    Child psychiatry & human development 30 (1999), S. 29-37 
    ISSN: 1573-3327
    Keywords: In-School Intervention ; Suspensions ; Reading ; Consistency ; Parents ; Schools ; Children ; Bullies ; Victims ; Anti-social Behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study developed a method of in-school intervention that dramatically reduced the suspension rate and violence in elementary schools. It suggests that children who were not read to by their parents often become bullies and/or victims of bullies. Other parental practices, including inconsistent discipline in the home, also may be contributing factors.
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  • 135
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    Apoptosis 4 (1999), S. 255-261 
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell cycle ; G2/M phase ; Fas ; Jurkat cell.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The relationship between the cell cycle and Fas-mediated apoptosis was investigated using Jurkat cells. Analysis of the inducibility of apoptosis by anti-Fas antibody during the cell cycle synchronized by the thymidine double-block method, showed that apoptosis was induced in only 50% of the G2/M phase cells, while most of cells in the other phases underwent apoptosis. These observations indicate that G2/M phase cells are more resistant to Fas-mediated apoptosis than cells in other phases. Furthermore, a detailed analysis of G2/M phase found that only 20–30% of the cells underwent apoptosis 12 h after the removal of the second thymidine block (pre-G2/M phase). This suggests that Fas-mediated apoptosis is potently suppressed during the pre-G2/M phase. A possible explanation for the observation that cells in the pre-G2/M phase are less sensitive to anti-Fas antibody is lower expression level of Fas. To test this possibility, Fas expression levels on the cell surface during the cell cycle were examined. The content of Fas on the cell surface, however, did not change appreciably during the cell cycle. Thus, the suppression of apoptosis in the pre-G2/M phase is determined downstream after the receipt of the apoptotic signal through Fas.
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  • 136
    ISSN: 1573-675X
    Keywords: Apoptosis ; B/T blood lymphocytes ; γ-glutamyltransferase ; glutathione ; glutathione S transferase ; membrane permeability ; type I (IDDM) ; type II (NIDDM) diabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have compared the concentrations of intracellular glutathione (GSH), glutathione-dependent antioxidative enzymes, the cell death rate and immunophenotype profile of peripheral blood mononuclear cells (PBMC) from healthy donors and from patients with insulin-dependent type I (IDDM) or non insulin-dependent type II (NIDDM) diabetes mellitus. The IDDM and NIDDM patients had above-normal absolute lymphocyte counts, whereas the percentages of CD3, CD4 and CD8 T lymphocytes were significantly reduced. In contrast, the absolute number and percentage of B lymphocytes was higher in diabetic patients than in healthy donors. The low intracellular reduced glutathione (GSH) and the unbalanced profile of key enzymes involved in GSH metabolism, gamma glutamyltransferase (γ-GT) and glutathione-S-transferase (GST), account for the increased oxidative status of PBMC from diabetic patients. The plasma membranes of PBMC from diabetic patients were less permeable to propidium iodide than those of PBMC from healthy donors, indicating that the apoptotic cell death rate was lower in the cells from diabetic patients. These differences are potentially useful markers of pathogenic metabolic changes which occur during clinical diabetes and if they are confirmed could be used to identify the onset of diabetes.
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  • 137
    ISSN: 1573-675X
    Keywords: Apoptosis ; fluorescence microscopy ; seminoma ; TdT.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis morphology (DNA condensation) and internucleosomal DNA cleavage (TdT assay) were measured simultaneously on double fluorescence labeled testis tumor sections, employing conventional immunofluores cence microscopy. Six different apoptosis indices (AI) were determined based either solely on morphological or biochemical criteria, or on a combination of both processes. Measurements were performed in metastasized and non-metastasized seminoma, and in histological regions located distantly and associated with the tumor. Preliminary results on 19 histologies revealed that up to 66% of apoptotic cells were not detected, depending on the method used for apoptosis detection. Besides, no changes of solely morphologically defined AI was found in the different histological regions. By contrast, significant changes (p 〈 0.0004) in the different histological regions were detected when measuring AIs, e.g., defined by DNA fragmentation occuring without DNA condensation in apoptotic cells. Those changes were not detected in metastasized seminoma. These data, for the first time allow a comparison of two widely used approaches for apoptosis detection. Furthermore, the results reveal differences in apoptotic processes in tissue associated with non-metastasized seminoma detectable by a modified evaluated TdT assay but not by morphological changes, although this TdT method fails to show the total amount of apoptotic cells.
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  • 138
    ISSN: 1573-675X
    Keywords: Apoptosis ; bcl-2 ; Ca2+ ; flow cytometry ; hybridoma ; K+ ; Mg2+ ; necrosis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have addressed the possibility that Ca2+, Mg2+ and K+ ions play a central role in governing the morphological and biochemical changes attributed to apoptotic cell death. By removing Ca2+, Mg2+ or K+ ions from the cell culture medium we were able to assess the contribution of each ion to hybridoma cell growth and viability. The differences were explained in terms of a possible reduction in their respective intracellular levels. From several lines of evidence, the deprivation of K+ ions was the most detrimental to cellular growth and viability and induced significant levels of early apoptotic cells. Another effect of this deprivation was to weaken the plasma membranes without causing membrane breakdown; exposure to high agitation rates confirmed fragility of the cell membranes. Removal of Mg2+ caused a reduction in the levels of early apoptotic cells and predisposed cells to high levels of primary necrotic death. The lower levels of apoptotic cells failed to demonstrate the classic nuclear morphology associated with apoptosis, while retaining other apoptotic features. These results highlighted the importance of utilizing several assays for the determination of apoptosis. The absence of Ca2+ appeared to be the mildest insult, but its deprivation did accelerate a significant decline in culture by increasing apoptotic death. Hybridoma cells overexpressing the apoptotic suppresser gene bcl-2 were protected from the predominantly necrosis inducing effects of Mg2+ ion deprivation and apoptosis inducing effects of Ca2+ ion deprivation. However, apoptosis was not as effectively suppressed in bcl-2 cells responding to incubation in K+ free medium. The inclusion of bcl-2 activity in the mechanisms of Ca2+ Mg2+ or K+ deprivation induced cell death emphasizes a close relationship between ionic dissipation and the apoptotic process.
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  • 139
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    Apoptosis 4 (1999), S. 365-372 
    ISSN: 1573-675X
    Keywords: Apoptosis ; chemoprevention ; colorectal cancer ; cyclooxygenase ; NSAIDs.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Epidemiological, clinical and animal studies indicate non-steroidal anti-inflammatory drugs (NSAIDs) to be chemopreventive for colorectal cancer. The best established target for NSAIDs are the two isoforms of cyclooxygenase (COX), a key enzyme in the biosynthesis of prostaglandins. Recent investigations using human colorectal tumor cell lines have focused on the cellular and molecular mechanisms potentially underlying the chemopreventive effect of NSAIDs. These studies have used ‘traditional’ NSAIDs and their metabolites which either do not inhibit COX, are non-selective for the COX isoforms or selectively inhibit COX-1 over COX-2, and recently developed NSAIDs that are highly selective for COX-2. In vitro, apoptosis is the dominant anti-proliferative effect of each of these classes of NSAID and sensitivity to NSAID-induced apoptosis increases with the malignant potential of the tumor cells. Limited in vivo evidence backs up these findings. Cell cycle arrest also contributes to the in vitro growth inhibitory effect of traditional NSAIDs. The induction of apoptosis by NSAIDs may result from the inhibition of the COX isoforms but other as yet undefined paths to NSAID-induced apoptosis clearly exist. A member of each class of NSAID is under trial as a chemopreventive agent for colorectal cancer.
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  • 140
    ISSN: 1573-675X
    Keywords: Apoptosis ; carcinogenesis ; colon cancer ; cyclooxygenase ; nonsteroidal anti-inflammatory drugs.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract NSAIDs are potent chemopreventive agents for colon cancer. Although their mechanism of action is unknown, it probably relates to their modulation of colon epithelial cell kinetics, i.e. apoptosis and/or cell proliferation. NSAIDs are pleiotropic in their biochemical activities; their best known effect is inhibition of prostaglandin H synthase (PHS), the enzyme catalyzing the biosynthesis of prostaglandins. Current data appear to lead to two conflicting conclusions. One body of data indicates that PHS is important in induction of apoptosis and colon carcinogenesis and that its inhibition by NSAIDs is required for induction of apoptosis and their overall chemopreventive effect. Another set of data indicates that NSAIDs may induce apoptosis and prevent colon cancer without inhibiting the activity of PHS. Both sides of this argument are presented and discussed. This apparent contradiction may be resolved if one accepts that both mechanisms are correct but that they act on different steps of this multistep process.
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  • 141
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    Apoptosis 4 (1999), S. 21-29 
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell cycle ; E2F transcription factor ; nuclear phosphoprotein ; retinoblastoma ; transforming growth factor beta ; tumour suppressor gene.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The retinoblastoma gene and its protein product (Rb) have been studied intensively for their role in development, oncogenesis, cell growth, differentiation and cell cycle regulation. In addition, Rb appears to be a key factor in protecting cells from apoptosis. It is likely that Rb plays an essential role in cell survival by regulating the activity of multiple apoptotic mediators. Rb expression as a nuclear phosphoprotein is essential for normal cell cycle function. Clearly, any damage to the cell cycle or to DNA integrity is a potent trigger of apoptosis and Rb involvement. The E2F transcription factor is a critical component in the Rb-dependent apoptotic pathway(s), and can act either in concert or independently of the p53 tumour suppressor. Until recently, it was suggested that Rb, E2F and p53 modulate the apoptotic threshold by acting upstream of certain death proteases involved in programmed cell death. However, Rb activity can also be regulated downstream by the interleukin-converting enzyme-like (ICE-like) proteases, which abolish Rb activity by cleavage of aspartate-enriched regions within its C-terminus. Finally, Bcl-2, which inhibits multiple-factorial-induced apoptosis, does so, in part, by modulating the phosphorylation state of Rb. Taken together, Rb acts not only as a tumour suppressor protein which controls cell cycle function, but also determines the final destiny of a cell through apoptosis.
