bluuebunny/crossref_metadata_2025 huggingface dataset:
Homocysteine, factor VII and antithrombin III in subjects with different gene dosage for cystathionine β‐synthase
Authors: Brattström L. , Israelsson B. , Tengborn L. , Hultberg B.
Published: June 2005

Cystathionine β‐synthase deficiency results in severe homocysteinaemia, precocious arteriosclerosis and frequent thromboembolism. In addition, antithrombin III activity and factor VII are low. Arteriosclerosis seems to be increased in heterozygotes as well (cystathionine β‐synthase gene dosage 50%) but rare in Down syndrome (cystathionine β‐synthase gene dosage 150%). In the present study total plasma homocysteine was high in three homozygotes, slightly increased in 20 obligate heterozygotes but not reduced in nine subjects with Down syndrome when compared to controls. After methionine loading, increases of homocysteine were pathologically high in 14 of 20 heterozygotes but was not, as expected, low in subjects with Down syndrome. Antithrombin III activity and factor VII antigen tended to be low in homozygotes but were normal in heterozygotes. In Down syndrome antithrombin III activity was reduced and factor VII antigen normal. There were no correlations between levels of homocysteine, antithrombin III activity and factor VII antigen. Thus, subjects with Down syndrome seem not to exhibit the expected gene dosage effect on homocysteine metabolism which could explain their reduced proneness to develop arteriosclerosis, nor do antithrombin III activity or factor VII antigen seem to be related to homocysteine metabolism.
Molecular analysis of a human liver mitochondrial ornithine transcarbamylase deficiency
Authors: Berrez J.‐M. , Bardot O. , Thiard M.‐C. , Alvarez F. , Latruffe N.
Published: June 2005

The liver of a young girl which had been successfully transplanted was investigated at the ornithine transcarbamylase (OTC, EC 2.1.3.3) gene expression level. Northern blot hybridization using a human OTC cDNA probe showed a greater than 80% decrease in specific OTC mRNA although having the same molecular size as a normal control. OTC polypeptide was simultaneously synthesized with a normal molecular size but at a low level (20%) as shown by immunoblotting. The OTC enzyme from the deficient liver exhibited very little catalytic activity (7.2% as compared to the normal subject). These results may support several explanations of this disease such as mutation of the OTC gene promoter leading to a low transcriptional activity or mutation of the encoding sequence which results in a modified translation product but with a normal size. mRNA instability may also occur.
Neonatal cardiomyopathy and lactic acidosis responsive to thiamine
Authors: Bakker H. D. , Scholte H. R. , Luyt‐Houwen I. E. M. , van Gennip A. H. , Abeling N. G. G. M. , Lam J.
Published: June 2005

A congestive cardiomyopathy was diagnosed in a girl at the age of 4 weeks. In the weeks following she developed general muscle hypotonia and plasma lactate increased to 8.5 mmol/L. Biochemical investigations of a muscle biopsy at the age of 3 months showed a deficiency in the oxidation of all substrates tested: pyruvate plus malate, 2‐ketoglutarate and palmitate plus malate. After freezing and thawing of the homogenate and the addition of essential cofactors, the oxidation of the ketoacids normalized. The oxidation defect in the untreated homogenate can be explained by a deficiency in one of the cofactors (such as thiamine pyrophosphate, NAD+or CoASH), or by a defect in the oxidative phosphorylation. Treatment with thiamine and carnitine resulted in a decrease in blood lactate to normal levels and a dramatic clinical improvement. Suspension of thiamine caused deterioration of her clinical condition and lactic acidaemia. The thiamine therapy was then continued. The girl is now 6 years old and in perfect health.
Hyperglycaemia associated with lactic acidaemia in a renal allograft recipient with type I glycogen storage disease
Authors: Chen Y.‐T. , Scheinman J. I.
Published: June 2005

Renal disease is a frequent and serious complication of type I glycogen storage disease. A type I glycogen storage disease patient with focal segmental glomerulosclerosis and progressive renal insufficiency underwent a renal allograft transplantation. Despite the same cornstarch therapy, the post‐transplantation course was complicated by worsening of the metabolic control manifested by exacerbated lactic acidaemia and hyperlipidaemia. This lactic acidaemia was remarkable for its association with hyperglycaemia. Hyperglycaemia accompanied by lactic acidaemia is strikingly unusual in type I glycogen storage disease, since this is a disease characterized by hypoglycaemia and an inverse relationship between blood glucose concentration and lactate levels. Both fasting insulin and C‐peptide levels in the patient were greater than similar age‐matched type I glycogen storage disease controls, indicating hyperinsulinaemia. The most likely mechanism responsible for the combined hyperglycaemia and lactic acidaemia was insulin resistance due to glucocorticoid treatment, instituted for immunosuppression. The hyperglycaemia associated with the lactic acidaemia was transient and resolved with steroid tapering. The exacerbated hyperlipidaemia, however, persisted after renal transplantation. Type I glycogen storage disease patients may be prone to glucocorticoid‐induced insulin resistance, since the cellular metabolism in these patients may already be compromised with ineffective insulin action and/or reduced insulin output.
Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase‐deficient lymphocytes
Authors: Takeda E. , Kuroda Y. , Naito E. , Yokota I. , Saijo T. , Hirose M. , Miyao M.
Published: June 2005

