bluuebunny/crossref_metadata_2025 huggingface dataset:
Inborn errors of metabolism with a protein‐restricted diet: Effect on polyunsaturated fatty acids
Authors: Sanjurjo P. , Ruiz J. I. , Montejo M.
Published: December 2002

Previous studies have shown that phenylketonuric patients display a deficiency in long‐chain polyunsaturated fatty acids. A study has now been performed on 13 cases (5 with methylmalonic acidaemia and 8 with urea cycle disorders) whose dietary treatment also implies a limitation in protein‐rich food. Plasma and red‐cell phospholipid fatty acid profiles were studied. The most relevant results were a lower percentage of docosahexaenoic acid in plasma and red‐cell phospholipids (0.91% ± 0.53% vs 2.88% ± 1.17% and 2.07% ± 0.92% vs 3.62% ± 1.01% (p < 0.001)) and a lower percentage of arachidonic acid in plasma (5.22% ± 2.02% vs 8.3% ± 2.11% (p < 0.001)).

A long‐chain polyunsaturated acid deficiency has also been confirmed in this group of metabolic patients and a dietary supplement is recommended since this population is subject to a special risk factor with regard to adequate psychomotor development. By extrapolating these data to the general population, the possibility can be inferred that long‐chain polyunsaturated fatty acids are semi‐essential in infant nutrition far beyond the breast‐feeding period.
Dihydropyridmidinase deficiency and congenital microvillous atrophy: Coincidence or genetic relation?
Authors: Assmann B. , Hoffmann G. F. , Wagner L. , Bräutigam C. , Seyberth H. W. , Duran M. , Van Kuilenburg A. B. P. , Wevers R. , Van Gennip A. H.
Published: December 2002

We describe a boy of consanguineous parents who suffered from intractable diarrhoea due to congenital microvillous atrophy, a recessively inherited autosomal disorder. He developed severe cholestatis starting at 2 weeks of age and leading to liver cirrhosis. His psychomotor development appeared only slightly delayed. At the age of 7 months he died due to septicaemia. In addition to disturbances of electrolyte balance and renal tubular function, which could be attributed to microvillous atrophy, marked elevations of dihydrouracil and dihydrothymine as well as moderately elevated excretion of uracil and thymine in urine were repeatedly demonstrated, suggesting a disorder of pyrimidine degradation. An enzymatic defect of 5,6‐dihydropyrimidine amidohydrolase (EC 3.5.2.2, dihydropyrimidinase, DHP) was demonstrated in liver biopsy. As both of these recessive disorders seem to be extremely rare, it remains speculative, whether he suffered from two independently inherited metabolic diseases or whether this represents a hitherto undescribed contiguous gene syndrome.
The heart and pericardial effusions in CDGS‐I (carbohydrate‐deficient glycoprotein syndrome type I)
Authors: Kristiansson B. , Stibler H. , Conradi N. , Eriksson B. O. , Ryd W.
Published: December 2002

Pericardial effusions were found in 6 of 10 children with carbohydrate‐deficient glycoprotein syndrome type I (CDGS‐I). In three cases pericardectomy was necessary. Blood concentrations of several glycoproteins and albumin were low. Similar abnormal isoforms of four glycoproteins were found in blood (B) and pericardial fluid (PF). There was a significant negative correlation between the mean concentration ratio PF/B and the molecular mass (MW) of 11 proteins. For proteins with MW <100 kDa there were significant correlations in the controls, but not in the patients, between the PF/B ratio and both the MW and the sialic acid contents in the (glyco‐)proteins. The pericardium exhibited focal mixed inflammatory changes with mesothelial proliferation, with widened endoplasmic reticulum and flocculent and/or lamellated material. Damage to a pericardial protein barrier is suggested to be involved in pericardial effusion in CDGS‐I.
Improvement in exercise tolerance in isovaleric acidaemia with L‐carnitine therapy
Authors: Lee P. J. , Harrison E. L. , Jones M. G. , Chalmers R. A. , Leonard J. V. , Whipp B. J.
Published: December 2002

The effect of 4 weeks' treatment with oral‐L‐carnitine (100 mg/kg per day) on carnitine status and metabolic parameters during an incremental ramp exercise test in a 12‐year‐old girl with isovaleric acidaemia was examined to determine its possible therapeutic role. The maximum work rate achieved increased from 110 to 120 watts; oxygen consumption at anaerobic threshold from 600 to 800 L/min; peak oxygen consumption from 1270 to 1450 L/min; and oxygen pulse, a measure of cardiac output, from 7.0 to 8.1 L/beat. These changes were associated with increases in plasma and urinary free and acyl carnitine concentrations but no change in physical activity. This observed effect of L‐carnitine on exercise performance may be on cardiac or skeletal muscle function or both. We conclude that, in this single patient with isovaleric acidaemia, L‐carnitine supplementation had objective benefits and further studies on more patients are warranted.
A novel acid α‐glucosidase mutation identified in a Pakistani family with glycogen storage disease type II
Authors: Kroos M. A. , Waitfield A. E. , Joosse M. , Winchester B. , Reuser A. J. J. , MacDermot K. D.
Published: December 2002

A novel mutation, C118t, in exon 2 of the acid α‐glucosidase gene has been found in an infant with glycogen storage disease type II. This mutation is predicted to result in protein truncation. The phenotype was that of the severe infantile form of the disorder with lack of motor development, but with eye regard, social smile and vocalization. The parents were heterozygous for C118T and belong to an Islamic community opposed to termination of pregnancy. As the C118T mutation results in the loss of one of two AvaI sites present in an informative PCR product, reliable premarriage carrier detection became possible and was acceptable to the members of this extended family.
Niemann–Pick disease type C and defective peroxisomal β‐oxidation of branched‐chain substrates
Authors: Sequeira J. S. S. , Vellodi A. , Vanier M. T. , Clayton P. T.
Published: December 2002

