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PubMed1976

A diagnostic triad for portal cirrhosis.

Abnormal serum aminotransferase activities with dominance of aspartate aminotransferase over alanine aminotransferase activity, and elevated serum adenosine deaminase activity and immunoglobulin. A concentration, were commonly encountered among patients with portal cirrhosis. The full triad was present in 31 of 49 cases (63%). As isolated abnormalities, these features were not uncommon in patients with other diseases of the liver and biliary tree, but the full triad was found only in 11 of 163 such cases (6.8%). The presence of this triad in a patient with unexplained hepatomegaly is indicative of portal cirrhosis.

Adenosine Deaminase↗
PubMed1983

Comparison of protein electrostatic potential along the catalytic triad of serine proteinases.

Intraproteic electrostatic potentials along the catalytic triad in serine proteinases are compared for eight enzymes for which three-dimensional co-ordinates are available. We used our bond-increment method to calculate the potential and we considered all protein atoms, including hydrogens. It was found that counter ions which may be located in the vicinity of charged surface side chains play a decisive role in determining enzymatic action. If ionizable side chains are neutralized the electrostatic potential curve across the catalytic triad is of minimum character in all investigated enzymes. It stabilizes the (-+-) charge distribution which models the Ser- -His+ -Asp- transition state structure which is formed during the catalytic process. Based on the close similarity of the electrostatic pattern in various enzymes we call attention to the possibility that convergent evolution produced not only the effective catalytic triad but also a minimum-type potential which accelerates the enzymatic reaction.

Amino Acid Sequence↗
PubMed1988

Competition for sucrose-pellets in triads of male Wistar rats: the individuals' performances are differing but stable.

After having individually been accustomed to consume palatable sucrose-pellets, the individual's competition-rate for sucrose-pellets within its familiar triad has been observed in male Wistar rats. In this fixed-triad, food competition paradigm high-performing rats (high competition-rate, majority of pellets consumed), medium-performing rats (medium competition-rate, consumption of some pellets) and poor-performing rats (almost completely abstaining from competition with only rare incidence of pellet consumption) can be distinguished. Intra-group rank-orders, defined according to the individuals' competition-rates (expressed as a score), were present in many triads and, once established, these were stable over months. No additional differences were observed between high- and poor-performing rats, neither when these were individually tested in an open field or in the elevated plus-maze, nor with regard to the preference for a sucrose solution.

Animals↗
PubMedDate not supplied

Claude Beck: cardiac compression triads.

Claude Beck described two triads of clinical findings which he found constituted the essential components of acute and chronic cardiac tamponade. The first of these triads consisted of hypotension, an increased venous pressure, and a quiet heart. It has come to be recognized as "Beck's triad," a collection of findings most commonly produced by acute intrapericardial hemorrhage. Subsequent studies have shown that these classic findings are observed in only a minority of patients with cardiac tamponade. However, Beck deserves credit for presenting a physiologic basis for the signs of cardiac compression.

Cardiac Tamponade↗
PubMed1992

What is the terrible triad?

In 1936 Campbell asserted that "impairment of the anterior crucial and mesial ligaments is associated with injuries of the internal cartilage." O'Donoghue in 1950 called attention to "that unhappy triad (1) rupture of the medial collateral ligament, (2) damage to the medial meniscus, and (3) rupture of the anterior cruciate ligament" and recommended early surgical intervention. In 1955 he reported 33 cases with both medial collateral (MCL) and anterior cruciate ligament (ACL) tears, but there were only three lateral meniscus tears reported. Based on a recent report by Shelbourne and Nitz that questions the validity of this unhappy triad, a review of all arthroscopically confirmed acute injuries of second degree or worse to the ACL and MCL was undertaken. Of a total of 52 knees reviewed, 50 knees had third-degree ACL tears and two had second-degree ACL tears. One of the second-degree tears was associated with a second-degree MCL and one with a third-degree ACL tear. Neither had an associated meniscus tear. Forty-five third-degree ACL tears were associated with third-degree MCL tears (group 1) and five with second-degree MCL tears (group 2). Eighty percent (36 knees) of group 1 had lateral meniscus tears. Only 29% of group 1 (13 knees) had associated medial meniscus tears. None of these medial meniscus tears was isolated. Eighty percent (four knees) of group 2 had lateral meniscus tears with only one associated medial meniscus tear. Again, there were no medial meniscus tears in the absence of a lateral meniscus tear. We did not find the combination of injury originally described as the unhappy triad.

