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PubMed1979

The triad of hemochromatosis, hepatoma and erythrocytosis.

The triad of hemochromatosis, hepatoma and erythrocytosis is a rare combination. Hemochromatosis is often not recognized until the patient presents with the symptoms of hepatocellular carcinoma and erythrocytosis, and the development of erythrocytosis is an important clue to the under-lying hepatoma. The high serum iron concentration and the high saturation of the iron-binding protein, as well as the typical bone marrow hemosiderin pattern, are important aids in the recognition of hemochromatosis. To date, all patients with this triad have been elderly males. The clinical course is usually one of rapid deterioration and death. The seven previously reported cases have been reviewed and the relationship of the erythrocytosis to the increased production of erythropoietin is discussed.

Aged↗
PubMed2005

The functional role of selenocysteine (Sec) in the catalysis mechanism of large thioredoxin reductases: proposition of a swapping catalytic triad including a Sec-His-Glu state.

Thioredoxin reductases catalyse the reduction of thioredoxin disulfide and some other oxidised cell constituents. They are homodimeric proteins containing one FAD and accepting one NADPH per subunit as essential cofactors. Some of these reductases contain a selenocysteine at the C terminus. Based on the X-ray structure of rat thioredoxin reductase, homology models of human thioredoxin reductase were created and subsequently docked to thioredoxin to model the active complex. The formation of a new type of a catalytic triad between selenocysteine, histidine and a glutamate could be detected in the protein structure. By means of DFT (B3LYP, lacv3p**) calculations, we could show that the formation of such a triad is essential to support the proton transfer from selenol to a histidine to stabilise a selenolate anion, which is able to interact with the disulfide of thioredoxin and catalyses the reductive disulfide opening. Whereas a simple proton transfer from selenocysteine to histidine is thermodynamically disfavoured by some 18 kcal mol(-1), it becomes favoured when the carboxylic acid group of a glutamate stabilises the formed imidazole cation. An identical process with a cysteine instead of selenocysteine will require 4 kcal mol(-1) more energy, which corresponds to a calculated equilibrium shift of approximately 1000:1 or a 10(3) rate acceleration: a value close to the experimental one of about 10(2) times. These results give new insights into the catalytic mechanism of thioredoxin reductase and, for the first time, explain the advantage of the incorporation of a selenocysteine instead of a cysteine residue in a protein.

Animals↗
PubMed2004

Vectorial electron relay at ITO electrodes modified with self-assembled monolayers of ferrocene-porphyrin-fullerene triads and porphyrin-fullerene Dyads for molecular photovoltaic devices.

Systematic series of indium tin oxide (ITO) electrodes modified covalently with self-assembled monolayers (SAMs) of ferrocene-porphyrin-fullerene triads and porphyrin-fullerene dyads were designed to gain valuable insight into the development of molecular photovoltaic devices. The structures of SAMs on ITO have been investigated by UV/Vis absorption spectroscopy, atomic force microscopy, and cyclic voltammetry. The photoelectrochemical and photophysical (fluorescence lifetime and time-resolved transient absorption) properties were also determined. The highest quantum yield of photocurrent generation (11 %) among donor-acceptor linked systems which are covalently attached to the surface of ITO electrodes was achieved with SAMs of ferrocene-zinc porphyrin-fullerene linked triad on ITO electrodes. The quantum yields of photocurrent generation correlate well with the charge-separation efficiency and the lifetime of the charge-separated state of the porphyrin-fullerene linked systems in solution. These results provide valuable information for the construction of photonic molecular devices and artificial photosynthetic systems on ITO electrodes.

Journal Article↗
PubMed2006

A triad based on an iridium(III) bisterpyridine complex leading to a charge-separated state with a 120-micros lifetime at room temperature.

A triad D-Ir-A, where Ir is an Ir(III) bisterpyridine complex connected through an amidophenyl spacer to D, a triphenylamine electron donor, and to A, a naphthalene bisimide electron acceptor, has been synthesized and electrochemically investigated. The photoinduced processes in the triad, which is more than 4-nm long, have been characterized by steady-state and time-resolved optical spectroscopy by comparison with the model dyads D-Ir, Ir-A, and the reference monomers D, Ir, and A. A sequential electron transfer occurs upon excitation of the D and Ir units, leading to the charge-separated state D+-Ir- -A in 100 % yield and subsequently to D+-Ir-A- in about 10 % yield. The final charge-separated state has a lifetime at room temperature of 120 micros in air-free acetonitrile and of 100 micros in air-equilibrated solvent. Excitation of the A units does not yield intramolecular reactivity, but the resulting triplet-excited state localized on the acceptor, D-Ir-3A, displays intermolecular reactivity.

