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Biomedical subjects

K Asayama

Publications and source records attributed to K Asayama.

At least 37 records · Page 2Linked to original sources
PubMed2000

Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in comparison with myoglobin and creatine kinase isoenzyme MB.

Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight cytoplasmic protein and present abundantly in the myocardium. When the myocardium is injured, as in the case of myocardial infarction, low molecular weight cytoplasmic proteins including H-FABP are released into the circulation and H-FABP is detectable in a blood sample. We have already developed a direct sandwich-ELISA for quantification of human H-FABP using two distinct types of monoclonal antibodies specific for human H-FABP. In this study we investigated the clinical validity of H-FABP as a biochemical diagnostic marker in the early phase of acute myocardial infarction (AMI). To evaluate the diagnostic usefulness of H-FABP in the early phase of AMI, blood samples were obtained from the following patients within 12 hours after the appearance of symptoms, and serum levels of H-FABP were compared with those of conventional diagnostic markers, such as myoglobin and creatine kinase isoenzyme MB (CK-MB). Blood samples were collected from patients with confirmed AMI (n=140), patients with chest pain who were afterwards not classified as AMI by normal CK-MB levels (non-AMI) (n=49) and normal healthy volunteers (n=75). The serum concentration of H-FABP was quantified with our direct sandwich-ELISA. The concentration of myoglobin mass was measured with a commercial RIA kit. The serum CK-MB activity was determined with an immuno-inhibition assay kit. The overall sensitivity of H-FABP, within 12 hours after the appearance of symptoms, was 92.9%, while it was 88.6% with myoglobin and 18.6% with CK-MB. The overall specificity of H-FABP was 67.3%, while it was 57.1% with myoglobin and 98.0% with CK-MB. The diagnostic efficacy rates with these markers were 86.2% (H-FABP), 80.4% (myoglobin) and 39.2% (CK-MB), respectively. The diagnostic validity of H-FABP was further assessed by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) of H-FABP was 0.921, which was significantly greater than with myoglobin (AUC: 0.843) and CK-MB (AUC: 0.654). These parameters, such as sensitivity, specificity, diagnostic efficacy and diagnostic accuracy, obtained for patients with chest pain within 3 hours and/or 6 hours after the onset of symptoms were almost the same as those for patients within 12 hours after symptoms. H-FABP is more sensitive than both myoglobin and CK-MB, more specific than myoglobin for detecting AMI within 12 hours after the onset of symptoms, and shows the highest values for both diagnostic efficacy and ROC curve analysis. Thus, H-FABP has great potential as an excellent biochemical cardiac marker for the diagnosis of AMI in the early phase.

Aged↗
PubMed1999

Numerous conglomerate inclusions in slowly progressive familial amyotrophic lateral sclerosis with posterior column involvement.

A 59-year-old woman with slow progression of the loss of motor function and predominant lower motor manifestation during a 14-year period showed familial amyotrophic lateral sclerosis (fALS) with posterior column involvement, neuropathologically. Conglomerate inclusions (CIs) were observed in the remaining neurons in various areas, including the spinal anterior horn, posterior horn, Clark's column, accessory cuneate nucleus, tegmental reticular formation, motor nucleus of the trigeminal nerve, nucleus of the facial nerve, hypoglossal nucleus, medial nucleus of the thalamus, dentate nucleus, and motor cortex (Betz cells). Immunohistochemically, it was newly identified that the CIs showed marked immunoreactions with antibodies to phosphorylated and non-phosphorylated neurofilaments and to 64, 120, and 200 kD neurofilaments. The CIs were partially immunoreactive with the anti-ubiquitin antibody, although they reacted only weakly (or not at all) with anti-Cu/Zn superoxide dismutase (SOD1) antibody. Ultrastructurally, the CIs were comprised of neurofilaments. These data suggest that this case might have been different from an example of fALS with Ile 113 Thr mutation in the SOD1 gene.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Advanced glycation endproducts are deposited in neuronal hyaline inclusions: a study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation.

To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) mutation, we investigated the immunohistochemical localization of N(epsilon)-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Immunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.

Adult↗
PubMed1999

Astrocytic hyaline inclusions contain advanced glycation endproducts in familial amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutation: immunohistochemical and immunoelectron microscopical analyses.