To explore the relationship between ribonucleotide reductase and immunodysfunction in adenosine deaminase deficiency, the effects of deoxyadenosine on ribonucleotide reductase in ADA‐deficient lymphocytes was investigated. An assay system for ribonucleotide reductase in intact permeabilized lymphocytes was developed to approximate physiological conditions. The activity of cytidine diphosphate (CDP) reductase in resting but not in proliferating lymphocytes in culture was inhibited by 1 to 10 µmol/L deoxyadenosine. The resting cells were protected from the toxicity of 1 µmol/L deoxyadenosine by 5 mmol/L nicotinamide or 30 µmol/L deoxycytidine and from that of 10 µmol/L deoxyadenosine by 30 µmol/L deoxycytidine. These findings suggest that depletion of nicotinamide adenine dinucleotide might be the principal cause of death in resting lymphocytes with ADA deficiency. It is concluded that the mechanism of deoxyadenosine toxicity on non‐replicating lymphocytes, which may not be mediated by ribonucleotide reductase inhibition, is closely related to the mechanism of immunodysfunction in patients with ADA deficiency.
Demonstration of 4‐Aminobutyric acid aminotransferase deficiency in lymphocytes and lymphoblasts
Authors: Gibson K. M. , Sweetman L. , Nyhan W. L. , Jansen I. , Jaeken J.
Published: June 2005

Lysates of lymphocytes, isolated from whole blood, and Epstein‐Barr virus transformed cultured lymphoblasts catalysed the transamination of 4‐aminobutyric acid with 2‐oxoglutaric acid as co‐substrate. 4‐Aminobutyric acid aminotransferase activity in lymphocyte and lymphoblast sonicates derived from 12 unrelated control individuals (6 each) was 39 ± 19 pmol min−1 (mg protein−1) (mean ± 1 SD). Activities in lysates of both types of cell derived from a Flemish patient were less than 3% of control. 4‐Aminobutyric acid aminotransferase activity in sonicates derived from the parents and a healthy sibling were 15–37% of the control mean for lymphocytes and 13–20% of the control mean in lymphoblasts, respectively.Km values in a control lymphoblast sonicate were 0.63 and 0.08 mmol L−1 for 4‐aminobutyric and 2‐oxoglutaric acids, respectively. These data indicate that the parents and healthy sibling are heterozygous and the patient is homozygous for a defective gene responsible for 4‐aminobutyric acid aminotransferase deficiency, and that inheritance is autosomal recessive.
EEG findings as an aid to the diagnosis of neonatal non‐ketotic hyperglycinaemia
Authors: Mises J. , Moussali‐Salefranques F. , Laroque M. L. , Ogier H. , Coude F. X. , Charpentier C. , Saudubray J. M.
Published: June 2005

The periodic EEG pattern during the first week associated with lethargy and myoclonic jerks is the major clinical sign in non‐ketotic hyperglycinaemia. The blood and urine glycine level may be at the upper limit of the normal range in some cases. Diagnosis must be done with this characteristic clinical picture associated with a high CSF glycine level.
Modification of fibroblast propionyl CoA carboxylase activity by valine as a possible diagnostic technique in non‐ketotic hyperglycinaemia
Authors: Fox J. S.
Published: June 2005

Propionyl CoA carboxylase activity is inhibited in normal but increased in NKH cells by valine. The effects are probably not large enough for diagnostic use.
Molecular basis of ornithine transcarbamylase deficiency lacking enzyme protein
Authors: Saheki T. , Imamura Y. , Inoue I. , Miura S. , Mori M. , Ohtake A. , Tatibana M. , Katsumata N. , Ohno T.
Published: June 2005

We report an ornithine transcarbamylase(OTC)‐deficient male patient who had no detectable immunoreactive materials but did have active mRNA for OTC‐related protein. The total absence of OTC activity in the liver of the patient was caused by a complete lack of immunoreactive material, as determined by Ouchterlony double immunodiffusion, single radial immunodiffusion, and sodium dodecylsulphate‐polyacrylamide gel electrophoresis of immunoprecipitate and of liver homogenate.

However, mRNA coding for the precursor of OTC was clearly detected in autopsy specimens of the patient's liver as well as of controls in a cell‐free translation system consisting of rabbit reticulocyte lysates and [35S]methionine. The labelled precursor of OTC synthesizedin vitro with mRNA from the patient could be transported into rat liver and kidney mitochondria and processed to form a protein with a mulecular weight indistinguishable from mature OTC, suggesting that there was no defect in the protein structure necessary for its transport into mitochondria. These results suggest that the primary defect of the OTC deficiency was located in the structural gene and that the labile OTC‐related protein, after being synthesized with its mRNA, was degraded too rapidly to be detected by the method used.
Familial hyperlysinaemia due to L‐lysineα‐ketoglutarate reductase deficiency: Results of attempted treatment
Authors: v. d. Heiden C. , Brink M. , de Bree P. K. , v. Sprang F. J. , Wadman S. K. , de Pater J. M. , van Biervliet J. P. G. M.
Published: June 2005

A mentally retarded male infant with persistent hyperlysinaemia due to L‐lysineα‐ketoglutarate reductase deficiency is described. The effect of dietary restriction of lysine on his mental and behavioural development was examined.

