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PubMed1985

Nociceptive pathways: anatomy and physiology of nociceptive ascending pathways.

In primates, the principal nociceptive pathways ascend in the anterolateral quadrant of the spinal cord. Among these, the spinothalamic tract (s.t.t.) is the best studied. Cells in Rexed's laminae I and V project to the ventro-posterolateral (v.p.l.) thalamic nucleus. Other cells in the same and deeper laminae terminate in the intralaminar complex. Spinothalamic tract cells may be nociceptive-specific or multireceptive. Those ending in v.p.l. have restricted, contralateral receptive fields, whereas those projecting to the intralaminar region often have large, bilateral receptive fields. Spinoreticular tract (s.r.t.) cells are concentrated in laminae VII and VIII and may be nociceptive. It is proposed that the s.t.t. contributes to sensory-discriminative processing of pain and that the s.t.t. and s.r.t. play a role in the motivational-affective components of pain. Alternative nociceptive pathways are the spinocervical and postsynaptic dorsal column tracts.

Afferent Pathways↗
PubMed1993

L-arginine exerts a dual role in nociceptive processing in the brain: involvement of the kyotorphin-Met-enkephalin pathway and NO-cyclic GMP pathway.

1. Intracerebroventricular (i.c.v.) administration of L-arginine (L-Arg), at 10-100 micrograms per mouse, produced antinociception in mice, as assessed by the tail flick test; this antinociception was reversed by pretreatment (s.c.) with naltrindole (NTI), a delta-selective opioid antagonist, and by co-administered L-leucyl-L-arginine (Leu-Arg), a kyotorphin (endogenous Met-enkephalin releaser) receptor antagonist. 2. L-NG-nitroarginine methyl ester (L-NAME), a NO synthase inhibitor, but not D-NG-nitroarginine methyl ester, given i.c.v. at 3-10 micrograms per mouse, exhibited antinociceptive activity that was resistant to naloxone (s.c.), NTI (s.c.) and Leu-Arg (i.c.v.). 3. The L-NAME (i.c.v.)-induced antinociception was not reversed by L-Arg (i.c.v.), which was antinociceptive by itself, but was abolished by combined injection of L-Arg plus Leu-Arg (i.c.v.) or by L-Arg (i.c.v.) after NTI (s.c.). 4. Methylene blue (MB), a soluble guanylate cyclase inhibitor, at 0.1-1 microgram per mouse, produced antinociception by i.c.v. administration. The antinociception induced by MB (i.c.v.) or L-NAME (i.c.v.) was reversed by co-administered dibutyryl cyclic GMP. 5. These findings suggest that L-Arg plays a dual role in nociceptive processing in the brain, being antinociceptive via the kyotorphin-Met-enkephalin pathway and nociceptive via the NO-cyclic GMP pathway.

Analgesics↗
PubMed1996

Imaging evaluation of the optic nerve and visual pathway including cranial nerves affecting the visual pathway.

The radiologic investigation of the optic pathways has an integral part in the diagnostic evaluation of diverse lesions, such as inflammatory disease, vascular disorders, and benign and malignant tumors that afflict the optic pathways. These radiologic methods consist principally of computed tomography and magnetic resonance imaging, and, in vascular lesions, magnetic resonance angiography and conventional angiography.

Cranial Nerve Neoplasms↗
PubMed1998

Aspirin increases the bleeding side effects in essential thrombocythemia independent of the cyclooxygenase pathway: role of the lipoxygenase pathway.