To clarify the neuropathological significance of the deposition of N(epsilon)-carboxymethyl lysine (CML), an advanced glycation endproduct, in astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis (FALS), autopsy specimens from five members of two different families who had the superoxide dismutase 1 (SOD1) gene mutations were analysed. Immunohistochemically, most of the neuronal and astrocytic hyaline inclusions were intensely stained by the antibody against CML. The distributions and intensities of the immunoreactivities for CML and SOD1 were similar in the inclusions in both cell types. Immunoelectron microscopy showed that both inclusions consisted of CML-positive granule-coated fibrils and granular materials. No significant CML or SOD1 immunoreactivity was observed in the neurons and astrocytes of the normal control subjects. Our results suggest that astrocytic hyaline inclusions contain CML and SOD1 in FALS patients with SOD1 gene mutations, and that the formation of CML-modified protein (probably CML-modified SOD1) is related to the cell degeneration.

Adult↗
PubMed1999

Manganese superoxide dismutase in rat liver peroxisomes: biochemical and immunochemical evidence.

By using highly purified peroxisomes from rat liver, we have shown that peroxisomes contain manganese superoxide dismutase (MnSOD) activity and a 23 kDa protein immunoreactive with antibodies against purified mitochondrial MnSOD. Immunocytochemical studies have also revealed immunoreaction (immunogold) with MnSOD antibodies in mitochondria and peroxisomes. Studies of the intraperoxisomal localization of MnSOD have shown that in peroxisomes MnSOD is a component of the peroxisomal limiting membranes and dense core. Furthermore, the MnSOD level in peroxisomes was modulated by oxidative stress conditions such as ischemia-reperfusion or the treatment with ciprofibrate, a peroxisomal proliferator. These findings suggest that MnSOD in peroxisomes may play an important role in the dismutation of superoxide generated on the peroxisomal membrane for keeping the delicate balance of the redox state.

Animals↗
PubMed1999

Increased peroxisomal fatty acid beta-oxidation and enhanced expression of peroxisome proliferator-activated receptor-alpha in diabetic rat liver.

To determine whether the increased fatty acid beta-oxidation in the peroxisomes of diabetic rat liver is mediated by a common peroxisome proliferation mechanism, we measured the activation of long-chain (LC) and very long chain (VLC) fatty acids catalyzed by palmitoyl CoA ligase (PAL) and lignoceryl CoA ligase and oxidation of LC (palmitic acid) and VLC (lignoceric acid) fatty acids by isotopic methods. Immunoblot analysis of acyl-CoA oxidase (ACO), and Northern blot analysis of peroxisome proliferator-activated receptor (PPAR-alpha), ACO, and PAL were also performed. The PAL activity increased in peroxisomes and mitochondria from the liver of diabetic rats by 2.6-fold and 2.1 -fold, respectively. The lignoceroyl-CoA ligase activity increased by 2.6-fold in diabetic peroxisomes. Palmitic acid oxidation increased in the diabetic peroxisomes and mitochondria by 2.5-fold and 2.7-fold, respectively, while lignoceric acid oxidation increased by 2.0-fold in the peroxisomes. Immunoreactive ACO protein increased by 2-fold in the diabetic group. The mRNA levels for PPAR-alpha, ACO and PAL increased 2.9-, 2.8- and 1.6-fold, respectively, in the diabetic group. These results suggest that the increased supply of fatty acids to liver in diabetic state stimulates the expression of PPAR-alpha and its target genes responsible for the metabolism of fatty acids.

ATP-Binding Cassette Transporters↗
PubMed1999

Decreased activity of plasma cholesteryl ester transfer protein in children and adolescents with insulin-dependent diabetes mellitus.