An 18‐month‐old infant presented with hypotonia, motor delay, hepatosplenomegaly, rickets and steatorrhoea. Biochemical investigations revealed typical features of Niemann–Pick disease type C. In addition, there was evidence of defective peroxisomal β‐oxidation of branched‐chain substrates (3α,7α,12α‐trihydroxycholestanoic acid and pristanic acid). The steatorrhoea and fat‐soluble vitamin malabsorption responded well to bile acid therapy. Possible causes for the double defect are considered.
Aberrant phenylalanine metabolism in phenylketonuria heterozygotes
Authors: Guldberg P. , Henriksen K. F. , Lou H. C. , Güttler F.
Published: December 2002

The wide variation in phenylalanine hydroxylating capacity observed among patients with phenylketonuria (PKU) is primarily due to allelic heterogeneity at the phenylalanine hydroxylase (PAH) locus. In this study, we examined phenylalanine metabolism after an oral phenylalanine load in 148 carriers of known PAH gene mutations. As a group, heterozygotes formed less tyrosine than normozygotes (p<0.001), and there was a tendency that carriers of a severe PAH mutation formed less tyrosine than carriers of a mild mutation. Nevertheless, the interindividual variation was extensive, and we identified a group of individuals who formed no or very little tyrosine after the phenylalanine load. This tyrosine response was accompanied by a decreased ability to eliminate the phenylalanine test dose but did not correlate with the intrinsic severity of the mutant PAH allele. Examination of the entire coding region of the PAH gene revealed no additional sequence alterations in these subjects. Our data suggest that a subset of PKU heterozygotes have reduced phenylalanine hydroxylating capacity approaching or equalling the levels observed in genetic compounds with non‐PKU mild hyperphenylalaninaemia (MHP). Awareness of this phenotypic overlap between PKU carriers and genetic compounds with two mutant alleles may be useful for clinicians and paediatricians involved in diagnosis and genetic counselling.
Accurate detection of Smith–Lemli–Opitz syndrome carriers by measurement of the rate of reduction of the ergosterol C‐7 double bond in cultured skin fibroblasts
Authors: Honda M. , Tint G. S. , Shefer S. , Honda A. , Batta A. K. , Xu G. , Chen T. S. , Salen G.
Published: December 2002

The activity of ergosterol Δ7‐reductase (3β‐hydroxysteroid Δ7‐reductase) was measured in cultured skin fibroblasts from 7 controls, 10 Smith–Lemli–Opitz syndrome (SLOS) patients, and 10 parents (obligate carriers). The fibroblasts were exposed to delipidated medium supplemented with lovastatin for 24h and the enzyme activity was determined by incubating cell‐free homogenate with ergosterol (ergosta‐5,7,22‐trien‐3β‐ol) and measuring the mass of brassicasterol (ergosta‐5,22‐dien‐3β‐ol) formed by gas chromatography–mass spectrometry with selected‐ion monitoring. In carriers, the activity was significantly lower than in controls (22±2 vs 65±10 pmol/min per mg protein, p<0.0005), and no overlap was observed. The mean activity in carriers' fibroblasts was more than 100 times higher than in patients' cells (0.2 pmol/min per mg protein). The use of ergosterol avoids the many problems caused by the instability and lack of availability of radiolabelled 7‐dehydrocholesterol. The present method makes it possible to discriminate SLOS carriers from both controls and patients using a commercially available substrate and common analytical equipment.
Holoprosencephaly: A paradigm for the complex genetics of brain development
Authors: Roessler E. , Muenke M.
Published: December 2002

Holoprosencephaly (HPE) is the most common major developmental defect of the forebrain in humans. Clinical expression is variable, ranging from a small brain with a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial HPE. Significant aetiological heterogeneity exists in HPE and includes both genetic and environmental causes. Recently, defects in the cell signalling pathway involving the Sonic Hedgehog (SHH) gene, as well as defects in the cholesterol biosynthesis, have been shown to cause HPE in humans. These discoveries and current genetic approaches serve as a paradigm for studying normal and abnormal brain morphogenesis.
Studies on the oxidation of phytanic acid and pristanic acid in human fibroblasts by acylcarnitine analysis
Authors: Verhoeven N. M. , Jakobs C. , Ten Brink H. J. , Wanders R. J. A. , Roe C. R.
Published: December 2002

The α‐oxidation of phytanic acid and the β‐oxidation of pristanitc acid were investigated in cultured fibroblasts from controls and patients affected with different peroxisomal disorders using deuterated substrates. Formation of [ω‐2H6]4,8‐dimethylnonanoylcarnitine ([ω‐2H6]C11‐carnitine) from [ω‐2 H6]phytanic acid and [ω‐2H6]pristanic acid was used as marker for these processes. Analysis was performed by tandem mass spectrometry.

In normal cells, formation of [ω‐2H6]C11‐carnitine from both [ω‐2H6]phytanic acid and [ω‐2H 6]pristanic acid was observed. When peroxisome‐deficient fibroblasts were incubated with these substrates, [ω‐2H6]C11‐carnitine was not detectable or, in two cases, very low, which results from deficiencies in both peroxisomal α‐ and β‐oxidation. In cells with an isolated β‐oxidation defect at the level of the peroxisomal bifunctional protein, formation of [ω‐2H6]C11‐carnitine could also not be detected.