Acetylsalicylic acid (ASA) is currently recommended as an antithrombotic for patients with essential thrombocythemia (ET) who are at an increased risk of thrombotic events. However, ASA is also associated with an increased risk of bleeding in these patients as compared to the risk of bleeding in other patients treated with ASA. Recent data suggest that while ASA inhibits platelet thromboxane A2 (TxA2) synthesis in all individuals, ASA has little effect or inhibits the lipoxygenase pathway (i.e., 12-hydroxyeicosatetranoic acid or 12-HETE synthesis) in some individuals, and enhances 12-HETE synthesis in others. These differential effects are associated with a pronounced prolongation of the bleeding time vs. no prolongation of the bleeding time, respectively, i.e., in ASA responders and ASA nonresponders, respectively. To determine if the increased risk of ASA-induced bleeding seen in ET patients is associated with an effect on 12-HETE synthesis, we compared the relative effects of ASA on the bleeding time, platelet TxA2 and 12-HETE synthesis, and platelet aggregation and adhesion in ET patients and healthy volunteers. ASA (300 mg, taken orally) prolonged the bleeding time in 82% of the ET patients but only 27% of the healthy volunteers although platelet TxA2 synthesis and ADP- and collagen-induced aggregation were inhibited significantly in both groups. In contrast, platelet 12-HETE synthesis was unchanged and platelet adhesion was decreased in those patients and volunteers whose bleeding times were prolonged by ASA, whereas platelet 12-HETE synthesis was increased significantly and platelet adhesion was unaffected in those patients and volunteers whose bleeding times were not prolonged, and in some cases shortened by ASA. These results confirm previous data that demonstrate that ASA has different effects on platelet 12-HETE synthesis and platelet adhesion in different individuals, i.e., inhibitory or no effect in ASA responders (in whom ASA prolonged bleeding) vs. enhancing effects in ASA nonresponders (in whom ASA did not prolong bleeding). These results also indicate that there is a greater percentage of ASA responders in patients with ET than that seen in the general population, a difference that is associated with an effect of ASA on the lipoxygenase pathway. This may explain the increased bleeding side effects seen in the ET patient population.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2000

Transforming growth factor-alpha-mediated growth pathways in human gastro-intestinal cell lines in relation to the gastrin autocrine pathway.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) increase transcription of the gastrin gene, and the gastrin peptide may be phosphorylated by EGF-stimulated tyrosine kinase. Our aims were to compare EGF/TGF-alpha interactions in 2 human gastro-intestinal cell lines: MGLVA1, with a strong gastrin autocrine pathway, and C170HM2, with a weak pathway. Both cell lines expressed the TGF-alpha gene. MGLVA1 expressed TGF-alpha protein as determined by immuno-cytochemistry, which was absent in C170HM2. Both cell lines expressed the same level of EGF receptors, as assessed by flow cytometry; however, MGLVA1 did not have enhanced in vitro proliferation in response to EGF or TGF-alpha, unlike C170HM2. The basal growth of MGLVA1 was inhibited by anti-sera against TGF-alpha, the EGF receptor and G17. C170HM2 was not inhibited by any of the anti-sera. Neutralisation of TGF-alpha resulted in undetectable cell-associated progastrin levels in MGLVA1 (untreated had 391.7 fmol/5 x 10(6) cells). The progastrin level of C170HM2 remained unaffected. Tyrosine kinase activity, as assessed by phosphopeptide concentration, of unstimulated MGLVA1 was 2.6 times higher than that of C170HM2 in the cell membrane fraction (0.097 compared to 0.037 microg/mg protein, p < 0.001) and 4.8 times higher in the cytosolic fraction (0.269 compared to 0.056 microg/mg protein, p < 0.05). Following treatment with EGF, the phosphopeptide concentration increased in both the membrane and cytosolic fractions of both cell lines. Tyrphostin B42, which inhibits autophosphorylation of the EGF receptor, inhibited the basal growth of MGLVA1 (IC(50) 1.3 microM) and C170HM2 (9.5 microM, p < 0.05 from MGLVA1). Herbimycin, which inhibits pp60(c-src) kinase, reduced the basal growth of MGLVA1 (0.67 microM) but not C170HM2. Immunofluorescence studies confirmed the presence of tyrosine-phosphorylated proteins and pp60(c-src) within the cytoplasm of unstimulated MGLVA1 cells. There was no specific immunofluorescence for either parameter in C170HM2 cells until after treatment with EGF.