Adult↗
PubMed2005

Female athlete triad.

Although eating disorders have received much attention over the last few years in athletics, its prevalence was not always well appreciated. Over the years, professional organizations began to pay close attention to the effects of eating disorders, and with this heightened awareness, professionals as well as the general public began to recognize eating disorders as a major problem in our society. In the early 1990s, the American College of Sports Medicine (ACSM) convened the Task Force on Women's Issues in Seattle, Washington . During this conference, members of the ACSM discussed issues related to females and athletics with specific attention to eating disorders, amenorrhea, and osteoporosis. They collectively called these pathologies the Female Athlete Triad (Triad) and hence coined the phrase in 1993. Since the publication, much time and effort has been devoted towards research and understanding of the Triad. In trying to understand this complicated problem, one must grasp the concept that the three pathologies are interrelated and difficult to explain without the influence of any of the other components.

Adolescent↗
PubMed2006

Triad-related homicides in Hong Kong.

This study provides an overview of the first systematic research on triad-related homicide in a Chinese society. In the 10-year period from 1989 to 1998, 11.9% of all homicides or a total of 95 triad-related homicides were extracted from the Hong Kong Homicide Monitoring Database. These events resulted in 124 victims (13.2 percent of all victims) and involved 526 known offenders. Triad homicides were classified into various types based on different combinations of circumstances, motivation, and outcomes including unintended outcomes.

Adult↗
PubMed2004

The crystal structure of three site-directed mutants of Escherichia coli dihydrodipicolinate synthase: further evidence for a catalytic triad.

Dihydrodipicolinate synthase (DHDPS, EC 4.2.1.52) catalyses the branchpoint reaction of lysine biosynthesis in plants and microbes: the condensation of (S)-aspartate-beta-semialdehyde and pyruvate. The crystal structure of wild-type DHDPS has been published to 2.5A, revealing a tetrameric molecule comprised of four identical (beta/alpha)(8)-barrels, each containing one active site. Previous workers have hypothesised that the catalytic mechanism of the enzyme involves a catalytic triad of amino acid residues, Tyr133, Thr44 and Tyr107, which provide a proton shuttle to transport protons from the active site to solvent. We have tested this hypothesis using site-directed mutagenesis to produce three mutant enzymes: DHDPS-Y133F, DHDPS-T44V and DHDPS-Y107F. Each of these mutants has substantially reduced activity, consistent with the catalytic triad hypothesis. We have determined each mutant crystal structure to at least 2.35A resolution and compared the structures to the wild-type enzyme. All mutant enzymes crystallised in the same space group as the wild-type form and only minor differences in structure are observed. These results suggest that the catalytic triad is indeed in operation in wild-type DHDPS.

Binding Sites↗
PubMed2000

Sulfhydryl oxidation overrides Mg(2+) inhibition of calcium-induced calcium release in skeletal muscle triads.

We studied the effect of oxidation of sulfhydryl (SH) residues on the inhibition by Mg(2+) of calcium-induced calcium release (CICR) in triad-enriched sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle. Vesicles were either passively or actively loaded with calcium before eliciting CICR by dilution at pCa 4.6-4.4 in the presence of 1.2 mM free [ATP] and variable free [Mg(2+)]. Native triads exhibited a significant inhibition of CICR by Mg(2+), with a K(0.5) approximately 50 microM. Partial oxidation of vesicles with thimerosal produced a significant increase of release rate constants and initial release rates at all [Mg(2+)] tested (up to 1 mM), and shifted the K(0.5) value for Mg(2+) inhibition to 101 or 137 microM in triads actively or passively loaded with calcium, respectively. Further oxidation of vesicles with thimerosal completely suppressed the inhibitory effect of [Mg(2+)] on CICR, yielding initial rates of CICR of 2 micromol/(mg x s) in the presence of 1 mM free [Mg(2+)]. These effects of oxidation on CICR were fully reversed by SH reducing agents. We propose that oxidation of calcium release channels, by decreasing markedly the affinity of the channel inhibitory site for Mg(2+), makes CICR possible in skeletal muscle.