Cells with an isolated defect in the α‐oxidation of phytanic acid, obtained from patients affected with Refsum disease (McKusick 266500) or rhizomelic chondrodysplasia punctata (McKusick 215100), did not form [ω‐2H6]C11 ‐carnitine from [ω‐2H6]phytanic acid. The observed formation of [ω‐2H6]C11‐carnitine from [ω‐2H6]pristanic acid in these cells is in accordance with a normal peroxisomal β ‐oxidation in these disorders.

This study shows that separate incubation of fibroblasts with [ω‐2H 6]phytanic acid and [ω‐2H6]pristanic acid, followed by acylcarnitine analysis in the medium by tandem mass spectrometry, can be used for screening cell lines for deficiencies in the peroxisomal α‐ and β‐oxidation pathways.
Four novel mutations at the cystathionine β‐synthase locus causing homocystinuria
Authors: Coudé M. , Aupetit J. , Zabot M. T. , Kamoun P. , Chadefaux‐Vekemans B.
Published: December 2002

We describe four new mutations in the cystathionine β‐synthase gene: three point mutations localized in exons 3, 9 and 10 and one mutation in exon 12 which results in stop codon. Homocystinuria due to cystathionine β‐synthase (CBS, EC.4.2.1.22) deficiency (McKusick 236200), is the most common autosomal recessive inborn error of the transsulphuration pathway. Homocystinuric patients exhibit mental retardation, psychotic behaviour, dislocated lenses, vascular disease, osteoporosis and skeletal abnormalities. About 50% of affected subjects show biochemical improvements when treated with pyridoxine, the precursor of the CBS cofactor pyridoxal 5′‐phosphate. The severity of the disease varies among the patients: pyridoxine‐responsive patients usually have a milder clinical phenotype than pyridoxine‐nonresponsive patients. Human CBS cDNA has been cloned and its complete sequence, with minor differences in the coding region, has been published by three teams (Chassé et al 1995; Kraus et al 1993; Kruger and Cox 1994). The screening for mutations in homocystinuric patients has led to the identification of more than 50 mutations (Aral et al 1997; Dawson et al 1996; De Franchis et al 1994; Gallagher et al 1995; Hu et al 1993; Kluijtmans et al 1995; Kozich et al 1993; Kozich and Kraus 1992; Kraus 1994; Marble et al 1994; Shih et al 1995; Sebastio et al 1995; Sperandeo et al 1995). Two mutations are found to be most prevalent: (a) I278T only in pyridoxine‐responsive patients; (b) G307S mutation, the leading cause of homocystinuria in Ireland and in patients of ‘Celtic origin’ (Gallagher et al 1995). We describe here four novel mutations at the CBS locus.
Tamoxifen Increases Membrane Fluidity at High Concentrations
Authors: Severcan Feride , Kazanci Nadide , Zorlu Faruk
Published: December 2002

There are contradictory results in the literature relating to the effect oftamoxifen on membrane fluidity. The present work investigates the effect oftamoxifen on membrane dynamics to find out whether the concentration oftamoxifen can be one of the factors in this discrepancy. Turbidity(absorbance at 440 nm) and Fourier transform infrared spectroscopicstudies reveal that tamoxifen causes opposite effects on membranefluidity at low (1 mol.%) and high (30 mol.%) tamoxifen concentrations. Lowtamoxifen concentrations increase the absorbance in the gel and liquidcrystalline phase, whereas high tamoxifen concentrations decrease theabsorbance in gel and liquid crystalline phase, whereas tamoxifenconcentrations decrease the absorbance. Observations on both phasesshow that the bandwidth of the CH2 stretching bands decreases with1 mol.% tamoxifen and increases with 30 mol.% tamoxifen present, indicatinga decrease in membrane fluidity at low tamoxifen concentrations and anincrease in fluidity at high tamoxifen concentrations. It is seen that theapparent discrepancy in the literature on the effect of tamoxifen onmembrane fluidity mainly arises from the tamoxifen concentration used andthe confusion on the concept of lipid fluidity and lipid order.
Progressive neurological deterioration and MRI changes in cblC methylmalonic acidaemia treated with hydroxocobalamin
Authors: Enns G. M. , Barkovich A. J. , Rosenblatt D. S. , Fredrick D. R. , Weisiger K. , Ohnstad C. , Packman S.
Published: December 2002

Cobalamin C (cblC) defects result in decreased activity of both methylmalonyl‐CoA mutase and N5‐methyltetrahydrofolate:homocysteine methyltransferase (methionine synthase), with subsequent methylmalonic aciduria and homocystinuria. Patients typically show failure to thrive, developmental delay and megaloblastic anaemia. Vitamin B12 therapy has been beneficial in some cases. We report a now 4‐year‐old Hispanic girl with cblC disease documented by complementation analysis, with progressive neurological deterioration and worsening head MRI changes while on intramuscular hydroxocobalamin begun at age 3 weeks. Oral carnitine and folic acid were added at age 1 year. Blood levels of methylmalonic acid were reduced to treatment ranges. In the absence of acute metabolic crises, she developed microcephaly, progressive hypotonia and decreased interactiveness. Funduscopic examination was normal at age 13 months. At age 19 months, she developed nystagmus, and darkly pigmented fundi and sclerotic retinal vessels were observed on examination. Her neonatal head MRI was normal. By age 1 year, the MRI showed diffuse white‐matter loss, with secondary third and lateral ventricle enlargement, a thin corpus callosum, and normal basal ganglia. At age 15 months, progression of the white‐matter loss, as well as hyperintense globi pallidi, were present. Interval progression of both grey‐ and white‐matter loss was seen at age 27 months. We therefore caution that progressive neurological deterioration and head MRI abnormalities may still occur in cblC disease, despite early initiation of hydroxocobalamin therapy and improvement in toxic metabolite concentrations in physiological fluids.
Large heterozygous deletion masquerading as homozygous missense mutation: A pitfall in diagnostic mutation analysis
Authors: Zschocke J. , Quak E. , Knauer A. , Fritz B. , Aslan M. , Hoffmann G. F.
Published: December 2002

