An analytical solution for the SSFP signal in MRI.

Among previous analyses of the steady-state free-precession (SSFP) signal in rapid MRI, one treatment resulted in equations that require the evaluation of infinite binomial series. Here, an analytical solution is derived by a transformation into the power series expansion of the derivative of the inverse sine function, which is essentially a root. The treatment is extended to include higher-order signals. The results demonstrate the identity of the vastly different equations for the SSFP signals reported so far. Applications consist of the derivation of closed expressions for the signal in echo-shifted MRI and a corresponding analysis of TrueFISP sequences.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute G_i/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca²⁺/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

Effect of Ethanol and Stress on Plasma Catecholamines and Their Relation to Changes in Emotional State and Performance

The "tension reduction hypothesis" of ethanol was investigated with respect to stress- and ethanol-induced changes of plasma catecholamines and their relations to changes in emotional state and performance. Twenty-two healthy male volunteers were tested under the influence of 0.8 g/kg ethanol and compared to 22 matched controls receiving a placebo drink. Stress was induced by mental arithmetic applied prior to and 45 min after fluid consumption. Plasma epinephrine (E) and norepinephrine (NE) obtained from an indwelling cannula inserted 50 min prior to stress application were determined prior to and after each stress session. Percentage changes were compared within and between groups and correlated with respective changes of emotional states and performance in mental arithmetic. While ethanol decreased performance and stress-related emotional arousal, it did not affect stress-induced changes in plasma catecholamines. Rather, the fluid (ethanol as well as placebo) increased NE levels. Emotional tension reduction was associated with low resting or average levels of E in the placebo group but this relationship was disrupted by ethanol. High NE resting levels and drink induced increases predicted emotional tension reduction with placebo but an increase in stress induced depression with alcohol. "Biochemical tension reduction" (represented by both reduced E and NE stress response) may be predicted from generally lower levels of activation and elation by alcohol but not with the placebo condition. Although performance was positively related to low NE resting levels and stress responses, no influence of alcohol on this relationship was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ethanol on plasma amino acids and related compounds of stressed male rats

Plasma amino acid levels in rats are known to be affected by ethanol or by immobilization stress. This paper investigated the effect of ethanol on plasma amino acid levels of stressed rats. Rats received ethanol (2 g/kg, IP) 15 minutes prior to a 30-min immobilization period. Blood samples were obtained from individual rats before, during and after stress. Ethanol lowered the concentration of most plasma amino acids (AA) or related compounds in stressed rats (e.g., aspartic acid, threonine, serine, glycine, alanine, valine, tyrosine, phenylalanine, tryptophan). Some compounds remained unaffected (e.g., taurine, cystine, ethanolamine and methylhistidines) and one (phosphoethanolamine) increased initially. A comparison of the effects of ethanol on plasma AA and related compounds in resting and stressed rats shows similarities and differences. In general, ethanol tends to change the concentrations of these compounds away from normal levels in nonstressed rats, whereas in stressed rats, ethanol tends to antagonize stress-induced changes. This study shows that ethanol can affect individual AA and related compounds differently in nonstressed and stressed rats and that ethanol reduces stress-induced changes. The latter finding supports the "tension-reduction hypothesis" of ethanol.     

Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks,chromosomal instability,and reduced life span in mice

The Brca2 tumor-suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51-interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51-interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2(lex1)) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2(lex1) mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2(lex1) mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy-terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51.     

Über funktionelle Unterschiede zwischen Dünn-und Dickdarm—dargestellt an den verschiedenen Reaktionen der Darmschleimhaut bei Angebot von Lösungen nicht penetrabler Solute und steigender Osmolarität

