A search for unknown blood-borne oncogenic viruses

In previous decades, infants who received blood transfusions shortly after birth or in utero might have been infected at a particularly vulnerable age by some blood-borne oncogen it virus. A cohort of such infants has therefore been followed into adult life to see if they suffered any excess of neoplastic disease or of non-neoplastic mortality. A total of 12,690 infants were identified who were transfused between 1 January 1942 and 31 December 1970, in most cases for the prevention or treatment of haemolytic disease of the newborn. All but 361 (2.8%) were found to have been registered with a National Health Service (NHS) practitioner and were followed in the NHS central records until they died, emigrated, were removed from NHS lists or until 1 January 1992, whichever occurred first. Mortality and cancer incidence were compared with that expected from national rates. No marked disparity was observed and there was no excess of childhood leukaemia. The incidence of non-Hodgkin's lymphoma at 15 to 49 years of age was about twice that expected, but the excess was not statistically significant.     

Das Heidelberger Seminar „Invasive Notfalltechniken“ (INTECH) 2001–2004

Prehospital emergency medicine in Germany is based on a specially trained physician-staffed system, in order to realize a differentiate therapy at the scene. In the last years, the special education and the qualification were more and more discussed after the determination of deficits in the prehospital management of special emergency situations. In the presented paper we described the concept and organization of a practice-oriented training model of invasive emergency techniques, as like as the emergency cricothyrotomy, the thoracic tube and the intraosseous access. The relevance and the efficacy are discussed based on an evaluation of the participants. Practice-oriented training models seem to be adequate instruments in order to close the leak in educational programs and can help to improve the qualification of the physician-staffed system, generally.     

Maturation of executive function in autism.

BACKGROUND: Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. METHODS: 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. CONCLUSIONS: These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.     

Epidemiology and the prevention of cancer: some recent developments

The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author. The Editors     

The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome

The Williams-Beuren syndrome (WBS) is a complex developmental disorder with multisystemic manifestations including supravalvular aortic stenosis (SVAS), a so-called elfin face, a hoarse voice, and a specific cognitive phenotype. Most WBS patients have a >1 Mb deletion on one of their chromosomes 7 in q11 but except for elastin, whose haploinsufficiency causes the cardiovascular malformations, it is unknown which genes in the deletion area contribute to the phenotype. We have investigated a family with a cytogenetically balanced translocation t(7;16)(q11.23;q13) in which affected individuals manifested a broad spectrum of clinical phenotypes ranging from a hoarse voice as the only feature to the full WBS phenotype. Molecular cytogenetic and DNA sequence analyses of the translocation breakpoint showed that the cytogenetic rearrangement disrupts the elastin gene locus within intron 5 in the exact same manner in all translocation carriers. The recently described large inversion of the 7q11.23 region was not present in this family. Our data demonstrate that disruption of the elastin gene by a translocation breakpoint may cause classical WBS, atypical WBS, SVAS, or no recognisable phenotype, and provide a clear example for extensive phenotypic variability associated with a position effect in humans.     

Fast implementation of the single scatter simulation algorithm and its use in iterative image reconstruction of PET data

In positron emission tomography (PET), scatter correction is usually performed prior to image reconstruction using a more or less exact model of the scatter processes. These models require estimates of the true activity and object density distributions of the imaged object. The problem is that these estimates are computed from measured data and, therefore, already contain scattered events. The purpose of this work was to overcome this problem by incorporating scatter characteristics directly into the process of iterative image reconstruction. This could be achieved by an optimized implementation of the single scatter simulation (SSS) algorithm, which results in a significant speed-up of the scatter estimation procedure. The scatter simulation was then included in the forward projection step of maximum likelihood image reconstruction. The results demonstrate that this approach leads to a more exact estimation of the scatter component which cannot be obtained by a simple sequential data processing strategy.     

Serine/threonine protein phosphatases and synaptic inhibition regulate the expression of cholinergic-dependent plateau potentials

We previously identified cholinergic-dependent plateau potentials (PPs) in CA1 pyramidal neurons that were intrinsically generated by interplay between voltage-gated calcium entry and a Ca(2+)-activated nonselective cation conductance. In the present study, we examined both the second-messenger pathway and the role of synaptic inhibition in the expression of PPs. The stimulation of m1/m3 cholinergic receptor subtypes and G-proteins were critical for activating PPs because selective receptor antagonists (pirenzepine, hexahydro-sila-difenidol hydrochloride, 4-diphenylacetoxy-N-methylpiperidine methiodide) and intracellular guanosine-5'-O-(2-thiodiphosphate) prevented PP generation in carbachol. Intense synaptic stimulation occasionally activated PPs in the presence of oxytremorine M, a cholinergic agonist with preference for m1/m3 receptors. PPs were consistently activated by synaptic stimulation only when oxytremorine M was combined with antagonists at both GABA(A) and GABA(B) receptors. These latter data indicate an important role for synaptic inhibition in preventing PP generation. Both intrinsically generated and synaptically activated PPs could not be elicited following inhibition of serine/threonine protein phosphatases by calyculin A, okadaic acid, or microcystin-L, suggesting that muscarinic-induced dephosphorylation is necessary for PP generation. PP genesis was also inhibited following irreversible thiophosphorylation by intracellular perfusion with ATP-gamma-S. These data indicate that the expression of cholinergic-dependent PPs requires protein phosphatase-induced dephosphorylation via G-protein-linked m1/m3 receptor(s). Moreover, synaptic inhibition via both GABA(A) and GABA(B) receptors normally prevents the synaptic activation of PPs. Understanding the regulation of PPs should provide clues to the role of this regenerative potential in both normal activity and pathophysiological processes such as epilepsy.     

