[Perioperative care of patients with diastolic heart failure. Interface to anesthesia]. / Perioperative Betreuung von Patienten mit diastolischer Herzinsuffizienz. Schnittstelle zur Anästhesie.

Diastolic heart failure leads to an increase in perioperative morbidity and mortality. The prevalence of this disease is rising and multiple risk factors have already been identified. Besides higher age and female gender, arterial hypertension, diabetes mellitus and coronary artery disease in particular have to be considered. Clinical examination and laboratory analyses are important for preoperative evaluation; however, echocardiography plays the most important role in the diagnostics of diastolic heart failure. The transmitral flow profile can be used to differentiate the grades of diastolic dysfunction using the ratio between early passive ventricular filling (E) and late active filling due to atrial contraction (A). Data concerning the ideal anesthesia technique are for the most part lacking; however, the application of thoracic epidural anesthesia seems to be beneficial. A great deal of attention has to be paid to the intraoperative volume status of patients with diastolic dysfunction as hypovolemia and hypervolemia can both have detrimental effects. Arrhythmias and major changes in blood pressure put this special group of patients at additional risks.

A cross-language comparison of /d/-/th/ perception: evidence for a new developmental pattern.

Previous studies have shown that infants perceptually differentiate certain non-native contrasts at 6-8 months but not at 10-12 months of age, whereas differentiation is evident at both ages in infants for whom the test contrasts are native. These findings reveal a language-specific bias to be emerging during the first year of life. A developmental decline is not observed for all non-native contrasts, but it has been consistently reported for every contrast in which language effects are observed in adults, In the present study differentiation of English /d-th/ by English- and French-speaking adults and English- and French-learning infants at two ages (6-8 and 10-12 months) was compared using the conditioned headturn procedure. Two findings emerged. First, perceptual differentiation was unaffected by language experience in the first year of life, despite robust evidence of language effects in adulthood. Second, language experience had a facilitative effect on performance after 12 months, whereas performance remained unchanged in the absence of specific language experience. These data are clearly inconsistent with previous studies as well as predictions based on a conceptual framework proposed by Burnham [Appl. Psycholing. 7, 201-240 (1986)]. Factors contributing to these developmental patterns include the acoustic properties of /d-th/, the phonotactic uniqueness of English /th/, and the influence of lexical knowledge on phonetic processing.

Is a common grouping mechanism involved in the phenomena of illusory continuity and stream segregation?

Two auditory phenomena--stream segregation and illusory continuity through a wide-band noise interruption--were studied to determine whether the same principles of perceptual organization applied to both. A cycle was formed of a repeating alternation of two short bursts of narrow-band noise (NBN), one centered at a high frequency (H) and the other at a low frequency (L), with shorter bursts of wide-band noise (WBN) inserted between successive NBNs (H WBN L WBN H WBN...). In some conditions, listeners could hear a single NBN moving up and down behind the WBN bursts, although there was no NBN present with the WBN. Listeners rated the strength of this illusory continuity. Center frequency separation, rate of onsets, and bandwidth of the NBNs were varied. Increases in values of all three variables decreased illusory continuity. Other listeners rated the stream segregation of the H and L bands when successive NBNs were separated either by WBN bursts (as above) or by silences. The same three acoustic variables were manipulated. Increases in all three variables decreased the perception of a single stream. The similar disruptive effects on illusory continuity and on the one-stream percept in the stream segregation task support the idea that both phenomena depend on a common preliminary process of linking together the parts of a sequence that have similar frequencies.

Inhibitory properties of the regulatory domains of human protein kinase Calpha and mouse protein kinase Cepsilon.

Two fusion proteins in which the regulatory domains of human protein kinase Calpha (Ralpha; amino acids 1-270) or mouse protein kinase Cepsilon (Repsilon; amino acids 1-385) were linked in frame with glutathione S-transferase (GST) were examined for their abilities to inhibit the catalytic activities of protein kinase Calpha (PKCalpha) and other protein kinases in vitro. Both GST-Ralpha and GST-Repsilon but not GST itself potently inhibited the activities of lipid-activated rat brain PKCalpha. In contrast, the fusion proteins had little or no inhibitory effect on the activities of the Ser/Thr protein kinases cAMP-dependent protein kinase, cGMP-dependent protein kinase, casein kinase II, myosin light chain kinase, and mitogen activated protein kinase or on the src Tyr kinase. GST-Ralpha and GST-Repsilon, on a molar basis, were 100-200-fold more potent inhibitors of PKCalpha activity than was the pseudosubstrate peptide PKC19-36. In addition, a GST-Ralpha fusion protein in which the first 32 amino acids of Ralpha were deleted (including the pseudosubstrate sequence from amino acids 19-31) was an effective competitive inhibitor of PKCalpha activity. The three GST-R fusion proteins also inhibited protamine-activated PKCalpha and proteolytically activated PKCalpha (PKM), two lipid-independent forms of PKCalpha; however, the IC50 values for inhibition were 1 order of magnitude greater than the IC50 values obtained in the presence of lipid. These results suggest that part of the inhibitory effect of the GST-R fusion proteins on lipid-activated PKCalpha may have resulted from sequestration of lipid activators. Nonetheless, as evidenced by their abilities to inhibit the lipid-independent forms of the enzyme, the GST-R fusion proteins also inhibited PKCalpha catalytic activity through direct interactions. These data indicate that the R domains of PKCalpha and PKCepsilon are specific inhibitors of protein kinase Calpha activity and suggest that regions of the R domain outside the pseudosubstrate sequence contribute to autoinhibition of the enzyme.