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  • 142
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    Apoptosis 4 (1999), S. 115-143 
    ISSN: 1573-675X
    Keywords: Apoptosis ; radiation therapy ; radiosensitivity ; tumor response.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Ionizing radiation is an effective means of killing tumor cells. Approximately 50% of all American cancer patients are treated with radiotherapy at some time during the course of their disease, making radiation one of the most widely used cytotoxic therapies. Currently, much effort is focused on understanding the molecular pathways that regulate tumor cell survival following radiotherapy, with the long term goal of developing novel therapeutic strategies for specifically sensitizing tumors to radiation. At present, there is particular interest in the role of tumor cell apoptotic potential as a regulator of both intrinsic and extrinsic determinants of the response of tumors to radiation therapy. Here we review what is currently known about the role of apoptosis as a mechanism of tumor cell killing by ionizing radiation and the relative contribution of apoptosis to cellular radiosensitivity and the ability to control human cancers using radiotherapy. The following topics will be discussed: (1) radiation-induced apoptosis in normal and malignant cells, (2) clinical findings with respect to apoptosis in human cancers treated with radiotherapy, (3) the contribution of apoptosis to intrinsic radiosensitivity in vitro, (4) the relevance of apoptosis to treatment outcome in experimental tumor models in vivo and (5) the potential of exploiting apoptosis as a means to improve the therapeutic efficacy of radiotherapy.
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  • 143
    ISSN: 1573-675X
    Keywords: Apoptosis ; β-IMAGER ; dengue virus ; DNA fragmentation ; radioimager μ-IMAGER ; rabie virus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract DNA fragmentation is a key feature of the degradation phase of apoptosis. In this work we have developed an assay, based on radioimager (β-IMAGER and μ-IMAGER) quantification of radioactive nick end labelling (RANEL), which is quantitative, rapid and sensitive to study in vitro and in vivo induced apoptosis. To establish the technique, in vitro apoptosis of T cell lines was induced by stimulation of the Fas receptor; cells were labelled using TdT-mediated [α-33P] dCTP nick end labelling, after which then radioactivity was quantified using a β-IMAGER. We have also shown that the RANEL method can be applied to the quantification and visualisation, by μ-IMAGER analysis, of liver tissue sections from mouse Fas-induced fulminant hepatitis or from Dengue-1 virus infected individuals. Finally, this system has also been used to detect apoptosis induced by rabies virus in Jurkat T cells. These data have established a large field of application for the RANEL assay.
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  • 144
    ISSN: 1573-675X
    Keywords: Apoptosis ; cyclin D1 ; growth inhibition ; senescence.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It is now apparent that apoptosis is closely linked to the control of cell cycle progression. During the G1 to S progression, cyclin D1, p53, and the cyclin dependent kinase inhibitors p21WAF1 and p27kip1 can play roles in induction of apoptosis. During the G2 and M phases, premature activation of Cdk1 can cause cells to enter mitotic catastrophe, which results in apoptosis. In this review we focus on factors acting during G1 and S, particularly cyclin D1, and their effects on cell growth, senescence and apoptosis. We emphasize that cyclin D1 can have diverse effects on cells depending on its level of expression, the specific cell type, the cell context and other factors. Possible mechanisms by which cyclin D1 exerts these diverse effects, via cyclin dependent kinase-dependent and -independent pathways, are discussed.
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  • 145
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    Apoptosis 4 (1999), S. 239-243 
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell survival ; differentiation ; Drosophila ; EGFR ; hid ; ras.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The Drosophila epidermal growth factor receptor (EGFR), functioning through the Ras/Raf/MAPK pathway, promotes cell proliferation and differentiation. Recent work has demonstrated that EGFR functions via the same Ras/Raf/MAPK pathway to promote cell survival. This review summarizes the role of EGFR in differentiation and survival during Drosophila eye development.
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  • 146
    ISSN: 1573-675X
    Keywords: Apoptosis ; CD95 (Fas/APO-1) ; NF-κB/Rel ; T lymphocytes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The activity of NF-κB/Rel transcription factors can inhibit the apoptosis induced by TNF, UV or cancer therapy drugs in a number of cell types, including human T lymphocytes. Furthermore, the NF-κB/Rel inducer, phorbol-12-myristate-13-acetate (PMA), has been reported to suppress the CD95-induced apoptosis of human T lymphocytes. To verify whether the survival-enhancing effect of PMA required NF-κB/Rel activity, we generated two Jurkat cell sublines (AL.7 and AL.8) transfected with a pCMV4-IκBα construct, and two (AL.3 and AL.5) with the void pCMV4 vector. Compared to wild type, AL.3 and AL.5 cells, the AL.7 and AL.8 sublines displayed markedly lower amounts of NF-κB/Rel nuclear complexes and a reduced expression of a κB-controlled CAT reporter gene after 1 and 4 h of incubation with PMA, respectively. All the five cell types displayed negligible levels of apoptosis when cultured with medium or PMA alone; when stimulated with the mAb CH-11, the AL.7 and AL.8 sublines displayed apoptotic responses only slightly (〈0.5 fold) higher than control cells. On the other hand, the salvage activity of PMA was partially impaired in the AL.7 and AL.8 sublines. PMA inhibited apoptosis by 〉85% in wild type, AL.3 and AL.5 cells and by 〈60% in the AL.7 and AL.8 sublines; the apoptosis percentages in the mAb CH-11 + PMA cultures of the IκBα-transfected cells were 〉4-fold higher than in control cells. We conclude that the inhibition of the CD95-induced apoptosis by PMA relies on both NF-κB/Rel-dependent and -independent mechanisms. The partial contribution of these nuclear factors to the suppression of apoptosis indicates that the NF-κB/Rel activity can influence the extent of the CD95-induced T cell death.
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  • 147
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    Apoptosis 4 (1999), S. 5-10 
    ISSN: 1573-675X
    Keywords: Apoptosis ; atherosclerosis ; cytokines ; Fas ; p53 ; retinoblastoma.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Intimal cell death has been a recognized feature of advanced atherosclerotic disease. With the advent of DNA in situ end labelling and/or ultrastructural techniques, recent findings suggest that cells of an atheroma undergo programmed cell death or apoptosis. The pathophysiologic relevance of apoptosis in atherosclerotic disease is debatable. Apoptotic cell death may influence lesion progression and thus reduce overall plaque burden. Alternatively, apoptosis may prove a means of quenching the inflammation, converting cellular-rich lesions to so-called ‘stable’ fibrous hypocellular plaques or conversely weaken the fibrous cap causing plaque rupture, a major cause of acute coronary syndromes. Apoptotic cells within plaques are typically macrophages, smooth muscle cells and T-cells and the frequency of death varies in the different regions of the lesion. The precise signalling pathways of apoptosis in plaques are unknown. There is however, some evidence that production of immune cytokines may promote apoptosis through activation of the Fas ligand-mediated death pathway. Genetic signals that regulate apoptosis in the atheroma, at least in smooth muscle cells, may involve the tumour suppressor genes p105 RB and p53. Further studies as to the relevance of apoptosis in acute coronary syndromes and potential mechanisms are emerging.
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  • 148
    ISSN: 1573-675X
    Keywords: Apoptosis ; extrachromosomal c-myc genes ; hydroxyurea.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Hydroxyurea (HU) increases extrachromosomal DNA elimination in tumor cell lines. The c-myc oncogene is one of the many relevant amplified genes contained within the extrachromosomal DNA compartment. Spontaneous loss of amplified copies of c-myc induces terminal differentiation and apoptosis in the human HL-60 leukemia cell lines. In the present study, we evaluate HU's ability to induce apoptosis by eliminating extrachromosomally located c-myc oncogene in human tumor cell lines. The consequences of eliminating extrachromosomal DNA by HU were explored in two different cell lines using the TdT assay and acridine orange/ethidium bromide labeling. COLO 320 clone 3 and COLO 320 clone 21 cell lines contain the same number of amplified copies of c-myc oncogene, but located respectively on extrachromosomal DNA, and intrachromosomally in homogeneously staining regions. HU induced apoptosis in the COLO 320 clone 3 cell line by a time and concentration dependent mechanism but could not induce apoptosis in the COLO 320 clone 21 cell line. These results suggested that HU-induced apoptosis in COLO 320 cell lines depends on elimination of extrachromosomal amplified copies of the c-myc oncogene. The ability of HU to eliminate extrachromosomally amplified copies of the c-myc oncogene and to induce apoptosis should be considered when targeting malignancies with amplification of the c-myc oncogene in an extrachromosomal site.
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  • 149
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    Apoptosis 4 (1999), S. 383-388 
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell cycle ; proliferation ; ras.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Cell population homeostasis is a balance between cell proliferation on one hand and the rate of cell loss on the other hand. Normal tissue homeostasis requires the physiological deletion of cells by activation of apoptosis, a genetically determined program of autonomous cell death. ras is most probably the most important oncogene in human cancer. It is mutated in 30% of all tumors especially those of the gastrointestinal tract. In regulating apoptosis ras has many faces. it has both negative and positive effects depending on the stimulation and cell type. The responses of cells to ras signaling depends on the level of Ras expression, the activity of various pathways, and which of the cell cycle check points are functioning. New farnesyl transferase inhibitors and non-steroidal anti-inflammatory compounds may provide a new strategy for novel therapeutic modalities in the treatment of human cancer. The first clinical trials have been initiated, preliminary results are promising, although no firm results are yet available.
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  • 150
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell cycle synchronization ; HL60 ; hypusine ; K562 ; mimosine.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mimosine, a plant amino acid not found in proteins, has been widely used as a synchronizing agent, blocking the progression of cell cycle on the G1/S phase border. The mechanism by which this block is achieved is still unclear. We report that in HL60 cells the synchronization is related to an increase in apoptosis. Another human tumor cell line, K562, is insensitive to both phenomena thereby demonstrating that apoptosis observed in HL60 is line-specific. We hypothesize that the mimosine-induced apoptosis and alteration of the cell cycle is due to the inhibition of hypusine generation.
