bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Antimicrobial Activities of Several Mannich Bases and Their Derivatives
Authors: Gul Halise Inci , Sahin Fikrettin , Gul Mustafa , Ozturk Suzan , Yerdelen Kadir Ozden
Published: June 2005

The aim of this study was to evaluate the antimicrobial activities of several Mannich bases and their derivatives against pathogenic bacteria and fungi. 3‐Dimethylamino‐1‐phenyl‐1‐propanone hydrochloride (Ig1) as mono‐Mannich base, bis(β‐aroylethyl)methylamine hydrochlorides (B1, B5) as bis‐Mannich bases, 3‐aroyl‐4‐aryl‐1‐methyl‐4‐piperidinol hydrochlorides (C1, C5) as piperidinol derivatives, which are structural isomers of bis‐Mannich bases, N,N'‐Bis(3‐dimethylamino‐1‐phenylpropylidene)hydra zine dihydrochlorides (D1) as azine derivative of mono‐Mannich base Ig1, and some representative quaternary derivatives (Ig4 and C6), which are quaternary derivatives of Ig1 and C1, respectively, have been synthesized. Aryl parts were phenyl in B1 and C1, and 2‐thienyl in B5 and C5. Bis‐Mannich bases and quaternary Mannich bases were found to be effective antifungal derivatives. Quaternary mono‐Mannich base Ig4 has shown twice the amount of higher antifungal potency against the human pathogenic fungus Microsporum canis compared with the reference drug amphotericin‐B and it had equal potency against many other fungi species pathogenic in humans and plants. Ig4 was effective against Staphylococcus aureus among the bacteria tested. Preparation of bis‐Mannich bases and qua ternization procedure seemed suitable chemical modifications to prepare effective antifungal compounds. Especially quaternary derivatives Ig4, and to some extent C6, seem to be model compounds to develop new antimicrobial agents for further studies.
Artificial Glycosyl Phosphorylases
Authors: Rousseau Cyril , Ortega‐Caballero Fernando , Nordstrøm Lars Ulrik , Christensen Brian , Petersen Torben Ellebæk , Bols Mikael
Published: June 2005

α‐ and β‐Cyclodextrin 6A,6D‐diacids (1 and 2), β‐cyclodextrin‐6‐monoacid (14), β‐cyclodextrin 6A,6D‐di‐O‐sulfate (16) and β‐cyclodextrin‐6‐heptasulfate (19) were synthesised. Acids 1, 2 and 14 were made from perbenzylated α‐ or β‐cyclodextrin, by diisobutylaluminum hydride (DIBAL)‐promoted debenzylation, oxidation and deprotection. Addition of molecular sieves was found to improve the debenzylation reaction. Sulfates 16 and 19 were made by sulfation of the appropriately partially protected derivatives and deprotection. Catalysis of 4‐nitrophenyl glycoside cleavage by these cyclodextrin derivatives was studied. Compounds 1, 2 and 16 were found to catalyse the reaction, with the catalysis following Michaelis–Menten kinetics and depending first order on the phosphate concentration. In a phosphate buffer (0.5 M, 59 °C, pH 8.0), KM varied from 2–10 mM and the kcat/kuncat ratio from 80–1000 depending on the stereochemistry of the substrate and the catalyst, with 2 being the best catalyst and with the sulfated 16 also displaying catalytic ability. The monoacid 14 and the heptasulfate 19 were not catalytic.
Schwann cell behavior after nerve repair by means of tissue‐engineered muscle‐vein combined guides
Authors: Raimondo Stefania , Nicolino Silvia , Tos Pierluigi , Battiston Bruno , Giacobini‐Robecchi Maria G. , Perroteau Isabelle , Geuna Stefano
Published: June 2005

Schwann cells play a critical role in peripheral nerve regeneration. When a non‐nervous conduit is used to bridge a nerve defect, the conduit is soon colonized by a number of Schwann cells that make a pathway for regrowing axons. By using electron microscopy, immunohistochemistry, and reverse transcriptase‐polymerase chain reaction analysis, we have investigated the behavior of migratory glial cells along a particular type of autologous tissue‐engineered conduit made of a vein filled with fresh skeletal muscle, using the rat sciatic nerve model. With this particular type of autograft, our data show that many Schwann cells soon take up a close relationship with grafted muscle fibers, and especially with their basal lamina, which appears to serve as a migration pathway for them. The early and massive colonization of the conduit is sustained by both Schwann cell migration and proliferation, as demonstrated by PCNA immunostaining. Later, as they meet regenerating axons, Schwann cells become closely associated with them and eventually lose their connections with grafted muscle fibers because of the formation of perineurial envelopes. Because previous studies showed that α2a‐2b NRG1 is overexpressed at early stages along the muscle‐vein combined tubes, we have also investigated mRNA expression of its two receptors, erbB2 and erbB3. Both messengers are overexpressed, although with different time courses. Overall, our results provide some morphological and biochemical bases for explaining the effectiveness of fresh muscle‐vein combined nerve guides and throw an interesting light on the possible role of α2a‐2b NRG1 through the erbB2/erbB3 heterodimer receptor for nerve regeneration inside non‐nervous conduits. J. Comp. Neurol. 489:249–259, 2005. © 2005 Wiley‐Liss, Inc.
Cortical influences on sizes and rapid plasticity of tactile receptive fields in the dorsal column nuclei
Authors: Wang Xin , Wall John T.
Published: June 2005