Journal Article↗
PubMed2002

Architecture and function of atropisomeric molecular triads.

Molecular triads, B-A-B, in which the central unit A is aromatic or heteroaromatic, can exist as syn or anti conformers or atropisomers of correspondingly C or S shape. These stereoisomers are either discrete conformer species, often distinguished by NMR spectroscopy, or can be separated at ambient temperature as stable atropisomers. In the latter case syn and anti stereoisomers exhibit different (e.g., complex-forming) properties. Practical applications of atropisomeric triads as ligands in asymmetric dihydroxylation are also discussed.

Journal Article↗
PubMed2003

Down-regulation of fragile histidine triad expression in prostate carcinoma.

BACKGROUND: The fragile histidine triad (FHIT) gene is a tumor suppressor gene that belongs to the histidine triad family of nucleoside binding proteins. The gene encompasses the common human chromosomal fragile site, the FRA3B locus at chromosome 3p14.2, and is expressed in most normal adult tissues and tumor cell lines. Numerous studies have indicated that the FHIT gene on chromosome 3p may play an important role in human neoplasia, although very few studies have investigated the FHIT gene in prostate carcinoma. METHODS: Using immunohistochemical analyses, the authors studied the expression of FHIT in prostate tumors from 84 radical prostatectomy specimens to determine whether there were any correlations between FHIT expression and various clinicopathologic characteristics. RESULTS: The percentages of cells stained with antibody to FHIT were significantly lower overall for tumor cells compared with normal cells (P = 0.0001). FHIT immunostaining intensity also was significantly lower for tumor cells compared with normal cells (P = 0.0001). A weak but statistically significant correlation (P = 0.045) was demonstrated with the presence of extraprostatic extension in the patient samples. No other significant correlation was seen between the percentage of cells stained for FHIT or FHIT immunostaining intensity and Gleason grade, tumor stage, tumor size, lymph node metastasis, surgical margins, vascular invasion, perineural invasion, or the presence of high-grade prostatic intraepithelial neoplasia. CONCLUSIONS: The data presented indicate a down-regulation of the FHIT tumor suppressor gene in prostate carcinoma and, thus, propose a potential target for therapeutic intervention.

Acid Anhydride Hydrolases↗
PubMed2005

Cooperativity and proton transfer in hydrogen-bonded triads.

Ab initio MP2/6-311+G(3df,2pd) and MP2/aug-cc-pVTZ calculations have been carried out to investigate the structures and properties of AHXHYH(3) (A=F, Cl; X=F, Cl; Y=N, P) hydrogen-bonded complexes. Significant cooperative effects are observed in the XHYH3 dyads in the triads due to the presence of the polar near-neighbor AH. These effects are greater when the polar partner is HF, which is a better proton donor than HCl. Structural changes, red shifts of proton-donor stretching frequencies, nonadditive interaction energies, and electron density redistributions unambiguously demonstrate that the X--HY hydrogen bond (HB) is stronger in the triads than in the corresponding dyads, while the X--H bond of the proton donor becomes weaker. Even more pronounced cooperative effects are observed in the AHXH dyads due to the presence of the YH3 partner. These effects are weaker in complexes having PH3 rather than NH3 as the proton acceptor, since NH3 is a stronger base. Cooperativity also enhances the proton-donating ability of the YH3 moiety, with the result that all complexes except FHFHPH3 are cyclic. Cooperativity, together with the ease of breaking the Cl--H bond in ClHClHNH3 and FHClHNH3, leads to proton transfer (PT), so that these two complexes are better described as approaching hydrogen-bonded ClHCl- x +HNH3 and FHCl- x +HNH3 ion pairs.

Journal Article↗
PubMed2005

Psychometric evaluation of a measure of Beck's negative cognitive triad for youth: applications for African-American and Caucasian adolescents.