Blotting, Southern↗
PubMed1993

A study of intermediates involved in the folding pathway for recombinant human macrophage colony-stimulating factor (M-CSF): evidence for two distinct folding pathways.

The folding pathway for a 150-amino acid recombinant form of the dimeric cytokine human macrophage colony-stimulating factor (M-CSF) has been studied. All 14 cysteine residues in the biologically active homodimer are involved in disulfide linkages. The structural characteristics of folding intermediates blocked with iodoacetamide reveal a rapid formation of a small amount of a non-native dimeric intermediate species followed by a slow progression via both monomeric and dimeric intermediates to the native dimer. The transition from monomer to fully folded dimer is complete within 25 h at room temperature at pH 9.0. The blocked intermediates are stable under conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and thus represent various dimeric and folded monomeric species of the protein with different numbers of disulfide bridges. Peptide mapping and electrospray ionization mass spectrometry revealed that a folded monomeric species of M-CSF contained three of the four native disulfide bridges, and this folded monomer also showed some biological activity in a cell-based assay. The results presented here strongly suggest that M-CSF can fold via two different pathways, one involving monomeric intermediates and another involving only dimeric intermediates.

Amino Acid Sequence↗
PubMed1994

Detection of metabolites of the Entner-Doudoroff pathway by HPLC with pulsed amperometry: application to assays for pathway enzymes.

Three major metabolites in the Entner-Doudoroff pathway, 6-phosphogluconate, 2-keto-3-deoxy-6-phosphogluconate, and pyruvate can be detected and quantified by HPLC with pulsed amperometric detection. Resolution is achieved by ion-exchange chromatography at alkaline pH with isocratic elution in 5 to 10 min. Detection limits are in the subnanomolar range, and detector response is linear over 3-4 orders of magnitude. This method can be employed for the assay of the enzymes of the pathway, 6-phosphogluconate dehydratase (EC 4.2.1.12) and 2-keto-3-deoxy-6-phosphogluconate aldolase (EC 4.1.2.14), eliminating the need for coupling enzymes as in the previously employed spectrophotometric assays. The lag in pyruvate production seen in the coupled enzyme spectrophotometric assay for 6-phosphogluconate dehydratase is absent in the HPLC/pulsed amperometric detection assay. This lag represents an artifact of a slow tautomerism of 2-keto-3-deoxy-6-phosphogluconate which must precede its utilization by the coupling enzyme, 2-keto-3-deoxy-6-phosphogluconate aldolase. Kinetic data on the approach to equilibrium of 2-keto-3-deoxy-6-phosphogluconate aldolase-catalyzed interconversion of 2-keto-3-deoxy-6-phosphogluconate, pyruvate, and glyceral-dehyde-3-phosphate can be also accurately quantified by HPLC with pulsed amperometric detection.

Aldehyde-Lyases↗
PubMed1996

Embryonic development of Schwann cells: multiple roles for neuregulins along the pathway.

During the past few years important advances have been realized in the understanding of the molecular and cellular mechanisms operating in the differentiation of Schwann cells from neural crest cells. In particular the development of in vitro culture systems has allowed the analysis of commitment to the Schwann cell lineage, identification of an intermediate between the neural crest cell and the Schwann cell, and initial analysis of the factors controlling determination and differentiation processes. These studies point in particular to major roles for neuregulins which appear to be involved in the control of cell survival, proliferation, and differentiation, as well as of gene expression at different levels of the pathway.

Animals↗
PubMed1984

Integration in descending motor pathways controlling the forelimb in the cat. 10. Inhibitory pathways to forelimb motoneurones via C3-C4 propriospinal neurones.