The cerebral cortex influences subcortical processing. In the somatosensory system, descending cortical inputs contribute in specific ways to the sizes and plasticity of tactile receptive fields (RFs) in the thalamus, but less is known about cortical influences on these aspects of brainstem RFs. The present studies evaluated how loss of cortical inputs affects sizes and plasticity of RFs in the brainstem dorsal column nuclei (DCN) when peripheral inputs were normal and when peripheral inputs were acutely disrupted. Loss of cortical inputs was produced by acute lesion of somatosensory, motor, and adjacent cortex, whereas disruption of peripheral inputs was produced by cutaneous microinjection of lidocaine (LID). Modest or no changes in sizes of DCN RFs, comparable to changes during control periods of no treatment, were seen in response to cortical lesion. LID caused rapid enlargements in RFs when cortex was intact. LID also caused rapid RF enlargements after cortical lesion, and these enlargements were greater than post‐LID enlargements when cortex was intact. These results indicate that normally sized RFs continue to be produced in the DCN after loss of cortical input. Cortex is also not required for RF enlargements after LID; however, cortical inputs have a constraining effect on these enlargements. Considered with findings from previous thalamic studies, these results suggest that cortical influences on RF size and plasticity in the DCN and thalamus differ in some respects. J. Comp. Neurol. 489:241–248, 2005. © 2005 Wiley‐Liss, Inc.
Generalized approaches to spatial sampling design
Authors: Angulo J. M. , Ruiz‐Medina M. D. , Alonso F. J. , Bueso M. C.
Published: June 2005

Spatial sampling design methods are commonly used to select a finite set of locations where observations provide optimal information, under a prescribed criterion, for parameter estimation and spatial inter/extrapolation on the basis of an appropriate statistical model. In some situations, environmental applications may also involve information from soft data. Moreover, the objectives may include the analysis of specific characteristics of interest such as model singularities (e.g. heterogeneity, fractal properties, etc.). The generalized random field theory provides a suitable framework for the formulation and analysis of problems related to these situations. An important case in the geostatistical context is the analysis of intrinsic random fields based on generalized increments. In this article, we formulate the entropy‐based approach to spatial sampling design for random field prediction in a generalized framework, and discuss its potential application in relation to the above aspects. Copyright © 2005 John Wiley & Sons, Ltd.
Effects of socio‐demographic variables on health‐related quality of life determined by the quality of life index—German version
Authors: Prause W. , Saletu B. , Tribl G. G. , Rieder A. , Rosenberger A. , Bolitschek J. , Holzinger B. , Kapfhammer G. , Katschnig H. , Kunze M. , Popovic R. , Graetzhofer E. , Zeitlhofer J.
Published: June 2005

Study objective

The purpose of this study was to determine subjective health‐related quality of life (HRQoL) in a sample of the Austrian population over 14 years of age in order to evaluate the effect of socio‐demographic variables on HRQoL.

Design/Setting

HRQoL was determined by means of the quality of life index ‐ German version (QLI‐Ge). The influence of socio‐demographic variables on HRQoL was assessed by statistical analysis using the Kruskal‐Wallis test and an analysis of variance.

Participants

A random‐quota procedure was used to get balanced representation from regions and demographic groups of the Austrian population. The sample consisted of 1049 participants, 493 men and 556 women.

Main results

Age was found to influence the QLI‐Ge total score (index score) and most individual items, with increasing age resulting in a decrease in HRQoL. Differences between the sexes were observed in three dimensions: males scored higher in ‘physical well‐being’, ‘psychological well‐being’ and ‘occupational functioning’. Marital status impacted most items with married persons showing better values than divorced persons or singles. Profession had only a minor effect on HRQoL, the level of education showed no influence at all.

Conclusions

The socio‐demographic variables age, sex and objective living conditions had a major influence on subjectively rated HRQoL, whereas profession and education were found to play a minor role in this context. It is recommended that in the interpretation of studies assessing HRQoL the above‐mentioned objective factors be considered. This will be of particular importance when determining the effect of a pharmacotherapy on HRQoL in patients. Copyright © 2005 John Wiley & Sons, Ltd.
Varying Ti‐6Al‐4V surface roughness induces different early morphologic and molecular responses in MG63 osteoblast‐like cells
Authors: Kim H. J. , Kim S. H. , Kim M. S. , Lee E. J. , Oh H. G. , Oh W. M. , Park S. W. , Kim W. J. , Lee G. J. , Choi N. G. , Koh J. T. , Dinh D. B. , Hardin R. R. , Johnson K. , Sylvia V. L. , Schmitz J. P. , Dean D. D.
Published: June 2005

Osteoblast response to Ti implants depends not only on the chemistry of the implant but also on the physical properties of the implant surface, such as microtopography and roughness. This study was undertaken to examine early changes in cell morphology and gene expression during the early phase of osteoblast interaction with titanium alloy (Ti‐6Al‐4V) surfaces of two different roughnesses. MG63 osteoblast‐like cells were cultured for 2, 6, 24, and 72 h on smooth (Ra = 0.18 ±0.03 μm) and rough (Ra = 2.95 ±0.23 μm) Ti‐6Al‐4V surfaces. Changes in cell proliferation were assessed by measuring cell number after 72 h in culture. Morphological characteristics were observed by scanning electron microscopy after 2, 6, and 24 h of culture. Changes in gene expression for extracellular signal‐regulated kinase 2 (Erk2), type I collagen (α2[I] collagen), phospholipase C‐γ2 (Plc‐γ2), and β‐actin were measured by RT‐PCR after 6 and 24 h in culture. Cell number was significantly higher on the smooth surface. In scanning electron micrographs, cells on smooth Ti‐6Al‐4V were spherical and raised up from the surface after 2 h in culture. In contrast, cells on the rough surface adopted an irregular, elongated shape that spanned across pits in the surface. At 24 h, cells on the smooth surface had flattened, become elongate, and covered the surface. In contrast, cells on the rough surface appeared more differentiated in shape and the margins of the cells were irregular, with many processes extending out, following the contour of the surface. Of the genes examined, only Erk2 and β‐actin showed a change in expression with surface roughness. Both genes were upregulated (p < 0.05) on the rough surface at 6 h. These results indicate that Ti‐6Al‐4V surface roughness affects osteoblast proliferation, morphology, and gene expression, and that these effects can be measured after periods as short as 2–6 h. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Effect of microtextured surfaces on the performance of percutaneous devices
Authors: Walboomers X. F. , Jansen J. A.
Published: June 2005

