bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partner Violence, Social Support, and Distress Among Inner‐City African American Women
Authors: Thompson Martie P. , Kaslow Nadine J. , Kingree J. B. , Rashid Akil , Puett Robin , Jacobs Diana , Matthews Alex 
Published: December 2002

AbstractThis study examined the role of social support in the partner violence–psychological distress relation in a sample of African American women seeking medical care at a large, urban hospital (n = 138). Results from bivariate correlational analyses revealed that partner violence was related to lower perceived social support and greater psychological distress, and lower social support was related to more distress. Furthermore, findings based on path analysis indicated that low levels of social support helped account for battered women's increased distress. Findings point to the need for service providers to screen for partner violence in nontraditional sites, such as hospital emergency rooms, and to address the role of social support resources in preventive interventions with African American battered women.
Expression of human phenylalanine hydroxylase activity in T lymphocytes of classical phenylketonuria children by retroviral‐mediated gene transfer
Authors: Lin C.M. , Tan Y. , Lee Y.M. , Chang C.C. , Hsiao K.J. 
Published: December 2002

AbstractClassical phenylketonuria (PKU) is a metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene. At present, T lymphocyte‐directed gene therapy is the only means for which a safety record has been established. Thus, we investigated the applicability of this strategy to PKU gene therapy. We first looked for tetrahydrobiopterin (BH4) and dihydropteridine reductase (DHPR) activity, which are required for the phenylalanine hydroxylation reaction and BH4 regeneration, respectively, in T cells isolated from PKU children. We found that T cells contained a small amount of biopterin, but significant DHPR activity, and that the intracellular biopterin content could be increased by exogenous BH4 supplementation. Moreover, PKU T cells were capable of taking up phenylalanine efficiently and effluxing acquired tyrosine. Finally, a recombinant retrovirus containing the human PAH cDNA was constructed and used to transduce isolated PKU T cells. Viral‐transduced T cells produced high levels of PAH activity as compared to control mock‐infected T cells. These results indicate that T lymphocytes express all that is required for synthesizing/replenishing constituents of the phenylalanine hydroxylation reaction and expressing transduced phenylalanine hydroxylase cDNA.
Severe lactic acidosis and neonatal death in Pearson syndrome
Authors: Muraki K. , Goto Y. , Nishino I. , Hayashidani M. , Takeuchi S. , Horai S. , Sakura N. , Ueda K. 
Published: December 2002

AbstractPearson marrow‐pancreas syndrome, a fatal disease associated with mitochondrial DNA rearrangements, is characterized by refractory sideroblastic anaemia during infancy. Only a few neonates with Pearson syndrome have been reported with metabolic acidosis. A female neonate who exhibited severe metabolic acidosis and anaemia at birth is described here. Her condition progressively worsened, with pancytopenia and uncontrollable metabolic acidosis resulting in death at the age of 14 days. A 4988‐base pair deletion of mtDNA was detected in the patient's leukocytes, liver and muscle. When a neonate exhibits severe metabolic acidosis of unknown cause, the possibility of Pearson syndrome should be considered.
When to investigate for purine and pyrimidine disorders. Introduction and review of clinical and laboratory indications
Authors: Simmonds H. A. , Duley J. A. , Fairbanks L. D. , McBride M. B. 
Published: December 2002

AbstractWhen to suspect and thus investigate for inborn errors of purine and pyrimidine metabolism is a dilemma for even the most observant investigator. Often parents of affected children, or a history involving siblings, can provide valuable clues. The recognition of new purine and pyrimidine disorders requires skill and serendipity. But even identifying known disorders can prove difficult, since they cover a broad spectrum of illnesses, can have more than one symptom, or lead to early death. This problem is compounded by the fact that they are relatively recently described and therefore often little known, either in the clinic or laboratory. The considerable heterogeneity in clinical expression within families as well as between families means that asymptomatic homozygotes may not be recognized or can present at any time from early childhood through adolescence up to their eighth decade. Consequently, all siblings should be screened. These disorders should be suspected in any case of unexplained anaemia, failure to thrive, susceptibility to recurrent infection, or neurological deficits with no current diagnosis, including autism, cerebral palsy, delayed development, deafness, epilepsy, self‐mutilation, muscle weakness, the inability to walk or talk, and ‐ unusual in children and adolescents ‐ gout, sometimes with renal disease. Some disorders present with radiolucent kidney stones, in acute or chronic renal failure, alone or with any of the above, or as an intolerance/sensitivity to therapy (e.g. 5‐fluorouracil in malignancies or azathioprine immunosuppression in organ transplantation), often with life‐threatening consequences. Several parameters need to be evaluated to ensure correct diagnosis. Pitfalls which can mask diagnosis using only a single test are renal failure, blood transfusion, diet or drugs.
Decreased platelet membrane anisotropy in patients with adrenoleukodystrophy treated with erucic acid (22:1)‐rich triglycerides
Authors: Stöckler S. , Opper C. , Greinacher A. , Hunneman D. H. , Korenke G. C. , Unkrig C. J. , Hanefeld F. 
Published: December 2002

