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Morphological changes in the triads and sarcoplasmic reticulum of rat slow and fast muscle fibres following denervation and immobilization.

We observed the morphological features of the membrane systems (sarcoplasmic reticulum, transverse tubules and triads) involved with the excitation-contraction coupling in rat soleus and extensor digitorum longus muscle following two disuse protocols: denervation and immobilization. The immobilized positions were: maximum dorsal flexor (soleus were stretched and extensor digitorum longus were shortened), maximum plantar flexor (soleus were shortened and extensor digitorum longus were stretched), and midway between the dorsal flexor and plantar flexor. The arrangement of the membrane systems was disordered following both disuse conditions. Increases in transverse tubule network were apparent; there were clearly more triads than in normal fibres, and pentadic and heptadic structures (i.e., a close approximation of two or three transverse tubule elements with three or four elements of terminal cisternae of sarcoplasmic reticulum) were frequently appeared following both denervation and immobilization. The most notable difference between the influence of denervation and immobilization on the membrane systems is the time at which the pentads and heptads appeared. They appeared much earlier (1 week after denervation) in denervated than in immobilized (3 or 4 weeks after immobilization) muscle fibres. On the other hand, the frequency of pentads and heptads is clearly related to the fibre type (significantly higher in extensor digitorum longus) and to extent of atrophy. The different influences of immobilization in each leg position suggest that disuse, but with neurotrophic factor(s), influences on the membrane systems were affected by sarcomere length, and the neurotrophic factor(s) and muscle activity were not always necessary to form new membrane systems in disuse skeletal muscle fibres.

Animals↗

Depolarization-induced calcium release from isolated triads measured with impermeant fura-2.

Depolarization-induced Ca2+ release was studied in a mixture of triads and terminal cisternae isolated from rabbit skeletal muscle. The vesicles were actively loaded with known amounts of Ca2+ in the absence of precipitating anions in a solution containing 100 mM K propionate buffer. Changes in extravesicular Ca2+ were monitored with 10 microM Fura-2 (membrane impermeant form). Ca2+ release was initiated by diluting an aliquot of the loaded vesicles into a TEACl release solution designed to maintain a constant [K+].[Cl-] product. Fast release, defined as the percentage of total Ca2+ loaded which released in less than 10 sec, occurred when extravesicular free Ca2+ was in the submicromolar range and was unaffected by 5 mM caffeine under depolarizing conditions, change in external pH to 6.5, and an increase in external Mg2+ concentration from 0.1 to 0.2 mM. Thus, the Ca2+ release measured in these studies is distinct from Ca(2+)-induced Ca2+ release. The fast release more than doubled when a greater dilution (1:20 versus 1:10) of the loaded vesicles into the release solution, which would produce a larger depolarization, was used. The percentage of loaded Ca2+ which released rapidly in a particular triad preparation was similar to the percentage of vesicles structurally coupled as visualized by electron microscopy.

Animals↗

Regional mapping of catalase and Wilms tumor--aniridia, genitourinary abnormalities, and mental retardation triad loci to the chromosome segment 11p1305----p1306.

Gene dosage effects for catalase (CAT) were studied in two unrelated patients with an interstitial deletion involving 11p13 to determine precisely the sites of the genes for CAT and the Wilms tumor--aniridia, genitourinary abnormalities, and mental retardation triad (WAGR) in the 11p13 band. Case 1 had the aniridia-Wilms tumor association, and case 2 showed the AGR triad. The karyotypes identified by high resolution banding techniques were 46,XY,del(11)(pter----p13::p11.11----qter) for case 1 and 46,XY,t(2;17)(q23;q25),del(11)(pter----p13::p11.2----qter) for case 2. In both cases, the distal breakpoints of the deleted chromosomes 11 appeared to have occurred on the middle portion of 11p13 (11p1305----p1306). The level of erythrocyte CAT activities in case 1 was reduced (47% of normal), while that in case 2 was normal. The results suggested not only that both the CAT and WAGR should be mapped to chromosome region 11p1305----p1306, but also that in this region the CAT locus is more distally placed than the WAGR locus. Because of the proximity of the two gene loci, assays of erythrocyte CAT may be useful to identify a submicroscopic deletion in some patients with sporadic aniridia and to predict a risk of developing Wilms tumor.

