Occurrence of adrenocortical insufficiency in adrenomyeloneuropathy.
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Adolescent↗
Biomedical subjects
S Zierz
Publications and source records attributed to S Zierz.
Increased laminin A expression in regenerating myofibers in neuromuscular disorders.
Laminin is a basement membrane (BM) glycoprotein composed of three of five subunits, the A, M, B1, B2, and the S chain. Four forms of laminin, A-B1-B2, A-S-B2, M-B1-B2, and M-S-B2, have been identified. Laminin is implicated in various biological processes such as cell adhesion and differentiation. We studied immunohistochemically the expression of the four laminin subunits A, M, B1, B2 as well as of neural cell adhesion molecule (N-CAM, CD56), a marker of regenerating myofibers, in various neuromuscular disorders. In normal muscle, the predominant subunits of myofiber laminin were M, B1, and B2. The A chain was only faintly expressed in myofiber BM. In inflammatory myopathies and dystrophinopathies myofiber laminin A expression was greatly increased. An average of 80% and 63% of laminin A-positive myofibers in inflammatory myopathies and dystrophinopathies, respectively, were additionally CD56 positive. Laminin A and CD56 expression in denervating diseases and mitochondrial myopathies were negligible. Expression of M, B1, and B2 subunits did not seem to be altered in the diseased conditions examined above. The data suggest that laminin A is upregulated in inflammatory myopathies and dystrophinopathies and, most markedly in regenerating myofibers.
Antigens↗
Cu,Zn SOD in German families with ALS.
We studied the gene for Cu,Zn SOD in 15 German patients with familial ALS and did not find any mutation. Activity of the enzyme and its expression at the protein level was also normal in each patient and in 18 patients suffering from the sporadic form of ALS.
Amyotrophic Lateral Sclerosis↗
Neuroleptic associated extrapyramidal symptoms.
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Antipsychotic Agents↗
Cytochrome c oxidase in Alzheimer's disease.
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Alzheimer Disease↗
Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes.
Recently, the gene for the most common peroxisomal disorder, X-linked adrenoleukodystrophy (X-ALD), has been described encoding a peroxisomal membrane transporter protein. We analyzed the entire protein-coding sequence of this gene by reverse-transcription PCR, SSCP, and DNA sequencing in five patients with different clinical expression of X-ALD and in their female relatives; these clinical expressions were cerebral childhood ALD, adrenomyeloneuropathy (AMN), and "Addison disease only" (ADO) phenotype. In the three patients exhibiting the classical picture of severe childhood ALD we identified in the 5' portion of the X-ALD gene a 38-bp deletion that causes a frameshift mutation, a 3-bp deletion leading to a deletion of an amino acid in the ATP-binding domain of the ALD protein, and a missense mutation. In the patient with the clinical phenotype of AMN, a nonsense mutation in codon 212, along with a second site mutation at codon 178, was observed. Analysis of the patient with the ADO phenotype revealed a further missense mutation at a highly conserved position in the ALDP/PMP70 comparison. The disruptive nature of two mutations (i.e., the frameshift and the nonsense mutation) in patients with biochemically proved childhood ALD and AMN further strongly supports the hypothesis that alterations in this gene play a crucial role in the pathogenesis of X-ALD. Since the current biochemical techniques for X-ALD carrier detection in affected families lack sufficient reliability, our procedure described for systematic mutation scanning is also capable of improving genetic counseling and prenatal diagnosis.
Adrenoleukodystrophy↗
Mitochondrial respiratory chain enzyme activities in tetralogy of Fallot.