AbstractLow platelet count and bleeding diathesis have been observed in patients with adrenoleukodystrophy (ALD) treated with erucic acid (22:1)‐rich triglycerides (‘Lorenzo's oil’). To investigate possible alterations of biophysical membrane properties, we measured platelet membrane anisotropy, which is inversely related to membrane fluidity, in 16 patients with and in 3 patients without treatment. In patients on treatment, platelet membrane anisotropy was significantly decreased. Additionally, we found increased platelet concentrations of 22:1 and compromised in vitro platelet aggregation response. The decrease of platelet membrane anisotropy is probably a main cause of bleeding diathesis. Long‐term haematological side‐effects must be considered in ALD patients treated with Lorenzo's oil.
Fatty acid oxidation in fibroblasts from patients with defects in β‐oxidation and in the respiratory chain
Authors: Venizelos N. , von Döbeln U. , Hagenfeldt L. 
Published: December 2002

AbstractFatty acid oxidation has been studied with the tritium release assay in cultured fibroblasts from patients with defects in β‐oxidation and in the mitochondrial respiratory chain. Cells from all patients with β‐oxidation defects and cells from 10 of 16 patients with respiratory chain defects showed an impairment of fatty acid oxidation. The result of the tritium release assay is not only dependent on the proper function of the β‐oxidation cycle but is also influenced by the reoxidation of reduced cofactors. The assay can thus be used to study the expression of respiratory chain defects in cultured fibroblasts.
Mutations among Italian mucopolysaccharidosis type I patients
Authors: Gatti R. , DiNatale P. , Villani G.R.D. , Filocamo M. , Muller V. , Guo X.‐H. , Nelson P.V. , Scott H.S. , Hopwood J. J. 
Published: December 2002

AbstractA group of 27 Italian patients was screened for α‐L‐iduronidase mucopolysaccharidosis type I mutations. Mutations were found in 18 patients, with 28 alleles identified. The two most common mutations in northern Europeans (W402X and Q70X) accounted for 11% and 13% of the alleles, respectively. The R89Q mutation, uncommon in Europeans, was found only in one patient, accounting for 1 of 54 alleles (1.9%). The other mutations, P533R, A327P and G51D, accounted for 11%, 5.6% and 9.3% of the total alleles, respectively. Interestingly, the high frequency of the P533R mutation seems to be confined to Sicily and is higher than the 3% reported in a British/Australian study.
Varicella and varicella immunity in patients with lysinuric protein intolerance
Authors: Lukkarinen M. , Näntö‐Salonen K. , Ruuskanen O. , Lauteala T. , Säkö S. , Nuutinen M. , Simell O. 
Published: December 2002

AbstractTwo patients with lysinuric protein intolerance (LPI) had near‐fatal generalized varicella infection with severe interstitial pneumonitis, hepatitis, decreased platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and ferritin concentration, which in patients with LPI in normal circumstances exceed the upper reference values 3‐fold to 10‐fold, increased to >10 000U/L and >10 000 µg/L, respectively. The patients were treated with fresh frozen plasma, red‐cell transfusions and intravenous acyclovir for 14 days, and recovered clinically in a month. Retrospectively, 3 of the 32 other known Finnish patients with LPI had had varicella infection that had been more severe than that in the other children in the family or in subjects in the neighbourhood and had led to hospital admission. Varicella antibodies were measured in 24 patients; 5 had no antibodies and 5 had very low antibody titres. Primary vaccination of three patients with living varicella vaccine increased antibody titres measurably in one patient. We suggest that patients with LPI who have no varicella zoster antibodies should be treated with acyclovir if exposed to varicella and should be (re)vaccinated against chickenpox.
The biochemical and molecular spectrum of ornithine transcarbamylase deficiency
Authors: Tuchman M. , Morizono H. , Rajagopal B. S. , Plante R. J. , Allewell N. M. 
Published: December 2002

