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At least 919 records · Page 51Linked to original sources
PubMed2005

The direct and indirect allogeneic presentation pathway during acute rejection after human cardiac transplantation.

Alloreactive T cells may be activated via a direct or an indirect antigen presentation pathway. We questioned whether the frequency of interferon (IFN)-gamma producing cells determined by enzyme-linked immunospot (ELISPOT) assay is an effective tool to monitor the direct and/or indirect presentation pathway. Secondly, we wondered whether early and late acute rejection (AR) are associated with both pathways. Before (n = 15), during (n = 18) and after (n = 16) a period of AR, peripheral blood mononuclear cell (PBMC) samples were tested from 13 heart transplant recipients. The direct presentation pathway was always present. The number of IFN-gamma producing cells reactive to this pathway increased significantly (P = 0.04) during AR and the number decreased (P = 0.005) after AR therapy. In contrast, the indirect allogeneic presentation pathway was present in only eight of 18 AR samples. When the indirect presentation pathway was detectable, it increased significantly during AR. Five of eight of these AR occurred more than 6 months after transplantation. The ELISPOT assay, enumerating alloreactive IFN-gamma producing cells, is a valuable tool to determine the reactivity via both the direct and the indirect presentation pathway. The direct presentation pathway always plays a role in AR, while the indirect pathway contributes especially to late AR.

Adult↗
PubMed1986

Labelling of chlorophylls and precursors by [2-14C]glycine and 2-[1-14C]oxoglutarate in Rhodopseudomonas spheroides and Zea mays. Resolution of the C5 and Shemin pathways of 5-aminolaevulinate biosynthesis by thin-layer radiochromatography.

The C-5 of 5-aminolaevulinate, a tetrapyrrole precursor which accumulates when inhibitory laevulinate is present, is derived from either the C-2 of glycine by the 5-aminolaevulinate-synthase-mediated Shemin pathway or the C-1 of 2-oxoglutarate by the C5 pathway. Thin-layer-radiochromatographic procedures are described for determining whether [2-14C]glycine or 2-[1-14C]oxoglutarate labelled the macrocycle of bacteriochlorophyll a, in addition to or rather than the methyl ester or phytyl ester moieties of the side-chains. The method was also used for detecting whether the same substrates label the formaldehyde (C-5) or the succinate (C-1 to C-4) fragments, obtained by periodate cleavage of 5-aminolaevulinate. These methods therefore can readily distinguish between the Shemin and C5 pathways as was demonstrated by using Rhodopseudomonas spheroides and Zea mays (maize), respectively, as examples of each pathway. Both [2-14C]glycine and, to a lesser extent 2-[1-14C]oxoglutarate labelled the macrocycle of bacteriochlorophyll a formed during adaptation of respiring R. spheroides cells to photosynthetic (anaerobic, illuminated) conditions. This and earlier evidence suggested augmentation of the Shemin pathway by a minor C5 pathway contribution. The present studies revealed only Shemin pathway activity: with laevulinate present, [2-14C]glycine formed 5-[5-14C]aminolaevulinate as proved by H14CHO production during periodate cleavage. These methods were sufficiently sensitive also to detect the incorporation of 14CO2, from degradation of either substrate, into 5-aminolaevulinate via the Shemin pathway thus labelling the succinate fragment produced with periodate: this explains bacteriochlorophyll a labelling by 2-[1-14C]oxoglutarate and proves double labelling of 5-aminolaevulinate by [2-14C]glycine. The same techniques were applied to etiolated maize leaves exposed to aerobic illuminated conditions with laevulinate and either 2-[1-14C]oxoglutarate or [2-14C]glycine as substrates. Only the C5 pathway was detected: 2-[1-14C]oxoglutarate was converted to 5-[5-14C]aminolaevulinate, which yielded H14CHO on periodate cleavage. This is not inconsistent with our earlier 13C-NMR studies [Porra, R.J., Klein, O. and Wright, P. E. (1983) Eur. J. Biochem. 130, 509-516] showing that the C5 pathway formed all the 5-aminolaevulinate for chlorophyll biosynthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminolevulinic Acid↗
PubMed1993

The sum of the control coefficients of all enzymes on the flux through a group-transfer pathway can be as high as two.