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  • 151
    ISSN: 1573-675X
    Keywords: Apoptosis ; BAX ; caffeine ; cell cycle ; p53 ; radiation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The p53 tumour suppressor is stabilised following exposure to genotoxic agents, such as γ-radiation. Cell responses to p53 stabilisation include induction of apoptosis and/or cell cycle arrest. Several studies have suggested that γ-radiation stabilises p53 by blocking ubiquitin mediated proteolysis. Here we have compared the biological activities of p53 stabilized following exposure to γ-radiation or treatment with the proteosome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) in MCF7 cells with wild type p53. Stabilisation of p53 by ALLN was reversible and was not blocked by caffeine. Although ALLN was a more effective p53 stabilising agent than γ-radiation, ALLN was not as effective at inducing cell cycle arrest/apoptosis as γ-radiation. Although p53 stabilised by ALLN and γ-radiation were both able to bind DNA and activate transcription, ALLN did not increase expression of BAX, which is involved in p53-induced apoptosis. Therefore, p53 stabilised by different agents is not always biologically active to the same extent and additional alterations triggered by γ-radiation may enable p53 to activate a subset of critical target genes, such as BAX, which are required for p53 responses.
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  • 152
    ISSN: 1573-675X
    Keywords: Apoptosis ; caspases ; leukaemic cells ; minor groove binders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Treatment of HL60 and Jurkat leukaemic cell lines, both not expressing p53, with the new non-covalent DNA minor groove binder α-bromoacryloyl-distamycin (PNU 151807), induces apoptosis as shown either morphologically or by DNA laddering formation. We evaluated the p53-independent mechanisms of activation of apoptosis in these cell systems, by determining the levels of different caspases at different times after treatment with PNU 151807. Through Western blotting analysis we could measure the cleavage of the 110 Kd form of PARP in both HL60 and Jurkat cells and correspondingly the activation of CPP32-caspase 3. The levels of caspase-1 did not change at any time after drug treatment. By using the tetrapeptidic sequence recognized by caspase-3 (DEVD-AMC) or by caspase-1 (YVAD-AMC) linked to fluorogenic substrate, we also demonstrated that only the DEVD sequence was recognized and cleaved after drug treatment, while no significant changes were found for YVAD peptides. PNU 151807-induced DNA fragmentation and DEVD-cleavage were both inhibited by concomitant treatment with the specific inhibitor DEVD-CHO, but not by YVAD-CHO, clearly demonstrating the direct activation of caspase-3-like caspases in the induction of programmed cell death in these cell lines after minor groove binder exposure.
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  • 153
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell cycle ; p53 ; UV ; X-ray
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Although DNA-damaging agents such as ultraviolet (UV) and X-ray can induce apoptosis, the difference in the apoptotic mechanism is not clearly understood. In the present study, we investigated the effects of these two genotoxic agents on the induction of DNA damage and subsequent apoptotic cell death from the viewpoint of cell cycle regulation by using WiDr cells. Transient G1 arrest was observed after UV exposure, whereas G2 but not G1 arrest was induced after X-ray irradiation. UV-exposure could induce G1 arrest in both mutant-type (mt-p53) and wild-type p53 (wt-p53) cells, but obvious G1 arrest was not observed in the cells lacking in p53 expression. An increase in the DNA fragmentation was observed at S phase in UV-irradiated cells and at G2 phase in X-irradiated cells, respectively. UV-irradiated cells showed an increase production of p53 protein and accumulation of p21 protein. On the contrary, both p53 and p21 proteins remained at a low level in X-irradiated cells. Treatment with aphidicolin, an S phase blocking agent, prolonged cell cycle arrest and reduced the rate of apoptotic cell death in both UV-irradiated and X-irradiated cells. From these results, it is suggested that UV-induced apoptosis occurs mainly at S phase and is regulated by increased production of p53 and p21 proteins, while X-ray-induced apoptosis occurs after G2 blockade and may be independent of p53.
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  • 154
    ISSN: 1573-675X
    Keywords: Apoptosis ; caspase-inhibitors ; electron microscopy ; ionizing radiation ; lymphocytes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Resting lymphocytes are sensitive to radiation damage and die by apoptosis. We investigated the effect of caspase-inhibitors on radiation induced apoptosis in human peripheral blood lymphocytes. Lymphocytes were irradiated in vitro with 5 Gy 60 Co-γ-rays and cultured for 24 hours in the presence or absence of the caspase-inhibitors zVAD-fmk and zDEVD-fmk. Cell death was evaluated by electron microscopy. Irradiation in the absence of the inhibitors resulted in about 30% dead cells, almost all showing typical apoptotic morphologies. Addition of either one of the inhibitors could not rescue cells from death. Part of the dead lymphocytes (about 65%) still showed typical nuclear characteristics of apoptotic cells: sharply marginated, condensed chromatin, clumped into one sphere or into a crescent shaped mass. The remaining part of the dead cells had ultrastructural characteristics, aberrant from apoptic cells: clumping of the chromatin was less pronounced and less sharply marginated. Irregular clumps were formed. Data indicate that part of the lymphocytes go in apoptosis in a caspase-independent way. The other part shows caspase-dependent apoptosis with respect to the nuclear events.
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  • 155
    ISSN: 1573-675X
    Keywords: Apoptosis ; caspase-3 ; eosinophil ; interleukin-3 ; poly(ADP-ribose) polymerase ; theophylline.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In bronchial asthma, eosinophils are upregulated and their survival is suggested to be prolonged by the action of some cytokines such as Interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). We find here that the survival of eosinophils in the peripheral blood of patients with asthma is correlated with the serum levels of IL-3 but not of IL-5 and GM-CSF. Interestingly, theophylline is revealed to induce apoptosis of the prolonged survival eosinophils by IL-3, as judged by morphological changes and nucleosomal DNA fragmentation. During the apoptosis, caspase-3 in eosinophils stimulated by IL-3 is activated by theophylline. The substrate of caspase-3, poly (ADP-ribose) polymerase (PARP), is cleaved in the eosinophils after theophylline treatment. These results suggest that theophylline is able to induce apoptosis of the IL-3 activated eosinophils in patients with bronchial asthma, and that its clinical effectiveness may be due to the reduction of inflammatory cells in the airway.
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  • 156
    ISSN: 1573-675X
    Keywords: Apoptosis ; differentiation ; HT-29 cells ; L-745,337 ; p21WAF-1/cip1 ; sodium salicylate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In order to dissect out cyclooxygenase-dependent from cyclooxygenase-independent mechanisms in the antiproliferative effects of selective prostaglandin H synthase (PGHS)-2 inhibitors, we compared the effects of L-745,337 (a highly selective PGHS-2 inhibitor) with sodium salicylate (a weak PGHS inhibitor) on prostanoid production, induction of the cyclin-dependent kinase inhibitor p21WAF-1/cip1, mutant p53 (m273-p53) levels, apoptosis and differentiation in human colon adenocarcinoma HT-29 cells. L-745,337 dose-dependently suppressed the cyclooxygenase activity of HT-29 cells (IC50: 0.24 μM). Four-day treatment with L-745,337 caused a concentration-dependent inhibition of cell growth (IC50: 0.9 mM) associated with the induction of p21WAF-1/cip1 and an increase in the proportion of apoptotic nuclei (EC50: 0.1 and 0.34 mM, respectively) while reducing the levels of m273-p53 (IC50: 0.2 mM). Sodium salicylate, at the concentration of 10 mM that did not affect prostanoid formation, caused a 60% reduction of cell growth associated with a 3-fold induction of p21WAF-1/cip1 and a 60% increase in the proportion of apoptotic nuclei. Ultrastructural analysis showed that L-745,337 (0.5 mM) and sodium salicylate (10 mM) caused the induction of a differentiated phenotype. We conclude that high concentrations of L-745,337 and sodium salicylate inhibit colon cancer cell growth by a mechanism unrelated to cyclooxygenase inhibition that may involve p53-independent induction of the tumor suppressor p21WAF-1/cip1.
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  • 157
    ISSN: 1573-675X
    Keywords: Apoptosis ; chemoresistance ; cisplatin ; Fas ; FasL ; ovarian cancer.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Although cisplatin derivatives are first line chemotherapeutic agents for the treatment of ovarian epithelial cancer, chemoresistance is a major therapeutic problem. Although the cytotoxic effect of these agents are believed to be mediated through the induction of apoptosis, the role of the Fas/FasL system in chemoresistance in human ovarian epithelial cancer is not fully understood. In the present study, we have used cultures of established cell lines of cisplatin-sensitive human ovarian epithelial tumours (OV2008 and A2780-s) and their resistant variants (C13* and A2780-cp, respectively) to assess the role ofFas/FasL system in the chemo-responsiveness of ovarian cancer cells to cisplatin. Cisplatin was effective in inducing the expression of cell-associated Fas and FasL, soluble FasL and apoptosis in concentration and time-dependent fashion in both cisplatin-sensitive cell lines (OV2008 and A2780-s). In contrast, while cisplatin was effective in increasing cell-associated Fas protein content in C13*, it failed to up-regulate FasL (cell-associated and soluble forms) and induce apoptosis, irrespective of concentration and duration of cisplatin treatment. Concentrated spent media from OV2008 cultures after cisplatin treatment were effective in inducing apoptosis in C13* cells which was partly inhibited by the antagonistic Fas monoclonal antibody (mAb) suggesting that the soluble FasL present in the spent media was biologically active. In the resistant A2780-cp cells, neither Fas nor FasL up-regulation were evident in the presence of the chemotherapeutic agent and apoptosis remained low compared to its sensitive counterpart. Activation of the Fas signalling pathway, by addition to the cultures an agonistic Fas mAb, was equally effective in inducing apoptosis in the cisplatin-sensitive (OV2008) and -resistant variant C13*, although these responses were of lower magnitude compared to that observed with cisplatin in the chemosensitive cells. A significant interaction between cisplatin and agonistic Fas mAb was observed in the apoptotic response in OV2008 and C13* when cultured in the presence of both agents. Immunohistochemistry of human ovarian epithelial carcinomas reveals the presence of Fas in low abundance in proliferatively active cells but in high levels in quiescent ones. Although the expression pattern of FasL in the tumour was similar to that of Fas, the protein content was considerably lower. Taken together, these data suggest that the dysregulation of the Fas/FasL system may be an important determinant in cisplatin resistance in ovarian epithelial cancer cells. Our results are also supportive of the notion that combined immuno- and chemo-therapy (i.e., agonistic Fas mAb plus cisplatin) may provide added benefits in the treatment of both chemo-sensitive and -resistant ovarian tumours.