A further analysis has been made of inhibitory pathways to motoneurones via C3-C4 propriospinal neurones (PNs). Intracellular recording was made from triceps brachi motoneurones and effects from higher centres and forelimb afferents on corticospinal IPSPs were investigated after transection of the corticospinal tract at the C5/C6 border. The shortest latencies of the IPSPs evoked by stimulation of the pyramid were as brief as those of the pyramidal EPSPs (Illert et al. 1977). It is postulated that the minimal linkage of the pyramidal IPSPs is disynaptic via inhibitory C3-C4 PNs projecting directly to motoneurones. It was confirmed that pyramidal IPSPs usually are depressed by volleys in forelimb motor axon collaterals (Illert and Tanaka 1978). A quantitative comparison was made of the recurrent depression of pyramidal IPSPs and of IPSPs caused by activation of the Ia inhibitory interneurones. The result support the hypothesis of two parallel inhibitory cortico-motoneuronal pathways via C3-C4 PNs, one disynaptic via the inhibitory PNs and the other trisynaptic via excitatory PNs and Ia inhibitory interneurones. Pyramidal volleys also evoked late IPSPs which in some cases were not depressed from forelimb motor axon collaterals. It is postulated that the late IPSPs are partly due to activation of inhibitory C3-C4 PNs. Disynaptic pyramidal IPSPs were effectively facilitated by volleys in rubro-, tecto- and reticulospinal fibres - but not from vestibulospinal fibres - showing a convergence from the former descending tracts on common inhibitory C3-C4 PNs. Projection from forelimb afferents and corticospinal fibres on common inhibitory C3-C4 PNs was revealed by strong facilitation of disynaptic pyramidal IPSPs from cutaneous forelimb afferents. No corresponding effect was evoked from C2 neck afferents. Stimulation in the lateral reticular nucleus (LRN) evoked monosynaptic IPSPs in some motoneurones. The results of threshold mapping in and around the LRN suggest that the IPSPs are caused by antidromic stimulation of ascending collaterals of inhibitory neurones also projecting to motoneurones, possibly the inhibitory C3-C4 PNs.

Animals↗
PubMed1984

Effects of antidiuretic hormone on cellular conductive pathways in mouse medullary thick ascending limbs of Henle: I. ADH increases transcellular conductance pathways.

This paper reports experiments designed to assess the relations between net salt absorption and transcellular routes for ion conductance in single mouse medullary thick ascending limbs of Henle microperfused in vitro. The experimental data indicate that ADH significantly increased the transepithelial electrical conductance, and that this conductance increase could be rationalized in terms of transcellular conductance changes. A minimal estimate (Gminc) of the transcellular conductance, estimated from Ba++ blockade of apical membrane K+ channels, indicated that Gminc was approximately 30-40% of the measured transepithelial conductance. In apical membranes, K+ was the major conductive species; and ADH increased the magnitude of a Ba++-sensitive K+ conductance under conditions where net Cl- absorption was nearly abolished. In basolateral membranes, ADH increased the magnitude of a Cl- conductance; this ADH-dependent increase in basal Cl- conductance depended on a simultaneous hormone-dependent increase in the rate of the net Cl- absorption. Cl- removal from luminal solutions had no detectable effect on Ge, and net Cl- absorption was reduced at luminal K+ concentrations less than 5mM; thus apical Cl- entry may have been a Na+, K+, 2Cl- cotransport process having a negligible conductance. The net rate of K+ secretion was approximately 10% of the net rate of Cl- absorption, while the chemical rate of net Cl- absorption was virtually equal to the equivalent short-circuit current. Thus net Cl- absorption was rheogenic; and approximately half of net Na+ absorption could be rationalized in terms of dissipative flux through the paracellular pathway. These findings, coupled with the observation that K+ was the principal conductive species in apical plasma membranes, support the view that the majority of K+ efflux from cell to lumen through the Ba++-sensitive apical K+ conductance pathway was recycled into cells by Na+, K+,2Cl- cotransport.

Animals↗
PubMed1998

Simultaneous degradation of chloro- and methyl-substituted aromatic compounds: competition between Pseudomonas strains using the ortho and meta pathway or the ortho pathway exclusively.

