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Prenatal diagnosis of tyrosinaemia type I can be achieved in cultured amniotic cells and in chorionic villus material by testing the activity of fumarylacetoacetate hydrolase and by DNA analysis, and in amniotic fluid by succinylacetone measurement. This specific metabolite can be measured either by gas chromatography-mass spectrometry or by delta-aminolevulinate dehydratase inhibition assay. In a series of 65 at-risk cases tested with the enzyme inhibition assay, one case out of the 18 with the disease had a normal level of succinylacetone. This case is presented.

Quantum chemical calculations are used to explore the origins of regioselectivity for proton-, Pt(II)- and Pd(II)-promoted cyclizations of 1,5-hexadienes, 5-aminoalkenes, and allylic acetimidates. The strain associated with achieving carbonium ion-like transition state geometries is shown to be a key factor in controlling 5-exo vs. 6-endo selectivity.

Dialysis amyloidosis is one of the most incapacitating complications of long-term dialysis treatment. Quantitative assessment of amyloid deposition using radiolabelled tracers has been recently proposed but convincing evidence of its validity in uraemic patients remains to be provided. We studied the plasma kinetics of i.v. administered 125 I-labelled serum amyloid P component ( 125 I-SAP) in 20 chronic haemodialysis patients compared with those of nine healthy volunteers and three non-dialysed patients with systemic amyloidosis. Plasma clearance of the tracer was abnormal in 17 of 20 dialysis patients in whom plasma radioactivity declined in a bi-exponential mode, in contrast to the single-exponential slope observed in all healthy controls. 125 I-SAP plasma half-life of the second component, probably reflecting metabolic clearance, was significantly prolonged in these dialysis patients compared with the healthy controls (35.3 versus 24.6 h, P

Dialysis amyloidosis is one of the most incapacitating complications of long-term dialysis treatment. Quantitative assessment of amyloid deposition using radiolabelled tracers has been recently proposed but convincing evidence of its validity in uraemic patients remains to be provided. We studied the plasma kinetics of i.v. administered 125I-labelled serum amyloid P component (125I-SAP) in 20 chronic haemodialysis patients compared with those of nine healthy volunteers and three non-dialysed patients with systemic amyloidosis. Plasma clearance of the tracer was abnormal in 17 of 20 dialysis patients in whom plasma radioactivity declined in a bi-exponential mode, in contrast to the single-exponential slope observed in all healthy controls. 125I-SAP plasma half-life of the second component, probably reflecting metabolic clearance, was significantly prolonged in these dialysis patients compared with the healthy controls (35.3 versus 24.6 h, P0.001). Among the long-term haemodialysis patients the calculated extravascular distribution of 125I-SAP was significantly greater in those with severe arthropathy than in asymptomatic patients. These findings demonstrate for the first time that SAP clearance is disturbed in haemodialysis patients due to both failing renal elimination and retention in extravascular sites. The extravascular diffusion is greatly enhanced in patients with clinical evidence of amyloidosis. Therefore the study of plasma 125I-SAP kinetics promises to be a valuable tool to quantitate the extent of amyloidosis.

Functionalisation of the second coordination sphere of a molecularly imprinted Pd complex was achieved by localising within the polymeric cavity a crown-ether receptor capable of altering the catalytic activity of the reactive site.

In the title ionic compound, [Pt(C17H23)(C34H33P3)](BF4)·2CH2Cl2, the PtII atom adopts a square-planar coordination geometry with the large (Z)-8-mesityl­cyclo­oct-4-en-1-yl group occupying the fourth coordination site. The (triphos)Pt moiety and the mesityl group are attached to the cyclo­oct-4-ene motif at the 1- and 8-position in a syn configuration. The (BF4)− anion and one of the dichloromethane solvate molecules each are disordered over two sets of sites.

Mixtures of dipeptide monomers create stereochemically and constitutionally complex dynamic libraries of potential receptors. When (−)-cytidine was utilized as guest an 84-membered cyclic host was amplified (70–175 fold) from a nearly undetectable initial concentration. Only the specified diastereomeric combination of the two chiral building blocks yielded a dynamic library from which the macrocyclic receptor could be amplified.