Along the percutaneous part of implantable devices, like (semi‐)permanent catheters, epithelial downgrowth can occur. This process can eventually lead to implant loss. Various treatments for the catheter surface have been proposed, to improve their performance. The purpose of the current study was to investigate the effect of a microgroove pattern on the tube surface, on epithelial downgrowth. Catheterlike implants were made of silicone tubes, with anchoring cuffs made of titanium‐fiber mesh. A thin sheet of silicone with microgrooves was applied on the tubes. Two types of texturing were used, a square groove of 10 μm wide and 1 μm deep; or a V‐shaped groove of 40 μm wide. The grooves were directed either along the long axis of the catheter tube (grooves perpendicular to the skin surface) or circling around the catheter (grooves directed parallel to the skin surface). As controls, catheters with a smooth outer surface were used. Implants were placed in 30 rats, with a follow‐up period of 9 weeks. During this time, animals were inspected biweekly, and catheter exit sites were evaluated using a scoring system. At the end of the 9‐week period the implants and surrounding tissues were processed for histological evaluation. For the clinical evaluation of the exit sites, no statistical differences were found between the study groups. Histologically, epithelial downgrowth was observed for all samples. The histomorphometrical measurements showed that there were no differences in downgrowth between the smooth and parallel‐grooved catheters. However, there was increased epithelial downgrowth along the catheters with grooves perpendicular to the skin. In conclusion, a grooved microtexture can direct epithelial tissue ingrowth, but this study found no beneficial effects of the guidance phenomenon. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Electrochemical studies on zirconium and its biocompatible alloys Ti‐50Zr at.% and Zr‐2.5Nb wt.% in simulated physiologic media
Authors: Oliveira Nilson T.C. , Biaggio Sonia R. , Rocha‐Filho Romeu C. , Bocchi Nerilso
Published: June 2005

Different electrochemical studies were carried out for Zr and its biocompatible alloys Ti‐50Zr at.% and Zr‐2.5Nb wt.% in solutions simulating physiologic media, Ringer and PBS (phosphate buffered saline) solutions. The results from rest‐potential measurements showed that the three materials are spontaneously passivated in both solutions and that the Ti‐50Zr alloy has the greatest tendency for spontaneous oxide formation. Some corrosion parameters (such as the pitting and repassivation potentials) were obtained via cyclic voltammetry in both solutions, revealing that the Ti‐50Zr has the best corrosion protection while Zr has the worst. On the other hand, the pre‐anodization (up to 8 V vs. SCE) of the alloys in a 0.15 mol/L Na2SO4 solution led to a significant improvement in their protection against pitting corrosion when exposed to the Ringer solution. Elemental analyses by EDX showed that during pitting corrosion, there is no preferential corrosion of any of the alloying elements (Zr, Ti, Nb). © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Au(III), Pd(II), Ni(II), and Hg(II) alter NFκB signaling in THP1 monocytic cells
Authors: Lewis J. B. , Wataha J. C. , McCloud V. , Lockwood P. E. , Messer R. L. W. , Tseng W.‐Y.
Published: June 2005

The transcription factor NFκB plays a key role in the tissue inflammatory response. Metal ions released into tissues from biomaterials (e.g., Au, Pd, Ni, Hg) are known to alter the binding of NFκB proteins to DNA, thereby modulating the effect of NFκB on gene activation and, ultimately, the tissue response to biomaterials. Little is known about the effect of these metals on key signaling steps prior to NFκB‐DNA binding such as transcription factor activation or nuclear translocation, yet these steps are equally important to modulation of the pathway. Oxidative stress is known to alter NFκB proteins and is suspected to play a role in metal‐induced NFκB signaling modulation. Our aim in the current study was to assess the effects of sublethal levels of Ni, Hg, Pd, and Au ions on NFκB activation and nuclear translocation in the monocyte, which is acknowledged as an important orchestrator of the biological response to materials and the pathogenesis of chronic disease. Sublethal concentrations of Au(III), Ni(II), Hg(II), and Pd(II) were added to cultures of human THP1 monocytic cells for 72 h. In parallel cultures, lipopolysaccharide (LPS) was added for the last 30 min to activate the monocytic cells. Then cellular cytoplasmic and nuclear proteins were isolated, separated by electrophoresis, and probed for IκBα degradation (activation) and NFκB p65 translocation. Protein levels were digitally quantified and statistically compared. The levels of reactive oxygen species (ROS) in the monocytic cells were measured as a possible mechanism of metal‐induced NFκB modulation. Only Au(III) activated IκBα degradation by itself. Au(III) and Pd(II) enhanced LPS‐induced IκBα degradation, but Hg(II) and Ni(II) suppressed it. Au(III), Ni(II), and Pd(II) activated p65 nuclear translocation without LPS, and all but Ni(II) enhanced LPS‐induced translocation. Collectively, the results suggest that these metal ions alter activation and translocation of NFκB, each in a unique way at unique concentrations. Furthermore, even when these metals had no overt effects on signaling by themselves, all altered activation of signaling by LPS, suggesting that the biological effects of these metals on monocytic function may only be manifest upon activation. None of the metal ions elevated levels of ROS at 72 h, indicating that ROS were probably not direct modulators of the NFκB activation or translocation at this late time point. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Synthesis of deramciclane* labeled with tritium in various positions
Authors: Szammer János , Simon‐Trompler Edit , Banka Zoltán , Szúnyog József , Klebovich Imre
Published: June 2005