It has been suggested that myocardial ischemia is associated with a reduction in mitochondrial complex I activity. Respiratory chain enzyme activities were measured in right ventricular biopsies of eight infants with tetralogy of Fallot (TF), left ventricular biopsies of one of the infants with TF, right and left ventricular tissue of seven transplant recipients with atherosclerotic coronary artery disease (CAD), and in right ventricular biopsies of one infant without cardiac pathology (normal control). In right ventricular tissue the specific activity of complexes I+III was significantly lower in TF than in CAD (3.8 +/- 2.7 vs 23 +/- 12 nmol min-1 mg-1 non-collagen protein). In the right ventricular control specimen the activity of complexes I+III was 13.7-fold standard deviation higher than in TF and 1.5-fold higher than in CAD. Left ventricular respiratory chain enzyme activities measured in one patient with TF were lower than those in patients with CAD. Enzyme activities of left ventricular tissue were not significantly different from those of the right ventricle in CAD. The activity of the mitochondrial matrix enzyme citrate synthase did not differ between groups. The data indicate that the prominent reduction of complex I activity found in myocardial ischemia due to CAD is even more pronounced in myocardial hypoxemia due to TF.
Biopsy↗
Myotonic dystrophy and limb girdle muscular dystrophy in one family.
A family is reported in which a 29-year-old woman showed the clinical features of myotonic dystrophy while her 26-year-old brother presented with the clinical picture of limb girdle syndrome. In the affected female, direct genetic testing for the specific myotonic dystrophy mutation on chromosome 19 revealed abnormal expansion of a repeat unit containing the three nucleotides cytosine, thymine, and guanine (CTG)-typical for myotonic dystrophy-while her diseased brother displayed two normal alleles. This supports the hypothesis of the extremely rare occurrence of two clinically and genetically different myopathies in one family. Genetic analysis of six other family members showed that the father of the diseased siblings as well as all of his three brothers and sisters had a pathological CTG repeat expansion, and that the other two family members tested had a normal allelic pattern. The number of CTG repeats in the diseased women was approximately tenfold higher than in her asymptomatic relatives who revealed an abnormal allelic pattern. The increase in CTG repeats with transmission to a subsequent generation in this family was paralleled by a dramatic increase in the severity of myotonic dystrophy.
Adult↗
Limited trypsin proteolysis renders carnitine palmitoyltransferase insensitive to inhibition by malonyl-CoA in patients with muscle carnitine palmitoyltransferase deficiency.
Carnitine palmitoyltransferase (CPT) was studied in muscle homogenates of two patients with muscle CPT deficiency heterozygous for the Ser-113 Leu mutation in the CPT II gene. Total CPT activity was normal in both patients but was almost completely inhibited by malonyl-CoA and Triton X-100 whereas in controls 38% and 58% of total activity remained in the presence of malonyl-CoA and Triton X-100, respectively. The addition of 1% Tween 20 abolished about half of the activity in patients but not in controls. Preincubation of muscle homogenate with trypsin slightly increased the total activity and rendered the activity greatly insensitive to inhibition by malonyl-CoA in both patients and controls. The data support the view that in patients with muscle CPT deficiency both CPT I and II are active, but that CPT II is abnormally accessible to inhibition by malonyl-CoA.
Carnitine O-Palmitoyltransferase↗
Cauda equina syndrome with multiple lumbar diverticula complicating long-standing ankylosing spondylitis.
A patient with cauda equina syndrome complicating long-standing inactive ankylosing spondylitis is described. The first neurological symptoms started 15 years after the onset of ankylosing spondylitis. Over a follow-up period of 12 years the cauda equina syndrome showed a slowly progressive but disabling course leading to sensory disturbances in the lumbar and sacral dermatomes, weakness and wasting of the muscles innervated by these nerve roots, sphincter disturbances, and impotence. Magnetic resonance imaging, computed tomography, and lumbar myelography showed enlargement of the dural sac with multiple lubar diverticula eroding the lumbosacral vertebrae. The pathophysiology of the cauda equina syndrome in ankylosing spondylitis is unclear. Surgical treatment seems justified only in patients with a short history of neurological symptoms.
Cauda Equina↗
Two cases of neurological manifestations in eosinophilia: variations of one disease?
The hypereosinophilic syndrome is characterized by a long-lasting increase in circulating eosinophils in the absence of a definable etiology and by manifestations of multisystem involvement. It must be differentiated from the eosinophilia-myalgia syndrome related to the ingestion of L-tryptophan, although the clinical features may be similar. Two patients with hypereosinophilia not related to L-tryptophan intake are described who both became clinically symptomatic with neurological manifestations of acute and subacute onset: one with eosinophilic fasciitis and the other with painful polyneuropathy. Both responded well to corticosteroids.