The clinical use of molecular analyses in recessive disorders relies onthe exact characterization of both mutant alleles in the affected patient. Thiscan be problematic when only part of the gene is examined or when relevant DNA alterations are not recognized by standard methods. We present a child in whom phenylketonuria was apparently caused by homozygosity for the mutation E390G in exon 11 of the phenylalanine hydroxylase (PAH) gene. However, the clinical severity of the disease was not quite as mild as expected, the mutation was not identified in the father despite confirmed paternity, and the paternal allele showed a highly unusual pattern of polymorphic markers in the PAH gene. Presence of a large deletion involving exons 9, 10 and 11 of the phenylalanine hydroxylase gene was confirmed by long‐range PCR. Diagnostic DNA analyses should include a comprehensive examination of the whole relevant gene in the patient and confirmation of carrier status in both parents.
Changes of Transmembrane Ca2+ Gradient in the Formation of Macrophage-Derived Foam Cells
Authors: Yang Xiaoyi , Zhang Yuzhong , Huang Youguo , Yang Fuyu
Published: December 2002

Macrophages from C57BL/6J mice, an animal susceptible toatherosclerosis, were chosen as target cells to study changes in thetransmembrane Ca2+adient during the formation ofmacrophage-derived foam cells. The transmembrane Ca2+adientsof single living cells were examined using Fura-2/AM combined withFluo-3/AM by laser scanning confocal microscopy. Exposure to OxidizedLow Density Lipoprotein, decreases the Ca2+adient acrossmacrophage plasma membrane, but increases that across the nuclearmembrane. The altered transmembrane Ca2+adients could inducethe up-regulation of scavenger receptor in macrophages, resulting inthe formation of foam cells.
Liver transplantation for citrullinaemia improves intellectual function
Authors: Fletcher J. M. , Couper R. , Moore D. , Coxon R. , Dorney S.
Published: December 2002

Background: Arginosuccinic acid synthetase (ASA) (EC 6.3.4.5) deficiency (citrullinaemia) (McKusick 215700) is a well‐recognized cause of neonatal hyperammonaemic coma with poor long‐term intellectual function, despite good medical management.

Methods: Cadaveric hepatic transplantation was performed in a 12‐year‐old boy with citrullinaemia under poor biochemical control. Subsequent development of fulminant hepatic failure necessitated a second cadaveric transplant. Psychometric assessments before and after transplantation were performed using a variety of age‐appropriate tests.

Results: Normalization of plasma ammonium in our patient post transplantation has resulted in dramatic improvement in mental functioning and well‐being and he now enjoys a normal diet. Psychometric assessment confirmed decline in his abilities prior to transplantation with particular post‐transplantation improvement in perceptual organization and visuospatial abilities; these did not, however, return to normal. His family report considerable reduction in stress associated with the unpredictable nature of previous hyperammonaemic crises and recurrent hospitalization.

Conclusions: Liver transplantation should be considered as an early therapeutic option in children with citrullinaemia to prevent ongoing cerebral insult associated with hyperammonaemia.
Ligand Binding Characteristics of a Glycosylphosphatidyl Inositol Membrane-Anchored HeLa Cell Folate Receptor Epitope-Related to Human Milk Folate Binding Protein
Authors: Holm Jan , Hansen Steen Ingemann , Høier-Madsen Mimi , Korsbaek Lars , Beckmann Heidi , Josefsen Knud
Published: December 2002

The folate receptor (FR) in HeLa cells was characterized as to ligandbinding mechanism, antigenic properties and membrane anchor in order toobtain information to be used for the design of biological agentstargeting FR in malignant tumors. The receptor displayed the followingbinding characteristics in equilibrium dialysis experiments(37°C, pH 7.4) with [3H] folate: a high-affinity type of bindingthat exhibited positive cooperativity with a Hill coefficient >1.0and an upward convex Scatchard plot, a slow radioligand dissociation atpH 7.4 becoming rapid at pH 3.5 and inhibition in the presence of otherfolates. The molecular size of the receptor was 100 kDa on gel filtrationwith Triton X-100, or similar to that of high molecular weight human milkfolate binding protein (FBP). The latter protein represents a 25 kDamolecule which equipped with a hydrophobic glycosylphosphatidylinositol (GPI) membrane anchor susceptible to cleavage byphosphatidylinositol specific phospholipase C (PI-PLC) formsmicelles of 100 kDa size with Triton X-100. The HeLa cell FRimmunoreacted with antibodies against purified human milk FBP inELISA, and in a fluorescence activated cell sorting system, whereHeLa cells exposed to increasing concentrations of antibody showed adose-dependent response. Exposure to PI-PLC decreased the fraction ofimmunolabeled cells indicating a linkage of FR to cell membranes by aGPI anchor. HeLa cells incubated with radiofolate showed a continuousuptake with time, however, with a complete suppression of uptake in thepresence of an excess of cold folate. Prewash of cells at acidic pH toremove endogenous folate increased the uptake. Binding and uptake of [3H]folate was increased in cells grown in a folate-deprived medium. The HeLaFR seems to be epitope related to human milk FBP.
Intracellular degradation of fluorescent glycolipids by lysosomal enzymes and their activators
Authors: Madar‐Shapiro L. , Pasmanik‐Chor M. , Dinur T. , Dagan A. , Gatt S. , Horowitz M.
Published: December 2002