A measure of Beck's negative cognitive triad, the Cognitive Triad for Children (CTI-C), was evaluated for its psychometric properties and utility with a community sample of 880 African-American and Caucasian adolescents. High-school students ranging from 14 to 17 years of age completed the CTI-C, the Children's Depression Inventory (CDI) and the Children's Attributional Style Questionnaire-Revised (CASQ-R) on two occasions 4 months apart. The CTI-C was found to be internally consistent, Cronbach's alpha=.90, to have acceptable test-retest reliability, r=.70, and concurrent validity as demonstrated by a significant correlation with the CASQ-R, r=.53. A principal factor analysis with promax rotation did not yield support for Beck's tripartite model of negative cognitions about the self, world, and future but rather yielded three factors with a combination of cognitions from all three domains. African American adolescents who reported more maladaptive cognitions on the CTI-C reported fewer depressive symptoms on the CDI 4 months later compared to their Caucasian counterparts, suggesting some limitation to using the CTI-C to predict depressive symptoms in African-American youth; however, Factor 1 derived from a factor analysis with the sample was more consistent in predicting future symptoms among both African-American and Caucasian adolescents. This factor consisted largely of positively worded items, offering some support for low positive affect as a predictor of depressive symptoms in adolescents.

Adolescent↗
PubMed2003

Cleft palate, transforming growth factor alpha gene variants, and maternal exposures: assessing gene-environment interactions in case-parent triads.

We have previously reported a threefold risk of cleft palate only (CPO) among children homozygous for the less common allele A2 at the TaqI marker site of the transforming growth factor alpha gene (TGFA) (Jugessur et al. [2003a] Genet. Epidemiol. 24:230-239). Here we assess possible interaction between the child's TGFA TaqI A2A2 genotype and maternal cigarette smoking, alcohol consumption, use of multivitamins and folic acid. This was done by comparing the strength of genetic associations between strata of exposed and unexposed case-parent triads. We also looked for possible gene-gene interaction with the polymorphic variant C677T of the folic acid-metabolizing gene MTHFR. We analyzed a total of 88 complete CPO triads selected from a population-based study of orofacial clefts in Norway (May 1996-1998). No evidence of interaction was observed with either smoking or alcohol use. The risk associated with two copies of the A2 allele at TGFA TaqI was strong among children whose mothers did not use folic acid (relative risk=4.5, 95% confidence interval=1.3-15.7), and was only marginal among children whose mothers reported using folic acid (RR=1.4, 95% CI=0.2-12.7). Although the interaction between the child's genotypes at TGFA TaqI and MTHFR-C677T was not statistically significant, the effect of the TGFA TaqI A2A2 genotype appeared to be stronger among children with either one or two copies of the T-allele at C677T (RR=4.0, 95% CI=1.1-13.9) compared to children homozygous for the C-allele (RR=1.7, 95% CI=0.2-15.7). In conclusion, we find little evidence of interaction between the child's genotypes at TGFA TaqI and various exposures for cleft palate, with the possible exception of folic acid intake.

Adult↗
PubMedDate not supplied

The benefits of triad communication in home health care.

Triad communication can be used by the nurse to facilitate communication with a patient and a caregiver in home health care. The family members may be involved as listeners or in discussion with the patient, the nurse, or both. The caregiver is selected based on specific communication objectives and the third person's ability to assist in meeting these objectives. Triad communication can (a) support the family and patient, (b) increase the caregiver's understanding, (c) increase compliance, (d) increase the nurse's understanding, (e) reinforce instruction, (f) decrease manipulation, (g) promote communication between family members, and (h) facilitate positive patient-family relationships.

Caregivers↗
PubMed1992

Healing of the medial collateral ligament following a triad injury: a biomechanical and histological study of the knee in rabbits.

The effect of a partial medial meniscectomy and anterior cruciate ligament (ACL) transection on medial collateral ligament (MCL) healing was studied in skeletally mature rabbits. Two groups of animals, group I (isolated MCL rupture) and group II (MCL rupture with ACL transection and partial medial meniscectomy), were examined. At 6 and 12 weeks postoperatively, histological examination of the healing MCL and biomechanical evaluation of the varus-valgus (V-V) knee rotation and tensile properties of the femur-MCL-tibia complex (FMTC) were performed. Group II animals experienced substantial joint degeneration by 6 weeks. Progressive osteophyte formation was observed adjacent to the MCL insertions along with proximal migration of the MCL tibial insertion between 6 and 12 weeks. Histologic examination of the healing MCL substance from both groups showed disorganized collagen, inflammation, and fibroblast proliferation that decreased over time. For group II knees, the V-V knee rotation was found to be significantly elevated (4.7 to 5.2 times the contralateral control), and did not decrease with time. In contrast, the V-V knee rotations of the group I specimens were 1.8 times greater than control immediately following injury, and approached control values by 12 weeks. Tensile testing of the FMTCs revealed that the ultimate load increased with time for both groups, but group I had significantly higher values than group II. The linear stiffness in group I was not different than that group II and did not increase with time. For the mechanical (material) properties of the healed MCL substance, the modulus of the healing tissue for group II was only 40% that of group I. The structural properties of the FMTC and the mechanical properties of the MCL substance from both groups at 6 and 12 weeks were significantly different from the contralateral controls. We further demonstrated that immediately after ACL reconstruction, the V-V rotation of group II knees could be restored to group I levels. Recent clinical studies of MCL healing following isolated complete ligament tears have suggested that nonoperative management without immobilization leads to excellent treatment outcome. However, in more severe injuries involving additional tissues, poor quality of the healed ligament tissue and articular degeneration are observed. Our results demonstrate the deleterious effects of an untreated triad injury on the healing of the MCL substance and its insertions. Examination of the MCL substance suggests that a much larger healing mass is formed following a triad injury, which partially compensates for inferior ligament mechanical properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Healing of the rabbit medial collateral ligament following an O'Donoghue triad injury: effects of anterior cruciate ligament reconstruction.