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  • 158
    ISSN: 1573-675X
    Keywords: Apoptosis ; Bcl-2 ; chemoresistance ; NF-κB ; TNF ; vincristine.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Tumor necrosis factor (TNF) is a pleiotropic cytokine that potentiates the cytotoxic effects of chemotherapeutic drugs. Although emergence of resistance to chemotherapeutic drugs is a major problem in cancer therapy, its mechanism is incompletely understood. Recently, activation of a nuclear transcription factor NF-κB has been reported to be a signal for anti-apoptosis. In this report, we investigated the effect of TNF on activation of NF-κB, c-Jun N-terminal kinase (JNK), and apoptosis in vincristine-resistant human histiocytic lymphoma U937-VR cells. Unlike the parent clone (U937-VS), no activation of caspase-3, known to be required for apoptosis, was found in vincristine-resistant cells on exposure to vincristine. These cells were also more resistant than U-937-VS cells to doxorubicin, daunomycin, and taxol. TNF-induced NF-κB activation, IκB α degradation, and nuclear translocation of p65 were all found to be highly suppressed in the U-937-VR cells. NF-κB activation by LPS, H 2 O 2 , and okadaic acid was also suppressed. However, vincristine resistance enhanced TNF-induced JNK activation. When examined for apoptosis, vincristine resistance suppressed the cytotoxic effects and caspase-3 activation by TNF. The resistant phenotype in U937-VR cells was independent of the expression of the apoptosis-suppressor, Bcl-2. Thus, overall these results indicate that vincristine resistance correlates with suppression of NF-κB activation, cytotoxicity, and caspase-3 activation but enhancement of JNK activation by TNF.
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  • 159
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    Apoptosis 4 (1999), S. 311-315 
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell division ; CD95 ; CD95L ; Fas ; FasL ; Fas Ligand ; growth arrest.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In this review, we chronicle the discovery, biochemical characterization, and assignment of Fas (CD95) as receptor and Fas Ligand (FasL, CD95L) as ligand. We review the functional descriptions of the molecules as death-inducing receptor and ligand or as mediators of cell division and/or growth arrest. We suggest that bidirectional mediation of signals in receptor-ligand pairs may be a common and important mechanism regulating cell fate. Bidirectional signaling clearly impacts the interpretation of experimental studies of intercellular communication.
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  • 160
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    Protoplasma 207 (1999), S. 213-221 
    ISSN: 1615-6102
    Keywords: Apoptosis ; Tapetum ; Tillandsia albida ; Lobivia rauschii
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Programmed-cell-death events in the tapetum of two angiosperms (Lobivia rauschii Zecher andTillandsia albida Mez et Purpus) are described by ultrastructural methods. Tapetum degradation appears to be a type of programmed cell death, with the cellular remnants necessary for pollen development, acting as products of holocrine secretion. Diagnostic features of apoptosis during tapetum development are: general shrinkage of the whole cell and the nuclei; condensation of the chromatin at the periphery of the internal nuclear membrane; the enlargement of the endoplasmicreticulum cisternae to circumscribe portions of the cytoplasm; the persistence of mitochondria together with microfilament bundles until the last stages of tapetal degeneration.
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  • 161
    ISSN: 1433-0385
    Keywords: Key words: Hernia repair ; Children ; Laparoscopy ; Patient selection. ; Schlüsselwörter: Kinderchirurgie ; Leistenhernie ; intraoperative Laparoskopie ; Diagnostik ; Patientenselektion.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Aus epidemiologischen Untersuchungen ist bekannt, daß bei ca. 50 % der Kinder mit einseitiger Leistenhernie auf der Gegenseite ebenfalls ein offener Processus vaginalis vorliegt. 10–25 % dieser Kinder entwickeln in der Folge eine kontralaterale Hernie. Seit 1996 wird in unserer Klinik bei Säuglingen und Kindern mit klinisch unilateraler Leistenhernie mittels intraoperativer Laparoskopie durch den eröffneten Bruchsack der kontralaterale innere Leistenring inspiziert. Vorgehen: Bisher wurden 112 Kinder untersucht (Alter: 6 Monate bis 7 Jahre; 78 Jungen, 34 Mädchen). Nach Freipräparation des Bruchsacks wurde dieser eröffnet und ein 5,5-mm-Trokar durch den inneren Leistenring eingebracht. Nach Anlage des Pneumoperitoneums erfolgte mit einer 5-mm-(30 °)-Optik zunächst die orientierende Laparoskopie, anschließend mit der 70 °-Optik die Inspektion des kontralateralen inneren Leistenrings. Ergaben sich Hinweise für einen breit offenen Processus vaginalis (Typ III nach Chin), wurde in gleicher Narkose diese Seite ebenfalls offen chirurgisch exploriert. Ergebnisse: Laparoskopisch fand sich bei 19 Patienten (17 %) ein nach oben genannten Kriterien pathologischer Befund (6 Mädchen, 13 Jungen). Diese wurden auf der Gegenseite operiert und die laparoskopische Diagnose in allen Fällen bestätigt. Verfahrensbedingte Komplikationen traten nicht auf. Die Eingriffe erfolgten im Rahmen der Eintageschirurgie. Die Operationsdauer erhöhte sich durch die intraoperative Laparoskopie um im Median 6 min (3–11 min). Deutlich häufiger fanden sich pathologische Befunde bei Patienten unter 2 Jahren (14 von 19 Patienten). Schlußfolgerungen: Das beschriebene Verfahren erlaubt ohne nennenswerten zusätzlichen Zeitbedarf, Patienten zu selektionieren, die von einer einzeitigen offenen Exploration der gegenseitigen Leistenregion profitieren. Somit können Zweitoperationen mit erneuter Narkose und Hospitalisierung vermieden werden. Zusätzlich erlaubt die intraoperative Laparoskopie die allgemeine Beurteilung der Abdominalorgane sowie Klärung spezieller Fragen wie, z. B. die Vitalität reponierter Darmschlingen.
    Notes: Summary. Background: Approximately 50 % of children with a clinical unilateral inguinal hernia display a patent processus vaginalis on the contralateral side; half of these children subsequently develop an inguinal hernia.The management of this problem is still controversial. The purpose of this study was to evaluate the usefulness of intraoperative laparoscopy in a no-puncture technique through the opened hernia sack. Method: In 112 children (age 6 months to 7 years ) with clinical unilateral hernia laparoscopy (5 mm laparoscope, 30 ° and 70 °). In cases of a wide-open contralateral internal inguinal ring (type III) open surgical exploration was performed. Results: Nineteen patients (17 %) fulfilled the laparoscopic criteria of a type III ring; the diagnose was confirmed during open contralateral exploration. Fourteen of these patients were younger than two years. The median time for laparoscopy was 6 min (3–11 min). No complications associated with the laparoscopy were observed. Conclusions: Intraoperative laparoscopy during unilateral hernia repair allows the identification of patients who profit from bilateral open surgery during the same operation with little additional operating time and so far with no resulting complications. Application of this method may avoid a second hospitalization and operation, as well as an unnecessary routine bilateral open exploration. As an additional source of information through excellent visualization of the abdominal cavity, this method proved helpful to examine incarcerated bowel after repositioning.
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  • 162
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    Journal of bioenergetics and biomembranes 31 (1999), S. 327-334 
    ISSN: 1573-6881
    Keywords: Apoptosis ; redox ; mitochondria ; E h ; ROS ; ASK-1 ; thioredoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract The regulatory role of cellular redox state during apoptosis is still controversial. Early redoxsignaling can transduce divergent upstream signals to mitochondria and initiate apoptosis. Onthe other hand, release of mitochondrial cytochrome c triggers generation of reactive oxygenspecies (ROS) and renders apoptotic cells much more oxidized. Although the sequential caspaseactivation does not have apparent redox-sensitive components, redox signaling provides aseparate pathway that is parallel with the caspase cascade. The function of theapoptosis-associated redox change is uncertain. It could provide positive feedback mechanisms, such asactivating mitochondrial permeability transition and apoptosis signaling kinase (ASK-1). Sinceapoptotic cells are designated to be quickly eliminated, the dramatic cellular oxidation couldbe involved in the final degradation of apoptotic bodies and even the termination of theproteolytic activity after phagocytosis.