Pseudomonas sp. D7-4 and Pseudomonas sp. B13 FR1(pFRC20P) degraded mixtures of chloro- and methyl-substituted benzoates exclusively via an extended ortho pathway, whereas in Pseudomonas putida WR 201 both ortho and meta fission were induced by mixtures of 3-chloro- and 3-methylbenzoate or even by 3-chloro-benzoate alone. The competition behaviour of these strains was compared in batch and in chemostat cultures.. Despite misrouting of metabolites, strain WR201 was competitive, in a lot of the competition experiments, with mixtures of these substrates. Only in a narrow range of the mixing ratio of chloro- and methylbenzoate was the presence of both the meta and ortho pathways a disadvantage for competitiveness. Outside these ranges other attributes, such as high growth rates or short lag periods, or a respective strain were even more essential for one strain to outcompete another.

Benzoates↗
PubMed1986

A comparative study on the effects of inhibitors of the lipoxygenase pathway on neutrophil function. Inhibitory effects on neutrophil function may not be attributed to inhibition of the lipoxygenase pathway.

The effects of five inhibitors of the lipoxygenase pathway were evaluated on oxygen radical production, degranulation, chemotaxis, leukotriene B4 (LTB4) production by neutrophils. The lipoxygenase inhibitors tested were nordihydroguaiaretic acid (NDGA), esculetin, eicosatetraynoic acid (ETYA), 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone (AA-861), and 6,9-deepoxy-6, 9-(phenylimino)-delta 6.8-prostaglandin I1 (U-60,257). Neutrophils were activated by n-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA), A23187, or platelet activating factor (PAF). The effects of these inhibitors on NADPH oxidase activity and phospholipase A2 activity of isolated particulate fraction of neutrophils were also evaluated. ETYA inhibited neutrophil function induced by all the stimulators except PMA. AA-681 was unique in that it did not inhibit PAF-induced neutrophil activation. U-60,257 had virtually no effect on oxygen radical production and degranulation, but chemotaxis was moderately suppressed. NDGA effectively inhibited neutrophil function, except for chemotaxis. Esculetin inhibited only oxygen radical production, but this was due to inhibition on NADPH oxidase activity of neutrophil membrane. The inhibitory effect on neutrophil function and that of LTB4 production were not closely correlated. It is suggested that lipoxygenase inhibitors may modify neutrophil function by the mechanism not involving the lipoxygenase pathway. It is also suggested that LTB4 may not be a mediator in neutrophil oxygen radical production and degranulation induced by the stimulators used in the present study.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1987

An alternative metabolic pathway of 11-deoxycorticosterone in bovine adrenal in vitro: evidence for the presence of a pathway of 11-deoxycorticosterone oxidation at 19-position.

Comparative studies of 11 beta-, 18-, and 19-hydroxylation activities of 11-deoxycorticosterone (DOC) by bovine adrenal mitochondria revealed that an appreciable level of hydroxylation rate was observed in 19-hydroxylation (0.32 nmol/min/mg mitochondrial protein), as well as in 11 beta- and 18-hydroxylations (4.7 and 0.27 nmol/min/mg mitochondrial protein, respectively), at saturated substrate concentration in vitro. Also, the rates of the oxidation reactions of 19-hydroxy-11-deoxycorticosterone (19-OH-DOC) and 19-oxo-11-deoxycorticosterone (19-oxo-DOC) at the 19-position were about 5 times higher than the 19-hydroxylation rate of DOC. Although the affinities of 19-OH-DOC and 19-oxo-DOC for the enzyme(s) involved in the C-19 oxidation were about one-fifth those of DOC, these results strongly suggest the presence of the following pathway in bovine adrenal in vitro: DOC----19-OH-DOC----19-oxo-DOC----19-oic-DOC. This was further confirmed by a dynamic study of the formation and subsequent decay of the C-19 oxidized metabolites produced from DOC. At maximum concentrations of 19-OH-DOC and 19-oxo-DOC, the rates of production of, respectively, 19-oxo-DOC and 19-oic-DOC reached maximum. Furthermore, at the beginning of the incubation (1-4 min), an induction period in the formation of 19-oxo-DOC and 19-oic-DOC was observed and the formation of 19-oxo-DOC always preceded the appearance of 19-oic-DOC. These observations strongly support the existence of the pathway of the C-19 oxidation of DOC as mentioned above. It was also established that reduced pyridine nucleotide (NADPH) and molecular oxygen were required for these oxidation reactions. In addition, these three oxidation reactions were uniformly inhibited by the presence of carbon monoxide or metyrapone (0.01-1.0 microM), which is known to bind specifically with cytochrome P-450, while potassium cyanide (0.01-0.1 mM) did not affect them. These results suggest the possibility of the involvement of cytochrome P-450 in the C-19 oxidation reactions of DOC, 19-OH-DOC, and 19-oxo-DOC. We also showed that 19-oic-DOC is not further metabolized to other steroids such as 19-nor-11-deoxycorticosterone in bovine adrenal cortex.