The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures

The active derivative of vitamin A, retinoic acid (RA), is essential for normal embryonic development. The spatio-temporal distribution of embryonic RA results from regulated expression of RA-synthesizing retinaldehyde dehydrogenases and RA-metabolizing cytochrome P450s (CYP26). Excess RA administration or RA deficiency results in a complex spectrum of embryonic abnormalities. As a first step in understanding the developmental function of RA-metabolizing enzymes, we have disrupted the murine Cyp26A1 gene. We report that Cyp26A1-null mutants die during mid-late gestation and show a number of major morphogenetic defects. Spina bifida and truncation of the tail and lumbosacral region (including abnormalities of the kidneys, urogenital tract, and hindgut) are the most conspicuous defects, leading in extreme cases to a sirenomelia ("mermaid tail") phenotype. Cyp26A1 mutants also show posterior transformations of cervical vertebrae and abnormal patterning of the rostral hindbrain, which appears to be partially posteriorly transformed. These defects correlate with two major sites of Cyp26A1 expression in the rostral neural plate and embryonic tail bud. Because all of the Cyp26A1(-/-) abnormalities closely resemble RA teratogenic effects, we postulate that the key function of CYP26A1 is to maintain specific embryonic areas in a RA-depleted state, to protect them against the deleterious effect of ectopic RA signaling.     

Zum Stoffwechsel des Skeletmuskels

Zusammenfassung 1. Bei zwölf Hochleistungssportlern wurden in Ruhe, während Fahrradergometerarbeit und in der Erholungsphase Sauerstoffdruck, Kohlensäuredruck, pH, Standardbicarbonat und base excess im vorwiegend aus der arbeitenden Muskulatur stammenden Blut und im Arterienblut gemessen. Die erhaltenen Werte werden mit entsprechenden, bei untrainierten Personen gewonnenen Daten verglichen.2. Weder von den Trainierten noch von den Untrainierten wird bei maximaler Belastung der venöse kritische Sauerstoffdruck erreicht. Dies geht nicht nur aus den während Höchstbelastung gewonnenen Daten für den femoralvenösen O₂-Druck hervor, sondern auch aus dem Verhalten des Quotienten Lactat/Pyruvat.3. Die Dauerleistung des Trainierten wird in Meereshöhe wahrscheinlich nicht von der O₂-Versorgung des Muskelgewebes oder durch die Ansäuerung des Blutes bzw. des Gewebes begrenzt.4. Die Abnahme des venösen O₂-Druckes während Belastung ist nicht die Ursache einer vermehrten Lactatabgabe, welche bei den Untrainierten früher und ausgeprägter erfolgt als bei Trainierten. Vielmehr scheint sie die Folge einer begrenzten oxydativen Zelleistung zu sein.5. Folgende, beim Sportler gegenüber Untrainierten unterschiedlichen Befunde sprechen dafür, daß beim Trainierten während Belastung eine gegenüber dem Untrainierten erhöhte Muskeldurchblutung auftritt, welche für die Dauerleistung von Bedeutung sein dürfte: Während geringer Belastung sinkt P o _20076-0304 beim Sportler nur wenig ab. Eine Belastung von 200 W stellt für den Untrainierten eine maximale, für den Trainierten erst eine submaximale Arbeit dar. Bei beiden Gruppen beträgt hierbei der femoralvenöse O₂-Druck etwa 21 mm Hg. Ohne daß P o _20076-0304 noch wesentlich absinkt, vermag der Trainierte seine Leistung noch weiter auf 300 W zu steigern, was nicht allein mit der pH-bedingten und einer temperaturabhängigen Rechtsverschiebung der O₂-Dissoziationskurve erklärt werden kann.6. Nur im arteriellen Blut wird pH während Belastung vorwiegend durch die anfallende Milchsäure bestimmt. Dagegen ist pH_20076-0304 außerdem wesentlich vom CO₂-Druck abhängig. Sportler zeigen unter Maximalbelastung weder im arteriellen noch im femoralvenösen Blut niedrigere pH-Werte als nicht trainierte Personen. Eine stärkere Säuerung des Gewebes während maximaler Arbeit oder gar eine erhöhte Säureverträglichkeit des Gewebes als Trainingseffekt ist daher unwahrscheinlich.Mit Unterstützung durch die Deutsche Forschungsgemeinschaft und das Kuratorium für Sportmedizinische Forschung.