In simple metabolic pathways the control exerted by enzyme concentrations on the pathway flux adds up to one when the control is quantified in terms of control coefficients. In this paper we demonstrate that this classical summation theorem has to be modified in pathways where the enzymes participate by transferring a group between each other. We derive the corresponding new control theorem and show how it is consistent with standard metabolic control analysis. In group-transfer pathways lacking enzyme complexes, the sum of the flux control by enzyme concentrations and by the donor and acceptor couples of the pathway, equals two. In group-transfer pathways with enzyme-enzyme interactions the flux control by the dissociation rate constants of the enzyme-enzyme complexes must be added to obtain this sum of two. In all cases, the sum of the controls by all reaction activities remains one. Both by using the new theorem and by numerical simulations, we then demonstrate that, in group-transfer pathways with or without enzyme interactions, the sum of the control of enzymes on the pathway flux is higher than one and can reach a value of two. The total control of all enzymes on the concentration of any intermediate either with or without the transferred group can be equal to one, rather than to the zero found in the classical case. Examples of group-transfer pathways are the bacterial phosphoenolpyruvate:sugar phosphotransferase system, the main pathway for uptake of sugars in Enterobacteriaceae, and the electron-transfer chain in free-energy transducing membranes.

Enzymes↗
PubMed1993

Palpitations occur frequently following radiofrequency catheter ablation for supraventricular tachycardia, but do not predict pathway recurrence.

Radiofrequency ablation of extranodal pathways is an effective treatment for supraventricular tachycardia, but late recurrences of pathway conduction do occur. To determine if recurrence of palpitations following ablation predicts pathway recurrence, we interviewed 77 patients who were at least 4 weeks status-post successful ablation of an accessory pathway (43 overt, 11 concealed) or slow pathway (23) for AV nodal reentrant tachycardia. Palpitations were reported by 45 (58%) patients postablation, and 28 (36%) patients reported palpitations lasting > or = 10 seconds and/or felt their symptoms represented recurrent tachycardia (major palpitations). Repeat electrophysiological testing was performed 3 months postablation in 53 patients, including 34 patients with palpitations (22 with major symptoms). Eight (10%) patients had recurrent pathway conduction demonstrated on repeat testing: two had no symptoms prior to restudy and six had major symptoms. One patient had major symptoms, but was found to have inducible atrial tachycardia and not pathway recurrence on restudy. Thus, 15 (68%) of 22 patients with major symptoms who were restudied had no pathway recurrence or inducible arrhythmia to explain their symptoms. Of the 24 patients not restudied, none has had documented recurrent tachycardia or overt pathway conduction by electrocardiogram over a mean follow-up of 335 +/- 138 (range 132-616) days. Thus, palpitations, including palpitations reminiscent of preablation symptoms, are common following radiofrequency ablation and often do not predict pathway recurrence. Repeat electrophysiological testing is frequently required to document long-term success of radiofrequency ablation for supraventricular tachycardia in patients with recurrence of major symptoms.

Adult↗
PubMed1994

Radiofrequency catheter ablation of accessory pathways during entrainment of AV reentrant tachycardia.

Radiofrequency ablation of accessory pathways must sometimes be done during orthodromic atrioventricular reentrant tachycardia when manifest anterograde accessory pathway conduction is absent or retrograde fusion obscures accessory pathway location during ventricular pacing. Unfortunately, abrupt heart rate slowing upon radiofrequency induced termination of atrioventricular reentrant tachycardia often causes catheter dislodgment. We report our experience in circumventing this problem during radiofrequency ablation by using entrainment of atrioventricular reentrant tachycardia. The latter maintains retrograde activation pattern over the accessory pathway while preventing abrupt ventricular rate change. Eight patients (4 men and 4 women, mean age 37.3 +/- 17.9) with eleven left-sided accessory pathways were included. Ablation during entrainment was used as the first approach in three patients with concealed accessory pathways and one patient with a bidirectional accessory pathway. In another four patients, ablation during entrainment was used after technical difficulties in ablating during tachycardia. Only 1-3 radiofrequency applications were required to eliminate the accessory pathway using the entrainment technique. The catheter remained stable when accessory pathway conduction was interrupted by radiofrequency current. In conclusion, entrainment of atrioventricular reentrant tachycardia during radiofrequency application is useful for maintaining catheter position for accessory pathway ablation during atrioventricular reentrant tachycardia.