The effects of healing time and anterior cruciate ligament reconstruction on healing of the medial collateral ligament and stability of the knee joint were evaluated in a rabbit model of an O'Donoghue triad injury (rupture of the medial collateral ligament with removal of the anterior cruciate ligament and part of the medial meniscus). At time 0 and at 6 and 12 weeks postoperatively, the anterior-posterior translation and varus-valgus rotation of the knee, the structural properties of the femur-medial collateral ligament-tibia complex, and the mechanical properties of the substance of the medial collateral ligament were evaluated. Although anterior-posterior translation increased significantly with time, we could not demonstrate a significant temporal effect on varus-valgus rotation. The ultimate load, elongation at failure, and energy absorbed to failure improved with time. In addition, with time, failure of the complex occurred more often in the ligament substance than at the osseous insertion. Because healing time did not affect the cross-sectional area or modulus of the medial collateral ligament, the improved structural properties of the complex resulted not from improvements in the mechanical properties of the tissue but rather from healing of the tibial insertion site. By 12 weeks, the reconstructed knees had only minor signs of osteoarthrosis on the tibiofemoral surfaces; this is in contrast to the findings in anterior cruciate ligament-deficient knees in our earlier study. Additionally, at 12 weeks, the stiffness of the complexes from the reconstructed group was 1.3 times that of the anterior cruciate ligament-deficient group (p < 0.05), and te ultimate load had increased by a factor of 1.6 (p < 0.05). Our findings demonstrate that reconstruction of the anterior cruciate ligament in the rabbit helps to stabilize the joint, improves healing of the medial collateral ligament, and may decrease the incidence of early-onset osteoarthrosis after an O'Donoghue triad injury.

Animals↗
PubMed2008

Respiratory symptoms in a boy revealing Carney triad.

The association of gastrointestinal stromal cell tumor (GIST), paraganglioma, and pulmonary chondroma is known as the Carney triad, occurring predominantly in young adult females. We present the case of a 14-year-old male with respiratory symptoms resulting in the diagnosis Carney triad.

Adolescent↗
PubMed1996

Derivation of 3D coordinate templates for searching structural databases: application to Ser-His-Asp catalytic triads in the serine proteinases and lipases.

It is well established that sequence templates (e.g., PROSITE) and databases are powerful tools for identifying biological function and tertiary structure for an unknown protein sequence. Here we describe a method for automatically deriving 3D templates from the protein structures deposited in the Brookhaven Protein Data Bank. As an example, we describe a template derived for the Ser-His-Asp catalytic triad found in the serine proteases and triacylglycerol lipases. We find that the resultant template provides a highly selective tool for automatically differentiating between catalytic and noncatalytic Ser-His-Asp associations. When applied to nonproteolytic proteins, the template picks out two "non-esterase" catalytic triads that may be of biological relevance. This suggests that the development of databases of 3D templates, such as those that currently exist for protein sequence templates, will help identify the functions of new protein structures as they are determined and pinpoint their functionally important regions.

Amino Acid Isomerases↗
PubMed1998

Identification of the catalytic triad of the protein D2 protease in Pseudomonas aeruginosa.