Fluorescent glycolipids were utilized for detection of the intracellular, activator‐dependent, activities of β‐glucocerebrosidase and arylsulphatase A. Activities were measured in primary skin fibroblasts from normal individuals, from patients with Gaucher disease who had mutations within the β‐glucocerebrosidase gene, and from a prosaposin‐deficient patient. Fluorescent microscopy demonstrated that glucosylceramide or sulphatide labelled with a fluorescent probe (lissamine‐rhodamine) were endocytosed and reached the lysosomes. There, in the presence of active enzyme and the corresponding saposin, they were hydrolysed to fluorescent ceramide, which changed its intracellular localization. When these substrates were labelled with pH‐sensitive lissamine‐rhodamine, which loses its fluorescence at neutral or alkaline pH, the transport of the product, i.e. fluorescent ceramide, from the lysosomes resulted in disappearance of the cellular fluorescence. In cells of patients having mutations within the genes encoding the glucocerebrosidase or the prosaposin, there was a considerable reduction in the intracellular rate of substrate hydrolysis that could be followed by fluorescence microscopy or measured quantitatively in cell extracts.
Regression of neuropsychological deficits in early‐treated phenylketonurics during adolescence
Authors: Weglage J. , Pietsche M. , Denecke J. , Sprinz A. , Feldman R. , Grenzebach M. , Ullrich K.
Published: December 2002

Even early‐treated phenylketonuric patients suffer from phenylalanine‐associated (mild) neuropsychological impairment. To date it is still unclear whether patients' deficits show a progression on ageing. This unsolved question seems to be an important aspect in the still ongoing debate about how long and how strictly the patients should be maintained on diet. Twenty early‐treated (20±10, 9–30 days) adolescent phenylketonurics (10 boys, 10 girls) and 20 healthy controls, matched for age, sex and IQ, were inves‐tigated twice at a mean ages of 11 and 14 years for their IQ (Culture Fair Intelligence Test–Scale 2; CFT‐20), fine motor abilities (Motor PerformanceTask), sustained (Test d2) and selective attention (Stroop‐Task). At the first test, examinations revealed significant blood phenylalanine‐correlated neuropsychological deficits in PKU patients. In spite of raised blood phenylalanine concentrations during the following 3 years and significantly elevated concurrent blood phenylalanine concentrations, the repeated measurements revealed a significant decrease of patients' deficits compared to controls. Clinical‐neurological status of patients and controls was normal at both test times. The results indicate a decreased vulnerability of PKU‐patients with respect to their neuropsychological functioning against elevated blood phenylalanine levels on ageing.
Inborn errors of neurotransmitter receptors
Authors: Surtees R.
Published: December 2002

Inborn errors of neurotransmitter receptors are recently described gene mutations that directly affect receptor function. Currently three conditions are known to be caused by this mechanism: hyperekplexia; two forms of congenital inherited myasthenic syndromes; and autosomal dominant nocturnal frontal lobe epilepsy. Here, neurotransmitters, their receptors and known inborn errors of receptor function are reviewed.
Multiple mtDNA deletions: Clinical and molecular correlations
Authors: Santorelli F. M. , De Joanna G. , Casali C. , Tessa A. , Siciliano G. , Amabile G. A. , Pierelli F. , Vilarinho L. , Santoro L.
Published: December 2002

We studied six Italian patients harbouring multiple mitochondrial DNA (mtDNA) deletions in order to correlate clinical and molecular features. Earlier age at onset (17 vs 36 years), fewer ragged‐red fibres (none vs 35%), and lower proportions of deleted mtDNAs (9 vs 33%) were found in one patient with autosomal recessive inheritance as compared to five with dominant transmission. Our findings add to the features associated with multiple deletions of mtDNA.
A serine/alanine polymorphism in the nucleotide‐binding fold‐2 of the sulphonylurea receptor‐1 (S1369A) is associated with enhanced glucose‐induced insulin secretion during pregnancy
Authors: Krugluger W. , Festa A. , Shnawa N. , Bucher J. , Boltz‐Nitulescu G. , Schernthaner G. , Hopmeier P.
Published: December 2002