AbstractOrnithine transcarbamylase (OTCase) deficiency, the most commoninherited urea cycle disorder, is transmitted as an X‐linked trait. The clinical phenotype in affected males as well as heterozygous females shows a spectrum of severity ranging from neonatal hyperammonaemic coma to asymptomatic adults. The ornithine transcarbamylase enzyme is a trimer with three active sites per holoenzyme molecule, each of which is composed of an interdomain region of one polypeptide and a polar domain of the adjacent polypeptide. The OTC gene is located on the short arm of the X‐chromosome and one of the two alleles undergoes inactivation in female cells. Approximately 140 mutations have been found in families affected with OTCase deficiency, most having their own ‘private’ mutation. Large deletions of one exon or more are seen in approximately 7% of patients, small deletions or insertions are seen in about 9%, and the remaining mutations are single base substitutions. Approximately 15% of mutations affect RNA splicing sites. The recurrent mutations are distributed equally among CpG dinucleotide hot spots. Generally, mutations causing neonatal disease affect amino acid residues that are ‘buried’ in the interior of the enzyme, especially around the active site, while those associated with late onset and milder phenotypes tend to be located on the surface of the protein. Very few mutations have been found in the sequence of the leader peptide, proportionally much fewer than in the sequence of the mature enzyme. Only few of the mutations have been expressed in bacteria or mammalian cells for the study of their deleterious mechanisms. Examples of expressed mutations include R277W and R277Q associated with late‐onset disease, which markedly increase the Km for ornithine, shift the pH optimum to more alkaline and decrease the thermal stability of the purified mutant enzyme. R141Q (neonatal disease) disrupts the active site, whereas the purified R40H mutant has normal catalytic function and this mutation is likely to affect posttranslational processing such as mitochondrial targeting. It appears that most new mutations occur in male sperm and are then passed on to a transmitting heterozygous female. Uncommonly, mild mutations are transmitted by asymptomatic males to their daughters, subsequently resulting in clinical disease of males in future generations. The causes for variable expressivity of these mutations are currently unknown but are likely to involve a combination of environmental and genetic modifiers.
Inborn errors of pyrimidine degradation: Clinical, biochemical and molecular aspects
Authors: van Gennip A.H. , Abeling N.G.G.M. , Vreken P. , van Kuilenburg A.B.P. 
Published: December 2002

AbstractThe pyrimidines, uracil and thymine, are degraded in four steps. The first three steps of pyrimidine catabolism, controlled by enzymes shared by both pathways, result in the production of the neurotransmitter amino acid β‐alanine from uracil and the nonfunctional (R)‐(‐)‐β‐aminoisobutyrate from thymine. The fourth step is controlled by several aminotransferases, which have different affinities for β‐alanine, β‐aminoisobutyrate and GABA. Defects concerning the first three steps all lead to a reduced production of β‐alanine; defects of the transaminases involving the metabolism of β‐alanine and GABA lead to accumulation of these neurotransmitter substances. In addition, other metabolites will accumulate or be reduced depending on the specific enzyme defect. Analysis of the abnormal concentrations of these metabolites in the body fluids is essential for the detection of patients with pyrimidine degradation defects. Clinically these disorders are often overlooked because symptomatology is highly aspecific. The growth in our knowledge concerning inborn errors of pyrimidine degradation has emphasized the importance of the clinical awareness of these defects as a possible cause of neurological disease and a contraindication for treatment of cancer patients with certain pyrimidine analogues. The various defects are discussed and attention is paid to clinical, genetic and diagnostic aspects.
Regulation of the urea cycle enzyme genes in nitric oxide synthesis
Authors: Mori M. , Gotoh T. , Nagasaki A. , Takiguchi M. , Sonoki T. 
Published: December 2002