[(1R)‐endo]‐(+)‐3‐bromocamphor was dehalogenated with tritium gas to [3‐3H]camphor and via [3‐3H]phenylborneol converted to [3‐3H]deramciclane isolated as the fumarate salt (specific activity 51.8 GBq/mmol). This three step synthesis from [3‐3H]camphor gave an overall yield of 22%.

Benzyloxy‐acetic acid methyl ester was reduced with sodium‐borotritide to 2‐benzyloxy‐ethanol‐[1‐3H], and through a four step procedure was converted to 2‐dimethylaminoethyl‐[2‐3H] chloride. The latter was condensed with the sodium derivative of 2‐phenylborneol giving rise to [2‐dimethylamino‐[2‐3H]ethoxy]deramciclane isolated as the fumarate (specific activity 8.177 GBq/mmol). This six step synthesis from [3H]NaBH4 gave an overall yield of 6%. Copyright © 2005 John Wiley & Sons, Ltd.
Gi/Go protein‐dependent presynaptic mechanisms are involved in clozapine‐induced down‐regulation of tyrosine hydroxylase in PC12 cells
Authors: Tejedor‐Real Purificación , Vogel Roland , Mallet Jacques , Biguet Nicole Faucon
Published: June 2005

Although the clinical effects of antipsychotics have been extensively studied, the molecular mechanisms underlying their antipsychotic activity are unclear. Chronic clozapine has been reported to reduce significantly the expression of tyrosine hydroxylase (TH) in the mesolimbic system. To characterize the mechanisms of action of clozapine on TH expression, PC12 cells turned out to be a useful model, being by far less complex than the entire brain. Both the quantity of TH protein and the amount of TH mRNA in PC12 cells were found to be decreased during incubation of the cells in the presence of clozapine. This decline was followed by a decrease in the enzymatic activity of TH. The effect of clozapine was blocked by preincubation with N‐ethylmaleimide, a sulphydryl‐alkylating reagent that interferes in Gi/o protein‐mediated second messenger pathways. Clozapine may thus decrease TH expression by interacting with Gi/o protein‐coupled receptors, such as D2 and 5HT1A. Knowledge of the molecular mechanisms underlying the clinical effects of established antipsychotics will promote the development of new and more efficient antipsychotic drugs. © 2005 Wiley‐Liss, Inc.
Micro‐Raman spectroscopic study of pottery fragments from the Lapatsa tomb, Cyprus, ca 2500 BC
Authors: Sendova M. , Zhelyaskov V. , Scalera M. , Ramsey M.
Published: June 2005

Micro‐Raman spectroscopy was applied to the mineralogical characterization of Bronze Age Cypriot ceramic fragments from the Lapatsa Tomb collection of the Ringling Museum of Art. Micro‐probing was carried out on the surface and the results were compared with those of micro‐probing from the cross‐section of the two samples studied. Significant statistics were collected from 500 locations on each sample. Various phases were identified: quartz, albite, calcite, ilmenite, anatase, rutile, hematite and maghemite. It was determined that the different red coloration of both pieces is due not only to different hematite concentrations, but also to different grain sizes. The presence of low‐temperature albite and anatase suggests low firing temperatures. The presence of hematite suggests firing in an oxidizing atmosphere. Copyright © 2005 John Wiley & Sons, Ltd.
ΓD‐convergence for a class of quasilinear elliptic equations in thin structures
Authors: Amaziane B. , Goncharenko M. , Pankratov L.
Published: June 2005

We study the asymptotic behaviour of the solution of a stationary quasilinear elliptic problem posed in a domain Ω(ε)of asymptotically degenerating measure, i.e. meas Ω(ε)→ 0 asε→ 0, whereεis the parameter that characterizes the scale of the microstructure. We obtain the convergence of the solution and the homogenized model of the problem is constructed using the notion of convergence in domains of degenerating measure. Proofs are given using the method of local characteristics of the medium Ω(ε)associated with our problem in a variational form. Copyright © 2005 John Wiley & Sons, Ltd.
Long time behaviour of a flow in infinite pipe conforming to slip boundary conditions
Authors: Mucha Piotr Bogusław , Sadowski Witold
Published: June 2005

The paper analyses long time behaviour of solutions of the Navier–Stokes equations in a two‐dimensional pipe‐like domain. The system is studied with perfect slip boundary conditions with arbitrary inflow conditions at infinity. The main results show the existence of global in time solutions and of an attractor for the dynamical system generated by the model. The paper also establishes an upper bound for the Hausdorff dimension of the attractor. Copyright © 2005 John Wiley & Sons, Ltd.
Trace identities for solutions of the wave equation with initial data supported in a ball
Authors: Finch David , Rakesh
Published: June 2005