By restricting daily dietary lysine to 5.5 mg/kg body weight the fasting serum lysine became normal. Urinary lysine also became normal and the secondary metabolites homocitrulline, homoarginine,Nα‐acetyllysine andNε‐acetyllysine were no longer detected. After control of serum lysine for 2.5y it was felt that the patient's social behaviour, but not his mental development, had improved somewhat.
In vivostudies on the metabolic derangement in a patient with D‐glyceric acidaemia and hyperglycinaemia
Authors: Kølvraa S. , Gregersen N. , Christensen E.
Published: June 2005

In a mentally retarded boy, who excreted elevated amounts of glycine,d‐glyceric acid and acylglycines and whose cells exhibited diminishedd‐glycerate dehydrogenase and glycine cleavage activity, investigations have been undertaken aiming at characterizing the relationship betwnen the different accumulations. This was donein vivoby trying in a specific manner to alter in turn the degree of accumulation of each of the three classes of compounds and then monitoring changes in the others. The results suggest, that thed‐glyceric acid accumulation is directly caused by the genetic defect, since thed‐glyceric acid excretion was not altered by changes in degree of accumulation of either glycine or acylglycines. Similarly alterations in acylglycine excretion caused alterations in glycine but not ind‐glyceric acid excretion.

Based on these findings a model for the pathogenesis behind the accumulations of acylglycines and glycine is proposed.
Treatment of thecbl B form of methylmalonic acidaemia with adenosylcobalamin
Authors: Batshaw M. L. , Thomas G. H. , Cohen S. R. , Matalon R. , Mahoney M. J.
Published: June 2005

A 30‐month‐old girl was found to have thecbl B mutant form of methylmalonic aciduria by complementation analysis of fibroblasts. She was unresponsive to hydroxycobalamin and was treated with intramuscular adenosylcobalamin (AdoCbl), the deficient coenzyme, at a dose of 1 mg/24 h during a period of clinical stability. Serum cobalamin increased from 770 to 54 200 pg/ml. Mean urinary methylmalonic acid excretion was 409 mg/24 h prior to therapy. There was a transient fall in methylmalonic acid excretion during the first 5 days of therapy (range 167–245 mg/24 h) followed by a rise in excretion toward pretreatment levels (range 317–485 mg/24 h) during the second week of AdoCbl treatment. There was no change in plasma ammonia, glycine or serum bicarbonate level. We interpret the failure of this child to have a sustained and clinically significant response to AdoCbl as indicating that AdoCbl did not reach or enter the mitochondria intact, or in some other way was unavailable as a coenzyme for the methylmalonyl CoA mutase apoenzyme.
β‐Mannosidosis: Prenatal biochemical and morphological characteristics
Authors: Jones M. Z. , Rathke E. J. S. , Cavanagh K. , Hancock L. W.
Published: June 2005

Caprine β‐mannosidosis, an autosomal recessive disorder of glycoprotein catabolism, as yet undetected in man, was expressed in a 96/150 day gestation goat fetus. Deficiency of plasma, kidney, brain, liver and skin fibroblast acidic β‐mannosidase activity was associated witht he accumulation of tissue oligosaccharides. Characteristic lucent cytoplasmic lysosomal storage vacuoles were present in the brain, thyroid, kidney and other tissues. Axonal spheroids were present in the central nervous system. The biochemical and morphological prenatal expressions of β‐mannosidosis which were documented by this investigation may facilitate the identification of the disease in man.
Results of a study to detect the effects on neonates of copper and zinc deficiency during pregnancy
Authors: Favier A. , Ruffieux D. , Decoux G. , Arnaud J.
Published: June 2005

Conclusion

Our study shows a link between malformation and zinc deficiency in mother, or copper deficiency in newborn, but this is not a direct relationship to levels under a certain limit. We know that the level of copper or zinc in serum is not a good index of trace element deficiencies, and is disturbed by hormonal changes. Zinc deficiencies may thus be transitory and the first months of pregnancy are most dangerous. Unfortunately in our study we would not have detected such a deficiency at the beginning of pregnancy.
Historical outline of the biological importance of trace metals
Authors: Williams D. R.
Published: June 2005

A historical review of the discoveries that trace elements are involved in biological processes and relationships between trace metals and inherited disease. Ongoing experiments are appraised and a better understanding of the pathologies of inherited diseases anticipated.
Zinc metabolism in animals: Pathology, immunology and genetics
Authors: Chesters J. K.
Published: June 2005

Deficiency of dietary Zn rapidly reduces both appetite and growth, the latter effect being apparently caused by a failure of cell replication. Diagnosis of presymptomatic Zn deficiency depends largely on estimation of plasma Zn concentration but is complicated by reductions of it during a range of stressful conditions. In the latter cases, the decrease in plasma Zn concentration does not appear to be associated with inadequate Zn intake. Only two genetic defects of Zn metabolism are known in animals. One is associated with lethally inadequate concentrations of Zn in the milk of mice, the other with the A46 trait in Friesian cattle. A46 is a recessively inherited defect of Zn absorption which is lethal in the absence of major Zn supplementation of the diet. The characteristics of the disease are very similar to those of acrodermatitis enteropathica in man.
Acrodermatitis enteropathica
Authors: Aggett P. J.
Published: June 2005

A brief review of the clinical and biochemical features of Acrodermatitis enteropathica is given. This condition is now known to be caused by a systemic zinc deficiency secondary to a defect in the intestinal absorption of zinc and it illustrates the metabolic importance of this element in man.
Absence of hepatic molybdenum cofactor: An inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase
Authors: Wadman S. K. , Duran M. , Beemer F. A. , Cats B. P. , Johnson J. L. , Rajagopalan K. V. , Saudubray J. M. , Ogier H. , Charpentier C. , Berger R. , Smit G. P. A. , Wilson J. , Krywawych S.
Published: June 2005

Five patients with a combined deficiency of xanthine dehydrogenase, sulphite oxidase and, probably, also of aldehyde oxidase are described. This remarkable coincidence of three inborn errors of metabolism in a single individual was demonstrated to result from a deficiency of the ‘molybdenum cofactor’, an essential constituent of all three enzymes. The main biochemical findings in these patients included: hypouricaemia, xanthinuria, an increased excretion of sulphite, thiosulphate andS‐sulphocysteine and a decreased excretion of inorganic sulphate. Plasma molybdenum was normal. The ultimate diagnosis was made by the measurement of ‘molybdenum cofactor’ in a liver biopsy specimen in three out of five patients.