Zusammenfassung Bei Instillation von Mannitlösungen steigender Osmolarität in durchblutete, in situ belassene Jejunum- und Colonschlingen von Ratten reagieren beide Darmabschnitte unterschiedlich.Während die durch Enterosorption binnen 30 min in das Jejunum gelangte Flüssigkeitsmenge 250% des Instillats ausmacht, beträgt der analoge Wert beim Colon nur 100%. Die enterosorbierten Mengen an Na⁺, Cl^– und Urea sind im Jejunum wesentlich größer als im Colon, da nicht nur die enterosorbierte Flüssigkeitsmenge größer ist, sondern weil auch die intraintestinalen Konzentrationen höher liegen.Zwischen den Ca⁺⁺-Konzentrationen im Jejunum und Colon bestehen keine Unterschiede, die K⁺-Konzentration ist im Colon höher. Bei Berücksichtigung der Wasserbewegungen ist die enterosorbierte Ca⁺⁺-Menge im Jejunum, die K⁺-Menge dagegen im Colon größer.Während der Versuchszeit — 30 min — erfolgt im Jejunum ein osmolarer Konzentrationsausgleich aller Lösungen mit dem Plasma, deren Konzentration kleiner als die 1,66 fache Blutisotonie ist. Im Colon stellt sich dieser Ausgleich auch für eine Lösung von 1,33 facher Blutisotonie nicht mehr ein.Die Colonschleimhaut verhält sich demnach so, als ob hier die Exsorption von Wasser, Na⁺, Cl^–, Ca⁺⁺ und Urea wesentlich stärker behindert wäre als die durch die Schleimhaut des Jejunums.Instillation großer Volumina stark hypertoner (ca. 2000 mOsmol/l) Lösungen, deren Solute nur schwer absorbiert werden können, führen zu einem so großen Einstrom von Blut- und Körperflüssigkeit in den Intestinaltrakt, daß Ratten in schwerer Exsiccose sterben. Dabei steigt der Anteil von Zellen am Blutvolumen von 48% auf 68% der Wassergehalt der geprüften Gewebe — quergestreifte und Herzmuskulatur, Gehirn — sinkt ab.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Unterschiedliche Flüssigkeits- und Substanzbewegungen durch die Mucosa der verschiedenen Abschnitte des Intestinaltraktes beim Kaninchen

Zusammenfassung Die Schleimhaut des Duodenums beim Kaninchen sezerniert eine blutisotone Flüssigkeit, deren Hauptcharakteristikum ihr HCO₃ ^–-Gehalt von fast 100 mMol/l ist. Auf die Instillation einer Lösung, die wie das duodenale Sekret zusammengesetzt ist, reagiert das Jejunum mit einer isotonen Absorption bei nur geringfügigen Konzentrationsänderungen der Konstituenten der Instillationslösung. Das Ileum reagiert analog dem Jejunum, nur sind die Absorptionsraten für Flüssigkeit und die geprüften Solute größer als im Jejunum. Im Colon kommt es zu einer Enterosorption von Flüssigkeit mit teilweise beträchtlichen Konzentrationserniedrigungen der in der Installationslösung enthaltenen Solute.Auf die Instillation einer blutisotonen NaCl-Lösung reagiert das Jejunum stets mit einer Absorption von Flüssigkeit. Na⁺ und Cl^– werden absorbiert, während HCO₃ ^–, K⁺ und Harnstoff netto sezerniert werden. Im Colon kommt es unter den Bedingungen des 30 min-Versuches zur enterosorption von Flüssigkeit, zur Absorption von osmotisch aktivem Material, Na⁺ und Cl^–, während HCO₃ ^–, K⁺ und Harnstoff sezerniert werden.Auf die Instillation reinen Wassers reagiert das Jejunum mit einer Absorption von Flüssigkeit sowie einer Enterosorption aller geprüften Solute in das Jejunum hinein, daß fast Konzentrationsgleichheit mit dem Plasma eingestellt wird. Im Colon kommt es im 30 min-Versuch teils zur Enterosorption, teils zur Absorption von Flüssigkeit. Nach 60 min wird in allen Fällen eine Absorption von Flüssigkeit beobachtet. Die Gleichgewichtskonzentrationen im Jejunum sind: Osmolarität 296,0 mOsmol/l, Na⁺ 78,6 mMol/l, Cl^– 24,6 mMol/l, HCO₃ ^– 54,8 mMol/l, K⁺ 2,2 mMol/l, Harnstoff 59,9 mg/100 ml. Die analogen Werte für das Colon lauten: Osmolarität 184,0 mOsmol/l, Na⁺ 11,6 mMol/l, Cl^– 12,9 mMol/l, HCO₃ ^– 25,9 mMol/l, K⁺ 16,4 mMol/l, Harnstoff 18,8 mg/100 ml.