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  • 163
    ISSN: 1573-6881
    Keywords: Apoptosis ; confocal microscopy ; cyclosporin A ; cytochrome c; ; ischemia/reperfusion ; mitochondrial permeability transition ; necrapoptosis ; necrosis ; oxidative stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Mitochondria are frequently the target of injury after stresses leading to necrotic and apoptoticcell death. Inhibition of oxidative phosphorylation progresses to uncoupling when opening ofa high conductance permeability transition (PT) pore in the mitochondrial inner membraneabruptly increases the permeability of the mitochondrial inner membrane to solutes of molecularmass up to 1500 Da. Cyclosporin A (CsA) blocks this mitochondrial permeability transition(MPT) and prevents necrotic cell death from oxidative stress, Ca2+ ionophore toxicity,Reye-related drug toxicity, pH-dependent ischemia/reperfusion injury, and other models of cell injury.Confocal fluorescence microscopy directly visualizes onset of the MPT from the movementof green-fluorescing calcein into mitochondria and the simultaneous release from mitochondriaof red-fluorescing tetramethylrhodamine methylester, a membrane potential-indicatingfluorophore. In oxidative stress to hepatocytes induced by tert-butylhydroperoxide, NAD(P)Hoxidation, increased mitochondrial Ca2+, and mitochondrial generation of reactive oxygen speciesprecede and contribute to onset of the MPT. Confocal microscopy also shows directly thatthe MPT is a critical event in apoptosis of hepatocytes induced by tumor necrosis factor-α.Progression to necrotic and apoptotic cell killing depends, at least in part, on the effect theMPT has on cellular ATP levels. If ATP levels fall profoundly, necrotic killing ensues. If ATPlevels are at least partially maintained, apoptosis follows the MPT. Cellular features of bothapoptosis and necrosis frequently occur together after death signals and toxic stresses. A newterm, necrapoptosis, describes such death processes that begin with a common stress or deathsignal, progress by shared pathways, but culminate in either cell lysis (necrosis) or programmedcellular resorption (apoptosis) depending on modifying factors such as ATP.
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  • 164
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    European journal of epidemiology 15 (1999), S. 133-139 
    ISSN: 1573-7284
    Keywords: Children ; Emergency room charge ; Hospitalisation ; Injuries ; Socio-economic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although many studies have shown an association between socio- economic environment and childhood injury mortality rates, little research has focused on the association between injuries which require hospitalisation and the child's socio-economic environment. All municipal emergency care was free of charge before the beginning of 1991, from then on a moderate patient charge was introduced by the City of Helsinki. An earlier report from a completely different social environment suggest that even a moderate user charge might create systematic discrimination against indigent families. We studied the childhood injury hospitalisation rates during 1989–1994 in Helsinki and analysed the association between rates of hospitalisation and local socio-economic and demographic factors. We also examined the effect of introduction of emergency room user charges on the rate of hospitalisation. Data from 1607 injuries from Helsinki City Hospital and 769 injuries from Helsinki University Central Hospital from years 1989 through 1994 were used. Annual rates of child hospitalisation were calculated at city level. Local socio-economic and demographic variables were derived from the Helsinki Bureau of Statistics. The possible association between the explanatory variables and hospitalisation rates at Helsinki City Hospital was calculated using annual data from the 33 health districts in Helsinki. The overall rate of hospitalisation for injuries declined but not statistically significantly. No association between socio-economic and demographic variables and hospitalisation rates was found. The moderate user charge had no effect on hospitalisation rates, proving that, in this setting, the demand for care was rather inelastic in paediatric injuries severe enough to require hospitalisation.
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  • 165
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    European journal of epidemiology 15 (1999), S. 907-912 
    ISSN: 1573-7284
    Keywords: Bedouin ; Children ; Diarrhea ; Environment ; Knowledge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Diarrhea is still a major cause of morbidity and mortality among children in developing countries. As it is due to multiple causative agents including viruses, bacteria and parasites, biological interventions are not currently available to markedly reduce incidence and severity. We examined maternal knowledge and reported behavior during diarrheal episodes, as well as environmental factors to determine their association with diarrhea. The children and mothers were from a Bedouin township in southern Israel, which has developed preventive and curative health care facilities. The Bedouin population in Israel is in transition from a nomadic to a settled life style. While almost all mothers exhibited good knowledge regarding food storage and prevention of diarrhea episodes in the children, the rate of illness in the children remained relatively high (two episodes per child year of observation). In a multivariate analysis, cessation of breastfeeding during diarrhea, child sleeping with siblings and lack knowledge about risk factors, were the major risk factors for illness with odds ratios (OR): 4.6, p = 0.02, 5.6, p = 0.03 and 1.7, p = 0.06, respectively. These data indicate that even in this population with free access to preventive medical care, greater efforts should be made to educate mothers regarding risk factor for diarrheal disease identification and the benefits of maintaining breastfeeding during diarrhea episodes.
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  • 166
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    European journal of epidemiology 15 (1999), S. 485-491 
    ISSN: 1573-7284
    Keywords: Blood lead levels ; Children ; Modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The key problem in environmental health is to identify the potential health hazards at the lowest possible cost based upon available environmental data. Biokinetic models such as IEUBK Lead 0.99d are very promising in this respect. We attempted a comparison between epidemiological data and predictions of the model. As input, we used the existing exposure data for the Katowice Voivodship (administrative district, Poland). Epidemiological analysis was based on the results of the screening programme ‘Prevention of the Environmental Lead Intoxication in Children Living in Katowice Voivodship’. The simulations consisted of predicted distributions of blood lead levels in children. They have been compared with observed distributions. Sensitivity analysis of simulations with respect to lead concentration in air, soil, water and diet has also been performed. The agreement between predicted and observed mean blood lead levels was quite good (relative difference of about 40%) as for the coarse exposure assessment employed. At the level of risk (fraction of population having blood lead levels exceeding 10 μg/dl) the difference is much higher (about a factor of 2). In order to explain this discrepancy we checked the goodness of fit for the log-normal distribution function (usually taken as a template distribution for lead in the population) in the right tail of the distribution. We noticed a systematic effect depleting the right tail of the actual distribution as compared with the log-normal one. Therefore one can expect that using (as a template) another skewed distribution better fitted in the right tail would improve the accuracy of risk assessment.
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  • 167
    ISSN: 1573-7284
    Keywords: Children ; ELISA ; Haemophilus influenzae type b ; Infants ; Natural immunity ; Vaccination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prior to possible introduction of large-scale vaccination programmes, an estimation and comparison of naturally acquired immunity against Haemophilus influenzae type b (Hib) was carried out in two populations of age-stratified infants and children (from birth to 14 years old) in Burkina-Faso (West Africa) (n = 206) and France (n = 206). Hib capsular polysaccharide antibodies were detected by an ELISA method. The difference in the percentages of minimum protective levels for the two populations were not significant (0.15 μg/ml) for newborns (0–1 month) but became significant as early as 2 to 3 months of age (p 〈 0.01) when lower levels were found among infants from Burkina-Faso. Subsequently, the percentages in both countries remained low until 11 months of age and showed no significant differences. For children between 12 and 35 months, the results ≥ 0.15 μg/ml were significantly higher in France (p ≤ 0.05). From 36 months, the percentage of minimum seropositivity increased in Burkina-Faso, so that the difference was no longer significant. In each country, the percentage of children with the minimum protective level varied significantly (p les; 0.05) according to age (0–47 months). None of the children from Burkina-Faso or France had antibody levels 〉 1.0 μg/ml before one year of age. Thereafter, only 9.51% of French children in the 12- to 17-month age stratum and 19.2% over 4 years of age had antibody levels 〉 1.0 μg/ml. There were no non-detectable results for children over 4 years of age, and the means for natural detectable Hib CP antibodies were 〉 0.15 μg/ml for both populations. Hib invasive infections depend on climate, socioeconomic status and ethnic and genetic factors. In Burkina-Faso, the large number of infants and children under 4 years of age susceptible to Hib infections suggests that large scale vaccination programmes are needed soon after birth. However, it would first be necessary to evaluate such factors as the frequency of Hib diseases in this population.
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  • 168
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    European journal of epidemiology 15 (1999), S. 685-687 
    ISSN: 1573-7284
    Keywords: Children ; Epidemiology ; Hib meningitis ; Italy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 1994, the Italian Ministry of Health implemented a National Surveillance System to obtain data on the incidence of bacterial meningitis and its causative agents, including Haemophilus influenzae type b (Hib). As a consequence, case reporting of Hib meningitis is increasing year by year; in 1996, there were 126 notifications, of which 73% were in children under 2 years of age. Although underreporting still exists, parallel prospective or retrospective epidemiological surveys conducted in some Italian Regions allowed for partial correction of the incidence of Hib meningitis (up to 18.5/100,000 population in 1994).
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  • 169
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    Journal of clinical immunology 19 (1999), S. 378-387 
    ISSN: 1573-2592
    Keywords: Apoptosis ; cytochrome c ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Whether we view the mitochondria as the headquarters for the leader of a crack suicide squad or as a prison for the leader of a militant coup, the role of the mitochondria in the apoptotic process is now well established. During apoptosis the integrity of the mitochondria is breeched, the mitochondrial transmembrane potential drops, the electron transport chain is disrupted, and proteins from the mitochondrial intermembrane space (MIS) such as cytochrome c are released into the cytosol, although not necessarily in that order. In the cytosol, cytochrome c forms part of a proteinaceous complex that directly activates caspase-9, one of the apical enzymes responsible for the dismantling of the cell. In this way a mitochondrial factor which is normally locked away from the rest of the cell can directly trigger apoptosis. The need to regulate the release of cytochrome c suggests that the mitochondria may be the decision center for whether a cell lives or dies. Various hypotheses have been formulated to explain how proteins of the MIS are released and how this process is regulated. These include the Bcl-2-regulated opening of a permeability transition pore or an increase in mitochondrial transmembrane potential followed by outer membrane rupture. It remains to be clarified which mitochondria specific events are essential for apoptosis and which are merely consequences of apoptosis.
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  • 170
    ISSN: 1435-1544
    Keywords: Key words Implantable cardioverter defibrillator ; Sudden cardiac death ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Implantable cardioverter defibrillators (ICDs) are the treatment of choice in adults with symptomatic ventricular tachycardia or aborted sudden cardiac death. Treatment with implantable defibrillators is also possible in children, although experience in this patient group is scanty. A review of the literature on the subject of defibrillator therapy in combination with epicardial electrodes is provided. Endocardial electrodes, which have now become the gold standard in adult treatment, have only rarely been used in children. However, our own experience shows that endocardial electrodes can be implanted in most children, which generally obviates the need for thoracotomy.