Abnormalities, Multiple↗

The Currarino triad: complex of anorectal malformation, sacral bony abnormality, and presacral mass.

The Currarino triad is a unique complex of congenital caudal anomalies including anorectal malformation, sacral bony abnormality, and presacral mass. The usual symptomatology is constipation due to anorectal stenosis. Contrast enema and computed tomographic myelography are the imaging modalities of choice for diagnostic confirmation and clarification of the anomalies. The clinical features, unique radiologic appearance, and importance of a correct diagnosis of the Currarino triad are reviewed.

Abnormalities, Multiple↗

The "syncytial tissue triad": a model for understanding how gap junctions participate in the local control of penile erection.

Recent findings from both clinical and experimental studies document the importance of syncytial relaxation and contraction of corporal smooth muscle to penile erection and detumescence, respectively. However, the mechanism(s) permitting coordinated response generation among the vast array of largely inexcitable corporal smooth muscle cells is unclear. In this report the compelling evidence for a major role of intercellular communication through gap junctions to erectile function is reviewed. Moreover, a novel concept is advanced to explain more fully the putative mechanistic basis for integrative erectile tissue biology. Specifically, the presence of gap junctions, in concert with the autonomic nervous system and myogenic intracellular signal transduction mechanisms, is postulated to form a "syncytial tissue triad" that is largely responsible for the local modulation of corporal smooth muscle tone. It is reasonable to assume that the existence of this "syncytial tissue triad" confers a plasticity, adaptability, and flexibility to erectile function that may well account for the observed diversity of mechanisms known to regulate penile erection as well as the multifaceted etiology of erectile dysfunction.

Animals↗

Is the deterioration of liver viability due to hepatic warm ischemia or reinflow of pooled-portal blood in intermittent portal triad cross-clamping?

The effects of hepatic warm ischemia and portal pooling on the viability of the liver were investigated with respect to hepatic energy metabolism by performing intermittent portal triad cross-clamping (Pringle's maneuver) on dogs with or without portosystemic shunt. The dogs were divided into two groups of five: Group 1, non-shunt group, underwent Pringle's maneuver performed for 30 min and declamping for 30 min, a process that was repeated five times; and Group 2, shunt group, underwent the same procedure as Group 1, except for portosystemic shunt using a heparinized hydrophilic catheter between the splenic and jugular veins. The shunt was opened during Pringle's maneuver and was closed immediately at declamping. In the non-shunt group, portal pooling increased and systemic blood pressure decreased when Pringle's maneuver was performed, but in the shunt group portal and systemic blood pressures remained within the normal range. In the non-shunt group, the initial velocity of arterial blood ketone body ratio (KBR) recovery after each declamping significantly (P less than 0.01) decreased from 0.122 +/- 0.016 (per min) after the first declamping to 0.028 +/- 0.017 (per min) after the fifth declamping. Hepatic energy charge [= (ATP + 1/2 ADP)/(ATP + ADP + AMP)] decreased from 0.840 +/- 0.003 before ischemia to 0.749 +/- 0.003 30 min after the fifth declamping (P less than 0.001). The concentrations of lactate and total amino acids in arterial blood increased. On the other hand, in the shunt group, the initial velocity of KBR recovery and hepatic energy charge showed little change even after the fifth declamping (0.081 +/- 0.016 per min and 0.851 +/- 0.009, respectively). The concentrations of lactate and total amino acids showed almost no increase. The impairment of hepatic energy metabolism by intermittent portal triad cross-clamping is mainly due to reinflow of pooled-portal blood to the previously ischemic liver, rather than hepatic warm ischemia. The KBR may be useful for determining the degree of impairment of hepatic energy metabolism.

Amino Acids↗

E3 ubiquitin-protein ligase activity of Parkin is dependent on cooperative interaction of RING finger (TRIAD) elements.