The clinical hallmarks in these patients were: feeding difficulties, mental retardation, neurological symptoms, lens dislocation, an abnormal muscle tone, myoclonia and an abnormal physiognomy. The majority of these were already present in the neonatal period. So far, attempts at treatment have been unsuccessful.
Zellweger syndrome: Biochemical procedures in diagnosis, prevention and treatment
Authors: Schutgens R. B. H. , Wanders R. J. A. , Heymans H. S. A. , Schram A. W. , Tager J. M. , Schrakamp G. , van den Bosch H.
Published: June 2005

In patients with cerebro‐hepato‐renal (Zellweger) syndrome, the absence of peroxisomes results in an impairment of metabolic processes in which peroxisomes are normally involved. These include the catabolism of very long chain (>C22) fatty acids, the biosynthesis of ether‐phospholipids and of bile acids, the catabolism of phytanic acid and the catabolism of pipecolic acid. Many diagnostic tests for Zellweger syndrome have become available in recent years. In classic Zellweger syndrome abnormal C27‐bile acids, very long chain fatty acids, dicarboxylic acids and pipecolic acid accumulate in the plasma of the patients. Moreover, depending upon the diet, plasma phytanic acid concentrations may be elevated. In platelets the activity of acyl‐CoA: dihydroxyacetone phosphate acyltransferase is deficient; in erythrocytes from young (<4 months) patients the plasmalogen content of the phospholipids is decreased.

In cultured fibroblasts from skin and from chorionic villus and cultured amniotic fluid cells from Zellweger patients the plasmalogen level is lowered; there is a decreased activity of acyl‐CoA: dihydroxyacetone phosphate acyltransferase, alkyl dihydroxyacetonephosphate synthase and phytanic acid oxidase; thede novo biosynthesis of plasmalogens and the peroxisomal β‐oxidation of fatty acids are impaired and the intracellular localization of catalase is abnormal.

Dietary treatment of patients with Zellweger syndrome has not so far resulted in an objective clinical improvement. As Zellweger syndrome is usually fatal in early life, prenatal diagnosis of the disease is important.
Adrenoleukodystrophy: Biochemical procedures in diagnosis, prevention and treatment
Authors: Watkins P. A. , Naidu S. , Moser H. W.
Published: June 2005

The childhood form of adrenoleukodystrophy is an X‐linked recessive disorder which is characterized biochemically by elevated concentrations of saturated very long chain fatty acids in tissues and plasma and impaired very long chain fatty acid oxidation in fibroblasts and leukocytes from adrenoleukodystrophy patients. The most consistently observed increase is that in hexacosanoic acid (C26:0); thus, measurement of plasma C26:0 concentration by gas‐liquid chromatography provides a rapid, sensitive method of diagnosis. Prenatal diagnosis of adrenoleukodystrophy can be made by measurement of C26:0 concentrations in amniocytes and chorionic villus cells. Heterozygote (carrier) detection has also been accomplished by biochemical measurement of C26:0 in plasma and skin fibroblasts. In a study of over 200 obligate heterozygotes, >90% showed abnormal concentrations of C26:0. Hybridization studies using the cloned DNA fragment St14 detects polymorphisms in the distal end of the long arm of the X chromosome (Xq27–28) and six informative kindreds have shown co‐segregation of adrenoleukodystrophy and the St14 marker through 65 meioses. Thus, such studies can supplement very long chain fatty acid concentrations in heterozygote detection. Therapeutic interventions for adrenoleukodystrophy, such as dietary restriction of very long chain fatty acids, administration of clofibrate or carnitine, immunosuppression and adrenal hormone replacement, have not been successful. Recently, a modification of the very long chain fatty acid‐restricted diet has been employed in which this diet is supplemented with synthetic glycerol trioleate. The rationale for this diet is that decreased very long chain fatty acid synthesis by fibroblasts from patients with adrenoleukodystrophy was observed when oleic acid was added to the culture medium. In a study of 14 patients on this diet from 2 to 11 months, there was a mean reduction in plasma C26:0 levels of 46%, with one patient achieving a normal plasma level. The effect of lowering plasma very long chain fatty acid concentrations on the neurologic status of patients with adrenoleukodystrophy and on the development of symptoms in asymptomatic individuals with elevated very long chain fatty acid concentrations remains to be established.
Morphological observations in skeletal muscle from patients with a mitochondrial myopathy
Authors: Stadhouders A. M. , Sengers R. C. A.
Published: June 2005