AbstractNitric oxide (NO) is synthesized from arginine by nitric‐oxide synthase (NOS), and citrulline that is generated can be recycled to arginine by argininosuccinate synthase (AS) and argininosuccinate lyase (AL). Rats were injected with bacterial lipopolysaccharide (LPS) and expression of the inducible isoform of NOS (iNOS), AS and AL was analysed. In RNA blot analysis, iNOS mRNA was induced by LPS in the lung, heart, liver and spleen, and less strongly in the skeletal muscle and testis. AS and AL mRNAs were induced in the lung and spleen. Kinetic studies showed that iNOS mRNA increased rapidly in both spleen and lung, reached a maximum 2–5 h after the treatment, and decreased thereafter. On the other hand, AS mRNA increased more slowly and reached a maximum in 6–12 h (by about 10‐fold in the spleen and 2‐fold in the lung). AL mRNA in the spleen and lung increased slowly and remained high upto 24 h. In immunohistochemical analysis, macrophages in the spleen that were negative for iNOS and AS before LPS treatment were strongly positive for both iNOS and AS after this treatment. As iNOS, AS and AL were co‐induced in rat tissues and cells, citrulline–arginine recycling seems to be important in NO synthesis under the conditions of stimulation.Arginine is a common substrate of NOS and arginase. Rat peritoneal macrophages were cultured in the presence of LPS and expression of iNOS and liver‐type arginase (arginase I) was analysed. mRNAs for iNOS and arginase I were induced by LPS in a dose‐dependent manner. iNOS mRNA appeared 2 h after LPS treatment and increased up to a near‐maximum at 8–12 h. On the other hand, arginase I mRNA began to increase after 4 h with a lag time and reached a maximum at 12 h. Immunoblot analysis showed that iNOS and arginase I proteins were also induced. Induction of iNOS and arginase I mRNAs were also observed in LPS‐injected rats in vivo. Thus, arginase I appears to have an important role in downregulating NO synthesis in murine macrophages by decreasing the availability of arginine.A cDNA for human arginase II, an arginase isozyme, was isolated. A polypeptide of 354 amino acid residues including the putative NH2‐terminal presequence for mitochondrial import was predicted. It was 59% identical with arginase I. mRNA for human arginase II was present in the kidney and other tissues but was not detected in the liver. Arginase II mRNA was co‐induced with iNOS mRNA in murine macrophage‐like RAW 264.7 cells by LPS. This induction was enhanced by dexamethasone and dibutyrul cAMP, and was prevented by interferon‐γ.These results indicate that NO synthesis is regulated by arginine‐synthesizing and ‐degrading enzymes in a complicated manner.
Plasma chitotriosidase activity in Gaucher disease patients who have been treated either by bone marrow transplantation or by enzyme replacement therapy with alglucerase
Authors: Young E. , Chatterton C. , Vellodi A. , Winchester B. 
Published: December 2002

AbstractA marked elevation in plasma chitotriosidase (chitinase) activity has recently been observed in patients with Gaucher disease (Hollak et al 1994). It has been suggested that this phenomenon may serve as a useful marker for the efficacy of treatment with enzyme replacement therapy. We report our findings on the comparison of plasma chitotriosidase levels in 8 patients treated with the modified human placental enzyme alglucerase and 8 patients treated by allogeneic bone marrow transplantation (BMT). Two years after transplantation the activity in the BMT patients had fallen by over 93% and has continued to fall. Now, 5‐12 years post‐BMT, 6 patients have normal levels of plasma chitotriosidase and 2 patients have activities slightly above the reference range. Patients have been treated with alglucerase for a considerably shorter time than the BMT patients. The chitotriosidase activities have fallen and are continuing to fall in 7 patients but at a slower rate than in the BMT group. In one patient there has been no appreciable change in activity over the last 6 months, which would suggest that she may be on too low a dosage.
Developing adenoviral‐mediated in vivo gene therapy for ornithine transcarbamylase deficiency
Authors: Raper S. E. , Wilson J. M. , Yudkoff M. , Robinson M. B. , Ye X. , Batshaw M. L. 
Published: December 2002

