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R Hoffmann

Publications and source records attributed to R Hoffmann.

At least 217 records · Page 12Linked to original sources
PubMed1997

Interleukin-1beta-induced inhibition of hair growth in vitro is mediated by cyclic AMP.

Interleukin (IL)-1 has been shown to be a potent inhibitor of hair growth in vitro. We hypothesized that this cytokine might be a decisive factor causing hair loss during the lymphocytic attack in alopecia areata. Neither the intracellular pathways involved in hair growth inhibition mediated by IL-1beta nor the signal transduction processes within hair follicles in general are known. We therefore investigated the intracellular signals involved in human hair growth in vitro. Hair follicles were isolated from scalp biopsies by microdissection, and hair growth was measured daily by image analysis. We assessed intracellular signal transducing elements using specific inhibitors or activators either alone or in combination with IL-1beta. The calcium ionophore A 23187 induced a rapid and complete arrest of hair growth, and phorbol-12-myristate-13-acetate (PMA), genistein, or IL-1beta decreased hair growth by approximately 60%-80%. IL-1beta-elicited hair growth arrest was not antagonized by calphostin C, a specific inhibitor of protein kinase C. In contrast, coincubation of IL-1beta with pertussis toxin or H 1004 neutralized the effect of IL-1beta, and dibutyryl-cAMP and cholera toxin, an activator of adenylate cyclase, inhibited hair growth. These data suggest that cAMP acts as a second messenger for IL-1beta-induced inhibition of hair growth. Moreover, our data indicate that in vitro hair growth is dependent on intracellular Ca2+ levels and activation of tyrosine kinase as well as protein kinase C. We were unable to detect a signal transducing element responsible for enhanced hair growth in vitro.

Calcimycin↗
PubMed1997

Synthesis and NMR spectroscopy of peptides containing either phosphorylated or phosphonylated cis- or trans-4-hydroxy-L-proline.

Many proteins are regulated by reversible O-glycosylation and O-phosphorylation. Whereas O-glycosylation of hydroxy-L-proline is common and well investigated, phosphorylation has not been proved so far in vivo, but this post-translational modification is entirely possible. As a first step to identify this phosphoamino acid, we describe both the syntheses of peptides phosphorylated at 4-hydroxy-L-proline and the 1H and 31P NMR parameters of these phosphopeptides. The model peptides were synthesized on solid-phase using Fmoc-strategy. Both natural isomers of 4-hydroxy-L-proline (containing the hydroxyl group in either the cis or trans position) were introduced without side-chain protection. All peptides were globally phosphorylated with O,O'-tert-butyl-N,N-diethylphosphoramidite on the solid phase and cleaved with trifluoroacetic acid. Additionally, we synthesized two classes of phosphonopeptides that mimic phosphopeptides, namely H- and methylphosphonopeptides. The NMR data were based on the model peptide Gly-Gly-Hyp-Ala, which is regarded as a typical random-coil sequence. The NMR parameters showed a significant influence of the phosphate group on the cis-trans isomerization of the Gly-Hyp bond, which may reflect a possible regulation of proteins by changing their local conformations. The 1H and 31P NMR parameters differed for each isomer, and were distinct from the parameters of phosphorylated serine, threonine and tyrosine. These known shifts can be used to identify both cis- and trans-O-phospho-4-hydroxy-L-proline in vivo.

Chromatography, High Pressure Liquid↗
PubMed1997

Oxidized and phosphorylated synthetic peptides corresponding to the second and third tubulin-binding repeats of the tau protein reveal structural features of paired helical filament assembly.