The aims of the present study were to determine whether the activity of cholesteryl ester transfer protein (CETP) is altered in the plasma of children and adolescents with insulin-dependent diabetes mellitus (IDDM), and whether high-density lipoprotein-cholesterol (HDL-C) levels reflect CETP activity. Plasma CETP activity was measured by a micromethod for radioisotopic assay, using exogenous lipoproteins as donor and acceptors. The study subjects were 22 Japanese children and adolescents with IDDM (8M, 14F) with a mean age of 13.0 y. They were non-obese and did not suffer from any significant nephropathy. The age-matched control group consisted of 20 children (10M, 10F) with a mean age of 12.7y. Serum triglycerides were significantly decreased, while the levels of HDL-C and apolipoprotein (apo) A1 were markedly increased, in the IDDM patients. Plasma CETP activity was significantly lower in the IDDM patients than in the control children. None of the anthropometric indices nor the biochemical data correlated significantly with CETP activity in the IDDM patients. Suppression of CETP along with the putative activation of lipoprotein lipase due to peripheral hyperinsulinism appears to induce synergistically the increase in HDL-C in IDDM children.

Adolescent↗
PubMed1999

Effect of peroxisome proliferator on extracellular glutathione peroxidase in rat.

Glutathione peroxidase (GPX) activity measured using tert-butyl hydroperoxide as a substrate detects solely cellular/classical GPX (cGPX) in rat liver and kidney, and extracellular/plasma glutathione peroxidase (EC-GPX) in rat serum. To investigate the effect of peroxisome proliferator on EC-GPX, we measured activities of GPX and catalase in rat liver, kidney and serum, and then we performed immunoblot and Northern blot analyses in the kidney. Rats were fed on a diet containing either 2% (w/w) di-2-ethylhexyl phthalate (DEHP) or 0.25% (w/w) clofibrate for two or three weeks, respectively. Catalase activity was increased 1.4-fold (p < 0.001) in the treated liver, but not in the kidney. GPX activity was decreased to 59.2% (DEHP) and 70.4% (clofibrate) of the control (p < 0.001) in the serum but was unaltered in the liver and kidney. The immunoreactivity for EC-GPX was also significantly decreased in the DEHP-treated kidney compared with the control. The mRNA levels of EC-GPX and cGPX were unaltered. The immunostaining for 4-hydroxy-2-nonenal, a maker of lipid peroxide, was more intense in the treated kidney compared with the control. These results suggest that EC-GPX is post-transcriptionally decreased by peroxisome proliferator through the oxidative stress in the renal tubules. This may be a new deleterious effect of an endocrine disruptor DEHP.

Aldehydes↗
PubMed1999

Changes in serum leptin concentration during behavioral therapy in obese children.

To determine the pathophysiological implications of serum leptin level in obesity, we monitored the changes in serum leptin level during outpatient treatment with life style modification in children. Fifty-five obese Japanese children (34 boys and 21 girls; mean age, 9.64 years) were studied. The control children consisted of 42 nonobese subjects (27 boys and 15 girls). The serum leptin concentration was 4.35 +/- 0.46 ng/ml (mean +/- SEM) in the control girls and 2.93 +/- 0.21 ng/ml in the control boys. The serum leptin concentrations in the obese boys and girls were higher than those in their lean counterparts. The concentration in the obese boys (16.28 +/- 1.41 ng/ml) was similar to that in the obese girls (20.33 +/- 2.0 ng/ml). The logarithmic value of serum leptin concentration at the first blood sampling in obese children was correlated with percent overweight and percent body fat. In 36 obese children (24 boys and 12 girls) whose serum leptin concentrations were monitored serially during treatment of obesity, the percent overweight was significantly decreased after the initial sampling. In each individual, the changes in leptin concentration were roughly parallel to those in percent overweight. The ratio of the leptin concentration at the second blood sampling divided by the one at the first sampling in each individual was closely correlated with the respective delta percent overweight. These results suggest that the preceding course of obesity determines the serum leptin level of obese children on longitudinal basis, and that the leptin level reflects the degree of obesity on cross-sectional basis.

Behavior Therapy↗
PubMed1998

Differential expression of superoxide dismutase isoforms in neuronal and glial compartments in the course of excitotoxically mediated neurodegeneration: relation to oxidative and nitrergic stress.