Suppose u is the solution of the initial value problem

Suppose n ≥ 1 is odd, f and g are supported in a ball B with boundary S, and one of f or g is zero. We derive identities relating the norm of f or g to the norm of the trace of u on S × [0,∞) . These identities are derived using integral geometric and multiplier methods. Copyright © 2005 John Wiley & Sons, Ltd.
Filtered backprojection for thermoacoustic computed tomography in spherical geometry
Authors: Haltmeier M. , Schuster T. , Scherzer O.
Published: June 2005

Thermoacoustic computed tomography (TCT) is a novel imaging technique for non‐destructive evaluation and medical imaging. It uses electromagnetic energy as input and the induced thermoacoustic pressure field as measurement output. The determination of the unknown energy deposition function is based on the integral geometric problem of reconstructing a function from its integrals over certain spheres. We apply the method of approximate inverse to derive filtered backprojection type reconstruction algorithms in spherical scanning geometry. Numerical results are presented and show the validity of the resulting algorithms. Copyright © 2005 John Wiley & Sons, Ltd.
A study on the orientation structure and mechanical properties of polyacrylonitrile precursors
Authors: Xu Qiang , Xu Lianghua , Cao Weiyu , Wu Sizhu
Published: June 2005

The polyacrylonitrile precursors were made through the two‐stage drawing process. The orientation structure was examined through wide‐angle X‐ray diffraction (WAXD). The orientation factors and the modulus were measured through the sound velocity method. The mechanical properties, such as the Young's modulus, the tensile strength and the breaking elongation ratio were obtained by the single fiber tensile test. The results showed that the Young's modulus and the strength of the precursors increased with draw ratio, which is accordant with the enhancement of the micromolecular orientation degree. Therefore the orientation factors obtained from the experiments were compared with the theoretical curves which were predicted through the Crawford and Kolsky's model. The physical meaning of the parameters m and n were analyzed. A good agreement of the orientation factor between the experimental data and the theoretical curve was achieved. Copyright © 2005 John Wiley & Sons, Ltd.
Factors affecting the efficacy of non‐fumigant nematicides for controlling root‐knot nematodes
Authors: Giannakou Ioannis O , Karpouzas Dimitrios G , Anastasiades Ioannis , Tsiropoulos Nicholas G , Georgiadou Athena
Published: June 2005

Second‐stage juveniles (J2) and egg masses of root‐knot nematodes as well as root debris heavily infected by the latter were exposed for different periods of time to six different doses of the nematicides cadusafos and fenamiphos. The efficacy of the nematicides increased significantly with increasing exposure time. Both nematicides were more effective against J2, although they could not provide acceptable control of J2 inside egg masses or heavily galled root debris. The effect of different application strategies on the efficacy and persistence of certain nematicides was also assessed in a field study. Cadusafos, fenamiphos, fosthiazate and oxamyl were applied in field micro‐plots either as a single full dose at the time of crop establishment or as multiple reduced‐rate applications at 14‐day intervals throughout the cropping period, and their efficacy and persistence were determined using bioassays and analytical studies. Fosthiazate was the most efficient nematicide studied, and this was mainly attributed to its long soil persistence. Oxamyl also provided adequate nematode control for the first 48–56 days after its application, regardless of the application method used and its relatively rapid field dissipation. Fenamiphos and cadusafos failed to provide adequate nematode control, although cadusafos was the most persistent of the nematicides tested. The failure of fenamiphos to provide adequate nematode control was mainly attributed to its rapid degradation by soil micro‐organisms, which were stimulated after its repeated low‐rate application at 14‐day intervals. In contrast cadusafos failure was attributed to the inability of the nematicide to reduce nematode populations even at relatively high concentrations in soil. Copyright © 2005 Society of Chemical Industry
Genetic screening, testing and treatment: How far can we go?
Authors: Scriver C. R.
Published: June 2005

Treatment comes in three forms: care, control, cure; each will be part of any new development in the management of genetic disease, either Mendelian or complex. Diagnosis recognizes three states of disease: impairment, disability, and handicap when the disease is symptomatic and has manifestations. Genetics in health care has the potential to prevent these manifestations by interventions at the presymptomatic stage. Wherever cause of disease involves genotypic variation that undermines homeostasis, genetic testing and screening could play a predictive role. The area of greatest interest will be the common multifactorial diseases. While some persons worry that geneticists have taken society too fast and far along the road to ruin, it is closer to the truth that we have actually gone rather slowly and not very far along the road to better personal and collective health. With wisdom and caution the new opportunities for genetic testing or screening will become part of health care; and sooner rather than later when better treatments for our inherited infirmities are found.
Somatic gene therapy for phenylketonuria and other hepatic deficiencies
Authors: Eisensmith R. C. , Woo S. L. C.
Published: June 2005

Gene therapy is the delivery of genetic material to specific cell types of an organism to alter its physiology or function. This technology is being explored as a means of treating diseases caused by deficiencies of hepatic gene products. The two diseases being used as models for hepatic gene therapy are classical phenylketonuria (PKU) and haemophilia B. Vectors derived from adenoviruses can be used to completely correct these diseases in animal models. The phenotypic correction generated in these studies is transient, and cannot be duplicated by vector readministration. The transient nature of transgene expression results from the destruction of the virally‐transduced cells by a cellular immune response directed against the late viral gene products that are also expressed in the target cells. The inability to repeatedly administer virus is caused by a humoral immune response directed against viral proteins present at the time of infusion. If the host immune response is suppressed, transgene expression can persist for 6 months or more. These findings suggest that host immunomodulation in combination with further modification of the adenoviral vector to reduce or eliminate late viral gene expression may permit long‐term expression of potentially therapeutic gene products in mammalian liver.
Metabolic fuel utilization and pyruvate oxidation during the postnatal period
Authors: Medina J. M. , Tabernero A. , Tovar J. A. , Martín‐Barrientos J.
Published: June 2005