AbstractThere are a number of reasons for choosing ornithine transcarbamylase (OTC) deficiency as a candidate for gene therapy: the gene has been cloned; the disorder is relatively common; the current clinical outcome is poor; and there are authentic animal models. In considering the development of gene therapy for OTC deficiency, we focused on the use of in vivo gene therapy with an adenoviral vector. Using the partially OTC‐deficient sparse fur mouse we found transduction and expression could be achieved using an intravenous infusion of a recombinant adenovirus containing the OTC cDNA. The results were transient as a result of immune activation in response to the vector and vector‐transduced cells. By modifying the adenoviral construct, creating an E1 deletion–E2 temperature‐sensitive mutation, we blunted the cytotoxic T lymphocyte immune response and achieved correction of biochemical abnormalities for 2–3 months. We also found that transduction and expression following gene transfer occurred sufficiently rapidly to protect against acute hyperammonaemia within 24 h. Subsequent preclinical studies in mice and non‐human primates demonstrated that E1–E4‐deleted vectors had a substantially improved safety profile and similar efficacy. With this evidence of efficacy and safety of adenoviral vectors, we are embarking on a phase I trial of intravascular gene transfer using an E1–E4‐deleted vector in adults with partial OTC deficiency.
Peroxisomal localization of α‐oxidation in human liver
Authors: Casteels M. , Croes K. , Van Veldhoven P. P. , Mannaerts G. P. 
Published: December 2002

AbstractIt was found that α‐oxidation in rat liver is a peroxisomal process, consisting of an activation, a 2‐hydroxylation, and a reaction leading to the production of formate. α‐Oxidation of 3‐methyl‐substituted fatty acids was quantified by measuring the production of formate and CO2, and the production of a 2‐hydroxy‐3‐methylacyl‐CoA‐intermediate was demonstrated. We wanted to extend these findings to human liver, in view of the controversy over the subcellular localization of α‐oxidation in man.In homogenates from human liver, rates of α‐oxidation were highest when measured in the presence of ATP, CoA, Mg2+, 2‐oxoglutarate, ascorbate and Fe2+. In subcellular fractions prepared by differential centrifugation and in fractions obtained after subfractionation of a peroxisome‐enriched fraction on a Percoll gradient, production of formate and of a 2‐hydroxy‐3‐methylacyl‐CoA intermediate coincided with the peroxisomal marker catalase. In broken fractions, production of CO2 was almost negligible as compared to formate production.We conclude from our findings that in human liver, as in rat liver, α‐oxidation of 3‐methyl‐substituted fatty acids is a peroxisomal process, consisting of an activation reaction, a 2‐hydroxylation reaction and a reaction or reactions leading to the generation of formate as a primary product which is subsequently converted to CO2. Furthermore activation, 2‐hydroxylation and generation of formate appear to be coupled (see Casteels et al 1996). These data demonstrate that Refsum disease should indeed be classified as a peroxisomal disease.
Allergic disease as an association of steroid sulphatase deficiency
Authors: Sakura N. , Nishimura S. , Matsumoto T. , Ohsaki M. , Ogata T. 
Published: December 2002

AbstractTen of 31 patients with steroid sulphatase (STS) deficiency were found to have an allergic disease (bronchial asthma, allergic rhinitis, or atopic dermatitis). STS deficiency may predispose patients to allergic disease.
Adult psychosocial outcome in early‐treated phenylketonuria
Authors: Ris M. D. , Weber A. M. , Hunt M. M. , Berry H. K. , Williams S. E. , Leslie N. 
Published: December 2002

AbstractConcerns about the psychosocial risk of adults with early‐treated phenylketonuria (ETPKU) are predicated on four sources of scientific data: (1) consistent documentation of increased behavioural risk in children with ETPKU; (2) recent evidence of neurocognitive impairment in adults with ETPKU; (3) reports of neuroimaging abnormalities in adults with ETPKU; and (4) preliminary evidence of increased rates of psychiatric disturbance in this population. We studied the psychosocial adjustment of 25 patients, aged 18 years and older, with ETPKU. On most pscyhosocial outcome measures, patients were indistinguishable from 15 sibling controls. However, on a self‐report inventory of psychiatric symptoms, 20% of the patients demonstrated significant morbidity. Psychosocial outcome of these patients was unrelated to concurrent or historical biological dietary disease factors, unlike neurocognitive outcome. A strong relationship was demonstrated, however, between neurocognitive measures and psychosocial morbidity. These findings indicate that a significant minority of patients with ETPKU develop psychosocial difficulties with multiple clinical elevations on a psychiatric inventory. However, most adults with ETPKU cope with the challenges of young adulthood with the same degree of success as their unaffected siblings. Neuropsychological surveillance during childhood and adolescence is important in identifying patients at risk for both neurocognitive and psychosocial morbidity.