To examine the cellular distribution of radical scavenging enzymes in glia, in comparison to that in neurons and their behaviour during excitotoxically induced neurodegenerative processes, protein levels and the cellular localization of cytosolic and mitochondrial superoxide dismutase (Cu/Zn- and Mn-SOD) were investigated in the rat brain undergoing quinolinic acid (Quin)-induced neurodegeneration. Evidence for the specificity of the applied antibodies to detect immunocytochemically these SOD isoforms was obtained from electron microscopy and Western blotting. In control striatum Mn-SOD was clearly confined to neurons, whereas Cu/Zn-SOD was found, rather delicately, only in astrocytes. Microglia failed to stain with antibodies to both SOD isoforms. Quin application resulted in an initial formation of oxygen and nitrogen radicals as determined by the decline in the ratio of ascorbic to dehydroascorbic acid and by increased levels of nitrated proteins, an indicator for elevated peroxynitrite formation. Morphologically, massive neuronal damage was seen in parallel. Astroglia remained intact but showed initially decreased glutamine synthetase activities. The levels of Mn-SOD protein increased 2-fold 24 h after Quin injection (Western blotting) and declined only slowly over the time period considered (10 days). Cu/Zn-SOD levels increased only 1.3-fold. Immunocytochemical studies revealed that the increase in Mn-SOD is confined to neurons, whereas that of Cu/Zn-SOD was observed only in astroglial cells. Quiescent microglial cells were, as a rule, free of immunocytochemically detectable SOD, whereas in activated microglia a few Mn-SOD immunolabeled mitochondria occurred. Our results suggest a differential protective response in the Quin lesioned striatum in that Mn-SOD is upregulated in neurons and Cu/Zn-SOD in astroglia. Both SOD-isoforms are assumed to be induced to prevent oxidative and nitric oxide/peroxynitrite-mediated damage. In the border zone of the lesion core this strategy may contribute to resist the noxious stimulus.

Animals↗
PubMed1998

Presence of Cu/Zn superoxide dismutase (SOD) immunoreactivity in neuronal hyaline inclusions in spinal cords from mice carrying a transgene for Gly93Ala mutant human Cu/Zn SOD.

This investigation deals with the immunocytochemical localization of Cu/Zn superoxide dismutase (SOD) in the spinal cord neurons of transgenic mice that overexpress Gly93Ala mutant human Cu/Zn SOD and demonstrate clinicopathological features similar to human amyotrophic lateral sclerosis (ALS) with Cu/Zn SOD mutation. At low magnification of light microscopy, the gray and white matter of the spinal cord of Gly93Ala mice showed more intense Cu/Zn SOD immunoreactivity than that of control mice. At higher magnification, the cytoplasm of control mice neurons displayed a distinct staining for Cu/Zn SOD, whereas the surrounding neuropil was only weakly stained. In contrast, the intensity of Cu/Zn SOD immunoreactivity in the cytoplasm of the majority of Gly93Ala mice neurons was similar to that in the neuropil. Almost all neuronal hyaline inclusions (NHIs) of Gly93Ala mice were positively immunostained by antibodies to Cu/Zn SOD, ubiquitin and phosphorylated neurofilament protein (NFP), the intensities of which were much higher in the NHIs than in the surrounding cytoplasm. In control mice, significant Cu/Zn SOD precipitation was not observed to be limited to any particular region of the neuronal cytoplasm. Intracytoplasmic vacuoles in the neuronal soma and processes of Gly93Ala mice were not stained by any of these antibodies. These results indicate that Cu/Zn SOD colocalizes with ubiquitin and phosphorylated NFP in NHIs of mice expressing mutant Cu/Zn SOD; similar findings have been shown for Lewy body-like inclusions of familial ALS patients with Cu/Zn SOD mutation. Moreover, our results point to the possibility that Cu/Zn SOD mutation may have a role in the abnormal Cu/Zn SOD accumulation in the NHIs, in association with motor neuron degeneration.

Animals↗
PubMed1998

Effect of selenium deficiency on cellular and extracellular glutathione peroxidases: immunochemical detection and mRNA analysis in rat kidney and serum.