The sulphonylurea receptor‐1 (SUR‐1) regulates glucose‐induced insulin secretion by controlling K+‐ATP channel activity of the pancreatic β‐cell membrane. In this study, we investigated the putative role of a T/G‐polymorphism (exon 33, codon 1369; S1369A) in the adenosine diphosphate‐sensing nucleotide‐binding fold‐2 (NBF‐2) of the SUR‐1 on glucose‐induced insulin secretion during an oral glucose tolerance test in pregnant women (PW; n=182). Compared to PW with the T/T genotype, statistically significant elevated C‐peptide concentrations were found 60 min after glucose intake in PW with the T/G and G/G genotype (T/T 9.0±0.4 ng/ml vs T/G 10.8±0.4 ng/ml or G/G 10.8±0.7 ng/ml, p=0.01). Furthermore, compared to PW with T/T genotype the ΔC‐peptide (60/0 min) was significantly enhanced in PW with T/G or G/G genotype (T/T 6.7±0.3 vs T/G 8.9±0.4 or G/G 8.9±0.7, p=0.0009). A significant correlation of C‐peptide concentrations with blood glucose (BG) 60 min after glucose intake was only found in PW with the T/T genotype (r=0.6, p<0.0004). Similarly, a significant correlation of insulin concentrations with BG 60 min after glucose intake was observed in PW with T/T genotype (r=0.5, p<0.0001) and T/G genotype (r=0.24, p<0.03) but not in PW with G/G genotype (r=0.01, p=0.9). From our data we conclude that in PW with the alanine substitution in the NBF‐2 region, the insulin response of the pancreatic β‐cell after glucose intake is enhanced and does not correlate with actual BG levels
Quantitative measurement of total and free 3‐hydroxy fatty acids in serum or plasma samples: short‐chain 3‐hydroxy fatty acids are not esterified
Authors: Jones P. M. , Burlina A. B. , Bennett M. J.
Published: December 2002

Diagnostic protocols for disorders of mitochondrial fatty acid oxidation (FAO) generally include the measurement of plasma acylcarnitines. Many biochemical intermediates of FAO resulting from a metabolic block require carnitine conjugation for transport out of the mitochondria, and so occur as fatty acid–carnitine conjugates in the blood. Both short‐ and long‐chain acylcarnitines are generally determined, and this procedure has a critical role to play in the diagnosis of disorders of the very long‐chain, medium‐chain and short‐chain acyl‐CoA dehydrogenase defects. Less is known about the utility of acylcarnitines for the measurement of the various chain length intermediates of the 3‐hydroxyacyl‐CoA dehydrogenase steps of β‐oxidation. This study utilizes stable‐isotope dilution gas chromatography–mass spectrometry to determine the serum or plasma concentrations of free 3‐hydroxy fatty acids (3‐OHFAs) of chain lengths C6 to C16. The 3‐OHFA concentrations are determined in samples from normal individuals, hyperketotic individuals and patients with long‐chain L‐3‐hydroxyacyl‐CoA dehydrogenase and short‐chain L‐3‐hydroxyacyl‐CoA dehydrogenase deficiencies, both before and after hydrolysis. The results of the study indicate the relative amounts of conjugated intermediates of all chain lengths. Long‐chain 3‐OHFAs (C14 and C16) are found in elevated concentrations after hydrolysis, whereas short‐chain and medium‐chain 3‐OHFAs (C6 to C12) show no difference in concentrations between the two samples in all subjects tested, suggesting that only long‐chain 3‐hydroxy species form conjugates. This finding has important implications for the use of the acylcarnitine assay for the diagnosis of defects involving short‐chain and medium‐chain 3‐hydroxy fatty acids.
Bone marrow transplantation for the treatment of X‐linked adrenoleukodystrophy
Authors: Suzuki Y. , Isogai K. , Teramoto T. , Tashita H. , Shimozawa N. , Nishimura M. , Asano T. , Oda M. , Kamei A. , Ishiguro H. , Kato S. , Ohashi T. , Kobayashi H. , Eto Y. , Kondo N.
Published: December 2002

The effects of bone marrow transplantation (BMT) in X‐linked childhood adrenoleukodystrophy (ALD) are described in four Japanese patients. Two older patients, 10‐year‐old boys with IQ 60 and difficulty in school, had favourable results. IQ levels and MRI findings were generally maintained after BMT. One patient showed improvement of gait disturbance. They have both attended ordinary schools after BMT, although a learning disorder persists. On the other hand, two other younger patients with a rapid course and indeterminate IQ at BMT showed deterioration of neurological functions. Indication for BMT seems to be a maintained IQ level, preferably higher than 80, since it seems to be difficult to normalize IQ level after BMT. Younger patients have higher risk of developing a rapidly progressive form of the disease. Identification of presymptomatic boys, and serial and careful follow‐up by neuropsychological and neuroradiological studies, are essential prerequisites to successful BMT in X‐ALD.
Enhanced lymphocyte proliferation in patients with adrenoleukodystrophy treated with erucic acid (22:1)‐rich triglycerides
Authors: Barmaki Pour R. , Stöckler‐Ipsiroglu S. , Hunneman D. H. , Gahr M. , Korenke G. C. , Pabst W. , Hanefeld F. , Peters A.
Published: December 2002

Lymphocytopenia and depression of natural killer cells have been observed in patients with adrenoleukodystrophy (ALD) treated with glycerol trioleate and glycerol trierucate (‘Lorenzo's oil’). To investigate possible alterations of cellular immunoreactivity, we measured lymphocyte proliferation in response to mitogens (PHA, Con A, PWM, OKT3) in 27 patients on treatment and in 14 patients without treatment. In patients on treatment, lymphocyte proliferation in response to the mitogens PHA and Con A was significantly higher than in patients without treatment. Lymphocyte proliferation in patients without treatment was comparable to that of normal control lymphocytes. Additionally, we found increased concentrations of erucic acid, C22:1, in lymphocytes from patients with treatment. The enhanced proliferation of lymphocytes in response to mitogens is an indication of increased reactivity of cellular immunity to unspecific immunological stimuli. Long‐term side‐effects on cellular immunoreactivity have to be considered in ALD patients treated with Lorenzo's oil.
Hypoglycinaemia and psychomotor delay in a child with xeroderma pigmentosum
Authors: Quackenbush E. J. , Kraemer K. H. , Gahl W. A. , Schirch V. , Whiteman D. A. H. , Levine K. , Levy H. L.
Published: December 2002