The microtubule-associated protein tau of normal brains is attached to tubulin through its 18-amino-acid repeat units. In the paired helical filaments (PHF) of Alzheimer's disease, however, tau is oligomerized in an abnormally hyperphosphorylated from (PHF-tau). tau contains two cysteine residues in repeat units 2 and 3, but only the R3-R3 homodimer is present in PHF-tau. A serine residue two amino acids downstream of the R3 cysteine is a major phosphate acceptor site for protein kinase C. In the work repeated here, we used synthetic peptides corresponding to R2, R3 and phosphorylated R3 to determine the binding of the tau repeat peptides to a peptide fragment corresponding to the C-terminal domain of beta-tubulin and to study the kinetics of homo- and heterodimer formation. Additionally, we studied two major biochemical properties of the peptides that distinguish between normal tau and PHF-tau: conformation and metabolic stability. All R2 and R3 peptides bound specifically to the tubulin peptide regardless of the state of phosphorylation or dimerization. The reverse-turn conformation of the tau repeat peptides in the presence of the tubulin peptide remained unaffected. Phosphorylation slightly loosened the turn structure of the monomeric and dimeric peptides, and did not univocally affect the serum stability of the peptides or the ability of the peptides to form dimers. The isolated R2 and R3 units formed homodimers approximately in the same rate. When the two peptides were mixed, however, the R2-R3 heterodimer was formed preferentially over the homodimers. The dimers were generally more stable in human serum than the monomers. Our results with the synthetic peptide fragments of tau indicate that neither oxidation nor phosphorylation of the repeat units is able to generate extended structure such as that found in PHF-tau. Additionally, phosphorylation of Ser324 does not appear to modulate the kinetics of oligomerization of tau, and in general biochemistry terms, does not affect disulfide bridge formation nearby. In agreement with studies at the full-protein level, the formation of homodimers of the peptides, a model of the self-association of tau, is not preferred. If the dimers are formed, however, their clearance is considerably slower than that of the monomers, explaining the remarkable protease resistance of PHF-tau in the affected brains.

Alzheimer Disease↗
PubMed1997

Fastest reduction of posttraumatic edema: continuous cryotherapy or intermittent impulse compression?

Sixty patients with foot or ankle trauma were randomized and treated in three groups. In intermittent impulse compression, an air pad under the foot was inflated every 20 seconds, thus activating the venous foot pump. In continuous cryotherapy, ice water circulates between the ice box and the cold pad. The ice water was changed once per day. In standard therapy, the injured extremity was treated with cool packs, which were changed 4 times per day. Beginning at admission, every 24 hours the circumference was measured around the ankle, midfoot, and forefoot. After 24 hours of treatment, there was a 47% reduction in swelling with the A-V impulse System, 33% with continuous cryotherapy, and 17% with cool packs. After 4 days of postoperative treatment, the A-V impulse System reduced the swelling by 74% versus 70% with continuous cryotherapy and 45% with cool packs. Both new methods are preferable to cool packs. Because of the better preoperative results, the A-V impulse System proved to be the most effective device.

Adult↗
PubMed1997

Phorbol-myristate-acetate, but not interleukin-1 beta or insulin-like growth factor-I, regulates protein kinase C isoenzymes in human dermal papilla cells.

The in vitro growth of human hair follicles is inhibited by interleukin (IL)-1 beta and phorbol esters, such as phorbol-myristate-acetate (PMA), but enhanced by insulin-like growth factor (IGF)-I. Although this process is only incompletely understood, the dermal papilla as a pivotal part of the hair follicle is almost certainly involved. Since protein kinase C (PKC) isoenzymes are activated by phorbol esters and are key enzymes in signalling pathways of several hormones, neurotransmitters, and growth factors, we addressed the question whether the action of the above-mentioned hair growth-modulating substances may affect PKC isoenzymes in cultured dermal papilla cells (DPC). By Western blot analysis, protein kinase C alpha, -epsilon, -gamma, -iota, -lambda, and the RACK1 receptor protein were detected in dermal papilla cell cultures, whereas the isoenzymes delta and mu were expressed only at low levels and protein kinase C-beta, -theta, and -zeta, were not present. After PMA stimulation, the PKC alpha, -epsilon, and -gamma were translocated from the cytosol to the membrane fraction and subsequently down-regulated. PKC iota was down-regulated but not translocated, and PKC lambda and RACK1 were not affected by PMA. Neither, IL-1 beta nor IGF had an effect on PKC or RACK1 expression. We conclude that cultured DPC express a distinct PKC isoenzyme pattern and that the PMA-induced growth arrest in cultivated hair follicles may be transmitted via protein kinases, whereas the effects of IL-1 beta or IGF may be transduced via other signal transduction pathways or other cell types.