Adolescent↗
PubMed1993

Electrophysiologic spectrum of atrioventricular nodal behavior in patients with atrioventricular nodal reentrant tachycardia undergoing selective fast or slow pathway ablation.

INTRODUCTION: The objective of this report is to delineate the atrioventricular (AV) nodal electrophysiologic behavior in patients undergoing fast or slow pathway ablation for control of their AV nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: One hundred sixteen consecutive patients with symptomatic AVNRT were included. Twenty-two patients underwent fast pathway ablation with complete abolition of AVNRT in all and development of complete AV block in five patients. Of 17 patients with intact AV conduction postablation, 12 had demonstrated antegrade dual pathway physiology during baseline study, which was maintained in three and lost in nine patients postablation. Two patients with successful fast pathway ablation developed uncommon AVNRT necessitating a slow pathway ablation. Twenty-one patients demonstrated both common and uncommon forms of AV nodal reentry during baseline study. The earliest site of atrial activation was close to the His-bundle recording site (anterior interatrial septum) during common variety and the coronary sinus ostium (posterior interatrial septum) during the uncommon AV nodal reentry in all 21 patients. Ninety-six patients underwent successful slow pathway ablation. Among these, the antegrade dual pathway physiology demonstrable during baseline study (60 patients) was maintained in 25 and lost in 35 patients postablation. CONCLUSION: These data suggest that: (1) dual pathway physiology may persist after successful ablation, which might be a reflection of multiple reentrant pathways in patients with AVNRT; and (2) the retrograde pathways during common and uncommon AVNRT have anatomically separate atrial breakthroughs. These findings have important electrophysiologic implications regarding the prevailing concept of the AV nodal physiology in patients with AVNRT.

Adolescent↗
PubMed2006

Characteristics of slow pathway conduction after successful AVNRT ablation.

BACKGROUND: AV node slow pathway conduction can persist following successful ablation for AV node reentrant tachycardia (AVNRT). We hypothesized that careful examination of AV nodal conduction curves before and after effective AVNRT ablation in patients with persistent slow pathway conduction could shed light on this apparent paradox. METHODS AND RESULTS: Thirty patients (age 40.9 +/- 14.3; 8 male) were included. AV node function curves were created based on pre- and postablation atrial extrastimulus testing. Analysis of slow pathway function curves demonstrated significant decrease in AH for any given coupling interval after ablation (mean difference -68.1 [-94.5, -41.7] P < 0.001), graphically indicated by downward displacement of the curve. In addition, mean slow pathway effective refractory period (ERP) increased from 247.9 +/- 36.1 msec to 288.6 +/- 56.0 msec (P < 0.001); mean maximum AH interval decreased from 361.3 +/- 114.2 msec to 306.9 +/- 65.2 msec (P = 0.013); mean difference in minimum and maximum AH interval during slow pathway conduction decreased (from 94.5 +/- 75.8 msec to 59.6 +/- 46.2 msec (P = 0.016). Finally, mean difference between the fast and slow pathway effective refractory periods, the span of coupling intervals over which slow pathway conduction occurred, decreased (from 113.9 +/- 61.4 msec to 63.2 +/- 41.5 msec, P = 0.001). CONCLUSIONS: Ablation, which successfully eliminates inducible and spontaneous AVNRT in the presence of persistent slow pathway conduction, is associated with significantly altered slow pathway conduction characteristics, indicating the presence of a damaged or different slow pathway after ablation, incapable of sustaining tachycardia.

