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1.
Int J Cancer ; 88(3): 464-8, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11054677

ABSTRACT

Glutathione plays an important role in drug resistance of tumor cells and in their ability to resist oxidative stress. Improved salvage of glutathione can be obtained through increased activity of gamma-glutamyltransferase (GGT), which is of importance in the maintenance of cellular glutathione homeostasis. We investigated the regulation of GGT in 2 cisplatin-resistant and 1 cisplatin-sensitive colon carcinoma cell lines. Enzyme activity was induced in all 3 cell lines after acute exposure to cisplatin. The elevation was significantly higher in sensitive cells (3.3-fold) than in resistant (1.6- to 1.7-fold) cells. Exposure of cells to oxidative stress generated by menadione also resulted in enzyme induction but only in cisplatin-sensitive cells. Addition of anti-oxidants had different effects on the 2 inductions: N-acetylcysteine blocked the induction of both cisplatin and menadione, whereas catalase and glutathione-ester blocked only the menadione induction. Glutathione depletion alone was not sufficient to induce GGT in these cells. The data show that GGT is regulated by multiple mechanisms during anti-tumor drug treatment and oxidative stress and that reactive oxygen species were involved in the menadione, but not cisplatin, induction of the enzyme.


Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Colonic Neoplasms/drug therapy , Oxidative Stress , gamma-Glutamyltransferase/metabolism , Buthionine Sulfoximine/pharmacology , Colonic Neoplasms/metabolism , Drug Resistance, Neoplasm , Glutathione/analysis , Humans , Reactive Oxygen Species/metabolism , Tumor Cells, Cultured
2.
Acta Paediatr ; 83(9): 920-2, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7819686

ABSTRACT

Using high pressure liquid chromatography on strong cation exchange column, we analyzed capillary blood from 141 healthy full-term newborns for lactate and pyruvate concentrations. Total range of lactate was 367-3245 mumol/l and reference interval (mean +/- 2 SD) was 260-2212 mumol/l. Total range of pyruvate was 10-141 mumol/l and reference interval (10th/90th percentile) was 12-71 mumol/l.


Subject(s)
Infant, Newborn/blood , Lactates/blood , Pyruvates/blood , Adolescent , Adult , Capillaries , Female , Heel/blood supply , Humans , Lactic Acid , Male , Pyruvic Acid , Reference Values , Time Factors
3.
J Med Genet ; 31(5): 360-3, 1994 May.
Article in English | MEDLINE | ID: mdl-8064811

ABSTRACT

Aspartylglucosaminuria (AGU, McKusick 208400) is an autosomal recessive lysosomal storage disorder. Ninety percent of all patients are from Finland and only sporadic cases have been reported from elsewhere. In northern Norway, however, nine patients from seven families have been diagnosed with AGU. All these Norwegian patients were homozygous for the most prevalent Finnish AGU mutation (AGUFin) and show the polymorphism uniquely associated with AGUFin in Finland. Genealogical investigation of nine parents proved Finnish ancestry in all pedigrees. Therefore, AGU in Norway most likely resulted from immigration of Finnish carriers. These Finnish immigrants originated mostly from the Tornio valley area in northern Finland in a continuous immigration movement from 1700 to 1900. The majority settled in the western part of northern Norway, leading to a "cluster" of AGU in that particular area. The Finnish immigrants intermixed considerably with Lapps and these two ethnic origins should thus be considered as high risk groups for AGUFin in northern Norway.


Subject(s)
Acetylglucosamine/analogs & derivatives , Lysosomal Storage Diseases/epidemiology , Lysosomal Storage Diseases/genetics , Acetylglucosamine/urine , Adult , Aspartylglucosaminuria , Aspartylglucosylaminase/genetics , Base Sequence , DNA Primers , Female , Finland/ethnology , Genes, Recessive , Humans , Lysosomal Storage Diseases/ethnology , Male , Middle Aged , Molecular Epidemiology , Molecular Sequence Data , Norway/epidemiology , Pedigree , Point Mutation , Polymorphism, Genetic , White People
5.
Ultrastruct Pathol ; 16(3): 263-75, 1992.
Article in English | MEDLINE | ID: mdl-1316655