Adrenal Glands↗
PubMed1989

Strategies for representing metabolic pathways within biochemical systems theory: reversible pathways.

The search for systematic methods to deal with the integrated behavior of complex biochemical systems has over the past two decades led to the proposal of several theories of biochemical systems. Among the most promising is biochemical systems theory (BST). Recent comparisons of this theory with several others that have recently been proposed have demonstrated that all are variants of BST and share a common underlying formalism. Hence, the different variants can be precisely related and ranked according to their completeness and operational utility. The original and most fruitful variant within BST is based on a particular representation, called an S-system (for synergistic and saturable systems), that exhibits many advantages not found among alternative representations. Even within the preferred S-system representation there are options, depending on the method of aggregating fluxes, that become especially apparent when one considers reversible pathways. In this paper we focus on the paradigm situation and clearly distinguish the two most common strategies for generating an S-system representation. The first is called the "reversible" strategy because it involves aggregating incoming fluxes separately from outgoing fluxes for each metabolite to define a net flux that can be positive, negative, or zero. The second is the "irreversible" strategy, which involves aggregating forward and reverse fluxes through each reaction to define a net flux that is always positive. This second strategy has been used almost exclusively in all variants of BST. The principal results of detailed analyses are the following: (1) All S-system representations predict the same changes in dependent concentrations for a given change in an independent concentration. (2) The reversible strategy is superior to the irreversible on the basis of several criteria, including accuracy in predicting steady-state flux, accuracy in predicting transient responses, and robustness of representation. (3) Only the reversible strategy yields a representation that is able to capture the characteristic feature of amphibolic pathways, namely, the reversal of nets flux under physiological conditions. Finally, the results document the wide range of variation over which the S-system representation can accurately predict the behavior of intact biochemical systems and confirm similar results of earlier studies [Voit and Savageau, Biochemistry 26: 6869-6880 (1987)].

Biochemical Phenomena↗
PubMed1988

Control analysis of biochemical pathways: a novel procedure for calculating control coefficients, and an additional theorem for branched pathways.

A novel method for calculating control coefficients of individual enzymes on fluxes and concentrations in metabolic pathways is presented. This method is derived by applying the theorem on implicit functions to the equations defining the steady state metabolite concentrations; it allows verification of the existing summation theorems and connectivity relations, and leads to a novel theorem for flux control coefficients in branched pathways. The method and the novel theorem are illustrated by several examples.

Mathematics↗
PubMed1999

Examination of signal transduction pathway of stimulated B1 and B2 kinin receptors; MAP kinase pathway to AP-1 translocation in HEK 293 cells.

B1 or B2 kinin receptor-overexpressing HEK293 cells were stimulated with des-Arg9-BK or BK, respectively. Each agonist induced translocation of AP-1 into the nuclear fraction as well as activation of MAP kinases in each cells. MAP kinase inhibitor PD98059 suppressed translocation of AP-1 and agonist-induced MAP kinase activation in both cells. These results indicate that stimulation of B1 or B2 receptor expresses a feature of the signal transduction pathway of MAP kinase activation to translocation of AP-1. This signal transduction pathway of HEK cells through B1 and B2 receptors may be similar in response to respective agonists.