To determine the effect of selenium (Se) deficiency on expression of glutathione peroxidase (GSH-Px) 1 and 2, we measured GSH-Px activity in rat serum, liver and kidneys, serum immunoreactive GSH-Px 2, and the mRNAs of kidney GSH-Px 1 and 2. We purified rat GSH-Px 2 and raised polyclonal antibodies. Immunoreactive GSH-Px 2 was measured by rocket immunoelectrophoresis. GSH-Px 2 was purified 1470-fold with a specific activity of 250 units/mg. Immunoblotting detected only GSH-Px 2 in rat serum, and much less GSH-Px 2 than GSH-Px 1 in kidney. Immunoblot signal of kidney GSH-Px 1 and 2 decreased progressively in Se deficient rats. Serum GSH-Px activity in Se deficient rats at 1, 2, 3, and 4 weeks declined to 33, 20, 10, and 9% of the control, while the serum level of immunoreactive GSH-Px 2 was 58, 24, 15, and 10% of the control, suggesting the presence of an inactive protein at week 1. GSH-Px activity declined to 4 and 11% of the control in the liver and kidney at 4 weeks. The mRNAs of kidney GSH-Px 1 and 2 showed similar decreases, and were 24 and 23% of the control at 4 weeks. GSH-Px mRNA levels were better preserved than GSH-Px activity, suggesting that GSH-Px expression was regulated at both pre-translational and translational levels.

Animals↗
PubMed1998

Relationships between an index of body fat distribution (based on waist and hip circumferences) and stature, and biochemical complications in obese children.

OBJECTIVE: To determine the clinical utility of a new age-adjusted measure of body fat distribution (based on waist and hip circumferences) and stature, in relation to biochemical complications in obese children. DESIGN: Cross-sectional, clinical study. The formula to calculate the common standard deviation score (SDS) of waist-to-hip ratio/height (WHR/Ht) was obtained from the data of control children. The relationship between WHR/Ht SDS, as the age-adjusted measure, in obese children and their clinical laboratory data was evaluated. SUBJECTS: Outpatient obese Japanese children (102 boys and 75 girls) and control children (508 boys and 549 girls), ranging in age from 6-15 y. MEASUREMENTS: Height, body weight, waist girth, hip girth, triceps and subscapular skinfold thicknesses, as anthropometric measures. Percent overweight, percent body fat, waist girth, WHR and WHR/Ht SDS as criteria for obesity. Clinical laboratory analyses for fasting blood samples of obese children. RESULTS: The WHR/Ht SDS closely correlated with age in obese children, thus reflecting the progress of abdominal obesity during growth. The obese boys were more hyperlipidaemic than the girls were, although the percent overweight was similar in both genders. The percent overweight, percent body fat, waist girth and WHR/Ht SDS all correlated well with triglyceride (TG), alanine aminotransferase (ALT) and insulin in boys, whereas only waist girth and WHR/Ht SDS showed a close correlation with TG and insulin in girls. The obese subjects were subdivided according to the number of abnormal values observed in TG, ALT and insulin. For obese boys, all five indices of obesity were higher in the groups with complications than in the group without. In the girls, only the WHR/Ht SDS constantly differed between subgroups. WHR/Ht SDS most obviously distinguished the groups with complications from the other group with a wide margin of difference (2-fold in boys and > 2-fold in girls) in the mean values. CONCLUSION: The WHR/Ht SDS can serve as an index predicting the occurrence of biochemical complications in obese children ranging from the age of 6-15 y.

Adipose Tissue↗
PubMed1998

Evaluation of systemic inflammatory response syndrome criteria as a predictor of mortality in emergency patients transported by ambulance.

Based on the concept of the systemic inflammatory response syndrome (SIRS), a one year retrospective study was carried out to examine SIRS criteria as a simple and rapid predictor of outcome for emergency patients. Among a total of 2,180 patients transported to the emergency room by ambulance, 318 (14.8%) had primary SIRS and 389 (17.8%) met SIRS criteria at some point during the entire treatment period. The admission rate for primary SIRS increased sequentially as more SIRS criteria were met, rising from 15.4% in non-SIRS to 100% when all four criteria were met. The mortality of primary SIRS also increased sequentially as more SIRS criteria were met, rising from 1.4% in non-SIRS to 35.3% when all four criteria were met. Furthermore, heart rate, C-reactive protein and platelet count were considered to be potentially useful new criteria for a group of SIRS patients with a high risk of mortality (high-risk SIRS), based on a comparison of variables between SIRS patients who died and SIRS patients who survived. The mortality associated with primary SIRS increased sequentially as more high-risk SIRS criteria were met, rising from 7.6% when none were met to 50.0% when two criteria were met. Considering the high specificity of primary SIRS for admission (89.5%) and mortality (86.8%), SIRS criteria have clinical and prognostic importance in the management of emergency patients. Given the high mortality (29.9%), the new high-risk SIRS criteria may also be useful as entry criteria for clinical trials of innovative therapies for patients with SIRS.