The transplacental supply of nutrients is interrupted at birth, which diverts maternal metabolism to lactation. After birth, energy homeostasis is rapidly regained through milk nutrients which supply the newborn with the fatty acids and ketone bodies required for neonatal development. However, immediately after birth and before the onset of suckling there is a time lapse in which the newborn undergoes a unique kind of starvation. During this period glucose is scarce and ketone bodies are not available owing to the delay in ketogenesis. Under these circumstances, the newborn is supplied with another metabolic fuel, lactate, which is utilized as a source of energy and carbon skeletons. Neonatal rat lung, heart, liver and brain utilize lactate for energy production and lipogenesis. Lactate is also utilized by the brain of human babies with type I glycogenosis. Both rat neurons and astrocytes in primary culture actively use lactate as an oxidizable substrate and as a precursor of phospholipids and sterols. Lactate oxidation is enhanced by dichloroacetate, an inhibitor of the pyruvate dehydrogenase kinase in neurons but not in astrocytes, suggesting that the pyruvate dehydrogenase is regulated differently in each type of cell. Despite the low activity of this enzyme in newborn brain, pyruvate decarboxylation is the main fate of glucose in both neurons and astrocytes. The occurrence of a yeast‐like pyruvate decarboxylase activity in neonatal brain may explain these results.
Neurological presentations of mitochondrial diseases
Authors: Zeviani M. , Bertagnolio B. , Uziel G.
Published: June 2005

We present here a report on a 5‐year experience in clinical investigation, diagnostic management and molecular genetic studies of neuromitochondrial disorders, defined on the basis of morphological, biochemical and genetic findings. Leigh disease is the most frequent clinical presentation in infancy and childhood, but symptoms at onset are poorly informative. In paediatric cases, lactic acidosis and neuroradiological abnormalities are frequent, and can be of help for the diagnostic orientation. In the adult population, muscle weakness, ophthalmoplegia with ragged‐red fibres, retinitis pigmentosa, progressive myoclonal ataxia, and early‐onset stroke‐like episodes, are frequently combined in complex syndromes that are often familial (maternally inherited) and/or associated with well‐established mutations in mitochondrial DNA (mtDNA). However, the presence of overlap syndromes and features common to many neuromitochondrial diseases can complicate the clinical evaluation and the diagnostic approach. The pathogenicity of a given mtDNA mutation can frequently be ascertained by correlating the degree of heteroplasmy with the clinical or biochemical phenotypes. Moreover, transmitochondrial cybrids can be used to test the effects of either mitochondrial or nuclear gene abnormalities in a fully controlled, user‐friendly and highly informative system.
The treatment of congenital lactic acidoses
Authors: Morris A. A. M. , Leonard J. V.
Published: June 2005

Congenital lactic acidoses form a heterogeneous group of disorders: this paper considers primarily defects of the pyruvate dehydrogenase complex and the respiratory chain. Attempts to treat these disorders are hampered by uncertainty concerning the pathophysiology and by the central role of the enzymes in cellular metabolism. Few strategies are of proven efficacy, though many have been tried, including dietary manipulation, enhancement of residual enzyme activity, artificial electron acceptors and free‐radical scavengers. Evaluation of treatment is complicated by the rarity, heterogeneity and unpredictable course of the diseases. Double‐blind placebo‐controlled trials are needed.
Hyperphenylalaninaemia due to impaired dihydrobiopterin biosynthesis: Leukocyte function and effect of tetrahydrobiopterin therapy
Authors: Fukuda K. , Tanaka T. , Hyodo S. , Kobayashi Y. , Usui T.
Published: June 2005

We have described the clinical and biochemical status of two patients with tetrahydrobiopterin (BH4) deficiency due to impaired dihydrobiopterin biosynthesis. BH4 administration appeared to improve the mental and psychological status more than did neurotransmitter replacement therapy alone. This enhancement of activities of daily life was seen with a dose of BH4 as low as 1.25 mg kg−1 day−1. Granulocyte adherence capacity was below normal and recovered after BH4 therapy in both patients. B‐cell differentiation capacity was altered either before or after therapy.
Diagnosis of classical Morquio's disease:N‐acetylgalactosamine 6‐sulphate sulphatase activity in cultured fibroblasts, leukocytes, amniotic cells and chorionic villi
Authors: Yuen M. , Fensom A. H.
Published: June 2005

The tritiated disulphated trisaccharide 6‐sulpho‐N‐acetylgalactosamine‐glucuronic acid‐6‐sulpho‐N‐acetyl[1‐3H]galactosaminitol was prepared from chondroitin 6‐sulphate for use as a substrate forN‐acetylgalactosamine 6‐sulphate sulphatase. The reaction product was separated on ECTEOLA cellulose rather than Dowex 1×2. The mean activities of normal fibroblasts, leukocytes and amniotic cells were 8.43, 2.59 and 3.14 nmol h−1 mg protein−1, respectively. Fibroblasts from five patients with classical Morquio's disease (mucopolysaccharidosis IVA; MPSIVA) and one patient with neonatal multiple sulphatase deficiency displayed activities of less than 5% of control mean. Activity in amniotic cells from a pregnancy where the fetus was affected with MPS IVA was 6% of control mean. Activity was also found to be present in normal specimens of chorionic villi (mean value 1.21 nmol h−1 mg protein−1), demonstrating the feasibility of first trimester prenatal diagnosis of MPS IVA by assay of activity in this tissue.
Liver‐specific glucose‐6‐phosphatase is not present in human placenta
Authors: Chen Y. T. , Kato T.
Published: June 2005