We reported recently that protein D2 (OprD) porin of Pseudomonas aeruginosa bears protease activity (FEBS Letters 394, 179-182, 1996). To identify the catalytic residues of OprD, we introduced the site-directed mutations replacing the putative catalytic triad His156, Asp208, and Ser296 with glutamine, asparagine, and alanine, respectively. The OprD proteins purified from the chromosomal oprD-deficient mutants harboring the plasmids encoding the site-directed mutations showed protease activity less than 0.1% of that of the wild-type OprD. These site-directed mutageneses caused undetectable changes in the pore-forming activity of OprD as measured by single-channel conductance by the planar lipid bilayer. The minimum inhibitory concentration of imipenem in mutants having the replaced catalytic triads was identical with that in the wild-type strain. On the other hand, introduction of the mutation at His367 replacing with glutamine, the site that is supposed to be unrelated to the catalytic sites, showed the unchanged protease activity. These results unequivocally demonstrate that OprD is the protease bearing porin and catalyzes the reaction at His156, Asp208, and Ser296 residues.

Alanine↗
PubMed1995

An intramolecular triplex structure from non-mirror repeated sequence containing both Py:Pu.Py and Pu:Pu.Py triads.

A plasmid insert containing the (TA)7GATC(TA)7 inverted repeat and an adjacent (AG)7 tract adopts a cruciform structure at neutral pH. However, under acidic conditions the cruciform becomes readily disrupted in favor of a triplex. The (AG)7.(CT)7 duplex and one strand of the (TA)7GATC(TA)7 element are engaged in the three-stranded DNA formation, as determined using single-stranded DNA specific probes. The structure extrudes by displacing the (TA)7 strand adjacent to the (AG)7, and folding it back into the major groove of the (AG)7.(CT)7 duplex. This new variant of H-DNA is supercoil and pH dependent, requiring pH 6.1 or lower to form. The triplex is stabilized by T:A.T and A+:G.C triads. This unusual triad composition (50% of T:A.T and 50% of A+:G>C), that has not previously been observed in intramolecular triplexes, violates both the widely accepted division of triplexes into Py:Pu.Py or Pu:Pu.Py types and the requirement for mirror repeat symmetry.

Base Sequence↗
PubMed1994

Effect of repeated portal-triad cross-clamping during partial hepatectomy on hepatic regeneration in normal and cirrhotic rats.

The effects of ischemia/reperfusion during 70% partial hepatectomy on hepatic regeneration was evaluated in normal rats and thioacetamide-induced cirrhotic rats. Total hepatic ischemia and reperfusion (15 min each) by portal-triad cross-clamping was repeated two times in normal rats and four times in cirrhotic rats during hepatectomy. The labeling index of hepatocytes on Day 1 after operation (POD) and hepatic regeneration ratio on POD 28 were measured. In normal rats, the repeated ischemia/reperfusion decreased the survival rate from 100 to 77% (P < 0.05), lowered the hepatocyte labeling index from 33.5 +/- 2.5 to 16.7 +/- 6.5%, and diminished the hepatic regeneration ratio from 199 +/- 17 to 137 +/- 12% (P < 0.01). However, portal-systemic shunt improved those levels to 100, 30.6 +/- 13.7, and 169 +/- 19%, respectively (P < 0.01). In cirrhotic rats, no portal congestion was observed and hepatic regeneration was not suppressed by ischemia/reperfusion. Thus, portal pooling and the reperfusion of pooled portal blood may be the cause of inhibition on hepatic regeneration and not ischemia/reperfusion of the liver itself. Therefore, repeated portal-triad cross-clamping for short periods of time during the resection of cirrhotic liver is not harmful for hepatic regeneration.

Animals↗
PubMed2001

Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down syndrome brain.

Information on the various factors leading to impairments in the developing brain of fetal Down Syndrome patients is limited to few histological reports. We therefore attempted to describe expression levels of proteins in brain using the proteomic technique of two-dimensional electrophoresis with subsequent mass spectroscopical identification of protein spots and quantification with specific software. Cortical tissue was obtained from autopsy of human fetal abortus. Protein levels of GTP-binding nuclear protein ran, guanine nucleotide-binding protein g(o), alpha subunit 2, guanine nucleotide-binding protein g(i)/g(s)/g(t) beta subunit 1, -beta subunit 2, guanine nucleotide-binding protein beta subunit 5, nucleoside diphosphate kinase A, nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta, Rho GDP-dissociation inhibitor 1, biphosphate 3'-nucleotidase, small glutamine-rich tetra-tricopeptide repeat-containing protein and histidine triad nucleotide-binding protein were studied. Quantification revealed statistically significant reduced levels of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal DS brain as compared to controls. We conclude that in early prenatal life proteins involved in neural differentiation, migration and synaptic transmission are impaired in DS cortex. These results may help to understand the abundant mechanisms leading to abnormalities in the wiring, structure and function of DS brain.

Brain↗