Altered G protein activity in a desensitization-resistant mutant of the Y1 adrenocortical tumor cell line.

Mutant isolates [designated desensitization resistant (DR)] from the Y1 mouse adrenocortical tumor cell line resist agonist-induced desensitization of adenylyl cyclase by preventing the uncoupling of receptors from their guanyl nucleotide-binding regulatory G proteins. In this study, we tested the hypothesis that an underlying G protein defect is associated with the DR phenotype. We found that the G protein reagent guanyl-5'-yl imidodiphosphate [Gpp(NH)p] shifted beta2-adrenergic receptors from a high affinity state to a low affinity state 4-fold more effectively in mutant DR cells than in parent Y1 cells. In the DR mutant, Gpp(NH)p was able to shift receptors to a low affinity state in the absence of NaCl, whereas the effect of Gpp(NH)p in parent Y1 cells was dependent upon the presence of NaCl. Moreover, these differences in sensitivity to Gpp(NH)p and NaCl were transferred to Gs alpha-deficient S49(CYC-) lymphoma cell membranes in G protein reconstitution assays. These observations suggested that the DR mutation was associated with altered activity of the stimulatory G protein, Gs. Cloning and sequence analysis demonstrated that Gs alpha transcripts in the DR mutant were normal, suggesting that another factor involved in guanyl nucleotide exchange is responsible for the altered G protein activity in DR mutant cells.

Molecular strategies for the dominant inhibition of protein kinase C.

The regulatory (R) domain of PKC alpha fused to glutathione-S-transferase (GST-R alpha) competitively inhibited PKC activity associated with extracts of Y1 mouse adrenocortical tumor cells and the activities of several specific PKC isozymes. GST-R alpha did not inhibit the activities of cAMP-dependent protein kinase, cGMP-dependent protein kinase or calmodulin-dependent myosin light chain kinase. GST-R alpha inhibited PKC activities 20 times more potently than did a synthetic peptide corresponding to the pseudosubstrate sequence of PKC alpha. In intact yeast cells, the R domain prevented PKC beta-1-induced inhibition of growth and cytokinesis. These results indicate that the R domain of PKC alpha acts as a specific, dominant inhibitor of PKC activity, and suggest that the PKC alpha R domain may provide a useful genetic tool to assess the roles of PKC in various signal transduction processes.

Regulatory domain of human protein kinase C alpha dominantly inhibits protein kinase C beta-I-regulated growth and morphology in Saccharomyces cerevisiae.

This study demonstrates that the isolated regulatory (R) domain (amino acids 1-270) of human protein kinase C alpha (PKC alpha) is a potent inhibitor of PKC beta-I activity in a yeast expression system. The PKC alpha R domain fused to glutathione-S-transferase competitively inhibited the activity of yeast-expressed rat PKC beta-I in vitro (Ki = 0.2 microns) and was 400-fold more potent than a synthetic pseudosubstrate peptide corresponding to amino acids 19-36 from PKC alpha. In contrast, the fusion protein did not affect the activity of the purified catalytic subunit of cAMP-dependent protein kinase. The PKC alpha R domain (without glutathione-S-transferase [GST]) also was tested for its ability to inhibit PKC beta-I activity in vivo, in a yeast strain expressing rat PKC beta-I. Upon treatment with a PKC-activating phorbol ester, yeast cells expressing rat PKC beta-I were growth-inhibited and a fraction of the cells appeared as long chains. Coexpression of the R domain with rat PKC beta-I blocked the phorbol ester-induced inhibition of yeast cell growth and the phorbol ester-dependent alterations in yeast cell morphology. These results indicate that the R domain of PKC alpha acts as a dominant inhibitor of PKC activity in vivo and thus provides a useful genetic tool to assess the roles of PKC in various signal transduction processes.