Über die jahreszeitlich bedingten änderungen der Empfindlichkeit der Froschlunge gegenüber Acetylcholin

Zusammenfassung Die Empfindlichkeit des Froschlungenpräparates, das im Winter auf Acetylcholinkonzentrationen von 110¹⁶ und darunter anspricht, nimmt in den Sommermonaten um mehrere Zehnerpotenzen ab. Da für die Verwertung des Präparates zur Bestimmung derartig kleiner A.Ch.-Konzentrationen die genaue Kenntnis dieser Empfindlichkeitsänderung notwendig ist, wurde die Umstellung des Präparates während der Monate September und Oktober durch tägliche Versuche verfolgt. Es zeigte sich, daß die Umstellung im September beginnt, besonders rasch in der zweiten Oktoberhälfte fortschreitet und Ende Oktober bereits beendet ist. Dabei steigt die Kontraktionshöhe bei der A.Ch.-Konzentration 110⁴ auf das Doppelte, bei 110¹² auf das Zehnfache. Die Konzentration 110¹⁶, die im Sommer keine sichtbare Wirkung hatte, bewirkt noch eine Verkürzung der Lungen um fast 10%. Auch die Verhältniszahlen, d. h. das Verhältnis der Kontraktionshöhe einer A.Ch.-Konzentration 110^x zur Kontraktionshöhe auf einen Prüfreiz 110⁴, die im Sommer recht niedrig lagen, wuchsen stetig an. Die ursprüngliche Größe und Konstanz der Verhältniszahlen ist im letzten Drittel des Oktober wieder erreicht.     

Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells

Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners, and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation, especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into ‘neighborhoods’ comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning, neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular etiology of tumor-specific translocation patterns.     

Carriers for drugs and enzymes based on copolymers of allyl glycidyl ether with acrylamide

Copolymerization of acrylamide with allyl glycidyl ether yielded water soluble polymers containing an epoxy group; addition of a crosslinking agent, N,N′-methylenebis(acrylamide), to the copolymerization mixtures resulted in the formation of similar though water insoluble polymers. Condensation of a potent beta-adrenergic antagonist Alm? H, which contains a reactive amino group, with a polymer containing an epoxy group yeilded a pharmacologically active polymer. The polymer containing the epoxy group was also converted, by reaction with sodium thiosulfate and subsequent reduction, into a mecapto groups containing polymer which was also water soluble. The latter polymer was converted by condensation with a beta-adrenergic antagonist Alm? COCH₂Br, which contains a reactive bromoacetamido group, into a pharmacologically active polymer.     

Prolongation of small bowel allograft survival with a sequential therapy consisting of a synthetic MHC class II peptide and temporarily low-dose cyclosporine A

It has been extensively documented the role of the indirect pathway of allorecognition in allograft rejection. However, recent data demonstrate that the manipulation of this pathway could be also sufficient to promote prolongation of allograft survival. In the present study we evaluated the effect of preoperative immunization with the WF-specific MHC class II peptides RT1.D2 and RT1.B2 in combination with low-dose CsA from days 0 to 7 (5 mg/kg/day) and from days 8 to 30 (1 mg/kg/day) after WF small bowel transplantation. Seven days before and on the day of transplantation, LEW recipients were immunized with the two WF MHC class II peptides RT1.B2 and RT1.D2. The CsA monotherapy induced an allograft survival of 49.3 +/- 6.1 days. MHC class II peptide immunization had a limited effect on allograft survival for RT1.D2 (47.1 +/- 3.8 days) and induced prolongation of allograft survival for RT1.B2 (73.6 +/- 34.6 days). This effect seems to be based on the absence or silence of RT1.B2-reactive T cells and rejection seems to be correlated with the presence of RT1.B2-specific T cells in the late phase. Therefore, the combination of RT1.B2 with low-dose CsA shifts the immunological response and protects small bowel allograft rejection.     

Die Kultur von Tuberkelbacillen aus Larynxabstrichen

Ohne Zusammenfassung     

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.     

Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats

The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.     

Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage

ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2-/- mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascade.     

Our statistical programs in Excel

We prefer to use a spreadsheet program when teaching statistics. We have written several programs to cover the methods students use. The input data are typed in the spreadsheet MS Excel, we mark the data, and the program creates an output table. The outputs are both in Czech and English, they contain the basic results useful for students, various alternatives, test criteria, acceptance regions, and p-values. Since the programs are user-friendly, they make it easier on students.