Type I glycogen storage disease (McKusick 23220), an inherited absence or deficiency of glucose‐6‐phosphatase (EC 3.1.3.9) activity in the liver, kidney and intestine, is associated with the accumulation of glycogen in those organs. Previous reports have shown that glucose‐6‐phosphatase exists in human placenta and that detection of a heterozygote for this disorder from placenta might be possible. Our finding of a normal glucose‐6‐phosphatase activity in a placenta from a patient at risk for type Ia glycogen storage disease prompted us to examine in more detail placental glucose‐6‐phosphatase. Unexpectedly, we found the properties of the placental enzyme differed from that in normal liver, and the placental enzyme hydrolyzed glucose‐6‐phosphate, mannose‐6‐phosphate, β‐glycerol phosphate and glucose‐1‐phosphate equally well. Our data suggest the enzyme deficient in type I glycogen storage disease cannot be detected in placenta.
A new variant of glycogen storage disease type 1: Probably due to a defect in the glucose‐6‐phosphate transport system
Authors: Igarashi Y. , Otomo H. , Narisawa K. , Tada K.
Published: June 2005

A new variant of glycogen storage disease (GSD) Type 1, with clinical symptoms and laboratory findings consistent with those of glucose‐6‐phosphatase (G6Pase) deficiency, is described. Assay of G6Pase in liver from the patient immediately after biopsy by the method of Nordlie and Arion gave low activity (0.8µmol/min per g liver) in the absence of detergent, but was normal (10.2µmol/min per g liver) after addition of detergent. Liver stored for a day at −25°C had normal activity (3.4µmol/min per g liver) without detergent. In patients with GSD Type 1a, G6Pase activity was very low both with and without detergent. These findings suggest a defect in glucose‐6‐phosphate transport in the microsomal membrane of the patient's liver. The integrity of microsomal membrane was destroyed by storage at −25°C, when activity of G6Pase in the patient's liver could be demonstrated. This may be the first example of a disorder involving the transport system of an intracellular membrane.
Neutral 17β‐hydroxysteroid oxidoreductase deficiency in testes causing male pseudohermaphroditism in an infant
Authors: Harkness R. A. , Thistlethwaite D. , Darling J. A. B. , Skakkebaek N. E. , Corker C. S.
Published: June 2005

A deficiency of neutral 17β‐hydroxysteroid oxidoreductase activity in tests has been diagnosed in an infant with male pseudohermaphroditism.In vivo stimulation tests of testicular endocrine function with human chorionic gonadotrophin provided an accurate diagnosis in contrast to estimates of enzymic activityin vitro in testes and other tissues. The discrepancy in testes may be due to the absence of gonadotrophin stimulation in the latter studies. Thein vitro studies show that there are at least two forms of 17β‐hydroxysteroid oxidoreductase under independent genetic control and that only one form is localized to the testes. The diagnosis before puberty has allowed early treatment by removal of the abnormal testes which should prevent the usual presenting clinical signs of marked masculinization and hirsutism at puberty.
Keratan sulphate excretion in a patient with Kniest dysplasia
Authors: Pennock C. A. , Gordon I. R. S. , Longdon K. , Burman D.
Published: June 2005

The clinical and radiological features of a patient with Kniest dysplasia, a form of metatropic dwarfism, are described. The patient excreted glycosaminoglycans (mucopolysaccharides) in normal amounts during infancy but subsequently showed abnormal keratan sulphate excretion. The significance of these findings and the possibility that Kniest dysplasia represents another mucopolysaccharidosis are discussed.
Infantile type 2 sialidosis in a Pakistani family — a clinical and biochemical study
Authors: King M. , Cockburn F. , MacPhee G. B. , Logan R. W.
Published: June 2005

Two siblings of consanguineous parents presented in infancy with failure to thrive, mild coarsening of facies, visceromegaly and corneal opacities. One showed reduced hepatic β‐galactosidase activity suggesting a GM1‐gangliosidosis variant. Both patients developed progressive coarsening of facies, slow neurological deterioration, macular cherry‐red spots and punctate cataracts over the first decade. Urine screening with thin layer chromatography revealed abnormal excretion of two slow‐moving oligosaccharide bands and leukocyte and fibroblast neuraminidase activity was grossly reduced. The mother, phenotypically normal, showed levels of neuraminidase compatible with heterozygosity.

These patients have primary neuraminidase deficiency. The clinical and biochemical variables are reviewed.
Human placental steroid sulphatase—purification and monospecific antibody production in rabbits
Authors: van der Loos C. M. , van Breda A. J. , van den Berg F. M. , Walboomers J. M. M. , Jöbsis A. C.
Published: June 2005

Human steroid sulphatase was purified 43‐fold from placental microsomes using a four step procedure: solubilization with Miranol H2M, Bio‐Gel A 1.5m chromatography, column chromatofocusing and Sephadex G‐75 chromatography. The purified enzyme that appeared electrophoretically homogeneous was used to immunize rabbits. Protein blotting demonstrated that the resulting antiserum mainly reacted with a polypeptide of 63 000 dalton, which is about the size of placental steroid sulphatase. The antiserum was freed from minor impurities by absorbing it to Sepharose 4B with immobilized antigens prepared from a steroid sulphatase deficient placenta.
A carbamylphosphate synthetase deficiency with no detectable immunoreactive enzyme and no translatablemRNA
Authors: Graf L. , McIntyre P. , Hoogenraad N. , Brown G. , Haan E. A.
Published: June 2005