A Pd(ii)-catalyzed homo-coupling of Au(i)-aryls is reported. The reaction is driven by a Pd(0)/Au(i) redox reaction that generates a gold mirror and Pd(ii), and illustrates one of the challenges for developing dual catalytic Au–Pd systems.

The indications, results and outcomes of 508 genetic amniocenteses performed during a 6-years period in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of Quebec were reviewed. The geographical distribution of the residences showed that women living in urban communities were more likely to have an amniocentesis than those coming from rural communities. Advanced maternal age was the most frequent indication (62%) while a family history of hereditary disease was an indication in 9%, which is higher than in other published series. The rate of abnormal results in SLSJ was similar to those obtained in other series except for the rate found in amniocenteses done for hereditary diseases (4.3% versus 17.4-45.5%). All the pregnancies for which an abnormal result, but balanced translocations, was found were interrupted or ended spontaneously.

Chromosomal in situ hybridization allows the detection and the definition of single copy DNA segments of very small size. In a particular case, we demonstrate the inactivity of this molecular cytogenetic technique. In this case, karyotype analysis revealed a chromosome 11p+. In situ hybridization of probes PBGD, D11S29, NCAM, and ETSI located at 11q23-qter shows that the extra chromosomal material on chromosome 11p+ is a duplication of the 11q23-qter region.

A retrospective study was performed in chronic hemodialysis patients comparing total parathyroidectomy (PTX) followed by immediate autografting (IA) (total PTX+IA) with subtotal parathyroidectomy (subtotal PTX). One hundred six patients with severe, uncontrolled hyperparathyroidism were referred to this center and underwent surgery during the period from 1980 to 1990. Long-term follow-up after PTX was available in 49 of them: 28 patients had total PTX+IA and 21 had subtotal PTX. The two surgical methods were evaluated with respect to preoperative severity of hyperparathyroidism, immediate postoperative results, and long-term parathyroid status, as evaluated by an RIA measuring intact immunoreactive parathyroid hormone (intact iPTH; normal values, 15 to 65 pg/mL). The initial degree of hyperparathyroidism was comparable in the two groups. An excellent short-term control of hyperparathyroidism was achieved in the great majority (95%) of patients with either surgical procedure. However, long-term normalization of parathyroid gland activity was achieved in only one third of patients whereas 33% had elevated intact iPTH levels (> 130 pg/mL; i.e., higher than twice the upper range of normal) and 32% had low intact iPTH levels (< 15 pg/mL), consistent with permanent hypoparathyroidism. No difference was found in the immediate failure rates: 0 of 28 cases after total PTX+IA compared with 2 of 21 cases after subtotal PTX. Similarly, long-term intact iPTH levels were comparable: 400 +/- 105 versus 212 +/- 82 pg/mL (mean +/- SE; P = not significant). Interestingly, long-term serum intact iPTH levels were higher in patients with nodular (N = 18) than with diffusely (N = 26) hyperplastic glands: 556 +/- 146 versus 126 +/- 52 pg/mL (P < 0.001) and recurrence of hyperparathyroidism was more frequent with nodular hyperplasia (11 of 18) than with diffuse hyperplasia (4 of 26) (P < 0.02). In conclusion, although excellent short-term results were obtained with both procedures, satisfactory long-term control of parathyroid gland function was achieved in only one third of the patients, the other two third remaining either hypoparathyroid or developing recurrent hyperparathyroidism. Last, the histological subtype of parathyroid glands was partially predictive of the recurrence of hyperparathyroidism.

Equimolar mixtures of NMRP and ATRP initiators lead to polystyrene that is unimodal by GPC; the mechanism of action most consistent with the data suggests that under the reaction conditions, TEMPO and Cl end groups scramble rapidly relative to the propagation rate, and result in a single type of polymer chain.