Adolescent↗
PubMed1998

Enhanced cellular glutathione peroxidase immunoreactivity in activated astrocytes and in microglia during excitotoxin induced neurodegeneration.

The cellular distribution pattern of cellular glutathione peroxidase (GPx) was analyzed immunocytochemically in the normal rat central nervous system (CNS) and following exposure to the excitotoxin quinolinic acid (Quin). In the normal CNS, GPx was localized predominantly to microglia, identified by staining with isolectin B4 or the monoclonal antibody OX-42. Three days after intrastriatal administration of 90 pmoles Quin, GPx immunoreactivity was increased in activated microglia and also in astrocytes costained for glial fibrillary acidic protein (GFAP). Whereas GPx-positive astrocytes were seen predominantly in the environment of the lesion, most intensive immunoreactivity was located in globular-shaped microglia in the lesion core. GPx staining was generally low in neurons and failed to increase its intensity after lesion. In the case of excitotoxin-induced generation of oxygen-derived free radicals, the elevation of GPx levels in microglia, and likewise in activated astroglia, may provide an important mechanism to withstand oxidative stress.

Animals↗
PubMed1997

Increased plasma cholesteryl ester transfer activity in obese children.

To determine whether enhanced activity of cholesteryl ester transfer protein (CETP) contributes to the development of atherogenic lipoprotein profiles in obese children, plasma CETP activity was assayed according to a micro-method, by co-incubating lipoprotein-deficient samples with exogenous donor and acceptor lipoproteins. The study subjects were 31 obese children (14 males and 17 females). Serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC:high-density lipoprotein (HDL)-C, LDL-C:HDL-C, apolipoprotein (apo) B, and apo B:apo Al were increased in obese children. Thus they appeared to exhibit an atherogenic lipoprotein profile, with a relative decrease in cholesterol carried by HDL compared with the cholesterol in the other lipoprotein fractions. The mean fasting plasma insulin level was also increased. CETP activity was significantly higher in the obese children than in nonobese control children, and was correlated with LDL-C, TC:HDL-C, LDL-C:HDL-C, and apo B:apo Al. These results suggest that an increase in plasma CETP activity results in atherogenic change in lipoprotein metabolism in obese children. The increase in CETP may be due to the adiposity or insulin resistance. Alternatively, dyslipidemia per se, physical inactivity or excessive fat intake, that are commonly found in obese children, may contribute to the increase in CETP activity.

Adolescent↗
PubMed1997

Superoxide dismutase-like immunoreactivity in spheroids in Hallervorden-Spatz disease.

Iron accumulation in the basal ganglia and spheroid formation are pathological hallmarks of Hallervorden-Spatz disease (HS). Since an overaccumulation of iron (iron thesaurosis) that exceeds the binding capacity of ferritin could cause oxidative damage, we studied the possible role of oxidative stress in the pathogenesis of HS. The basal ganglia and spinal cord from patients with HS were investigated at autopsy, using histochemistry for iron and immunohistochemistry for Cu/Zn superoxide dismutase (SOD1), Mn superoxide dismutase (SOD2) and ferritin. SOD1-like immunoreactivity (IR), SOD2-IR and ferritin-IR occurred frequently in spheroids observed in the basal ganglia, and associated iron accumulation indicated the possible existence of increased oxidative stress in HS patients. Spheroids in the spinal cord showed intense SOD1-IR and SOD2-IR in HS, in sharp contrast with the occasional weak SOD1-IR and SOD2-IR observed in spheroids from patients with amyotrophic lateral sclerosis (ALS). Neither increased ferritin-IR nor iron accumulation were observed in spinal spheroids from HS and ALS patients. These data may suggest that, at least in the spinal cord, SOD1-IR and SOD2-IR in spheroids in HS patients do not result from oxidative stress directly related to iron accumulation.

Adult↗