Adult↗
PubMed1969

Phenol and benzoate metabolism by Pseudomonas putida: regulation of tangential pathways.

Catechol occurs as an intermediate in the metabolism of both benzoate and phenol by strains of Pseudomonas putida. During growth at the expense of benzoate, catechol is cleaved ortho (1,2-oxygenase) and metabolized via the beta-ketoadipate pathway; during growth at the expense of phenol or cresols, the catechol or substituted catechols formed are metabolized by a separate pathway following meta (2,3-oxygenase) cleavage of the aromatic ring of catechol. It is possible to explain the mutually exclusive occurrence of the meta and ortho pathway enzymes in phenol- and benzoate-grown cells of P. putida on the basis of differences in the mode of regulation of these two pathways. By use of both nonmetabolizable inducers and blocked mutants, gratuitous synthesis of some of the meta pathway enzymes was obtained. All four enzymes of the meta pathway are induced by the primary substrate, cresol or phenol, or its analogue. Three enzymes of the ortho pathway that catalyze the conversion of catechol to beta-ketoadipate enol-lactone are induced by cis,cis-muconate, produced from catechol by 1,2-oxygenase-mediated cleavage. Observations on the differences in specificity of induction and function of the two pathways suggest that they are not really either tangential or redundant. The meta pathway serves as a general mechanism for catabolism of various alkyl derivatives of catechol derived from substituted phenolic compounds. The ortho pathway is more specific and serves primarily in the catabolism of precursors of catechol and catechol itself.

Acetates↗
PubMed1988

Opine utilization by Agrobacterium spp.: octopine-type Ti plasmids encode two pathways for mannopinic acid degradation.

Octopine-type strains of Agrobacterium tumefaciens degrade the opine mannopinic acid through a specific pathway which involves cleavage of the molecule at the C--N bond between the amino acid and the sugar moieties. Mannose was identified as a product of the reaction. This pathway was inducible by mannopinic and agropinic acids, but not by mannopine or agropine, the two other mannityl opines. The transport system for this pathway appeared to be specific for mannopinic acid. A second, nonspecific pathway for mannopinic acid degradation was also identified. This involved some of the catabolic functions associated with the metabolism of mannopine and agropine. This second pathway was inducible by mannopine and agropine but not by mannopinic or agropinic acids. The transport system for this pathway appeared to have a broad specificity. Transposon Tn5 insertion mutants affected in the specific catabolic pathway were isolated and analyzed. These mutants continued to catabolize mannopine and agropine. Both mapped to a region of the Ti plasmid previously shown to be associated with the catabolism of mannopinic acid. Restriction enzyme analysis of the Ti plasmid from strain 89.10, an octopine strain that is naturally unable to utilize mannopinic acid, showed a deletion in this same region encoding the specific mannopinic acid degradation pathway. Analysis of recombinant clones showed that the second, nonspecific pathway was encoded in a region of the Ti plasmid associated with mannopine and agropine catabolism. This region shared no structural overlap with the segment of the plasmid encoding the specific mannopinic acid degradative pathway.

Arginine↗
PubMed1998

Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli.

Arginine catabolism produces ammonia without transferring nitrogen to another compound, yet the only known pathway of arginine catabolism in Escherichia coli (through arginine decarboxylase) does not produce ammonia. Our aims were to find the ammonia-producing pathway of arginine catabolism in E. coli and to examine its function. We showed that the only previously described pathway of arginine catabolism, which does not produce ammonia, accounted for only 3% of the arginine consumed. A search for another arginine catabolic pathway led to discovery of the ammonia-producing arginine succinyltransferase (AST) pathway in E. coli. Nitrogen limitation induced this pathway in both E. coli and Klebsiella aerogenes, but the mechanisms of activation clearly differed in these two organisms. We identified the E. coli gene for succinylornithine aminotransferase, the third enzyme of the AST pathway, which appears to be the first of an astCADBE operon. Its disruption prevented arginine catabolism, impaired ornithine utilization, and affected the synthesis of all the enzymes of the AST pathway. Disruption of astB eliminated succinylarginine dihydrolase activity and prevented arginine utilization but did not impair ornithine catabolism. Overproduction of AST enzymes resulted in faster growth with arginine and aspartate. We conclude that the AST pathway is necessary for aerobic arginine catabolism in E. coli and that at least one enzyme of this pathway contributes to ornithine catabolism.