Type 1 hereditary tyrosinemia (HT) is an autosomal recessive disease characterized by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH; E.C.3.7.1.2). We have isolated human FAH cDNA clones by screening a liver cDNA expression library using specific antibodies and plaque hybridization with a rat FAH cDNA probe. A 1,477-bp cDNA was sequenced and shown to code for FAH by an in vitro transcription-translation assay and sequence homology with tryptic fragments of purified FAH. Transient expression of this FAH cDNA in transfected CV-1 mammalian cells resulted in the synthesis of an immunoreactive protein comigrating with purified human liver FAH on SDS-PAGE and having enzymatic activity as shown by the hydrolysis of the natural substrate fumarylacetoacetate. This indicates that the single polypeptide chain encoded by the FAH gene contains all the genetic information required for functional activity, suggesting that the dimer found in vivo is a homodimer. The human FAH cDNA was used as a probe to determine the gene's chromosomal localization using somatic cell hybrids and in situ hybridization. The human FAH gene maps to the long arm of chromosome 15 in the region q23-q25.

The incorporation of C2 symmetry into chiral ligand design is a well-recognized strategy for restricting the number of diastereomeric transition states in metal-catalyzed enantioselective processes.1 Equally powerful stereochemical restrictions may also be realized with chiral ligands lacking C2 symmetry through the use of electronic effects such as the trans influence.2 Such effects are a natural consequence of the use of chiral bidentate ligands equipped with strong and weak donor heteroatom pairs (e.g., PR3/NR3 or PR3/SR2). Such electronic effects have the potential to influence both the stability and reactivity of the intervening diastereomeric reaction intermediates in the catalytic cycle. While mixed phosphorus/nitrogen bidentate ligands incorporating this construct have been applied in enantioselective palladiumcatalyzed nucleophilic alkylation of allylic esters,3 chiral thioether-containing donor ligands have been less well developed.4 As seen in structure A, thioether complexation creates an S-chiral sulfur center; however, a potential liability associated with these ligands is the relatively low barrier to sulfur inversion (15-20 kcal/mol) for transition metal-coordinated thioethers.5 In this paper, we report a new class of mixed phosphorus/sulfur ligands 1-3 that incorporates a metal-bound thioether as a chiral control element in asymmetric catalysis. The utility of these ligands is illustrated in the palladium-catalyzed allylic alkylation6 with enol-malonate and amine nucleophiles.

The past several decades have witnessed enormous growth in what we know about the synthesis, reactivity, reaction mechanisms, molecular structures, and electronic structures of organometallic molecules. Curiously, however, we know far less about the thermodynamics of most organometallic transformations and, in particular, about the exact strengths of metal-ligand bonds. In principle, such information offers a better understanding of metal-ligand bonding, a better insight into the course(s) of known reactions, and a valuable advantage in designing new transformations.1–5 For organometallic chemistry involving actinides, lanthanides, and early transition elements, our thermochemical/calorimetric investigations were motivated by growing evidence that deviations in reactivity patterns from those of middle and late transition elements could not be explained by kinetic factors alone. In the present chapter, we briefly review some of our recent results in this area, focusing upon how ancillary ligands affect metal-ligand bond enthalpies, metal-ligand bonding patterns as a function of position in the Periodic Table, and the thermochemically-assisted design of a new catalytic reaction pattern: organolanthanide-catalyzed hydroamination.

An effective method for the destruction of P-based nerve agent simulants using the ester interchange reaction is described; depolymerization of polycarbonate in the presence of aryl phosphinates and KOBut (5 mol%) leads to a net breakdown of the toxic constituents of the simulants while immobilizing each component as a polymer end group; the data suggest that application of this approach to the destruction of nerve agents such as VX may be fruitful.

Reaction of (dppe)PtCO3 with S-VANOL or S-VAPOL yielded (dppe)Pt(S-VANOL) and (dppe)Pt(S-VAPOL), respectively. NMR data indicate that the VANOL ligand in the former complex adopts a C2-symmetric O,O‘-bound form, while the VAPOL ligand binds to the metal in a C,O-binding mode that partially disrupts the ligand aromaticity. When matched complexes of S-VANOL and S-VAPOL were synthesized with (S,S-chiraphos)PtCO3, both complexes adopt the symmetric O,O‘-mode. Mismatched complexes with (R,R-chiraphos)PtCO3 have both ligands adopting the C,O-binding mode; however, the S-VANOL complex could not be isolated. Competition experiments between S-VANOL and S-VAPOL for the (S,S-chiraphos)Pt2+ fragment indicate that VANOL is the thermodynamically preferred ligand.