Blotting, Western↗
PubMed1997

Neurotrophin-3- and norepinephrine-mediated adrenergic differentiation and the inhibitory action of desipramine and cocaine.

In the presence of neurotrophin-3 (NT-3), high-affinity norepinephrine (NE) uptake by quail neural crest cells was significantly increased as judged by in vitro colony assay of adrenergic differentiation. In the presence of the related neurotrophins nerve growth factor (NGF) or brain-derived neurotrophic (BDNF) factor, or of basic fibroblast growth factor (bFGF), there were no significant changes. When NE was added to the culture medium in addition to NT-3, more colonies contained dopamine-beta-hydroxylase (DBH)-immunoreactive cells, an enzyme that is characteristic for adrenergic cells. The NE-mediated increase in the portion of colonies that contained DBH-immunoreactive cells was prevented by the tricyclic antidepressant desipramine (DMI) and by cocaine, two types of drug that block cellular transport of NE. To further examine whether NE acts via uptake, colony assays were performed in the presence and absence of adrenergic antagonists and agonists. These would be expected to mimic the DMI and NE effects, respectively, if the mechanism of action involved activation of adrenergic autoreceptors. Neither class of drug showed a detectable effect within a wide range of concentrations. Immunocytochemistry using antibodies against beta 1 and beta 2 adrenergic receptors further supported the notion that DMI action and beta-receptor expression are not causally related. Ratio imaging was subsequently used in an attempt to elucidate the mechanism of NE action. Within a few minutes of addition of NE to the culture medium, there was an increase in intracellular free calcium in a subset of neural crest cells. Taken together, our data indicate that NT-3 is involved in the appearance of the NE transporter (NET) during embryonic development; internalized NE directly or indirectly increases adrenergic differentiation as measured by immunoreactivity of the adrenergic biosynthetic enzyme DBH; and norepinephrine uptake inhibitors have treatogenic potential.

Adrenergic Uptake Inhibitors↗
PubMed1997

[Pain in the breeding of fish].

Excessive breeding leading to suffering in animals only exists in ornamental fish, especially in gold fish or poecillids. These varieties are physically handicapped in locomotion, feeding and/or reproduction in comparisation to wild fish.

Animals↗
PubMed1996

Chronic arterial responses to stent implantation: a serial intravascular ultrasound analysis of Palmaz-Schatz stents in native coronary arteries.

OBJECTIVES: We used intravascular ultrasound (IVUS) imaging to evaluate the chronic vessel responses to Palmaz-Schatz stents. BACKGROUND: Palmaz-Schatz stents have been shown to inhibit early elastic recoil and late arterial remodeling while triggering neointimal hyperplasia. However, changes occurring in native vessels surrounding stent struts have not been well studied. METHODS: Postintervention and follow-up (mean [+/-SD] 5.4 +/- 3.8 months) serial IVUS imaging was performed in 25 stents without restenosis and 24 with in-stent restenosis. Intravascular ultrasound imaging using automatic transducer pullback at 0.5 mm/s allowed measurement at 1-mm axial increments of external elastic membrane (EEM), stent and lumen cross-sectional areas (CSAs) and calculation of peristent plaque plus media (P + M = EEM - stent) CSA, intrastent plaque (stent-lumen) CSA, arterial remodeling (delta EEM CSA), tissue growth outside the stent (delta P + M CSA) and tissue growth within the stent (delta stent-lumen CSA). Volumes were calculated using the Simpson rule. RESULTS: Mean EEM CSA increased significantly from 16.9 +/- 5.0 mm2 after intervention to 18.4 +/- 4.9 mm2 at follow-up (p < 0.0001), reflecting an increase in P + M CSA surrounding the stent (1.6 +/- 1.3 mm2). Greater tissue growth within the stent (2.4 +/- 2.2 mm2) correlated weakly, but directly with tissue growth surrounding the stent (r = 0.356, p = 0.0121). The ratio of peristent/intrastent tissue growth correlated weakly with arterial remodeling (r = 0.282, p = 0.0525). Restenotic stents had more tissue growth both within and surrounding the stent than did nonrestenotic stents. Volumetric measurements, which could be obtained in 15 lesions, showed similar results. CONCLUSIONS: After implantation there is a chronic increase in plaque mass both within and surrounding the stents. The increase in peristent plaque mass is associated with adaptive remodeling.