Mitochondrial metabolic dysfunction is considered to be the cause of certain congenital myopathies and a number of multisystem disorders in humans. The morphological hallmark of these diseases is the ‘ragged red’ fibre, which shows abnormally intensive oxidative enzyme reactions. Electron microscopy reveals that the numerically increased mitochondria in these fibres are often markedly enlarged and possess aberrant configurations of cristae. The mitochondrial matrix often contains lipid‐like inclusions or shows vacuolation. The most characteristic mitochondrial abnormality is the occurrence of highly ordered inclusions in the intracristal or intermembrane space. These inclusions appear to be true crystals, composed of proteinaceous material. It is argued that the activity of accumulation of proteins in the mitochondria is related to the nuclear and nucleolar hypertrophy noticeable in the ragged red fibres. Since protein crystals in mitochondria in particular occur when an increased capillary density around the ragged red fibres is present, it is suggested that oxygen free radicals and lipid peroxidation processes are involved in the ragged red fibre pathology.
Defects in oxidative phosphorylation. Biochemical investigations in skeletal muscle and expression of the lesion in other cells
Authors: Scholte H. R. , Busch H. F. M. , Luyt‐Houwen I. E. M. , Vaandrager‐Verduin M. H. M. , Przyrembel H. , Arts W. F. M.
Published: June 2005

Mitochondria are very vulnerable to genetic and environmental damage. If a patient is suspected of having a mitochondrial disease, elevated blood lactate, lowered blood free carnitine, abnormal urinary organic acids and carnitine esters and tissue histopathology may help with the diagnosis. For biochemical assessment of the defect, muscle is the tissue of choice even when involvement of other organs like heart or brain is more prominent.

We have studied isolated muscle mitochondria and homogenates from muscle biopsies in 250 patients, and have detected in more than one third mitochondrial defects in oxidative phosphorylation, dehydrogenases, non‐redox enzymes catalyzing synthesis of fuel molecules and in the carnitine system. Several patients showed more than one defect.

We have selected eight patients to illustrate how a relatively simple series of investigations in both isolated mitochondria and homogenate can be used for the identification of defects in oxidative phosphorylation in a small amount of muscle (200 mg or more). Identification of the defect(s) is important since it may provide the basis for rational treatment. A minority of the patients recovered partly or completely, which is unique in treatment of inborn errors of subcellular organelles.

An important aspect of mitochondrial dysfunction is the tissue specificity. The defect may be systemic but is often clinically expressed in only one or a few tissues. Rarely, tissue‐specific defects can be understood on the basis of tissue‐specificity of mitochondrial (iso‐)enzymes. Mitochondrial deficiencies of all biotin enzymes and most CoA‐linked enzymes are expressed in fibroblasts; most respiratory chain defects are not.

When mitochondrial ATP synthesis has been compromised by a mitochondrial defect, secondary lesions may be generated by changes in mitochondrial protein synthesis, activated proteases and phospholipases, increased matrix CoA and resulting carnitine deficiency, decrease in Krebs cycle intermediates and increased free radical formation and lipid peroxidation.
A model for hyperphenylalaninaemia due to tetrahydrobiopterin deficiency
Authors: Cotton R. G. H.
Published: June 2005

A model for tetrahydrobiopterin deficiency in mice is described. Elevated levels of phenylalanine produced in the model were shown to be dramatically reduced after injection of tetrahydrobiopterin. A comparison of several reduced pterins for their efficacy in the system is described. The unnatural S isomer of tetrahydrobiopterin was shown to be active in the system.
Enzyme activities and phospholipid storage patterns in brain and spleen samples from niemann‐pick disease variants: a comparison of neuropathic and non‐neuropathic forms
Authors: Besley G. T. N. , Elleder M.
Published: June 2005

Phospholipid levels and enzyme activities were measured in brain and spleen samples from patients with the three major variants of Niemann‐Pick disease. Accumulations of sphingomyelin and bis(monoacylglycero)phosphate were demonstrated in spleen from types A and B and group C Niemann‐Pick disease, whereas only in type A Niemann‐Pick brain was the sphingomyelin concentration increased. Sphingomyelinase activity was markedly deficient in type A Niemann‐Pick brain and spleen but residual activity of approximately 12% of control was measured in type B Niemann‐Pick brain. Normal or raised sphingomyelinase and β‐glucosidase activities were measured in group C Niemann‐Pick brain and spleen. Significant (17% of control) residual β‐glucosidase activity was also measured in non‐neuropathic Gaucher brain. Normal levels of neutral sphingomyelinase activity were measured in brain samples from the three variants of Niemann‐Pick disease. Acid sphingomyelinase activity in group C Niemann‐Pick brain appeared normal with respect to enzyme extraction, pH optimum (pH5.0) and apparentKm (approximately 0.4 mmol/L). Isoelectric focusing of brain sphingomyelinase revealed a degree of heterogeneity with activity peaks between pI 4.5 and 6.5. No defect was observed in group C Niemann‐Pick brain and, although attenuated, all peaks were present in type B Niemann‐Pick brain.
Development of a protocol for newborn screening for disorders of the galactose metabolic pathway
Authors: Bowling F. G. , Brown A. R. D.
Published: June 2005

The protocol evaluated in this paper employs an enzymatic assay of galactose metabolites, thin layer chromatography, and an assay of galactose‐1‐phosphate uridyl transferase on a single sample of blood collected routinely for newborn screening. Its effectiveness was tested by a retrospective study of known galactosaemic blood samples, and also by a prospective study of 207 000 newborn samples from which 6 infants with severe transferase deficient galactosaemia and 2 infants with red cell epimerase deficiency were identified. The detection rate for severe transferase deficiency in the newborn population was 1:35 000. Advantages include low false positive rate, definitive diagnosis within 6 hours of sample receipt, and the use of technically simple and robust procedures. This protocol overcomes the difficulties encountered with previously described procedures.
Usefulness of an Estimation of Physiologic Ability and Surgical Stress (E‐PASS) Scoring System to Predict the Incidence of Postoperative Complications in Gastrointestinal Surgery
Authors: Oka Yoshio , Nishijima Junichi , Oku Kunihiko , Azuma Tatsuo , Inada Keiji , Miyazaki Satoru , Nakano Hiroshi , Nishida Yukihiro , Sakata Kazuya , Izukura Masaaki
Published: June 2005