Hypotonia is sometimes a diagnosis for which infants are referred for investigation in the neonatal period.. Hypotonia occurs in infants with different disorders: neuromuscular, metabolic and chromosomal disorders. Among chromosomal disorders, hypotonia is a differential diagnosis particularly in Down and Prader Willi syndromes. Thus, karyotyping and fluorescent in situ hybridyzation with specific probes should be considerd if a child is hypotonic and/or dysmorphic. In our laboratory, since almost two years, we have begun a study in neonates and children under six months referred for hypotonia. The aim of this study is to detect very early in infancy children with Prader Willi syndrome. For each case, routine chromosome analysis is performed. In all cases. When no cytogenetic chromosomal abnormalities have been found, a fluorescent in situ hybridyzation technique with SNRPN probe has been performed. The SNRPN probe detect 75 % of deletion in the Prader Willi syndrome region, the 25% of undected cases needed more investigation by other molecular techniques like research of maternal uniparental disomy The results showed that in cases referred only for hypotonia, around 15 % of cases have a microdeletion on chromosome 15 q11.2. The results showed a significative detection rate for pursuing the use of fluorescent in situ hybridyzation in cases of hypotonia in neonates and children under six months of age. The early detection in Prader Willi syndrome is very important because children with Prader Willi syndrome develop a morbid obesity and complication resultin from this obesity. Management is aimed at prevention of obesity and treatment of its consequence.

Williams syndrome occurs with a frequency of 1 in 20,000. Clinical features of this syndrome include short stature, mental handicap, cardiac malformatons and a characteristic facies. Many patients are sporadic but autosomal dominant inheritance ia apparent in some families. Moreover, in many patients, chromosomal abnormalities are present. Williams syndrome belongs to a group of microdeletion syndromes meaning that in the vast majority of cases, the deletion is located on the long arm of chromosome 7 and it is visible on chromosomes only using molecular cytogenetic. In this study, we wanted to show that the deletion is visible by routine chromosome analysis in a significative number of cases. For this study, we have reviewed and reanalysed our cases of Williams syndrome by R-bands routine cytogenetic technique and proved by fluorescent in situ hybridyzation. The data obtained in this study showed 25% of cytogenetic deletion with R-bands routine cytogenetic analysis. We know that all cases with a microdeletion are put in evidence with in situ hybridyzation with Elastine probe located in chromosome 7q11.2, the region of Williams syndrome. We compare our cytogenetic results with other centres in Quebec working with G-bands cytogenetic routine analysis, they never see the deletion with their cytogenetic routine analysis. We can conclude that the use of R-bands is probably helpful revealing a chromosomal deletion in some cases of Williams syndrome. Up now, these patients do not show a different phenotype or behavior when they are compared with those ones they do not have the chromosomal deletion.

The aim of this research is to evaluate how transport properties at the surface and in the core of high-performance concrete (HPC) slabs are affected by silica fume and by superplasticizer and retarding agent dosages. The transport properties were evaluated by measuring the air permeability at two depths under the surface finished with a wooden trowel. The experimental program is based on eight different high-performance concrete mixtures (77 to 93 MPa) made with a water-to-binder ratio of 0.30. An ordinary portland cement (OPC) and a blended silica-fume cement (SF) were used to compare the effect of silica fume on the air permeability of surface and core concrete. Four mixtures were produced with a retarding agent to assess the effect of set retardation on the surface properties of high-performance concrete. For each combination of cement type and retarding agent dosages, the superplasticizer dosage was selected to produce two slump levels of 100 ± 10 mm and 200 ± 20 mm. It was found that the air permeability of the concrete located just beneath the surface of HPC slabs can be 2 to 20 times higher than the core permeability. The ratio between the surface and core permeabilities depends on mix-design parameters such as silica fume, superplasticizer (slump), and retarding agent dosages. Increasing the slump of HPC (from 100 to 200 mm) systematically increased the surface permeability. The effect of slump (or superplasticizer dosage) on the surface permeability of the HPC decreased as compressive strength increased. The use of a retarding agent in HPC without silica fume increased the air permeability of the surface concrete. This effect is particularly important for the concrete containing a high dosage of superplasticizer. Silica fume proved very effective in inhibiting increased surface permeability due to the dosages of superplasticizers and retarding agents.