Acyltransferases↗
PubMed1987

Value of the resting 12 lead electrocardiogram and vectorcardiogram for locating the accessory pathway in patients with the Wolff-Parkinson-White syndrome.

The resting 12 lead electrocardiogram and vectocardiogram were reviewed in 47 patients with the Wolff-Parkinson-White syndrome (a) who had pre-excitation on the resting 12 lead electrocardiogram, (b) who had a single anterograde conducting accessory pathway assessed and located during preoperative electrophysiological study and during epicardial mapping at operation, and (c) in whom surgical division of the accessory pathway resulted in loss of pre-excitation. The site of the accessory pathway established during operation was compared with that established by evaluating the polarity of the delta wave and QRS complex on the resting 12 lead electrocardiogram. The electrocardiogram was assessed by the Rosenbaum criteria (Wolff-Parkinson-White type A, left-sided pathway; or type B, right-sided pathway), the Gallagher criteria (atrial pacing resulting in maximal pre-excitation), and the World Health Organisation criteria (a composite of previous studies). The Gallagher and World Health Organisation criteria were derived from patients demonstrating maximal pre-excitation that often required atrial pacing. The present study was designed to determine whether these criteria could be accurately applied to the resting 12 lead electrocardiogram on which the degree of pre-excitation was variable. The Rosenbaum criteria correctly identified a left sided accessory pathway in 26 of 34 patients and a right-sided accessory pathway in nine of 13 patients. The Gallagher and World Health Organisation criteria correctly identified the location in only 15 (32%) of the 47 patients. The resting vectorcardiogram was inaccurate for locating the accessory pathway. Although published criteria are useful for identifying the site of the accessory pathway from an electrocardiogram obtained when rapid atrial pacing is being used to achieve maximal pre-excitation, they are not suitable for identifying the exact site of an accessory pathway from the resting 12 lead electrocardiogram.

Adolescent↗
PubMed1997

Radiofrequency catheter ablation of accessory atrioventricular pathways: primary failure and recurrence of conduction.

OBJECTIVE: To identify possible factors associated with primary failure of radiofrequency ablation of accessory pathways or recurrence of accessory pathway conduction. PATIENTS AND METHODS: Radiofrequency ablation of accessory pathways failed in 25 of 243 patients, and recurrence of accessory pathway conduction occurred in an additional 13 patients. Factors possibly related to primary failure and recurrence were analysed. RESULTS: Primary failure and recurrence were less frequent in patients with left sided pathways (7% v 19%; 4% v 24%; P = 0.04). The factors that might relate to primary failure included an unstable catheter position (seven patients), a possible epicardial pathway (six patients), or misdiagnosis of accessory pathway location (two patients). The major factors for recurrence included the stability of the local atrial electrogram < or = 0.5 together with the stability of the local ventricular electrogram < or = 0.8, and prolonged time to pathway conduction block > or = 12 seconds). Thirty one patients underwent repeat ablation which was successful in 28. CONCLUSIONS: Primary failure and recurrence were more frequent in patients with right sided pathways. An unstable catheter position and a possible epicardial pathway location are the main contributing factors for primary failure, while unstable local electrograms and prolonged time to block are independent predictors for recurrence.

Adolescent↗
PubMed1974

Segmental reflex pathways in spinal shock and spinal spasticity in man.