Aged↗
PubMed1996

Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study.

BACKGROUND: Studies have suggested that restenosis within Palmaz-Schatz stents results from neointimal hyperplasia or chronic stent recoil and occurs more frequently at the articulation. METHODS AND RESULTS: Serial intravascular ultrasound (IVUS) was performed after intervention and at follow-up in 142 stents in 115 lesions. IVUS measurements (external elastic membrane [EEM], stent, and lumen cross-sectional areas [CSAs] and diameters) were performed, and plaque CSA (EEM lumen in reference segments and stent lumen in stented segments), late lumen loss (delta lumen), remodeling (delta EEM in reference segments and delta stent in stented segments), and tissue growth (delta plaque) were calculated. After intervention, the lumen tended to be smallest at the articulation because of tissue prolapse. At follow-up, tissue growth was uniformly distributed throughout the stent; the tendency for greater neointimal tissue accumulation at the central articulation reached statistical significance only when normalized for the smaller postintervention lumen CSA. In stented segments, late lumen area loss correlated strongly with tissue growth but only weakly with remodeling. Stents affected adjacent vessel segments; remodeling progressively increased and tissue growth progressively decreased at distances from the edge of the stent. These findings were similar in native arteries and saphenous vein grafts and in lesions treated with one or two stents. There was no difference in the postintervention or follow-up lumen (at the junction of the two stents) when overlapped were compared with nonoverlapped stents. CONCLUSIONS: Late lumen loss and in-stent restenosis were the result of neointimal tissue proliferation, which tended to be uniformly distributed over the length of the stent.

Aged↗
PubMed1996

Serum levels and in situ expression of TNF-alpha and TNF-alpha binding proteins in inflammatory liver diseases.

Cells respond to tumour necrosis factor-alpha (TNF-alpha) via binding to 75-kDa (type A) and 55-kDa (type B) receptors which have different intracellular signalling pathways and can also circulate as soluble molecules. Both receptors are co-expressed in many tissues, but their relative contributions to cellular TNF responses is for most situations unknown. In patients with viral and non-viral inflammatory liver diseases serum TNF-alpha was determined by an immunoenzymetric assay and soluble type A and B TNF receptors (TNF-alpha r) by enzyme-linked immunological and biological assays (ELIBA). In addition, cellular expression of TNF and its binding proteins were studied in liver biopsies by an indirect immunoperoxidase technique. Secretion of TNF-alpha and upregulation of TNF-alpha r-A were particularly prominent in viral hepatitis. Strong TNF-alpha in-situ production by mononuclear cells could be demonstrated in liver biopsies from patients with acute viral hepatitis. However, TNF-alpha r-A was detected only on hepatocytes. Serum TNF-alpha r-A was elevated two-fold in relative abundance over TNF-alpha r-B and was correlated to serum TNF-alpha (r = 0.6464, P < 0.0001). Soluble TNF-alpha r levels normalized, when the viral hepatitis was cleared, and successful therapy of hepatitis B was associated with a temporary rise of TNF-alpha r-A during the initial flare of aminotransferase. Patients with alcoholic hepatitis had also evidence of TNF-alpha activation but clearly differed from patients with viral induced liver diseases: Soluble TNF-alpha r-A and TNF-alpha r-B were highly elevated in equal proportions. In situ analysis in liver biopsies revealed a distinctive pattern of TNF-alpha r expression with strong cytoplasmic staining for both TNF-alpha r-A and B on scattered hepatocytes in addition to infiltrating mononuclear cells. The data propose that TNF release during antiviral immune responses is predominantly associated with TNF-alpha r-A upregulation and shedding, whereas upregulation and shedding of TNF-alpha r-B is more prominent in alcoholic hepatitis. As cytotoxicity and apoptosis by TNF are mediated mainly via TNF-alpha r-B, our results are consistent with more severe TNF-alpha induced liver damage in alcoholic hepatitis as compared to viral hepatitis.

Antigens, CD↗
PubMed1996

Cytokines and growth factors influence hair growth in vitro. Possible implications for the pathogenesis and treatment of alopecia areata.