Animals↗
PubMed1998

Heterogeneity of anterograde fast-pathway and retrograde slow-pathway conduction patterns in patients with the fast-slow form of atrioventricular nodal reentrant tachycardia: electrophysiologic and electrocardiographic considerations.

OBJECTIVES: This study sought to define the electrophysiologic and electrocardiographic characteristics of fast-slow atrioventricular nodal reentrant tachycardia (AVNRT). BACKGROUND: In fast-slow AVNRT the retrograde slow pathway (SP) is located in the posterior septum, whereas the anterograde fast pathway (FP) is located in the anterior septum; however, exceptions may occur. METHODS: Twelve patients with fast-slow AVNRT were studied. To determine the location of the retrograde SP, atrial activation during AVNRT was examined while recording the electrograms from the low septal right atrium (LSRA) on the His bundle electrogram and the orifice of the coronary sinus (CS). Further, to investigate the location of the anterograde FP, single extrastimuli were delivered during AVNRT both from the high right atrium and the CS. RESULTS: The CS activation during AVNRT preceded the LSRA in six patients (posterior type); LSRA activation preceded the CS in three patients (anterior type), and in the remaining three both sites were activated simultaneously (middle type). In the anterior type, CS stimulation preexcited the His and the ventricle without capturing the LSRA electrogram (atrial dissociation between the CS and the LSRA), suggesting that the anterograde FP was located posterior to the retrograde SP. In the posterior and middle types, high right atrial stimulation demonstrated atrial dissociation, suggesting that the anterograde FP was located anterior to the SP. In the posterior and middle types, retrograde P waves in the inferior leads were deeply negative, whereas they were shallow in the anterior type. CONCLUSIONS: Fast-slow AVNRT was able to be categorized into posterior, middle and anterior types according to the site of the retrograde SP. The anterior type AVNRT, where an anteriorly located SP is used in the retrograde direction and a posteriorly located FP in the anterograde direction, appears to represent an anatomical reversal of the posterior type which uses a posterior SP for retrograde and an anterior FP for anterograde conduction. Anterior type AVNRT should be considered in the differential diagnosis of long RP (RP > PR intervals) tachycardias with shallow negative P waves in the inferior leads.

Adult↗
PubMed1983

Circular dichroism spectroscopy of the intermediates that precede the rate-limiting step of the refolding pathway of bovine pancreatic trypsin inhibitor. Relationship of conformation and the refolding pathway.

Circular dichroism spectra of the partially folded trapped intermediates were measured in order to aid in the elucidation of the conformational forces which determine a nonrandom, nonsequential pathway of disulfide bond formation upon refolding of bovine pancreatic trypsin inhibitor. Whatever conformation was responsible for the kinetic rates of the intermediates should be stabilized by the presence of their trapped disulfide bonds. The near-ultraviolet spectra provide considerable information about the environments of the aromatic and disulfide side chains. The predominant single-disulfide intermediate has significant nonrandom conformation not present in the fully reduced protein, with aromatic rings and the disulfide bond in stabilized asymmetric environments. Forming either of the two nonnative, but kinetically important, second disulfides in this intermediate does not produce unequivocably different conformations. Forming a second native, but kinetically unproductive, disulfide produces a substantial decrease in randomness, which may hinder formation of the third disulfide. The largest conformational changes occur upon disulfide rearrangement to the stable, correctly refolded, two- and three-disulfide species. Interpretation of the far-ultraviolet spectra in terms of the secondary structure of the intermediates is uncertain, due to the atypical spectra of the folded forms of the protein. Consequently, we are unable to determine unambiguously the secondary structure of the intermediates. However, all the spectra show that nonrandom conformations of the polypeptide chain gradually appear as disulfide bond formation progresses, as expected from the nonrandom pathway of the latter.

Animals↗