Surgical intervention induces various host responses to maintain homeostasis. When postoperative inflammation is intense and persists for a long time, postoperative complications may occur, sometimes developing into multiple organ failure. Therefore, it is very important to assess surgical stress and predict the risk of morbidity and mortality. Using a new scoring system, an estimation of physiologic ability and surgical stress (E‐PASS) scoring system, surgical stress following gastrointestinal surgery was evaluated to assess the feasibility of this scoring system. This system comprises a preoperative risk score (PRS), a surgical stress score (SSS), and a comprehensive risk score (CRS) that is calculated from both the PRS and the SSS. The relationship of the E‐PASS score to the incidence of morbidity and mortality was examined. The relationship between the E‐PASS score and a sequential organ failure (SOFA) score was also evaluated. The CRS had a significant positive correlation between not only the incidence but also the grade of postoperative complications. Total maximum SOFA score in patients with a CRS of more than 1 was significantly higher than that in patients with a CRS of less than 1. In conclusion, the E‐PASS scoring system will be useful for predicting and recognizing the risk of postoperative complications. This scoring system is brief, simple, and reproducible and can be useful in all types of hospitals.
Groin Hernia Repair: Open Techniques
Authors: Amid Parviz K.
Published: June 2005

Since the introduction of the Bassini method in 1887, more than 70 types of pure tissue repair have been reported in the surgical literature. An unacceptable recurrence rate and prolonged postoperative pain and recovery time after tissue repair along with our understanding of the metabolic origin of inguinal hernias led to the concept of tension‐free hernioplasty with mesh. Currently, the main categories of inguinal hernia repair are the open repairs and the laparoscopic repairs. In the open category, repair of the hernia is achieved by pure tissue approximation or by tension‐free mesh repair. The most commonly performed tissue repairs are those of Bassini, Shouldice, and to a lesser extent McVay. In the tension‐free mesh repair category, the mesh is placed in front of the transversalis fascia, such as with the Lichtenstein tension‐free hernioplasty, or behind the transversalis fascia in the preperitoneal space, such as during the Nyhus, Rives, Read, Stoppa, Wantz, and Kugel procedures. Numerous comparative randomized trials have clearly demonstrated the superiority of the tension‐free mesh repair over the traditional tissue approximation method. Placing mesh behind the transversalis fascia, although a sound concept, requires extensive dissection in the highly complex preperitoneal space and can lead to injury of the pelvic structures, major hematoma formation, or both. In addition, according to the prospective randomized comparative study of mesh placement in front of versus behind the transversalis fascia, the latter offers no advantage over the former, and it is more difficult to perform, learn, and teach. More importantly, preperitoneal mesh implantation (via open and laparoscopic procedure) leads to obliteration of the spaces of Retzius and Bogros, making certain vascular and urologic procedures, in particular radical prostatectomy and lymph node dissection, extremely difficult if not impossible. In conclusion, according to level A evidence from randomized comparative studies, (1) mesh repair is superior to pure tissue approximation repairs, and (2) mesh implantation in front of the transversalis fascia is superior, safer, and easier than open or laparoscopic mesh implantation behind the transversalis fascia.
Groin Hernia Repair: Anesthesia
Authors: Kehlet Henrik , Aasvang Eske
Published: June 2005

The choice of anesthesia for groin hernia repair is between general, regional (epidural or spinal), and local anesthesia. Existing data from large consecutive patient series and randomized studies have shown local anesthesia to be the method of choice because it can be performed by the surgeon, does not necessarily require an attending anesthesiologist, translates into the shortest recovery (bypassing the postanesthesia care unit), has the lowest cost, and has the lowest postoperative morbidity regarding risk of urinary retention. Spinal anesthesia has no documented benefits for this small operation and should be avoided owing to the risk of rare neurologic side effects and the high risk of urinary retention. General anesthesia with short‐acting agents may be a valid alternative when combined with local infiltration anesthesia, although an anesthesiologist is required. Despite sufficient scientific data to support the choice of anesthesia, large epidemiologic and nationwide information from databases show an undesirable high (about 10–20%) use of spinal anesthesia and low (about 10%) use of local infiltration anesthesia. Surgeons and anesthesiologists should therefore adjust their anesthesia practices to fit the available scientific evidence.
Incisional Hernia: Open Techniques
Authors: Klinge Uwe , Conze Joachim , Krones Carsten J. , Schumpelick Volker
Published: June 2005

Even with the routine use of mesh, repairing an incisional hernia is a challenge. Increasing evidence of impaired wound healing in these patients supports routine use of an open prefascial, retromuscular mesh repair. Basic pathophysiologic principles dictate that for a successful long‐term outcome and prevention of recurrence a wide overlap underneath healthy tissue is required. The extent of this overlap should be 5 cm in all directions: surrounding the wound closure, subxiphoidal underneath the ribs, below the arcuate line, and retropubic.
Incisional Hernia Repair: Laparoscopic Techniques
Authors: LeBlanc Karl A.
Published: June 2005