Glycine is a nonessential amino acid that serves as both an inhibitory and an excitatory neurotransmitter. Hyperglycinaemia occurs in nonketotic hyperglycinaemia, a primary defect in the glycine cleavage pathway, and as a secondary feature of several inborn errors of organic acid metabolism. However, specifically low levels of glycine have never been reported. Here we report a child with complementation group C xeroderma pigmentosum (XP) characterized by a splice donor mutation in the XPC gene, multiple skin cancers and specific and persistent hypoglycinaemia. He has cognitive delay, lack of speech, autistic features, hyperactivity and hypotonia, all unexplained by the diagnosis of XP group C, a non‐neurological form of the disease. Treatment with oral glycine has improved his hyperactivity. Specific hypoglycinaemia could indicate a metabolic disorder producing neurological dysfunction. Whether it is related to or coincidental with the XP is unclear.
Let's Ask the Homeless People Themselves: A Needs Assessment Based on a Probability Sample of Adults
Authors: Acosta Olga , Toro Paul A.
Published: December 2002

A probability sample of 301 homeless adults from Buffalo, NY, was followed over 6 months to document the utilization of a variety of community services, examine services desired, and identify factors associated with service utilization, preference, and satisfaction. The following needs were all rated as at least equally important as the need for affordable housing: safety, education, transportation, medical/dental treatment, and job training/placement (most of these needs were also rated as difficult to obtain). Needs for formal mental health and substance abuse services were rated as relatively unimportant and easy to obtain, and for those who actually used them, respondents were often dissatisfied with them. Of 16 predictor variables examined in multivariate analyses, several showed consistent relationships with subsequent service use, preference, and satisfaction. Younger adults, persons of color, those with dependent children, and persons having fewer social supports reported less service utilization, less satisfaction with services received, different perceived needs for particular services, and/or greater difficulty obtaining services.
Psychometric Properties of the Multidimensional Scale of Perceived Social Support in Urban Adolescents
Authors: Canty-Mitchell Janie , Zimet Gregory D.
Published: December 2002

The psychometric properties of the Multidimensional Scale of Perceived Social Support (MSPSS) were investigated in 222 urban, largely African‐American adolescents (68%). High internal consistency was demonstrated, and factor analysis confirmed the three subscale structures of the MSPSS: family, friends, and significant other. Correlations with a family caring scale supported the discriminant validity of the Family subscale. These results confirm the reliability, validity, and utility of the MSPSS with an urban, largely African‐American adolescent sample. Implications of the findings are discussed.
Feminist and Community Psychology Ethics in Research with Homeless Women
Authors: Paradis Emily K.
Published: December 2002

This paper presents a feminist and community psychology analysis of ethical concerns that can arise throughout the process of doing research with women who are homeless. The unique contexts of the lives of women who are homeless demand that researchers redefine traditional ethical constructs such as consent, privacy, harm, and bias. Research that fails to do this may perpetuate the stereotyping, marginalization, stigmatization, and victimization homeless women face. Feminist and community research ethics must go beyond the avoidance of harm to an active investment in the well‐being of marginalized individuals and communities. Using feminist and community psychology ethics, this paper addresses some common problems in research with women who are homeless, and argues for the transformation of research from a tool for the advancement of science into a strategy for the empowerment of homeless women and their communities.
Family Conflict and Children's Internalizing and Externalizing Behavior: Protective Factors
Authors: Formoso Diana , Gonzales Nancy A. , Aiken Leona S.
Published: December 2002

The current investigation examined whether the positive association of family conflict to adolescent depression and conduct problems is attenuated by maternal, paternal, and peer attachment, and maternal and paternal monitoring, within a low‐income, multiethnic sample of 284 adolescents. Parental attachment and monitoring moderated the link from family conflict to conduct problems but not depression; the relationships among family conflict, the hypothesized protective factors, and conduct problems were further modified by adolescent gender but not ethnicity. In general, higher levels of the hypothesized protective factors attenuated the relationship between family conflict and conduct problems for girls but exacerbated this relationship for boys. These findings suggest that, in general, parental attachment and monitoring served as protective factors for girls while serving as additional risk factors for boys in conflictual families.
A History of Women and Feminist Perspectives in Community Psychology
Authors: Bond Meg A. , Mulvey Anne
Published: December 2002

Using an historical framework, we document and assess efforts to include women, women's issues, and feminism in community psychology and in the Society for Community Research and Action (SCRA). Initiatives of the SCRA Task Force/Committee on Women are traced from its inception to present. We also chronicle the dilemmas and difficulties of moving toward a feminist community psychology. The history is divided into five phases. Each phase is described in terms of women's involvement in the field and efforts to integrate feminist content into research and practice of the field. Reflections on the qualities of contexts that have both supported and inhibited inclusion are identified. We look to this history to try to understand the observation that while women have been increasingly visible in leadership roles and women's professional development has been encouraged, less progress has been made toward building a feminist community psychology.
The Importance of Community in a Feminist Analysis of Domestic Violence among American Indians
Authors: Hamby Sherry L.
Published: December 2002

There are over 500 native communities in the United States alone. Although popular conceptions in the majority culture commonly refer to these as a single American Indian group, native communities are in fact extremely diverse and heterogeneous. Issues of gender, class, and power are discussed from a feminist perspective with an emphasis on the diversity among native communities. Available evidence, while sketchy, suggests that male authority, male restrictiveness, and socioeconomic stress are associated with violence, but that the levels of these factors vary widely across native groups. For example, some native tribes practice matrilineal descent while others are patrilineal. This diversity has far‐reaching implications for the community context in which domestic violence occurs. An approach that integrates both feminist and community approaches seems best suited to address the problem of domestic violence in native North America.
The Listening Partners Program: An Initiative Toward Feminist Community Psychology in Action
Authors: Bond Lynne A. , Belenky Mary Field , Weinstock Jacqueline S.
Published: December 2002