Factors that influence the growth of the anagen hair follicle or initiate the switch to a catagen growth pattern have so far not been definitely determined, but there is increasing evidence that cytokines and growth factors play an important role during these processes. Recently we detected an aberrant in situ expression pattern of cytokines of the Th1 type (IFN gamma, IL-2) plus IL-1 beta expression in untreated alopecia areata (AA), and a switch to high levels of IL-10 TGF-beta 1 expression after successful treatment with the contact allergen diphenylcyclopropenone (DCP). Hence the question arose as to whether cytokines are able to arrest hair growth and whether IL-10 or TGF beta 1 have the capacity to antagonize this process. Using whole-organ cultures of microdissected human hair follicles we studied the effect of a panel of cytokines and growth factors on hair growth and on the gross morphology of the hair follicles in vitro. IL-2, IL-10 and IFN-gamma had no effect in this regard, whereas TGF beta 1 partially inhibited hair growth and EGF, TNF alpha and IL-1 beta completely abrogated it. EGF and TNF alpha induced the formation of a club-like hair follicle, similar to catagen morphology of the hair bulb, whereas hair follicles grown in the presence of IL-1 beta or TGF beta 1 showed no particular morphological changes. We conclude that cytokines and growth factors are pivotal regulators of hair growth at least in vitro. IL-1 is suggested as playing an important role during the pathogenesis of AA. Possible mediators of therapeutic contact dermatitis (IL-10, TGF beta 1, TNF alpha, PGE2) are, at least in vitro, not able to antagonize the IL-1 beta-triggered hair growth inhibition. Therefore, we infer that these mediators rather "modulate' the immune response in AA.

Alopecia↗
PubMed1996

[Supportive composite-hybrid fixation of percutaneous screw fixation of tibial head fractures].

Recent operative techniques with percutaneous screw fixation of the tibial plateau require a high level of patient compliance. Geriatric, non-cooperative patients and fractures with severe soft tissue injury have had to be excluded so far from this therapeutic regimen. Since September 1993, composite hybrid fixation, as a combination of ring fixation of the epimetaphyseal tibia with monolateral AO fixation of the tibial shaft, has been performed in 12 patients. The data were collected prospectively. Fractures were classified according to the AO and Moore classification; soft tissue damage was classified according to Tscherne and Gustilio. Fixation was performed with the cannulated AO system, 2.0 mm titanium K wires and 5.0 mm AO Schanz screws. In five patients, additional arthroscopic control of the reposition was performed. Average removal of the external fixator was 16 weeks postoperatively. Pin-tract infections occurred in all patients, mainly in the metaphyseal region. In one patient, a knee infection resulted from a subchondral intra-articular pin, which was treated by repetitive arthroscopic synovectomy. In two patients, a secondary loss of reposition (5-7 degrees varus) occurred. Despite a high rate of soft tissue damage (8/12), no osteitis or non-union occurred. As an alternative to extensive methods of ORIF, supportive composite hybrid fixation offers a new perspective of early functional treatment, weight bearing and a rare loss of reposition. It is favored in geriatric, non-cooperative patients and in fractures with severe soft tissue damage.

Adult↗
PubMed1996

Protein phosphotyrosine phosphatases in Ascaris suum muscle.

Two forms of protein tyrosine phosphatases were partially purified from the musculo-cutaneous layer of Ascaris suum. A 50-55-kDa soluble form of the phosphatase cross-reacted with antisera raised against human PTP-1B and TC-PTP. Like the enzyme of human origin the phosphatase from Ascaris exhibited a preference for anionic substrates (tyrosine-phosphorylated carboxymethylated and maleylated lysozyme) and was inhibited by micromolar concentrations of vanadate, molybdate, Zn2+, heparin, and poly(Glu4Tyr). As revealed by immuno-cytochemistry, the phosphatase was mainly localized and appeared equally distributed in the cytoplasm, apart from the myofibrils, possibly in loose association with cytoskeletal elements. A second tyrosine phosphatase of 180 kDa molecular mass was mainly found in detergent extracts from a microsomal fraction. It showed no cross-reactivity with antisera raised against soluble mammalian phosphatases and dephosphorylated a basic substrate (Tyr-phosphorylated myelin basic protein). It was resistant to common inhibitors of mammalian tyrosine phosphatases except Zn2+ and thiol reagents.