Repair of incisional hernias using the laparoscopic technique has continued to evolve since its inception in 1991. An analysis of the current literature has revealed that hernias as large as 1600 cm2 have been successfully repaired with this method. The average size appears to be about 105 cm2. Several choices of a biomaterial are available today, differing in the type of synthetic product or products that are used to manufacture them. Others incorporate an absorbable component. The goal of all of them is to prevent adhesion formation. The fixation devices that can be used are also varied. The results of laparoscopic incisional hernia repair are described. The conversion rate of these procedures is an impressive 2.4% with an enterotomy rate of 1.8%. These results affirm the low risk of this operation. The recurrence rate of 4.2% confirms the permanence of the repair. This procedure may become the standard of care in the near future.
Can attitudes of stoicism and cautiousness explain observed age‐related variation in levels of self‐rated pain, mood disturbance and functional interference in chronic pain patients?
Authors: Yong Hua‐Hie
Published: June 2005

The aims of the present study were (a) to examine the relationship between age, attitudes and self‐reported pain and suffering in a sample of chronic pain patients and (b) to determine the extent to which attitudes of stoicism and cautiousness might mediate between age and chronic pain experience. Psychometric measures were administered to 338 chronic pain patients. The results indicate that there were significant relationships between both age and attitudes with measures of pain, mood disturbance and functional interference. Attitudes were found to provide either a full or partial mediation of the relationship between age and various measures of chronic pain experience, thus emphasizing the importance of including these cognitive variables for clinical assessment. It appears that attitudes of stoicism may be more important than age as a predictor of self‐reported pain severity. However, with respect to mood and functional disturbance, age and perhaps, other age‐related factors, remain important additional predictors.
The long‐wavelength limit of plant photosynthesis
Authors: Pettai Hugo , Oja Vello , Freiberg Arvi , Laisk Agu
Published: June 2005

It is a common knowledge that the photosynthesis efficiency drops rapidly under the long‐wavelength light excitation above 680 nm. We discovered that in sunflower leaves attached to the plant the initial fall is replaced by an unexpected increase at much longer wavelengths, so that a detectable O2 evolution is remained till 780 nm. The quantum yield of O2 evolution at the local maximum at 745 nm reaches almost 20% of the yield at 650 nm. We conclude that extreme long‐wavelength chlorophylls may be present in the intact photosystem II antenna system, similarly to photosystem I.
Improving the Health of Women in Developing Countries: The Time Is Now
Authors: Rosenfield Allan , Schwartz Karyn
Published: June 2005

The health problems of women in developing countries remain far too low on the international community's list of priorities. Progress can be made toward decreasing maternal mortality in resource‐poor countries without sizable new research efforts. Strategies include improving access to emergency obstetric care and family‐planning services. Reducing maternal mortality rates by 75% is one of the key Millenium Development Goals. Making women's health a priority will improve the outlook for women in the developing world.
Morphology of Cyclotrichium taniguchii sp. nov. and C. cyclokaryon with establishment of a new genus, Dicyclotrichium gen. nov. (Ciliophora: Haptorida)
Authors: Xu Dapeng , Song Weibo , Hu Xiaozhong
Published: June 2005

The morphology and infraciliature of two planktonic marine ciliates, Cyclotrichium cyclokaryon, type species of the genus and C. taniguchii sp. nov. were investigated on live and protargol-impregnated specimens collected from the Jiaozhou Bay at Qingdao, China. Based on the present as well as previous studies, an improved diagnosis for the poorly defined genus Cyclotrichium is suggested: Didiniidae with ovoid to barrel-shaped body; cell-surface densely ciliated except in the domed proboscis region; anterior ends of kineties with long cilia forming one circumoral wreath of pectinelles; one circumoral kinety composed of a zig-zag structure; dorsal brushes absent. Cyclotrichium taniguchii is distinguished from its congeners by the combination of the following features: ellipsoid body shape, marine habitat, details of ciliature, and lack of a posterior tuft. Based on the characters of the ciliary pattern, a new genus, Dicyclotrichium gen. nov., with the type species Dicyclotrichiumsphaericum comb. nov. is established. The new taxon differs from Cyclotrichium by having two wreaths of pectinelles. Two known morphotypes are suggested to be assigned into this genus: Dicyclotrichium faurei comb. nov. [basionym: Askenasia faurei] and D. humilis comb. nov. [basionym: Askenasia humilis].
Reef-aggregating behaviour by symbiotic eunicid polychaetes from cold-water corals: do worms assemble reefs?
Authors: Roberts J.M.
Published: June 2005

In the north-east Atlantic, the dominant reef-framework forming coral species, Lophelia pertusa and Madrepora oculata, form a symbiotic association with the polychaete worm Eunice norvegica. The polychaete–coral symbiosis was studied by visually observing and photographing live animals in aquaria over many months and using time-lapse video under infra-red lighting to record activity patterns. The polychaetes act as reef aggregating agents by joining coral colonies and enhancing the development of reef patches in deep water. The symbiosis was investigated using samples collected from a relatively shallow site in a Norwegian fjord and from a deeper open ocean site in the Porcupine Seabight. The potential functional roles of this symbiosis are considered. The reef aggregating behaviour of the polychaete symbiont allied with the ability of the coral host to anastomose its branches, the polychaete tubes and debris falling onto the reef structure will help to shift the balance between reef growth and (bio)erosion in favour of growth.
Morphometry, sexual maturity, fecundity and epibiosis of the South American spider crab Libidoclaea granaria (Brachyura: Majoidea)
Authors: Schejter Laura , Spivak Eduardo
Published: June 2005