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  • 171
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    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. 128-132 
    ISSN: 1434-4726
    Keywords: Key words Cochlear implant ; Management of ; complications ; Children ; Postoperative care ; Infection ; Device failure ; Reimplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a retrospective analysis we evaluated the intra- and postoperative complications in children who underwent cochlear implantation between 1984 and 1993 at the Medizinische Hochschule Hannover. The data and records of 366 children were collected and analyzed. Relevant parameters were major complications such as significant infection, intraoperative bleeding, facial nerve injury, implant loss and device failure, as well as lesser complications, including delayed wound healing, chronic pain and vertigo. Late complications such as cholesteatoma or electrode dislocations were also registered. Cases of acute otitis media were managed with conservative treatment. Data presented indicate that cochlear implant surgery in children is a reliable and safe procedure with a low percentage of severe complications. Problems related to ear surgery can occur and should be manageable with standard procedures. Careful operative techniques and sufficient personal experience can help avoid severe postoperative problems.
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    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. S8 
    ISSN: 1434-4726
    Keywords: Key words Cholesteatoma ; Children ; Tympanoplasty
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied retrospectively 28 cases of cholesteatoma in children whose ages were 3 to 13 years old. All had undergone surgery between 1989 and 1995. The intact canal wall technique was the predominant method used in the initial operation, with long term goals of an anatomically normal and infection-free ear. Cholesteatoma was found postoperatively in 15 cases and was considered to be residual in 6 cases and recurrent in 9. The residual cholesteatoma was relatively uncommon and usually removable in an exploratory second operation. Our findings showed that the intact canal wall technique was the best initial operation if two-stage surgery was planned. Avoidance of a retraction pocket, which tends to progress to a recurrent cholesteatoma, is important to successful treatment.
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  • 173
    ISSN: 1861-387X
    Keywords: Medulloblastoma ; Prognosis ; Tenascin ; Apoptosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Medulloblastomas (MB) are the most common central nervous system malignancies in children. Numerous publications describe efforts to identify the predictive value of various patterns of MB pathology and immunohistochemistry, but received data appear to be controversial. Seventy-three patients with cerebellar MB were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to various tumor-associated antigens. Also, apoptosis detection by the in situ end-labeling method was performed. Survival analysis was made using univariate and multivariate models. Tenascin immunoreactivity and apoptotic index (AI)〉or=1.5% were found to be closely associated with poor prognosis according to an univariate analysis (P=0.008 and 0.003, respectively). The multivariate Cox proportional hazard model exhibited independent prognostic value for the apoptotic rate only (P=0.023). Tumors with tenascin expression and AI〉or=1.5% significantly prevailed among MB with metastatic dissemination, whereas expression of c-erbB2 oncoprotein and epidermal growth factor receptor was found to be more typical for cases with local tumor recurrence. We came to the conclusion that tenascin immunoreactivity and AI were useful for individual MB prognosis.
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  • 174
    ISSN: 1573-3629
    Keywords: Children ; visual acuity ; sociodemographic factors ; Hispanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sociodemographic correlates of visual impairment were examined in 6- to 19-year-old Hispanic children and adolescents using data from the Hispanic Health and Nutrition Examination Survey. Mexican American and Puerto Rican children whose parents had 0 to 6 years of education were more likely to remain visually impaired even when tested with their glasses or contact lenses, if any (i.e., with usual correction) than children whose parents reported 12 to 17 years of education. Mexican Americans residing below versus at or above the poverty line were more likely to remain visually impaired even with the usual correction. Mexican Americans enrolled in the Medicaid program or who were without health insurance were more likely to remain visually impaired than Mexican Americans with private health insurance. When tested without glasses or contact lenses, Cuban Americans and Mexican Americans born outside of the mainland United States had lower rates of visual impairment compared to those born in the United States; however, children in this latter group were more likely to remain visually impaired with usual correction than U.S.-born Mexican Americans. These findings suggest that Hispanic children from economically disadvantaged households and those born outside the United States may not be receiving optimal eye care that could improve visual function.
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  • 175
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    Liebigs Annalen 1999 (1999), S. 57-60 
    ISSN: 1434-193X
    Keywords: Benzyne ; Dehydroanthracene ; Matrix isolation ; Photochemistry ; Bergman reaction ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -9,10-Didehydroanthracene (1) is an interesting derivative of p-benzyne that has been subject of several studies. In contrast to an earlier report, the photochemical decarbonylation of 9,10-dicarbonyl-9,10-dihydroanthracene (2) does not lead to 1 but rather to the ring-opened ene-diyne 4. The key intermediate for this reaction is keto carbene 7 which is formed by monodecarbonylation of 2. Carbene 7 is labile towards visible-light irradiation and easily looses the second CO molecule to give 4. Carbene 7 and diyne 4 are characterized by IR and UV/Vis spectra, the IR spectra are compared to calculations at the B3LYP/6-31G(d,p) level of theory.
    Additional Material: 2 Ill.
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  • 176
    ISSN: 1434-193X
    Keywords: Nucleophilic addition ; Solvent effect ; Reversal of diastereoselectivity ; Temperature effect ; Imines ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Commonly observed, but rarely explored, is the possibility of modifying the diastereomeric excess (de%) by means of temperature. A complete reversal in the diastereofacial selectivity could be obtained whenever the diastereoisomers concerned are differentially favored by enthalpy and entropy. The enthalpic or entropic dominance of a diastereoisomer depends greatly on the reaction solvent used.
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  • 177
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    Liebigs Annalen 1999 (1999), S. 73-81 
    ISSN: 1434-193X
    Keywords: Donor-acceptor systems ; Cage compounds ; Stelladione ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -A number of condensations could be carried out using tricyclo[3.3.0.03,7]octane-2-one (stellanone, 4) and tricyclo[3.3.0.03,7]octane-2,6-dione (2,6-stelladione, 5) as starting materials. The components for condensations were 2-trimethylsilyl-1,3-dithiane (6), 1,1-bis(trimethylsilyl)-1H-cyclopropa[b]naphthalene (7), its 3,6-dimethoxy-substituted analogue 8, fluorene (12), xanthene (13), diethyl malonate (14), and malononitrile (15). The condensation reactions with 5 yielded mono- and disubstituted products, among them were the donor-acceptor-substituted 2,6-stellanes 33-35. The structures of 18 (prepared from stellanone and fluorene), 19, 24, 27, 31 and 32 (synthesized by condensation of 2,6-stelladione and 2-trimethylsilyl-1,3-dithiane and malononitrile, respectively) were determined by X-ray crystallography.
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  • 178
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    Liebigs Annalen 1999 (1999), S. 87-90 
    ISSN: 1434-193X
    Keywords: Water ; α-Nitrocycloalkanones ; ω-Nitro acids ; Surfactant ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The reaction of various α-nitrocycloalkanones 1 with aqueous 0.05 M NaOH, at 80 °C, in the presence of cetyltrimethylammonium chloride (CTACl) as a cationic surfactant, produces ω-nitro acids 2 in good yields. Reduction of the latter with HCOONH4/Pd-C, in methanol, at 80 °C affords ω-amino acids 3. The synthesis of methyl 9-oxodecanoate (8) is also reported.
    Additional Material: 2 Tab.
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  • 179
    ISSN: 1434-193X
    Keywords: O-Alkylation ; Ambident nucleophile ; Thiazolethione ; Thiohydroxamic acid ; Phase-transfer reaction ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -O-Alkylation of cyclic thiohydroxamic acids 1 and 3-5 has been studied with a view to developing an efficient method for the synthesis of N-(alkoxy)pyridine-2(1H)-thiones and N-(alkoxy)thiazole-2(3H)-thiones. Four issues have been addressed and the following conclusions can be drawn: (i) Thiones 1 and 5 exist as O-H acids in the solid state. (ii) According to NMR investigations (1H, 13C), the thione structures should be largely retained in CDCl3, [D6]DMSO, and CD3OD solutions of acids 1, 3-5, as is also the case for pyridinethione salts 2a-h. (iii) O-Alkylation of pyridinethione salts occurs in competition with S-alkylation. Selective O-alkylation is however possible, if thiohydroxamate salts with large countercations, such as M = NBu4, are treated with hard alkylating reagents in polar aprotic media. (iv) As tetrabutylammonium thiohydroxamates, such as 2f, are highly useful in the synthesis of cyclic thiohydroxamic acid O-esters, we have developed an efficient protocol for the preparation of N-(alkoxy)pyridine-2(1H)-thiones directly from acid 1 using phase-transfer conditions (alkyl halide or sulfonic acid ester, CH3CN, K2CO3, Bu4NHSO4). This method has proved particularly successful for the synthesis of N-(alkoxy)thiazole-2(3H)-thiones 11, 20-28, which were obtained in yields of up to 87%.
    Additional Material: 2 Ill.
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  • 180
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    Liebigs Annalen 1999 (1999), S. 129-134 
    ISSN: 1434-193X
    Keywords: Tetrahydro-2-vinylquinoxaline ; Cyclization ; Palladium ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Reaction of (Z)-1,2-bis(methoxycarbonyloxy)but-2-ene (2) with various N,N-bis(arylsulfonyl)-o-phenylenediamines 1 was catalyzed by a palladium complex associated with chiral ligands to give optically active 1,4-bis(arylsulfonyl)-1,2,3,4-tetrahydro-2-vinylquinoxalines 3 with up to 62% ee. The use of (S)-MeOBIPHEP as the chiral ligand and N,N-bis(p-tolylsulfonyl)-o-phenylenediamine (1i) as the nucleophile led to the highest ee at 25 °C, regardless of the solvent used. The enantioselectivity of the cyclization is strongly affected by the nature of the substituents at the nitrogen atom.
    Additional Material: 4 Tab.