A lethal carbamylphosphate synthetase (CPS: EC 6.3.4.16) deficiency (McKusick 23730) was found in a newborn girl; who presented on the second day of life with acute hyperammonaemia, hypotonia, seizures and who died in a coma 6 days after birth. The activity of the mitochondrial urea cycle enzymes, CPS and ornithine transcarbamylase (OTC: EC 2.1.3.3) were measured on a needle biopsy sample taken from liver and showed that CPS was 1.4% of the normal mean (0.09 nmol/min/mg protein) whereas OTC activity was normal (110 nmol/min/mg protein). Immunological analysis of the liver sample showed no detectable immunoreactive CPS and confirmed the presence of normal levels of OTC. RNA was extracted from postmortem liver andin vitro translation experiments showed that there was no translatable CPSmRNA and confirmed that no CPS protein was synthesized in this child. The absence of translatablemRNA is explicable in terms of a genetic defect which results in a failure to synthesizemRNA for CPS, or synthesis of a defective form ofmRNA which is not translated.
Kinetic properties of erythrocyte phosphofructokinase in patients with type VII glycogenosis from two families — close similarity to liver type phosphofructokinase
Authors: Shimizu T. , Kono N. , Mineo I. , Sumi S. , Nonaka K. , Tarui S. , Koyama W.
Published: June 2005

The kinetic properties of phosphofructokinases (PFKs) from normal human liver, muscle and erythrocytes, and from erythrocytes of two unrelated patients with type VII glycogenosis (muscle PFK deficiency, McKusick 23280) were analysed in this study. Sensitivity to inhibition by ATP and to inhibition by 3‐phosphoglycerate, 2‐phosphoglycerate, phosphoenolpyruvate and citrate were quite different for muscle and liver PFKs. The kinetic characteristics of normal erythrocyte PFK were intermediate between those of muscle and liver PFKs. The kinetic constants of erythrocyte PFK of a patient in one family were indistinguishable from those in the other family. In addition, kinetic behaviour of residual PFK activity in erythrocytes from patients in the two families were quite similar to those of normal liver PFK. These results of kinetic analyses provide convincing evidence for the concept that normal erythrocyte PFK consists of muscle and liver type subunits. Residual erythrocyte PFK activity in type VII glycogenosis is thus concluded to reflect the activity of liver type PFK existing in patient's erythrocytes.
Glutaric aciduria type I presenting with hypoglycaemia
Authors: Dunger D. B. , Snodgrass G. J. A. I.
Published: June 2005

We present a child with glutaryl CoA‐dehydrogenase deficiency (type I glutaric aciduria) who presented with bilateral subdural hydromas, and progressive choreoathetosis and dysarthria. The diagnosis was made when she was investigated for hypoglycaemia at the age of 3.5 years. Temporary adrenocortical insufficiency was also noted. Three years after diagnosis the adrenal insufficiency and hypoglycaemia have resolved and treatment with riboflavin and ‘lioresal’, a GABA analogue, has prevented any further neurological deterioration.
Biochemical investigations on a patient with a defect in cytosolic acetoacetyl‐CoA thiolase, associated with mental retardation
Authors: Bennett M. J. , Hosking G. P. , Smith M. F. , Gray R. G. F. , Middleton B.
Published: June 2005

A severely mentally retarded boy with two normal siblings was persistently found to excrete elevated amounts of 3‐hydroxybutyrate and acetoacetate. Enzyme analysis in cultured fibroblasts revealed a probable deficiency in cytosolic acetoacetyl‐CoA thiolase which was about half the control activity with normal mitochondrial thiolase activities. Treatment with reduced dietary fat was initiated and a rapid reduction of the ketosis to biochemical normality was demonstrated. Shortly after initiating dietary treatment he presented with severe gastrointestinal problems and the histological features of colitis cystica superficialis. This appeared to respond to intravenous hydrocortisone therapy with an apparent complete recovery.
Cyclic adenosine monophosphate excretion in urine of patients and carriers of congenital nephrogenic diabetes insipidus
Authors: Uttley W. S. , Atkinson B. , Adams A. , Shirling D.
Published: June 2005

Urinary excretion of cyclic adenosine monophosphate (cAMP) is assessed in response to pitressin stimulation in three patients with nephrogenic diabetes insipidus, four carriers and seven controls. There is no significant difference in cAMP excretion between these groups when corrected for surface area, nor is there any significant increase in excretion after pitressin stimulation. There is very close correlation between urinary cAMP and both urinary concentration and urinary creatinine excretion. Urinary cAMP after pitressin stimulation does not discriminate between carriers of nephrogenic diabetes insipidus and control subjects.
Copper deficiency in the mitochondria of cultured skin fibroblasts from patients with menkes syndrome
Authors: Kodama H. , Okabe I. , Yanagisawa M. , Kodama Y.
Published: June 2005

The mitochondrial copper concentrations and cytochrome C oxidase activity of the fibroblasts from the patients with Menkes syndrome were investigated. Both the mitochondrial copper concentrations and cytochrome C oxidase activity of fibroblasts from patients with Menkes syndrome were lower than those of the control fibroblasts. These data indicate that the mitochondria of fibroblasts from patients with Menkes syndrome are in a state of copper deficiency. The activity decline of cytochrome C oxidase, a mitochondrial cuproenzyme, seems to be caused by copper deficiency in the mitochondria.