Adenosine Triphosphate↗
PubMed2002

Electron tomography of frozen-hydrated isolated triad junctions.

Cryoelectron microscopy and tomography have been applied for the first time to isolated, frozen-hydrated skeletal muscle triad junctions (triads) and terminal cisternae (TC) vesicles derived from sarcoplasmic reticulum. Isolated triads were selected on the basis of their appearance as two spherical TC vesicles attached to opposite sides of a flattened vesicle derived from a transverse tubule (TT). Foot structures (ryanodine receptors) were resolved within the gap between the TC vesicles and TT vesicles, and some residual ordering of the receptors into arrays was apparent. Organized dense layers, apparently containing the calcium-binding protein calsequestrin, were found in the lumen of TC vesicles underlying the foot structures. The lamellar regions did not directly contact the sarcoplasmic reticulum membrane, thereby creating an approximately 5-nm-thick zone that potentially constitutes a subcompartment for achieving locally elevated [Ca(2+) ] in the immediate vicinity of the Ca(2+)-conducting ryanodine receptors. The lumen of the TT vesicles contained globular mass densities of unknown origin, some of which form cross-bridges that may be responsible for the flattened appearance of the transverse tubules when viewed in cross-section. The spatial relationships among the TT membrane, ryanodine receptors, and calsequestrin-containing assemblage are revealed under conditions that do not use dehydration, heavy-metal staining, or chemical fixation, thus exemplifying the potential of cryoelectron microscopy and tomography to reveal structural detail of complex subcellular structures.

Animals↗
PubMed1999

Consequences of breaking the Asp-His hydrogen bond of the catalytic triad: effects on the structure and dynamics of the serine esterase cutinase.

The objective of this study has been to investigate the effects on the structure and dynamics that take place with the breaking of the Asp-His hydrogen bond in the catalytic triad Asp175-His188-Ser120 of the serine esterase cutinase in the ground state. Four molecular dynamics simulations were performed on this enzyme in solution. The starting structures in two simulations had the Asp175-His188 hydrogen bond intact, and in two simulations the Asp175-His188 hydrogen bond was broken. Conformations of the residues comprising the catalytic triad are well behaved during both simulations containing the intact Asp175-His188 hydrogen bond. Short contacts of less than 2.6 A were observed in 1.2% of the sampled distances between the carboxylate oxygens of Asp175 and the NE2 of His188. The simulations showed that the active site residues exhibit a great deal of mobility when the Asp175-His188 hydrogen bond is broken. In the two simulations in which the Asp175-His188 hydrogen bond is not present, the final geometries for the residues in the catalytic triad are not in catalytically productive conformations. In both simulations, Asp175 and His188 are more than 6 A apart in the final structure from dynamics, and the side chains of Ser120 and Asp175 are in closer proximity to the NE2 of His188 than to ND1. Nonlocal effects on the structure of cutinase were observed. A loop formed by residues 26-31, which is on the opposite end of the protein relative to the active site, was greatly affected. Further changes in the dynamics of cutinase were determined from quasiharmonic mode analysis. The frequency of the second lowest mode was greatly reduced when the Asp175-His188 hydrogen bond was broken, and several higher modes showed lower frequencies. All four simulations showed that the oxyanion hole, composed of residues Ser42 and Gln121, is stable. Only one of the hydrogen bonds (Ser42 OG to Gln121 NE2) observed in the crystal structure that stabilize the conformation of Ser42 OG persisted throughout the simulations. This hydrogen bond appears to be enough for the oxyanion hole to retain its structural integrity.