Activity in three segmental pathways was compared in normal subjects, patients with spinal shock, and patients with established spinal spasticity. The Achilles tendon reflex (ATR) was used to estimate transmission in the Ia monosynaptic pathway. Evidence is produced implying that vibration activates motoneurones principally through a polysynaptic pathway. The tonic vibration reflex (TVR) was used to estimate transmission in this Ia polysynaptic pathway. The percentage of the motoneurone pool (M-response) that could be activated by these pathways was used as a measure of transmission. The H reflex (vibration)/H reflex (control) ratio was used as an estimate of the degree of presynaptic inhibition of the Ia monosynaptic pathway. The findings led to the following conclusions. (1) In spinal shock presynaptic inhibition is greater than normal, transmission in the Ia monosynaptic pathway is reduced, and in the Ia polysynaptic pathway virtually abolished. (2) In established spasticity presynaptic inhibition is impaired, transmission in the Ia monosynaptic pathway is increased, but transmission in the Ia polysynaptic pathway never recovers. (3) The failure of presynaptic inhibition associated with spasticity is a gradual process. A hypothesis to explain these findings is proposed.

Achilles Tendon↗
PubMed1996

The beta-ketoadipate pathway and the biology of self-identity.

The beta-ketoadipate pathway is a chromosomally encoded convergent pathway for aromatic compound degradation that is widely distributed in soil bacteria and fungi. One branch converts protocatechuate, derived from phenolic compounds including p-cresol, 4-hydroxybenzoate and numerous lignin monomers, to beta-ketoadipate. The other branch converts catechol, generated from various aromatic hydrocarbons, amino aromatics, and lignin monomers, also to beta-ketoadipate. Two additional steps accomplish the conversion of beta-ketoadipate to tricarboxylic acid cycle intermediates. Enzyme studies and amino acid sequence data indicate that the pathway is highly conserved in diverse bacteria, including Pseudomonas putida, Acinetobacter calcoaceticus, Agrobacterium tumefaciens, Rhodococcus erythropolis, and many others. The catechol branch of the beta-ketoadipate pathway appears to be the evolutionary precursor for portions of the plasmid-borne ortho-pathways for chlorocatechol degradation. However, accumulating evidence points to an independent and convergent evolutionary origin for the eukaryotic beta-ketoadipate pathway. In the face of enzyme conservation, the beta-ketoadipate pathway exhibits many permutations in different bacterial groups with respect to enzyme distribution (isozymes, points of branch convergence), regulation (inducing metabolites, regulatory proteins), and gene organization. Diversity is also evident in the behavioral responses of different bacteria to beta-ketoadipate pathway-associated aromatic compounds. The presence and versatility of transport systems encoded by beta-ketoadipate pathway regulons is just beginning to be explored in various microbial groups. It appears that in the course of evolution, natural selection has caused the beta-ketoadipate pathway to assume a characteristic set of features or identity in different bacteria. Presumably such identities have been shaped to optimally serve the diverse lifestyles of bacteria.

Adipates↗
PubMed1994

Pathways of nodal metastasis from pelvic tumors: CT demonstration.

Although the normal pathways of lymphatic drainage from the pelvic organs have been well described in the anatomy literature, the pathways of nodal metastasis from individual pelvic neoplasms are not well illustrated in the imaging literature. The authors retrospectively reviewed computed tomographic scans of the abdomen and pelvis in patients with various pelvic neoplasms, including those of the ovary, testis, prostate, cervix, bladder, anorectum, and other sites, to define the pathways of nodal metastasis. In most patients, pathways of nodal metastasis correlated well with the normal lymphatic pathways described in the anatomy literature, including the superficial inguinal pathway; the anterior, lateral, hypogastric, and presacral routes of the pelvic pathway; and the paraaortic pathway. However, there also were various uncommon pathways of nodal metastasis, such as metastasis along the gonadal vessels, mesenteric and mesocolic nodes, posterior iliac crest nodes, and inferior phrenic nodes. Understanding these common and uncommon lymphatic pathways of metastasis will help radiologists detect disease spread from pelvic tumors.

Humans↗
PubMed2003

Distribution and phylogenies of enzymes of the Embden-Meyerhof-Parnas pathway from archaea and hyperthermophilic bacteria support a gluconeogenic origin of metabolism.