ABSTRACT

From 1986 to 1991, 472 muscle biopsy specimens from patients from different hospitals in Norway were examined. Of these, 364 were embedded for electron microscopy, and 194 were examined with electron microscopy. Ultrastructural alterations in the mitochondria were detected in 49 of these specimens. Characteristic electron microscopic findings included subsarcolemmal accumulation of abnormal mitochondria of various shapes and sizes, often containing electron-dense granules and sometimes lipid vacuoles in the mitochondria and diffusely electron-lucent matrix space. Paracrystalline inclusion bodies were seldom seen in specimens from young patients, but in some cases mitochondrial electron-dense granules at the cristae were found. These amorphous densities are consistent with lipoproteins, suggesting that they may represent an early stage of paracrystalline inclusions. Biochemical and genetic exploration of the patients with biopsy specimens suggesting mitochondrial disease indicated maternally genetic inheritance and an enzyme defect in the respiratory chain in 21 patients in two families. Three patients had MELAS syndrome, 7 Marinesco-Sjögren syndrome, and 2 Kearns-Sayre syndrome. Five family members had ptosis, cardiomyopathy, mild myopathy, and increased lactate in cerebrospinal fluid and serum. In addition to the diseases mentioned above, changes in the mitochondria were detected in other conditions such as Rett's syndrome (n = 1), ornithine transcarbamylase deficiency (n = 2), and hypothyroidism (n = 2) as well as in 3 patients with clinical and laboratory results indicative of inflammatory myopathy and 3 patients with clinical and laboratory findings consistent with peripheral neuropathy. It is concluded that, although ultrastructural changes in the mitochondria may represent unspecific findings, electron microscopic examination of muscle biopsy specimens is a useful screening method to select specimens for further biochemical analysis and to obtain an early and more precise diagnosis of the disease.


Subject(s)
Mitochondria, Muscle/ultrastructure , Biopsy , Humans , Inclusion Bodies/ultrastructure , Microscopy, Electron , Muscles/pathology , Muscular Diseases/genetics , Muscular Diseases/pathology
6.
J Ment Defic Res ; 35 ( Pt 2): 154-9, 1991 Apr.
Article in English | MEDLINE | ID: mdl-2072394

ABSTRACT

Myopathy represents one of the major features of Marinesco-Sjögren syndrome (MSS). Seven patients with MSS from three different families were studied with morphological and neurophysiological methods. In two patients ragged-red fibres were found after Gomori trichrome staining. Transmission electron microscopy (EM) showed that subsarcolemmal accumulation of abnormal mitochondria regularly occurred and in one patient paracrystalline inclusion bodies were found. The EMG showed myopathic changes while the nerve condition velocities were normal. A delayed normalization of exercised-induced hyperlactatemia was noted. These findings show that mitochondrial myopathic changes are present in MSS.


Subject(s)
Mitochondria, Muscle/ultrastructure , Muscle Hypotonia/pathology , Neuromuscular Diseases/pathology , Spinocerebellar Degenerations/pathology , Adolescent , Adult , Biopsy , Cerebellum/pathology , Chromosome Aberrations/diagnosis , Chromosome Aberrations/genetics , Chromosome Aberrations/pathology , Chromosome Disorders , Exercise Test , Female , Genes, Recessive/genetics , Humans , Lactates/blood , Lactic Acid , Male , Microscopy, Electron , Muscle Hypotonia/diagnosis , Muscle Hypotonia/genetics , Muscles/pathology , Neurologic Examination , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/genetics , Pyruvates/blood , Pyruvic Acid , Spinocerebellar Degenerations/diagnosis , Spinocerebellar Degenerations/genetics , Tomography, X-Ray Computed
7.
Tidsskr Nor Laegeforen ; 111(2): 202-6, 1991 Jan 20.
Article in Norwegian | MEDLINE | ID: mdl-1998182

ABSTRACT

Mitochondrial myopathy can be caused by several metabolic defects in the mitochondria. Cells with high levels of oxidative metabolism, such as skeletal muscle, myocardium and brain cells, are particularly vulnerable to these defects. We describe the structural changes in muscle biopsies from 49 patients with mitochondrial myopathy. The younger patients were often symptom-free, but the possibility of a genetic defect was suggested by the family history. "Ragged-red fibres" were found in 10% of the biopsies. Typical paracrystalline inclusions were seen in the mitochondria of the oldest patients. Electron-lucent matrix and increased thickness of the inner membranes of the mitochondria in particular were found in the younger patients. Disorganization of cristae, with cristolysis and unfolding of the cristae was also found. We suggest that structural mitochondrial changes in mitochondrial myopathy constitute a stepwise process and that the mitochondrial alterations of the cristae may represent an early stage in the morphogenesis of mitochondrial disease.