Aspartic Acid↗
PubMed2001

Role of the conserved Ser-Tyr-Lys triad of the SDR family in sepiapterin reductase.

Sepiapterin reductase (EC 1.1.1.153; SPR) is an enzyme involved in the biosynthesis of tetrahydrobiopterin; and SPR has been identified as a member of the NADP(H)-preferring short-chain dehydrogenase/reductase (SDR) family based on its catalytic properties for exogenous carbonyl compounds and molecular structure. To examine possible differences in the catalytic sites of SPR for exogenous carbonyl compounds and the native pteridine substrates, we investigated by site-directed mutagenesis the role of the highly conserved Ser-Tyr-Lys triad (Ser and YXXXK motif) in SPR, which was shown to be the catalytic site of SDR-family enzymes. From the analysis of catalytic constants for single- and double-point mutants against the triad, Ser and YXXXK motif, in the SPR molecule, participate in the reduction of the carbonyl group of both pteridine and exogenous carbonyl compounds. The Ser and the Tyr of the triad may co-act in proton transfer and stabilization for the carbonyl group of substrates, as was demonstrated for those in the SDR family. But either the Tyr or the Ser of SPR can function alone for proton transfer to a certain extent and show low activity for both substrates.

Alcohol Oxidoreductases↗
PubMed2003

Effects of pathological mutations on the stability of a conserved amino acid triad in retinoschisin.

A three-dimensional model has been calculated for the discoidin domain of retinoschisin (RS1), the protein involved in the X-linked juvenile retinoschisis. The model allows for a mapping of the pathological retinoschisis missense mutations and a rationale for the structural effects of an evolutionary conserved surface exposed triad (W122-R200-W163). Molecular dynamics simulations of the triad mutants models, together with ab initio energy calculations of the complexes corresponding to the triad show that the observed pathological mutations sensibly destabilize local interactions and the entire fold. Moreover the presented model reveals evidence of a putative site for membrane association.

Amino Acid Sequence↗
PubMed1999

Identification of the catalytic triad in the haloalkane dehalogenase from Sphingomonas paucimobilis UT26.

The haloalkane dehalogenase from Sphingomonas paucimobilis UT26 (LinB) is the enzyme involved in the gamma-hexachlorocyclohexane degradation. This enzyme hydrolyses a broad range of halogenated aliphatic compounds via an alkyl-enzyme intermediate. LinB is believed to belong to the family of alpha/beta-hydrolases which employ a catalytic triad, i.e. nucleophile-histidine-acid, during the catalytic reaction. The position of the catalytic triad within the sequence of LinB was probed by a site-directed mutagenesis. The catalytic triad residues of the haloalkane dehalogenase LinB are proposed to be D108, H272 and E132. The topological location of the catalytic acid (E132) is after the beta-strand six which corresponds to the location of catalytic acid in the pancreatic lipase, but not in the haloalkane dehalogenase of Xanthobacter autotrophicus GJ10 which contains the catalytic acid after the beta-strand seven.

Binding Sites↗
PubMed1997

Currarino triad: anorectal malformation, sacral bony abnormality, and presacral mass--a review of 11 cases.

Currarino et al, in 1981, described an association of a congenital anorectal stenosis, or another type of low anorectal malformation, an anterior sacral defect, and presacral mass. Eleven patients with this anomaly were treated at the Department of Pediatric Surgery, Seoul National University Children's Hospital from 1984 to 1995. Among these patients, low-type imperforate anus (IA) was seen in three cases and anorectal stenosis was present in eight cases. Presacral masses included seven teratomas, two meningoceles, one dermoid cyst, and one enteric cyst with dermoid cyst. All had a deformed sacrum. Among the eight with anorectal stenoses, posterior sagittal anorectoplasty (PSARP) with diverting colostomy was performed in seven cases, and repeated rectal dilatation was performed in one case. Among the three low-type IA, anoplasty was performed in two cases and PSARP was performed in one case. Although PSARP is a safe and satisfactory method facilitating the excision of the presacral mass, in meningoceles the repair should be performed before correction of anorectal malformation because of the risk of meningitis that can occur when surgeries are done simultaneously. In two cases, untethering of a tethered spinal cord was performed. All patients are continent. Because the incidence of Currarino triad is high when there is an anorectal stenosis (38% in the present series), the Currarino triad should be suspected in anorectal stenosis. Magnetic resonance imaging is a preferred diagnostic method because the incidence of association of tethered cord in this triad is high (18% in the present series).