Animals↗
PubMed1996

Analysis of interinstitutional observer agreement in interpretation of dobutamine stress echocardiograms.

OBJECTIVES: This study sought to determine the degree of interinstitutional agreement in the interpretation of dobutamine stress echocardiograms. BACKGROUND: Dobutamine stress echocardiography involves subjective interpretation. Consistent methods for acquisition and interpretation are of critical importance for obtaining high interobserver agreement and for facilitating communication of test results. METHODS: Five experienced centers were each asked to submit 30 dobutamine stress echocardiograms (dobutamine up to 40 micrograms/kg body weight per min and atropine up to 1 mg) obtained in patients undergoing coronary angiography. Thus, a total of 150 dobutamine stress echocardiograms were interpreted by each center without knowledge of any other patient data. Left ventricular wall motion was assessed using a 16-segment model but was otherwise not standardized. No patient was excluded because of poor image quality or inadequate stress level. Echocardiographic image quality was assessed using a five-point scale. RESULTS: Angiographically significant coronary artery disease (> or = 50% diameter stenosis) was present in 95 patients (63%). By a majority decision (three or more centers), the sensitivity, specificity and accuracy of dobutamine echocardiography were 76%, 87% and 80%, respectively. Abnormal or normal results of stress echocardiography were agreed on by four or all five of the centers in 73% of patients (mean kappa value 0.37, fair agreement only). Agreement on the left anterior descending artery territory (78%) was similar to that for the combined right coronary artery/left circumflex artery territory (74%), and for specific segments the agreement ranged from 84% to 97% and was highest for the basal anterior segment and lowest for the basal inferior segment. Agreement was higher in patients with no (82%) or three-vessel coronary artery disease (100%) and lower in patients with one- or two-vessel disease (61% and 68%, respectively). Agreement on positivity or negativity of stress test results was 100% for patients with the highest image quality but only 43% for those with the lowest image quality (p = 0.003). CONCLUSIONS: The current heterogeneity in data acquisition and assessment criteria among different centers results in low interinstitutional agreement in interpretation of stress echocardiograms. Agreement is higher in patients with no or advanced coronary artery disease and substantially lower in those with limited echocardiographic image quality. To increase interinstitutional agreement, better standardization of image acquisition and reading criteria of stress echocardiography is recommended.

Cardiotonic Agents↗
PubMed1996

Topical immunotherapy in alopecia areata. What, how, and why?

At present the induction and elicitation of an ACD with potent contact allergens such as DCP appear to be the most effective, but still not definitively curative, approach in treating extensive forms of AA. Experimental data suggest that cytokines and growth factors such as IL 1 beta are involved in the pathogenesis of AA as well as the therapeutic effect mediated by contact sensitizers. It seems reasonable to assume that factors inherent in the late phase of ACD modulate a T-cell mediated mechanism responsible for AA, thus inducing hair regrowth. Such counteracting activities are most likely mediated by proinflammatory cytokines such as TNF-alpha, IL-10, or TGF-beta 1. This hypothesis may oversimplify the underlying immunologic mechanisms, but the effectiveness of topical immunotherapy in AA would be compatible with this concept. This mode of treatment is, however, a rather rough approach and recurrences are possible. It is hoped that advances in basic science will eventually allow us to find a more specific mode of treatment.

Administration, Topical↗
PubMed1996

Dobutamine stress echocardiography after coronary artery bypass grafting. Transthoracic vs biplane transoesophageal imaging.