The parkin gene codes for a 465-amino acid protein which, when mutated, results in autosomal recessive juvenile parkinsonism (AR-JP). Symptoms of AR-JP are similar to those of idiopathic Parkinson's disease, with the notable exception being the early onset of AR-JP. We have cloned and expressed human Parkin in Escherichia coli and have examined Parkin-mediated ubiquitination in an in vitro ubiquitination assay using purified recombinant proteins. We found that Parkin has E3 ubiquitin ligase activity in this system, demonstrating for the first time that the E3 activity is an intrinsic function of the Parkin protein and does not require posttranslational modification or association with cellular proteins other than an E2 (human Ubc4 E2 was utilized in this ubiquitination assay). Mutagenesis of individual elements of the conserved RING TRIAD domain indicated that at least two elements were required for ubiquitin ligase activity and suggested a functional cooperation between the RING finger elements. Since the activity assays were conducted with recombinant proteins purified from E. coli, this is the first time TRIAD element interaction has been demonstrated as an intrinsic feature of Parkin E3 activity.

Amino Acid Motifs↗

Interlocking triads of growth control in tumors.

A pair of growth control triads are used to describe coincident tumor growth and liver regeneration after partial hepatectomy. The models are extensions of previous growth control models which describe tumor growth in an unperturbed host (Michelson and Leith, 1991, Bull. math. Biol. 53, 639-656; idem, 1992, Proceedings of the Third International Conference on Communications and Control, Vol. 2, pp. 481-490; idem, 1992 Bull. math. Biol. 55, 993-1011; idem, J. theor. Biol. 169, 327-338). The linkage between the two triads depends upon systemic signals carried by soluble factors, and mathematical descriptors based upon biological first principals are proposed. The sources of the growth factors, their targets and the processing of their signals are investigated. Analyses of equilibrium in the constant coefficients case and simulated growth curves for the dynamic system are presented, and the effects of growth factor-induced mitogenesis and angiogenesis are discussed in particular. A case is made for early and late responses in the coupled control system. The biology of the signal processing paradigm is placed within a new theoretical context and discussed with regard to tumor adaptation, liver differentiation and the development of a tumor hypoxic fraction.

Animals↗

Native skeletal muscle dihydropyridine receptor exists as a supramolecular triad complex.

One of the central elements of excitation-contraction coupling, the voltage-sensing dihydropyridine receptor, is believed to exist as a high-molecular-mass complex in the triad junction. Although freeze-fracture electron microscopical analysis suggests a tetrad complex, no direct biochemical evidence exists demonstrating the actual size of the native membrane complex. Using a combination of various two-dimensional gel electrophoresis techniques, we show here that the principal alpha1-subunit of the dihydropyridine receptor and its auxiliary alpha2-subunit form a triad complex of approximately 2800 kDa under native conditions. Established Ca2+-ATPase tetramers and calsequestrin monomers were employed for the internal standardization of the gel systems used. Thus, the large voltage-sensing complex appears to be tightly associated, since it does not disintegrate during subcellular fractionation and native electrophoresis procedures. Our findings support the cell biological hypothesis that native dihydropyridine receptor units form a tetrad structure within the transverse tubules.

Animals↗

Assessing Sediments from Upper Mississippi River Navigational Pools Using a Benthic Invertebrate Community Evaluation and the Sediment Quality Triad Approach

Benthic invertebrate samples were collected from 23 pools in the Upper Mississippi River (UMR) and from one station in the Saint Croix River (SCR) as part of a study to assess the effects of the extensive flooding of 1993 on sediment contamination in the UMR system. Sediment contaminants of concern included both organic and inorganic compounds. Oligochaetes and chironomids constituted over 80% of the total abundance in samples from 14 of 23 pools in the UMR and SCR samples. Fingernail clams comprised a large portion of the community in three of 23 UMR pools and exceeded abundances of 1,000/m2 in five of 23 pools. Total abundance ranged from 250/m2 in samples from pool 1 to 22,389/m2 in samples from pool 19. Abundance values are comparable with levels previously reported in the literature for the UMR. Overall frequency of chironomid mouthpart deformities was 3% (range 0-13%), which is comparable to reported incidence of deformities in uncontaminated sediments previously evaluated. Sediment contamination was generally low in the UMR pools and the SCR site. Correlations between benthic measures and sediment chemistry and other abiotic parameters exhibited few significant or strong correlations. The sediment quality triad (Triad) approach was used to evaluate data from laboratory toxicity tests, sediment chemistry, and benthic community analyses; it showed that 88% of the samples were not scored as impacted based on sediment toxicity, chemistry, and benthic measures. Benthic invertebrate distributions and community structure within the UMR in the samples evaluated in the present study were most likely controlled by factors independent of contaminant concentrations in the sediments.