The Listening Partners intervention is described and analyzed as a synthesis of feminism and community psychology, within a developmental framework. Working from an empowerment perspective, this social action, peer group intervention supported a community of poor, rural, isolated, young, White mothers to gain a greater voice, claim the powers of their minds, and collaborate in developmental leadership—creating settings that promote their own development and that of their families, peers, and communities. High quality dialogue, individual and group narrative, and collaborative problem‐solving were emphasized, in a feminist context affirming diversity, inclusiveness, strengths, social‐contextual analyses, and social constructivist perspectives. The power of enacting a synergy of feminism and community psychology is highlighted.
Community Narratives: Tales of Terror and Joy
Authors: Rappaport Julian
Published: December 2002

Inspired by a literary‐feminist reading of biblical texts, it is suggested that the mission of community psychology/social science can be understood as a calling to use our tools (research methods, critical analysis and observation, scholarship, social influence) to assist others in the job of turning tales of terror into tales of joy. Such work is the essence of personal and social change. These are not things we can do alone; they require collaboration between us and the people of concern. Applying concepts from narrative theory, including description and critical analysis of community and setting narratives, dominant cultural narratives, and personal stories, we can learn from our own communities and we can use our resources to help make known (perhaps even help to imagine new) tales of joy. Some of these themes are illustrated in three very different contexts: a religious community that has made itself inclusive of gay and lesbian people, a mutual help organization that offers a sense of community and hope for the future to people with a history of serious mental illness, and a public elementary school.
Speaking for Ourselves: Feminist Methods and Community Psychology
Authors: Cosgrove Lisa , McHugh Maureen C.
Published: December 2002

Although feminist and community psychology share a number of epistemological and methodological perspectives that guide their respective theories and research practices, it has been argued that community psychology has not fully integrated a feminist perspective into the discipline. This paper examines how community psychology and feminist research methods might combine to help us better understand women's experiences without essentializing or universalizing those experiences. The authors offer a series of suggested directions for feminist research that may also prove promising for community psychology. Particular attention is paid to feminist social constructionist approaches insofar as they address the complex relationship between epistemology and methodology.
Making a Difference: The Social Ecology of Social Transformation
Authors: Maton Kenneth I.
Published: December 2002

A multidisciplinary and multilevel framework for social transformation is proposed, encompassing four foundational goals: capacity‐building, group empowerment, relational community‐building, and culture‐challenge. Intervention approaches related to each goal are presented at the setting, geographic community, and societal levels. Four exemplars of social transformation work are then discussed: the Accelerated Schools Project, Meyerhoff Program, ManKind Project, and women's movement. These examples illustrate the synergistic relationship among the four transformational goals, within and across levels of analysis, which is at the heart of the social transformation process. The paper concludes with three challenges to guide our efforts as we enter the new century: (1) to move social transformation to the center of our consciousness as a field; (2) to articulate jointly with allied disciplines, organizations, and citizen groups an encompassing, multidisciplinary, and multilevel framework for social transformation; and (3) to do the above with heart, soul, and humility.
Predictors of Condom Use in Mexican Migrant Laborers
Authors: Organista Kurt C. , Organista Pamela Balls , Bola John R. , Javier E. , García de Alba G. , Morán Marco Antonio Castillo
Published: December 2002

The purpose of this study was to explore predictors of condom use with occasional sex partners and regular sex partners, as well as carrying condoms in a new high‐risk group for HIV infection, Mexican migrant laborers. This study extends previous findings by (1) exploring additional predictors not previously examined, (2) utilizing a large sample of male and female Mexican migrant laborers, (3) carefully controlling for the effects of various demographic and lifestyle variables related to condom use, and (4) assessing the interactive effects of gender on predictors of condom use. Snowball sampling was used to survey 501 adult Mexican migrant laborers. Results revealed that condom use with occasional sex partners was predicted by carrying condoms and condom self‐efficacy and that women were more likely to use condoms with occasional partners when both men and women knew someone with HIV/AIDS. Condom use with regular sex partners was predicted by procondom social norms, less negative attitudes toward condoms, not knowing someone with HIV/AIDS, and condom self‐efficacy. Carrying condoms was predicted by procondom social norms, less negative attitudes toward condoms, condom self‐efficacy, worry about contracting HIV/AIDS, and women were more likely than men to carry condoms when both men and women were married. Understanding these findings, future research directions, and implications for condom promotion strategies with Mexican migrant laborers are discussed.
The Impact of Welfare Reform on Men's Violence against Women
Authors: Riger Stephanie , Krieglstein Maryann
Published: December 2002

Welfare reform is likely to have a profound effect on the lives of poor women who are being abused. This article proposes exchange theory and the feminist “backlash hypothesis” as frameworks with which to assess the impact of welfare reform on violence levels in abusive relationships. Exchange theory suggests that if a woman leaves welfare and obtains employment that increases her economic resources, violence against her will decrease. The backlash hypothesis makes a different prediction: Violence will increase as men attempt to compensate for women's enhanced status or independence. Both approaches are examined in light of current data. As demonstrated here, the incorporation into social policy analyses of feminist thinking about dominance and power will enrich our understanding of the impact of social policy changes on people.