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  • 181
    ISSN: 1434-193X
    Keywords: Fluorine ; Lactones ; Annulation ; Ketene ; Sulfoxides ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Enantiomerically pure α,α-dichloro β-fluoroalkyl γ-p-tolylthio γ-butyrolactones trans-6a-c have been obtained with excellent stereocontrol (〉 98:2) and enantiomeric purity (〉 98:2) by sulfoxide-directed lactonization (Marino's annu-lation reaction) of β-fluoroalkyl vinyl sulfoxides (R)-(E)-5a-c with dichloroketene. Highly chemoselective dechlorination and desulfurization reactions performed on trans-6c efficiently provided the β-chlorodifluoromethyl γ-butyrolactone (S)-8c, the absolute stereochemistry of which was determined by X-ray diffraction analysis of its γ-p-tolylthio precursor (2R,3S)-7c.
    Additional Material: 1 Ill.
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  • 182
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    Liebigs Annalen 1999 (1999), S. 141-143 
    ISSN: 1434-193X
    Keywords: Nitrosobenzene ; 4-Methoxy-N-methyleneaniline ; 1,3,5-Tris(4-methoxyphenyl)-1,3,5-triazinane ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -A 1:1 adduct produced in the reaction of nitrosobenzene (2) with 1,3,5-tris(4-methoxyphenyl)-1,3,5-triazinane (3) has been shown by X-ray diffraction structure analysis to be the N′-(4-methoxyphenyl)-N-phenyl-N-oxyformamidinium species 5.
    Additional Material: 1 Ill.
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  • 183
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    Liebigs Annalen 1999 (1999), S. 155-161 
    ISSN: 1434-193X
    Keywords: Alkylation ; Oxazolines ; anti-α-Alkyl α-hydroxy β-amino acids ; Lithium dianion ; Penicillin G acylase ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -As part of an ongoing project concerning the synthesis of enantiomerically pure α-hydroxy β-amino acids, we have now developed a general strategy allowing the synthesis of anti-α-alkyl α-hydroxy β-amino acids. Our procedure involves the intermediate formation of trans-oxazolines, which are alkylated at C-5 with good to high diastereoselectivity and then hydrolysed under mildly acidic conditions, affording in quantitative yield the corresponding hydroxy amides. The starting (R)-3-amino-3-phenylpropanoic acid and (S)-3-aminobutanoic acid were obtained in enantiomerically pure form by selective enzymatic hydrolysis of the corresponding phenylacetylamides with penicillin G acylase.
    Additional Material: 3 Ill.
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  • 184
    ISSN: 1434-193X
    Keywords: Palladium catalysis ; Homogeneous catalysis ; Anilines ; Alkylation ; Oxazolidinones ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Palladium-catalyzed reaction of acidic anilines with (Z)-2-butene-1,4-diyl dicarbonate affords N-aryl-4-vinyloxazolidin-2-ones. The success of the reaction depends on the acidity of the aniline and requires in situ conversion of the dicarbonate into carbamate carbonate by nucleophilic attack of the aniline conjugate base followed by palladium-catalyzed intramolecular cyclization.
    Additional Material: 1 Tab.
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  • 185
    ISSN: 1434-193X
    Keywords: Density functional calculations ; Vinylcyclopropane-cyclopentene rearrangement ; [1,3]-Sigmatropic shift ; Biradical-like transition structure ; Substituent effects ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The effect of donor substitution by the hydroxy group and of acceptor substitution by the cyano group on the activation energies of the vinylcyclopropane-cyclopentene rearrangement was calculated by the spin-restricted RB3LYP/6-31G* method for reactant structures and by the spin-unrestricted UB3LYP/6-31G* method for transition structures. The activation energies of the rearrangement of hydroxy- and cyano-substituted vinylcyclopropanes are very similar for substitution in the same position. In agreement with earlier findings the substituent effects on the activation energies are closely connected with the radical stabilizing properties of the substituents. As indicated by singlet/triplet splitting energies, the transition structures are essentially biradicaloid. In spite of spin pairing in the transition structure the substituent effects on bond lengths and on stabilization energies are very similar to those of the free radicals corresponding to the two radical substructures. Thus, the transition structures may be considered, in good approximation, as structures consisting of two weakly interacting radicals.Supporting information for this article is available on the WWW under -http://www.wileY-Vch.de/contents/jc_2046/1999/98349_s.pdf or from the author.
    Additional Material: 5 Ill.
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  • 186
    ISSN: 1434-193X
    Keywords: Cyclopropanes ; Rearrangements ; Cyanohydrins ; Schiff bases ; Small ring systems ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The direct cyclization of 2-amino-4-chloro-3,3-dimethylbutanenitrile with potassium tert-butoxide in THF afforded 1-amino-2,2-dimethylcyclopropane-1-carbonitrile and a dimerization product. Various new cis- and trans-1-(tert-butylamino)-2-benzyl-2-methylcyclopropane-carbonitriles and© the corresponding cyclopropanecarboxamides have been synthesized, with focus on the isolation of the pure stereoisomeric cyclopropanecarboxamides. The relative configuration of the stereoisomers was established by X-ray crystallographic analysis of one of the model compounds. A new route to the latter functionalized cyclopropanes was developed by reaction of 1-methoxycyclopropylamines with potassium cyanide. Some remarkable rearrangements of 1-aminocyclopropane-1-carbonitriles into azetidine and oxazine derivatives via Favorskii-derived intermediates are reported. Various aspects of the chemistry of geminally functionalized cyclopropanes are discussed.
    Additional Material: 1 Ill.
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  • 187
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    Liebigs Annalen 1999 (1999), S. 267-275 
    ISSN: 1434-193X
    Keywords: Vinylallenes ; Organocuprates ; Substitution ; Stereoselective synthesis ; Copper catalysis ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Enyne acetates 2, 4, 6, and 8, as well as enyne oxiranes 10, with different substitution patterns react with organocuprates regioselectively under 1,5-(SN2′′)-substitution to provide vinylallenes 11 and 12. With lithium dimethylcuprate, reduced vinylallenes originating from a (formal) transfer of a hydride ion to the substrate are formed in some cases. The products are usually obtained as mixtures of (E/Z)isomers; however, pure (E)-vinylallenes are formed occasionally. The 1,5-substitutions can also be carried out with catalytic amounts of copper reagents. The reaction of chiral enyne acetate (S)-2a with tBu2CuLi · LiCN proceeds enantioselectively, so that this transformation constitutes a new case of remote stereocontrol.
    Additional Material: 1 Tab.
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  • 188
    ISSN: 1434-193X
    Keywords: Nitrogen heterocycles ; Open-chain analogue of Reissert compound ; Hydrofluoroborate salts ; α,β-Ethylenic esters ; 1,3-Dipolar cycloaddition ; Azomethine ylide ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The reaction of the hydrofluoroborate salt of an open-chain analogue of a Reissert compound with some α,β-ethylenic esters does not give a [4 + 2] cycloadduct, as previously described in the case of ethyl acrylate. The reaction starts with a 1,3-dipolar cycloaddition of a münchnone imine 5c, d. The [3 + 2] cycloadducts 13 evolve via a rearrangement-condensation sequence to give a substituted 2-pyridone derivative 18 or 19. The proposed mechanism has been verified by the isolation and structural X-ray analysis of some compounds of the reaction sequence.
    Additional Material: 5 Ill.
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  • 189
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    Liebigs Annalen 1999 (1999), S. 335-360 
    ISSN: 1434-193X
    Keywords: 2-tert-Butylhydropyrimidinones ; 3-Aminocarboxylic acid derivatives ; Cyclic imino esters ; Lithium enaminates ; Alkylations ; β-Amino acids ; Asymmetric synthesis ; Kinetic resolution ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Racemic and enantiopure 2-tert-butyltetrahydropyrimidinones (from pivalaldehyde and 3-aminocarboxylic acids) are converted to Alloc-, Boc-, and Z-protected cyclic imino esters (7-10, Schemes 2-4). These are deprotonated to Li enaminates (K, L). Reactions with electrophiles (prim., sec. alkyl, allyl, benzyl, propargyl halides, aldehydes, imines, enoates) give good yields and are highly diastereoselective (products 11-42, Schemes 5-10). A two-step cleavage (removal of protecting group and hydrolysis) under very mild conditions converts the heterocyclic products to α-branched β-amino acid methyl esters (43-61, Schemes 11-13). The structure of the products is determined by NMR spectroscopy (Figure 1), by chemical correlation (Scheme 14), and by X-ray analysis (Figure 2, 3, 7, Table 1). A structure of the Li enaminates is proposed (Figure 4). Mechanistic models are derived for the reactions occurring with formation of two stereogenic centers with relative topicity like (Figures 5, 6).
    Additional Material: 7 Ill.
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  • 190
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    Liebigs Annalen 1999 (1999), S. 373-378 
    ISSN: 1434-193X
    Keywords: Alkaloids ; Cross-coupling ; N-Heterocycles ; Palladium ; Synthesis design ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Thermal or acetyl chloride induced cyclization of bromoenamide 10 affords the pentacyclic derivative 12 with high yield and regioselectivity. From this common synthetic intermediate, palladium-catalyzed reactions allow the total synthesis of indolopyridine alkaloids 1-6.Supporting information for this article is available on the WWW under -http://www.wileY-Vch.de/contents/jc_2046/1999/98332_s.pdf or from the author.
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  • 191
    ISSN: 1434-193X
    Keywords: Reverse-turn mimics ; γ-Turns ; β-Turns ; β-Hairpins ; NMR spectroscopy ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The solid-phase synthesis and characterization of a series of peptides (3-9), containing reverse-turn mimetic bicyclic lactams (1a, 1b), was reported in the preceding paper. The bicyclic lactams (1a, 1b) possess high structural similarity to the two central residues of a β-turn. The conformational preferences of the constrained peptides have been investigated by NMR spectroscopy and IR spectroscopy. Our experimental results have been complemented by computer modelling studies and show that the constrained peptides (3-9) form an inverse γ-turn or a type-II′ β-turn through intramolecular hydrogen bonding, depending on the nature of the reverse-turn mimic. In N-acetylated tetrapeptide mimics incorporating the two different bicyclic lactams (a series and b series), H5 is available for either a γ-turn (7-membered ring with the carbonyl group of the bicyclic lactam) or a β-turn (10-membered ring with the carbonyl group of residue 2), as shown in Figures 7 and 9. The a series incorporating the (5,7)-bicyclic lactam predominantly induces the γ-turn conformation, while the b series incorporating the (5,6)-bicyclic lactam can promote either a γ-turn or a β-turn conformation, with the β-turn usually being preferred and with varying degrees of β-hairpin formation.