Graft failure or progressive native vessel disease can be a serious problem after coronary artery bypass grafting. However, because of poor image quality it may be difficult to evaluate these patients by transthoracic stress echocardiography. The purpose of this study, therefore, was to evaluate the effectiveness of dobutamine stress echocardiography in the detection of myocardial territories with compromised vascular supply (due to either an obstructed native vessel without graft, and obstructed graft, or a native vessel obstructed distal to bypass graft insertion with < or = 50% luminal diameter reduction on angiography) after coronary artery bypass grafting and to determine additional information obtained by biplane transoesophageal stress echocardiography. Sixty patients (54 men, mean age 59 +/- 8.5 years) who had undergone coronary bypass grafting (total number of graft vessels 198) were evaluated from 6 months to 14 years (mean 6.2 years) after surgery. Transthoracic dobutamine stress echocardiography, biplane transoesophageal dobutamine stress echo, and coronary angiography were performed and evaluated by independent examiners. An infusion of dobutamine up to a maximum of 40 micrograms.kg-1.min-1 was administered, and additional atropine (0.25-1.0 mg) was given if 85% of age-predicted maximal heart rate was not reached. Biplane transoesophageal echocardiography was performed in the transgastric short-axis view as well as transoesophageal 4- and 2-chamber views, allowing division of the left ventricle into a 14-segment scheme. Wall motion abnormalities induced with dobutamine stress were used to predict regional vascular insufficiency. A 4-point scale, ranging from 'excellent' (1) to 'impossible' (4) was used to assess each system's ability to evaluate all left ventricular segments. Forty-five patients, of whom 35 were identified by transthoracic echocardiography (sensitivity 78%), had at least one territory with a compromised vascular supply. In 15 patients, the vascular supply was uncompromised, with 13 showing no wall motion abnormalities inducible by transthoracic echocardiography (specificity 86%). However, biplane transoesophageal echocardiography had a higher sensitivity and specificity than transthoracic echocardiography in detecting compromised vascular supply, 93% and 93%, respectively. The former system correctly classified the vascular supplies in 113 of 120 vascular territories (94%), according to whether they were compromised or uncompromised. This was significantly more (P < 0.05) than by classification with transthoracic dobutamine echocardiography, by which system only 102 of the 120 vascular territories were correctly assessed (85%). Compared with the conventional transgastric monoplane short-axis view, examination using three different views via a biplane probe results in a higher sensitivity (93% vs 84%). Assessed on a 4-point scale, the ability to evaluate all left ventricular segments was 2.3 +/- 0.7 (mean +/- SD) for transthoracic echocardiography and 1.7 +/- 0.7 (P < 0.01) for biplane transoesophageal echocardiography. After coronary artery bypass grafting transthoracic dobutamine stress echocardiography has acceptable accuracy in the detection of regional vascular insufficiency. However, this accuracy can be improved using the higher image quality of transoesophageal echocardiography, combined with the advantages of several different views obtained by biplane transoesophageal echocardiography.

Aged↗
PubMed1996

Solid-phase synthesis of H- and methylphosphonopeptides.

We introduce solid-phase syntheses of H- and methylphosphonopeptides, giving access for the first time to a new class of mimics for o-phosphoamino acids. The model peptides H-GlyGlyXaaAla-OH (Xaa = Ser, Thr) were synthesized on a solid-phase using Fmoc/tBu strategy and HBTU/HOBt activation by incorporation of hydroxyl-protected serine and threonine. As selectively cleavable hydroxyl-protecting groups we used triphenylmethyl and tert-butyldimethylsilyl for both amino acids, as described in the literature. All peptides were phosphitilated with O, O-di-tert-butyl-N,N-diethylphosphoramidite and yielded H-phosphonopeptides after trifluoroacetic acid cleavage. Alternatively we phosphonylated the peptides with O-tert-butyl-N,N-diethyl-P-methylphosphonamidite, which was synthesized by a two-step one-pot procedure starting from commercially available chemicals. All H- and methylphosphonopeptides were obtained in high purities and yields, as shown by reversed-phase high-performance liquid chromatography and anion-exchange chromatography. The phosphonopeptides were characterized by 1H and 31P NMR. We confirmed their molecular masses by electrospray mass spectrometry and analyzed their fragmentation schemes, which seemed to be characteristic for each class of analogues. The H-phosphonopeptides lost phosphonic acid (H3PO3, 82 mass units) and the methylphosphonopeptides lost methylphosphonic acid (MeH2PO3, 96 mass units). Both H- and methylphosphonopeptides represent a new and simply accessible class of mimics for phosphopeptides. Compared with the corresponding phosphopeptides all phosphonopeptides were synthesized in higher yields and purities (> 80%).

Magnetic Resonance Spectroscopy↗