Journal Article↗

Interventional radiology in Carney triad.

Interventional therapeutic methods are presented in Carney triad, which is a syndrome defined as the simultaneous presence of gastric leiomyosarcoma, extra-adrenal paraganglioma, and pulmonary chondroma. The paragangliomas in the carotid bifurcation and the mediastinum were successfully treated via transarterial embolization with particles. Three intrapulmonary chondromas were ablated using MRI-guided laser-induced thermotherapy (LITT) after previous devascularization via transvenous pulmonary particle embolization. In summary, interventional techniques could be a therapeutic option in patients suffering from Carney triad.

Adult↗

The spectrum of imaging in Currarino triad.

The aim of this study was to evaluate the spectrum of findings and the efficacy of different imaging modalities in order to formulate recommendations for diagnostic imaging of Currarino triad (ASP syndrome), including screening of relatives. The imaging films of five female patients (age range 6 weeks to 12 months) were analysed retrospectively. The studied material consisted of US and MRI of the lower spine (5 patients each), lumbosacral plain radiography (4 patients), contrast enema (4 patients), urinary US (2 patients), genitography (1 patient) and myelo-CT (1 patient). Depiction of pathological findings with different imaging modalities was reviewed and validated with special respect to their demonstrability by US. Ultrasonography detected the sacral bony defect as well as the presacral pathology (meningocele and/or tumour) and thereby gave the basic diagnosis in all of the cases. It also depicted tethered cord and urinary tract abnormalities correctly. Magnetic resonance imaging gave a more distinct visualization of pre- and intraspinal pathology with additional demonstration of intraspinal lipoma in two cases. Regarding anorectal and genital malformations, radiographic contrast agent studies had been used in all patients. Two blind-ending retrorectal fistulas, depicted by enema, were missed by MRI. Patients with congenital or early infancy obstipation, anorectal malformations and complex urinary tract malformations should have spinal and pelvic sonography first. A plain film of the sacrum is recommended in equivocal cases. The need for MRI and contrast agent studies depends on the individual pathology, whereas presently MRI has made further radiographic imaging increasingly dispensable. A screening program with lumbosacral US or plain radiography for families with Currarino triad should be obligatory.

Abnormalities, Multiple↗

The 2-His-1-carboxylate facial triad: a versatile platform for dioxygen activation by mononuclear non-heme iron(II) enzymes.

General knowledge of dioxygen-activating mononuclear non-heme iron(II) enzymes containing a 2-His-1-carboxylate facial triad has significantly expanded in the last few years, due in large part to the extensive library of crystal structures that is now available. The common structural motif utilized by this enzyme superfamily acts as a platform upon which a wide assortment of substrate transformations are catalyzed. The facial triad binds a divalent metal ion at the active site, which leaves the opposite face of the octahedron available to coordinate a variety of exogenous ligands. The binding of substrate activates the metal center for attack by dioxygen, which is subsequently converted to a high-valent iron intermediate, a formidable oxidizing species. Herein, we summarize crystallographic and mechanistic features of this metalloenzyme superfamily, which has enabled the proposal of a common but flexible pathway for dioxygen activation.

Binding Sites↗

The RANK/RANKL/OPG triad in cancer-induced bone diseases.