    Additional Material: 10 Ill.
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  • 192
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    Liebigs Annalen 1999 (1999), S. 409-417 
    ISSN: 1434-193X
    Keywords: Deprotonation ; Oxiranyloxazolines ; Oxazolinyloxiranyllithium compounds ; Oxazolidines ; Acyloxiranes ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Deprotonation of oxazolinyloxiranes 1a, 1h, and 1k with sBuLi/TMEDA at -100 °C in Et2O furnishes oxazolinyloxiranyllithium compounds[1]1b, 1i, and 1l which are stable at low temperature and can be trapped with electrophiles to give substituted oxiranes 1c-1g and 1j. The reaction of 1b with aldehydes produced diastereomers syn (2a-d) and anti (3a-d). Oxiranyllithium 1i from trans-1-(4,4-dimethyl-2-oxazolinyl)-2-p-tolylepoxyethane (1h) was found to be configurationally stable while oxiranyllithium 1l, generated from the cis isomer 1k, was not. Oxazolinylepoxides 1d, 1j, and 1m could be deblocked to acyloxiranes 5a-e through oxazolidines 4a-e.
    Additional Material: 2 Ill.
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  • 193
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    Liebigs Annalen 1999 (1999), S. 419-430 
    ISSN: 1434-193X
    Keywords: Electrochemistry ; Electrosynthesis ; Nitrosobenzenes ; Nitrogen heterocycles ; 1-Aminoindoles ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -An electrochemical methodology offering efficient access to N-alkyl- and N-aryl-substituted 1-aminoindoles has been developed. N-Substituted 2-(ortho-nitrosophenyl)ethylamines, electrogenerated in a “redox” flow cell, undergo intramolecular cyclization to hydrocinnoline-type intermediates. Under slightly basic conditions, these undergo spontaneous ring-contraction to produce the N-substituted heterocycles in good yields. The reactions have been studied in slightly acidic and slightly basic aqueous alcoholic media.
    Additional Material: 11 Ill.
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  • 194
    ISSN: 1434-193X
    Keywords: Aminoacylsilanes ; Amino aldehydes ; Amino alcohols ; Allylation ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -A practical route is described for the synthesis of enantiopure β- and γ-amino alcohols with two stereocenters, starting from homochiral α- (1 and 5) and β- (13 and 16) -aminoacylsilanes, and involving stereoselective addition of allylmetal compounds and subsequent stereospecific protiodesilylation of the adducts. The degree of diastereoselectivity achieved in the nucleophilic addition step depends on both the nitrogen-protecting group and the reagents used. Diastereomeric excess (de) values equal to or higher than 98% were obtained in the TiCl4-promoted allylation of the N-Pht-aminoacylsilanes 1 and 13 and of the N-Ts-aminoacylsilane 5 with allyltrimethylsilane. Lower de values were obtained in the Sc(OTf)3-catalyzed allylation of 5 with tetraallyltin and in the additions of both allyltrimethylsilane and tetraallyltin to the N-Ts-β-aminoacylsilane 16. Protiodesilylation of the adducts, leading to the β- and γ-amino alcohols, was accomplished with TBAF, except in the case of the adducts obtained from 5. For these, a preliminary removal of the tosyl group was necessary, which was accomplished with simultaneous desilylation by treatment with Na in liquid ammonia.Supporting information for this article is available on the WWW under -http://www.wileY-Vch.de/contents/jc_2046/1999/98342_s.pdf or from the author.
    Additional Material: 1 Tab.
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  • 195
    ISSN: 1434-193X
    Keywords: meta Photocycloaddition ; Photochemistry ; Steric hindrance ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Irradiation of a series of 5-(2-methoxyphenyl)pent-1-enes substituted with a hydroxy or trimethylsilyloxy group at the α-, β-, or γ-position of the side-chain yields in all cases meta photocycloadducts, in which the configuration at the substituted carbon atom is mainly endo. This indicates that the diastereoselectivity originates from minimization of steric interactions between the side-chain substituent and the ortho-methoxy group at the arene unit. Hydrogen bonding does not seem to be involved. The introduction of the side-chain substituents also influences the regioselectivity of the addition: The linear to angular adduct ratios are significantly increased compared to the case of the parent compound.
    Additional Material: 3 Tab.
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  • 196
    ISSN: 1434-193X
    Keywords: 5-Aza-7-deaza-2′-deoxyguanosine ; Oligonucleotides ; Parallel DNA ; Protonated base pairs ; Tm values ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Oligonucleotides containing 5-aza-7-deaza-2′-deoxyguanosine (1) were synthesized. Solid-phase synthesis was performed with the phosphonate 15 or the phosphoramidite 5. The amino-unprotected phosphonate 4 was also employed. Hybridization studies of oligonucleotides containing 1 resulted in new base pairs leading to duplexes with parallel (ps) or antiparallel (aps) chain orientation. Among those with parallel chains a stable “purine-purine” base pair was observed between 5-aza-7-deazaguanine and guanine or 7-deazaguanine. Antiparallel stranded duplexes are formed when 5-aza-7-deazaguanine pairs with cytosine. This base pair has only two hydrogen bonds under neutral conditions but is stabilized by a third one in acidic medium. A new base pair is also detected between the base of 1 and isoguanine (neutral medium).
    Additional Material: 1 Ill.
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  • 197
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    Liebigs Annalen 1999 (1999), S. 523-523 
    ISSN: 1434-193X
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -By mistake wrong concentrations were given in the footnote of Table 1 and in the Discussion. Instead of c0 = 1.2 M read c0 = 0.12 M if 2-naphthalenethiol was used as hydrogen donor and instead of c0 = 1.8 M read c0 = 0.18 M if Bu3SnH was used to trap photoproducts. In Table 2 relative rate constants of radical 2d refer to radical 2e and vice versa as correctly stated in the Discussion. In the Experimental Section (Iodocyclization) read 2.25 g (8.86 mmol) of iodine instead of 2.25 g (1.10 mmol) of iodine.
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  • 198
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    Liebigs Annalen 1999 (1999), S. 527-538 
    ISSN: 1434-193X
    Keywords: Tris(pentafluorophenyl)borane ; Diarylborinic acid ; Arylboronic acid ; Chiral arylboron catalyst ; Lewis acid ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Arylboron compounds, ArnB(OH)3-n (n = 1-3), bearing electron-withdrawing aromatic groups such as triarylboranes, diarylborinic acids, and arylboronic acids represent a new class of air-stable and water-tolerant Lewis acid or Brønsted acid catalysts in organic synthesis. In particular, while tris(pentafluorophenyl)borane has primarily been used as a co-catalyst in metallocene-mediated olefin polymerization, its potential as a Lewis acid catalyst for organic transformation is now much more extensive. Diarylborinic acids and arylboronic acids have shown themselves to be powerful tools in the design of chiral boron catalysts. This article provides a comprehensive summary of the organic transformations catalyzed by arylboron compounds as acids.
    Additional Material: 2 Ill.
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  • 199
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    Liebigs Annalen 1999 (1999), S. 573-577 
    ISSN: 1434-193X
    Keywords: Structure elucidation ; Constitutional analysis ; Natural products ; HMBC ; Computational chemistry ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The computer program COCON is introduced as a tool for the comprehensive structure elucidation of unknown organic compounds. In particular, structural proposals made on the basis of the molecular formula and of 2D-NMR experiments can be analyzed for the existence of alternative constitutions being in agreement with the same data set. The computational speed grounds on the evaluation of ambiguous long-range connectivity information during the process of structure generation. The data set experimentally obtained for the marine natural product oroidin (1) was selected, because proton-poor compounds usually cause uncertainties in NMR-based structure determinations. The calculation results encourage to move from the experience-based analysis of NMR chemical shifts or of MS fragmentations to the automated evaluation of routinely available connectivity information.Supporting information for this article is available on the WWW under -http://www.wileY-Vch.de/contents/jc_2046/1999/98241_s.pdf or from the author.
    Additional Material: 6 Ill.
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  • 200
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    Liebigs Annalen 1999 (1999), S. 587-595 
    ISSN: 1434-193X
    Keywords: Phosphaalkenes ; Heterodiphospholes ; Cycloadditions ; Phosphaalkyne cyclooligomers ; Phosphorus-carbon cage compounds ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The first synthesis of a 1,2,4-oxadiphosphole 6 has been achieved by vacuum thermolysis of mesitylphosphaalkene 5. The novel heterocycle 6 exhibits an enormous potential for cycloaddition reactions, which predominantly proceed selectively at low temperatures. Compound 6 undergoes addition with two equivalents of phosphaalkynes 10 by a [4+2] cycloaddition/homo Diels-Alder reaction sequence to form novel oxatetraphosphadeltacyclenes 12 and 13. Tetrachloro-o-benzoquinone (14) undergoes a selective [4+1] cycloaddition with 12 and 13 leading to the spirocyclic products 15 and 16 containing λ5-phosphorus atoms. Treatment of the oxadiphosphole 6 with dimethyl acetylenedicarboxylate (17) provides the first access to a 1,2-oxaphosphole 18, which is formed after an initial [4+2] cycloaddition followed by a retro Diels-Alder reaction. An unexpected reaction of 6 is observed with tri-tert-butylazete (20) furnishing a new polycyclic system (→ 21).
    Additional Material: 4 Ill.
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