Libidoclaea granaria was collected as part of the by-catch of the Zygochlamys patagonica (Bivalvia: Pectinidae) fishery, between 36° and 39°40′S and at 80 to 128 m depth. Crab densities ranged from 0 to 150 individuals 100 m−2, with a mean of 9·8±20·4 individuals 100 m−2. Mature males and females ranged from 24 to 61 mm, and from 16 to 48 mm, carapace width (CW), respectively. The largest immature female measured 22·5 mm CW. The number of eggs carried by a female ranged from 1200 to 9300. Sponges were the most frequent epizoic organisms, followed by the lepadomorph cirriped Ornatoscalpellum gibberum, Serpulidae and Spirorbidae worms. Since all these organisms were reported on Z. patagonica beds, crabs are camouflaged to match their habitat. Small crabs usually had naked carapaces, indicating a high moult frequency. Larger crabs instead, had epibionts on their carapaces, suggesting a lesser moult frequency. The erosion of carapace spines and the heavy epibiosis of large specimens suggest the existence of a terminal anecdysis.
Population structure and reproduction of the hermit crab Dardanus deformis (Anomura: Diogenidae) in the Indian Ocean
Authors: Litulo Carlos
Published: June 2005

The population structure and fecundity of the hermit crab Dardanus deformis were studied. Monthly samples were obtained between January and December 2003 at Costa do Sol, Maputo Bay, southern Mozambique. A total of 604 individuals was analysed of which 273 were males, 164 non-ovigerous females and 167 ovigerous females. The overall size–frequency distributions were unimodal, with males reaching larger sizes than both ovigerous and non-ovigerous females. Females were slightly more abundant than males, but the overall sex ratio did not differ significantly from 1:1. Dardanus deformis showed continuous reproduction throughout the study period. A small number of juveniles was obtained, suggesting that recruitment may take place in a different habitat than that occupied by the adults. The egg number increased with female size, and the high incidence of ovigerous females, may suggest a higher reproductive activity probably as a result of the rapid embryonic development in the study area.
A re-assessment of rocky sublittoral biota at Hilsea Point Rock after fifty years
Authors: Hiscock Keith
Published: June 2005

A re-assessment of the rocky sublittoral biota at Hilsea Point Rock in south Devon, UK was undertaken 50 years after the first descriptive surveys. The overall appearance of the fauna and flora in 2003 was much as described in the 1950s but with some species not re-found in 2003 and some species added to the lists from the 1950s.
Seasonal variation in the leaf gas exchange of tropical forest trees in the rain forest–savanna transition of the southern Amazon Basin
Authors: Miranda Eduardo Jacusiel , Vourlitis George L. , Filho Nicolau Priante , Priante Pedro Correto , Campelo José Holanda , Suli George Sanches , Fritzen Clóvis Lasta , de Almeida Lobo Francisco , Shiraiwa Shozo
Published: June 2005

The photosynthetic light response of Amazonian semi-deciduous forest trees of the rain forest–savanna transition near Sinop Mato Grosso, Brazil was measured between July 2000 and September 2003 to test the hypothesis that the photosynthetic capacity of trees acclimated to different growth light environments will decline during the dry season. Maximum photosynthesis (Amax) and stomatal conductance (gmax) were significantly higher during the wet season; however, the physiological response to drought was not a clear function of growth light environment. For some species, such as Psychotria sp. growing in the mid-canopy, internal leaf CO2 concentration (Ci) was >30% lower during the dry season suggesting that declines in Amax were caused in part by stomatal limitations to CO2 diffusion. For other species, such as Brosimum lactescens growing at the top of the canopy, Tovomita schomburgkii growing in the mid-canopy, and Dinizia excelsa growing in the understorey, dry season Ci declined by <20% suggesting that factors independent of CO2 diffusion were more important in limiting Amax. Dry-season declines in gmax appeared to be important for maintaining a more consistent leaf water potential for some species (T. schomburgkii and D. excelsa) but not others (Psychotria sp.). These results indicate that while seasonal drought exerts an important limitation on the physiological capacity of semi-deciduous Amazonian forest trees, the mechanism of this limitation may differ between species.
Responses of seedling transplants to environmental variations in contrasting habitats of Central Amazonia
Authors: Benítez-Malvido Julieta , Martínez-Ramos Miguel , Camargo José Luis C. , Ferraz Isolde D. K.
Published: June 2005

In the Central Amazon we investigated whether seedling performance (survival, and relative growth rates in height and leaf numbers) was affected by initial seedling size (height and leaf numbers) in habitats that varied in their degree of human disturbance: cattle pasture, young secondary forest, 1-ha forest fragment and old-growth forest. Additionally, effects of photosynthetically active radiation (PAR), litter standing crop (LSC) and insect herbivory were evaluated 12 mo after transplantation in seedlings from the native canopy trees Chrysophyllum pomiferum, Micropholis venulosa and Pouteria caimito. Seedling performance changed rank across the understorey environment depending on species. Seedlings of Chrysophyllum thrived in all conditions but under high PAR, Micropholis thrived only in intermediate light conditions, whereas Pouteria thrived under high PAR. Effects of initial seedling size, PAR and herbivory after 1 y were specific to species, whereas LSC had no effect on performance. Initially larger seedlings resulted in lower survival for Chrysophyllum and Pouteria. Herbivory affected seedling performance in all species. Negative effects of herbivory were intensified under low PAR. Overall, our results showed that, as seedlings, species of the same family and characteristic of old-growth forests respond differently to the environmental constraints present in contrasting human-disturbed conditions. Larger seedlings may not always present greater tolerance to physical and biotic mortality risks.