The maintenance of skeletal integrity in a healthy individual requires a balanced regulation of the processes of bone formation, mediated by osteoblasts, and bone resorption, mediated by osteoclasts. This balanced process of bone remodeling becomes co-opted in the skeleton by tumor cells and this dramatically accelerates the process of remodeling and disrupts the normal equilibrium resulting in a spectrum of osteolytic to osteoblastic bone lesions. Certain tumor types, such as breast and prostate, frequently metastasize to the bone. It is now widely understood that the molecular triad--receptor activator of NF-kappaB ligand (RANKL), its receptor RANK, and the endogenous soluble RANKL inhibitor, osteoprotegerin (OPG)--play direct and essential roles in the formation, function, and survival of osteoclasts. Osteoclastic bone resorption contributes to the majority of skeletal sequelae, or skeletal-related events (SREs), in patients with bone metastases. In addition, osteoclastic bone resorption also contributes to the establishment of tumors in the skeleton. Therefore, blocking osteoclast activity and differentiation via RANKL inhibition may not only provide a beneficial treatment for skeletal complications of malignancy, but may also prevent bone metastases. In this review, we will first describe the operative role of osteoclasts and the RANK/RANKL/OPG triad in the pathophysiology of cancer-induced bone diseases, specifically solid tumor metastases to the bone. Secondly, we will describe a therapeutic approach that specifically targets the RANKL molecule.

Animals↗

Structural analysis of muscle development: transverse tubules, sarcoplasmic reticulum, and the triad.

Increased interest in the mechanism of excitation-contraction (E-C) coupling over the last few years has been accompanied by numerous investigations into the development of the underlying cellular structures. Areas of particular interest include: (1) the compartmentalization and specialization of an external and an internal membrane system, the T-tubules, and the sarcoplasmic reticulum, respectively; (2) interactions between the membrane proteins of both systems upon the formation of a junction, the triad; and (3) membrane-cytoskeletal interactions leading to the orderly arrangement of the triads with respect to the myofibrils. Structural studies using newly available specific molecular probes and a variety of in vivo and in vitro model systems have provided new insights into the cellular and molecular mechanisms involved in the development of the E-C coupling apparatus in skeletal muscle.

Animals↗

Testicular histology in triad syndrome.

A twenty-year-old patient with the triad syndrome had a Sertoli-cell-only histologic appearance in his intra-abdominal testes. Testicular histology was then reviewed in 6 other boys with the triad syndrome, and no spermatogonia were seen. While fertility is doubtful in patients with this syndrome, they additionally may not be at risk for germ cell testicular tumors.

Adult↗

Xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular reperfusion injury of the liver.

Although reactive oxygen metabolites may play a pivotal role in mediating microvascular reperfusion injury, the source of these radicals is still a matter of controversy. With the use of spectrophotometry and intravital microscopy we studied the role of xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular injury in rats. After 20 min of global hepatic ischemia and splanchnic vascular congestion, followed by 40 min of reperfusion (n = 8), xanthine oxidase activities in hepatic venous (26.9 +/- 4.7 nmol/ml x min) and systemic arterial blood (16.3 +/- 2.5 nmol/ml x min) were found significantly (p < .01) increased when compared with sham-operated controls (6.8 +/- 0.9 and 6.0 +/- 0.8 nmol/ml x min, n = 8). The increase of xanthine oxidase activity was accompanied by oxygen radical-mediated intravascular hemolysis. Intravital microscopy (n = 6) revealed accumulation of leukocytes within the postischemic hepatic microvasculature with stasis in sinusoids (75.9 +/- 8.9 per liver lobule) and adherence to the endothelial lining of postsinusoidal venules (534.7 +/- 125.3 per mm2 endothelial surface). Concomitantly, compromised microvascular reperfusion was characterized by perfusion deficits of individual sinusoids (25.6 +/- 4.0% nonperfused sinusoids). The xanthine oxidase inhibitor allopurinol (50 mg/kg b.wt., orally, n = 6) and the radical scavenger superoxide dismutase (60000 IU/kg b.wt., IV, n = 6) effectively (p < .01) inhibited both sinusoidal leukostasis (16.1 +/- 2.6 and 32.1 +/- 3.1 cells/lobule) and venular leukocyte adherence (247.6 +/- 7.9 and 205.0 +/- 38.0 cells/mm2), and, hence, reduced microcirculatory deteriorations, indicated by the attenuation of sinusoidal perfusion failure (2.8 +/- 0.8 and 9.0 +/- 3.1%). Our results support the hypothesis that portal triad crossclamping-induced microvascular reperfusion injury is triggered by superoxide radicals derived from the xanthine oxidase system.

Allopurinol↗