Enzymes of the gluconeogenic/glycolytic pathway (the Embden-Meyerhof-Parnas (EMP) pathway), the reductive tricarboxylic acid cycle, the reductive pentose phosphate cycle and the Entner-Doudoroff pathway are widely distributed and are often considered to be central to the origins of metabolism. In particular, several enzymes of the lower portion of the EMP pathway (the so-called trunk pathway), including triosephosphate isomerase (TPI; EC 5.3.1.1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12/13), phosphoglycerate kinase (PGK; EC 2.7.2.3) and enolase (EC 4.2.1.11), are extremely well conserved and universally distributed among the three domains of life. In this paper, the distribution of enzymes of gluconeogenesis/glycolysis in hyperthermophiles--microorganisms that many believe represent the least evolved organisms on the planet--is reviewed. In addition, the phylogenies of the trunk pathway enzymes (TPIs, GAPDHs, PGKs and enolases) are examined. The enzymes catalyzing each of the six-carbon transformations in the upper portion of the EMP pathway, with the possible exception of aldolase, are all derived from multiple gene sequence families. In contrast, single sequence families can account for the archaeal and hyperthermophilic bacterial enzyme activities of the lower portion of the EMP pathway. The universal distribution of the trunk pathway enzymes, in combination with their phylogenies, supports the notion that the EMP pathway evolved in the direction of gluconeogenesis, i.e., from the bottom up.

Archaea↗
PubMed2005

Identification of mitogen-activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae.

Hypoxia activates all components of the unfolded protein response (UPR), a stress response initiated by the accumulation of unfolded proteins within the endoplasmic reticulum (ER). Our group and others have shown previously that the UPR, a hypoxia-inducible factor-independent signaling pathway, mediates cell survival during hypoxia and is required for tumor growth. Identifying new genes and pathways that are important for survival during ER stress may lead to the discovery of new targets in cancer therapy. Using the set of 4,728 homozygous diploid deletion mutants in budding yeast, Saccharomyces cerevisiae, we did a functional screen for genes that conferred resistance to ER stress-inducing agents. Deletion mutants in 56 genes showed increased sensitivity under ER stress conditions. Besides the classic UPR pathway and genes related to calcium homeostasis, we report that two additional pathways, including the SLT2 mitogen-activated protein kinase (MAPK) pathway and the osmosensing MAPK pathway, were also required for survival during ER stress. We further show that the SLT2 MAPK pathway was activated during ER stress, was responsible for increased resistance to ER stress, and functioned independently of the classic IRE1/HAC1 pathway. We propose that the SLT2 MAPK pathway is an important cell survival signaling pathway during ER stress. This study shows the feasibility of using the yeast deletion pool to identify relevant mammalian orthologues of the UPR.

Basic-Leucine Zipper Transcription Factors↗
PubMed1990

Importance of preexcited QRS morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways.

The present investigation evaluates the ability of several electrocardiographic (ECG) and electrophysiologic methods to identify multiple accessory pathways in 47 patients in whom the presence and sites of multiple accessory pathways were confirmed intraoperatively. To establish ECG features that suggested the presence of multiple accessory pathways in these patients, we initially studied the 12-lead ECG during maximal preexcitation in 101 patients with single accessory pathways. Distinctive 12-lead ECG patterns were noted for six defined anatomic areas around the right and left atrioventricular groove. Multiple preexcited QRS morphologies, each typical for a separate accessory pathway, and atypical preexcited QRS morphologies were recorded during atrial fibrillation in 31 of 47 (66%) patients with multiple accessory pathways. By comparison, the ECG during sinus rhythm and rapid atrial pacing identified 14 (32%) and 26 (55%) of the patients, respectively. In 12 (26%) patients in whom evidence for multiple accessory pathways was absent from endocardial mapping data, atrial fibrillation provided the diagnosis. In five (11%) patients, atrial fibrillation was the only method that demonstrated the presence of multiple accessory pathways. A combination of ECG findings during atrial fibrillation and rapid atrial pacing plus endocardial mapping data identified 43 (91%) of the patients with multiple accessory pathways. There were two unique fusion patterns on the 12-lead ECG that were characteristic of specific multiple accessory pathway combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