Subject(s)
Carbohydrate Metabolism, Inborn Errors/pathology , Mitochondria, Muscle/ultrastructure , Muscular Diseases/pathology , Age Factors , Carbohydrate Metabolism, Inborn Errors/genetics , Carbohydrate Metabolism, Inborn Errors/metabolism , Female , Humans , Male , Microscopy, Electron , Mitochondria, Muscle/metabolism , Muscular Diseases/genetics , Muscular Diseases/metabolism
8.
Eur Neurol ; 30(6): 314-8, 1990.
Article in English | MEDLINE | ID: mdl-1963142

ABSTRACT

Two sisters with chronic progressive external ophthalmoplegia (CPEO) and their in all 7 healthy children were investigated. Both ophthalmoplegic patients had histopathological changes typical of mitochondrial myopathy. The same type of muscular pathology was also found among the healthy children. The most common muscular changes were subsarcolemmal accumulation of pathological mitochondria, including vacuoles, abnormal cristae and sometimes also inclusion bodies. Biochemical studies showed partial complex III deficiency, with low succinate-cytochrome c reductase activity in 1 of the ophthalmoplegic patients. These findings suggest that CPEO is a slowly progressive muscle disease, starting early in life. The widespread occurrence among the children may indicate maternal inheritance.


Subject(s)
Mitochondria, Muscle/ultrastructure , Ophthalmoplegia/pathology , Adolescent , Adult , Creatine Kinase/blood , Cytoplasmic Granules/ultrastructure , Electromyography , Exercise/physiology , Family , Female , Humans , Inclusion Bodies/ultrastructure , Lactates/blood , Lactates/cerebrospinal fluid , Male , Middle Aged , Mitochondria, Muscle/metabolism , Neural Conduction/physiology , Ophthalmoplegia/genetics , Ophthalmoplegia/physiopathology , Pyruvates/blood , Pyruvates/cerebrospinal fluid , Sarcoplasmic Reticulum/ultrastructure
9.
J Ment Defic Res ; 33 ( Pt 3): 261-5, 1989 Jun.
Article in English | MEDLINE | ID: mdl-2526881

ABSTRACT

Secondary cystathioninuria is associated with various pathological conditions (Gjessing, 1963; Gjessing & Mauritzen, 1965; Endres & Wuttge, 1978). In many cases, cystathioninuria has been associated with mental retardation (Harris et al., 1959; Robb et al., 1984). As far as the authors know, cystathioninuria has not previously been described in Down's syndrome. In 1981, in the author's institution for the mentally retarded, all patients with Down's syndrome were screened with regard to aminoaciduria, using thin layer chromatography. In the course of this process, a case of cystathioninuria was discovered. The results are presented in detail.


Subject(s)
Amino Acid Metabolism, Inborn Errors/genetics , Cystathionine/urine , Down Syndrome/genetics , Adult , Amino Acid Metabolism, Inborn Errors/urine , Down Syndrome/urine , Female , Humans , Pyridoxine/administration & dosage
10.
Acta Obstet Gynecol Scand ; 68(2): 145-8, 1989.
Article in English | MEDLINE | ID: mdl-2589041

ABSTRACT

Mitochondrial dysfunction is a newly found group of inborn errors of metabolism in which there is a failure in the aerobic energy production. Disorders of mitochondrial metabolism exhibit a wide range of clinical symptoms which are related to the nature, severity and tissue distribution of the metabolic defect. Most reported cases are published in the neurological literature. In this report we describe for the first time a family with mitochondrial dysfunction with a high incidence of pre-eclampsia/eclampsia. The diagnosis of a mitochondrial disorder is verified by electronmicroscopic, electromyographic, histochemical and biochemical examinations. During pregnancy, the energy demand is increased due to both fetal and maternal requirements. A mitochondrial dysfunction, clinically symptomless in the non-pregnant state, may therefore become manifest during pregnancy. Characteristic features of pre-eclampsia such as disturbed ion transport, disturbed prostaglandin synthesis, vasoconstriction, platelet aggregation and hyperuricemia may be explained by mitochondrial dysfunction.


Subject(s)
Eclampsia/genetics , Mitochondria/metabolism , Pre-Eclampsia/genetics , Adult , Eclampsia/metabolism , Eclampsia/physiopathology , Female , Humans , Infant, Newborn , Mitochondria, Muscle/ultrastructure , Pre-Eclampsia/metabolism , Pre-Eclampsia/physiopathology , Pregnancy , Pregnancy Outcome
13.
J Ment Defic Res ; 31 ( Pt 3): 299-301, 1987 Sep.
Article in English | MEDLINE | ID: mdl-3681958

ABSTRACT

This article describes a profoundly mentally retarded woman with spastic tetraplegia, deafness and abnormal liver function tests with a secondary cystathioninuria. The cystathioninuria could be corrected with vitamin B6 supplementation.