Samples from 20 concrete mixtures were submitted to microscopical examination in order to record the size-distribution of the circles intercepted by a plane and the chords intercepted by a line of traverse. These data were used to determine the flow length and other characteristics of the air-void system by using a numerical method developed earlier. The flow lengths were correlated to the results obtained from freezing and thawing tests previously carried out on the same concrete mixtures. They were also compared to spacing factors and Philleo factors obtained from the same experimental data. The results of these correlations confirm the validity of the flow length concept and the numerical method used to calculate it. They clearly suggest that the flow length is a better indicator of the frost durability of concrete than the commonly used Test Method for Microscopical Determination of Parameters of the Air-Void System in Hardened Concrete (ASTM C 457) spacing factor, and more realistic indication of the actual spatial distribution of air voids in concrete than the Philleo factor.

Many parameters affecting the quality of the air void characteristics measurement are reviewed and discussed. The difficulties more frequently encountered during the measurement process are described, and some simple rules are proposed in order to increase, as much as possible, the accuracy and reproducibility of the test. The influence of the sampling size is studied, and the variability of air content, specific surface, and spacing factor is estimated from a statistical analysis of about 600 different concrete mixtures. The influence of the operator's subjectivity is also investigated, and the effect produced by large air voids on the computation of the spacing factor is discussed.

The qualitative analysis of the 6 isomeric dimethylamphetamines (both methyl groups on the aromatic ring) is described. Their ultraviolet, mass, and proton magnetic resonance spectra are similar, but infrared spectra allow a positive identification to be made, and reference spectra are provided. Melting point and gas-liquid and thin layer chromatographic data are also presented.

The qualitative analysis of the aromatic bromination products of the 6 isomeric dimethoxyamphetamines and their hydrochloride or hydrobromide salts is described. Their ultraviolet, mass, and proton magnetic resonance spectra are not sufficiently different for distinction but infrared spectra allow a positive identification to be made and reference spectra are provided for the bromination products of 2,4-, 2,5-, 2,6-, 4,5-, and 3,5-dimethoxyamphetamines. The application of gas-liquid and thin layer chromatography for the analysis of these products is discussed. The bromination of 2,3-dimethoxyamphetamine consistently gave mixtures which could not be separated satisfactorily; spectra are included for completeness of the comparison of products.

A technique designed to measure quantitatively succinylacetone (4,6-dioxoheptanoic acid) is presented. It essentially involves the inhibition of delta-aminolevulinate dehydratase (EC 4.2.1.24) by succinylacetone. Prior to their use in the assay, the samples are heated at 100 degrees C for 30 min in order to transform all succinylacetoacetate (3,5-dioxooctanedioic acid) to succinylacetone. By this transformation of the first abnormal metabolite specific to hereditary tyrosinemia to the second and last one, which is a powerful inhibitor of delta-aminolevulinate dehydratase, we determine in one sensitive assay the total amount of both. Succinylacetone was measured in sera and urines from 19 patients with hereditary tyrosinemia. All sera and urines contained succinylacetone at concentrations ranging, respectively, from 2 to 100 mumol/l and from 190 to 6000 mumol/g creatinine. The technique was also adapted to dried blood spots on paper and was used as a test complementary to blood tyrosine determination in mass screening for hereditary tyrosinemia. A total of 2412 samples having concentrations of 60 mg/l or more of tyrosine were assayed, and ten showed the presence of succinylacetone. These were all from newborns with hereditary tyrosinemia. The test has proven to virtually eliminate false positives, and, thereby, much clerical work and parental anxiety.

The drugs 1-[1-(2-thienyl)cyclohexyl]piperidine, 1-[1-(2-thienyl) cyclohexyl] morpholine, 1-[1-(2-thienyl)cyclohexyl] pyrrolidine, 1-(1-phenylcyclohexyl) morpholine, and 1-(1-phenylcyclohexyl) pyrrolidine are identified by spectroscopic techniques. The ultraviolet and proton magnetic resonance spectra of analogs are similar, but mass and infrared spectra are distinctly different, and reference spectra are provided. Gas-liquid and thin layer chromatographic systems for the analysis are discussed.