Anal Canal↗
PubMed2001

Enhancing the potency of peptide-pulsed antigen presenting cells by vector-driven hyperexpression of a triad of costimulatory molecules.

Recombinant orthopox vectors (both replication-defective fowlpox [rF], and replication competent vaccinia [rV] have been developed that simultaneously express three T-cell costimulatory molecule transgenes. The constituents of this triad of costimulatory molecules (designated TRICOM) are B7-1, ICAM-1, and LFA-3. We have previously shown that infection of murine dendritic cells (DCs) with TRICOM vectors increases their level of expression of the triad of costimulatory molecules and enhances the efficacy of DCs to activate T cells. While DCs are arguably the most potent antigen presenting cell (APC), limitations clearly exist in their use due to the level of effort and cost for their generation. The studies reported here demonstrate that a generic APC population, murine splenocytes, can be made markedly more efficient as APCs by infection with either rF-TRICOM or rV-TRICOM vectors. Infection of splenocytes with either TRICOM vector led to significant improvement of APC capabilities in terms of: (a) enhancement of mixed lymphocyte reactions; (b) a reduction in the amount of signal 1 to activate naive T cells; and (c) a reduction in the amount of APCs required to activate T cells using a constant amount of signal 1. TRICOM-enhanced T-cell activation was shown to correspond to increases in type-1 cytokines and a reduced level of apoptosis, compared with T cells activated with uninfected or control vector-infected splenocytes. In vitro and in vivo experiments compared DCs with TRICOM-infected splenocytes. Infection of splenocytes with TRICOM vectors markedly enhanced their ability to activate T cells to levels approaching that of DCs. These studies thus demonstrate for the first time that an abundant and accessible population of APCs obtainable without lengthy culture or the use of costly exogenous cytokines (in contrast to that of DCs) can be made more potent as APCs with the use of vectors that express a triad of costimulatory molecules.

Animals↗
PubMed2003

Atypical Carney's triad with coincidental clear cell renal carcinoma in an 84-year old patient-a finding at autopsy.

Carney's triad is a syndrome of unknown etiology, representing a combination of gastrointestinal stromal tumors, bronchial chondromas and vagal, adrenal or paraadrenal paragangliomas. Two of the Carney's triad components-the paragangliomas and the gastrointestinal stromal tumors-are potentially lethal. Since its first description in 1977, 79 cases have been reported so far. We report an 84-year-old male patient, who died of a hypertensive cerebral hemorrhage. Well-differentiated clear cell carcinoma of the right kidney, chondroma of the right bronchus and multiple jejunal stromal tumors were detected at autopsy. To our knowledge, this is the first report of a coincidental clear cell renal carcinoma in a patient with an atypical Carney's triad.

Aged↗
PubMed2001

Reaction of Lys-Tyr-Lys triad mimics with benzylpenicillin: insight into the role of Tyr150 in class C beta-lactamase.

Small and simple molecules mimicking a Lys-Tyr-Lys triad and some 'mutant' derivatives were designed and synthesized. These-compounds react with benzylpenicillin in water (75mM phosphate buffer, pH 7), apparently through general base assistance by the phenolic moiety. Class C beta-lactamase has a Lys-Tyr-Lys triad in its active site, and our finding gives some insight into the role of this triad in the enzymatic beta-lactam hydrolysis mechanism.

Enzyme Inhibitors↗