Subject(s)
Cystathionine/urine , Intellectual Disability/complications , Deafness/complications , Female , Humans , Liver Function Tests , Middle Aged , Pyridoxine/therapeutic use , Quadriplegia/complications
15.
J Inherit Metab Dis ; 5(1): 55-7, 1982.
Article in English | MEDLINE | ID: mdl-6820415

ABSTRACT

Human skin fibroblasts deficient in pyruvate dehydrogenase and five normal control strains were incubated with one of the following labelled substrates: DL-[1-14C]-2-amino-n-butyric acid, DL-[3-14C]-2-amino-n-butyric acid, L-[1-14C]leucine, L-[1-14C]valine, L-[1-14C]alanine, and [1-14C]pyruvate. The rate of 14CO2-production in the deficient cells was normal from 2-aminobutyrate and leucine, increased from valine, and decreased from alanine and pyruvate. These results indicated that in human skin fibroblasts the decarboxylation of 2-oxobutyrate is catalysed by an enzyme system different from the pyruvate dehydrogenase complex.


Subject(s)
Aminobutyrates/metabolism , Pyruvate Dehydrogenase Complex Deficiency Disease , Valine/metabolism , Carbon Dioxide/metabolism , Cells, Cultured , Fibroblasts/metabolism , Humans , Oxidation-Reduction , Time Factors
16.
J Neurol Neurosurg Psychiatry ; 44(7): 574-82, 1981 Jul.
Article in English | MEDLINE | ID: mdl-7026736

ABSTRACT

A series of biochemical tests aimed at elucidating the fundamental cause has been applied to 20 patients with Friedreich's ataxia. Special emphasis was placed upon pyruvate metabolism. The results demonstrate no precisely identifiable defect in the metabolism of pyruvate but indicate an abnormality in glucose uptake and metabolism.


Subject(s)
Friedreich Ataxia/metabolism , Adolescent , Adult , Alanine/blood , Alanine/metabolism , Blood Glucose/analysis , Child , Child, Preschool , Friedreich Ataxia/blood , Friedreich Ataxia/diagnosis , Glucose/administration & dosage , Glucose/metabolism , Humans , Insulin/blood , Insulin/metabolism , Lactates/metabolism , Pyruvates/blood , Pyruvates/metabolism
17.
J Inherit Metab Dis ; 3(3): 85-6, 1980.
Article in English | MEDLINE | ID: mdl-6775144

ABSTRACT

Urinary amino acids have been determined in six patients with propionic acidaemia, one of whom also showed 3-methylcrotonylglycinuria. Two patients, including the subject with 3-methylcrotonylglycinuria, showed a gross aminoaciduria with features of both cystinuria and iminoglycinuria. We suggest a defect in certain amino acid transport systems in some patients with these disorders.


Subject(s)
Amino Acid Metabolism, Inborn Errors/urine , Amino Acids, Diamino/urine , Glycine/analogs & derivatives , Infant, Newborn, Diseases/urine , Propionates/blood , Amino Acids/urine , Child , Child, Preschool , Crotonates/urine , Cystinuria , Glycine/urine , Humans , Infant , Infant, Newborn
19.
J Inherit Metab Dis ; 1(4): 161-2, 1978.
Article in English | MEDLINE | ID: mdl-117250

ABSTRACT

Studies on fibroblasts from patients with lactic acidosis of different causes showed secondary metabolic changes in pathways of glucose metabolism. These secondary changes may be important clues to the diagnosis of the many different types of hereditary lactic acidosis.


Subject(s)
Acidosis/enzymology , Carbohydrate Metabolism, Inborn Errors/enzymology , Lactates/metabolism , Cells, Cultured , Child, Preschool , Citric Acid Cycle , Fibroblasts/metabolism , Glucose/metabolism , Glycolysis , Humans , Infant , Infant, Newborn , Pyruvates/metabolism
20.
J Inherit Metab Dis ; 1(3): 95-7, 1978.
Article in English | MEDLINE | ID: mdl-116085

ABSTRACT

Urinary excretion of aspartylglycosamines was investigated in eight patients by semiquantitative thin-layer chromatography, and bound glycosamines by a quantitative photometric method (Elson-Morgan reaction). Each patient showed a fairly constant level, relative to the creatinine, of aspartylglycosamines in urine. The least retarded patient, aged 31, excreted about 350 mg/g creatinine, one-third of that found in two severely retarded young patients, aged 4 and 7 years (1400 and 940 mg/g creatinine, respectively). Three days on a low-protein diet did not change the aspartylglycosamine excretion in the patient showing the highest excretion rate.


Subject(s)
Acetylglucosamine/analogs & derivatives , Amidohydrolases/deficiency , Aspartylglucosaminuria , Dietary Proteins , Glucosamine/analogs & derivatives , Mucolipidoses/urine , Acetylglucosamine/urine , Adolescent , Adult , Aspartic Acid/analogs & derivatives , Aspartic Acid/urine , Child , Child, Preschool , Creatinine/urine , Female , Humans , Intellectual Disability/urine , Male
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