Adult↗
Abnormal dystrophin expression in patients with limb girdle syndromes.
Clinical differential diagnosis between Becker muscular dystrophy (BMD) and limb gridle muscular dystrophy (LGMD) may be difficult because the BMD clinical phenotype tends to overlap with other limb girdle syndromes, especially with LGMD. Therefore we studied the expression of dystrophin, the protein product of the Becker and Duchenne muscular dystrophy gene, in muscle biopsy specimens of 30 patients (18 males, of whom 15 represented spradic cases, and 12 females) diagnosed as having LGMD according to traditional clinical, electrophysiological and histological criteria. For dystrophin analysis, six different monoclonal antibodies directed against different epitopes of the dystrophin molecule were used. Immunocytochemically, five of the 30 LGMD patients (17%) showed abnormal dystrophin staining patterns diagnostic of BMD. Western blotting in these five patients, all sporadic cases, showed dystrophin of reduced size and/or abundance. Analysis of blood or muscle DNA using multiplex polymerase chain reaction revealed deletions in the dystrophin gene in three of the five. Thus, 5 of 15 (33%) sporadic male patients previously thought to have LGMD were identified as having BMD.
Adolescent↗
Central and peripheral nervous system conduction in mitochondrial myopathy with chronic progressive external ophthalmoplegia.
Involvement of the peripheral and central nervous systems in mitochondrial myopathy with chronic progressive external ophthalmoplegia (CPEO) has been demonstrated clinically and electrophysiologically. Systematic electrophysiological investigations of the peripheral and central nervous systems, particularly of cortico-spinal tract function, however, are not available. We studied peripheral and central nervous system involvement in 28 patients with histologically and biochemically proven mitochondrial CPEO by motor and sensory nerve conduction tests, by somatosensory, auditory and visual evoked potentials and, for the first time, by transcranial magnetic stimulation. Nervous system involvement could be demonstrated in 24 patients, affecting the peripheral and central nervous systems in 18 and 10 patients, respectively. Evidence of cortico-spinal tract involvement was found in 4 patients, which was clinically expected in only 2. Therefore, dysfunction of the cortico-spinal tract in mitochondrial CPEO may occur more frequently than so far assumed. Generally, electrophysiological tests serve as valuable supplements to clinical examination in patients with mitochondrial CPEO and may be especially helpful in therapeutic studies, i.e., coenzyme Q administration.
Adolescent↗
Immersion and perfusion staining with 2,3,5-triphenyltetrazolium chloride (TTC) compared to mitochondrial enzymes 6 hours after MCA-occlusion in primates.
2,3,5-triphenyltetrazolium chloride (TTC) is commonly applied in rodents and cats as a marker of infarcted tissue as early as 20 min after the onset of focal ischaemia. At this stage it is suggested that it reflects hypoperfusion rather than failure of respiratory chain. Immersion of brain slices in TTC solution is preferable in comparison to perfusion with TTC in order to ensure, that enough TTC enters the post-occlusion tissue. We compared immersion technique versus perfusion technique 6 h after permanent occlusion of the left middle cerebral artery in 18 baboons. In addition, we assessed the function of the respiratory chain enzymes of stained and unstained tissue in three baboons. The immersion technique revealed an absence of TTC staining limited to subcortical structures in two animals. In seven experiments TTC indicated involvement of almost the entire MCA territory. The extent of the ischaemic lesion indicated by the perfusion technique was very similar. Tissue samples from the presumed infarcted areas revealed normal mitochondrial function. We conclude that perfusion and immersion technique do not cause significant different ischaemic delineation 6 h after middle cerebral artery occlusion. TTC staining appears to be a reliable method of evaluating volume of infarction in primates. Furthermore, absence of TTC staining 6 h after stroke onset is caused by energy or oxygen depletion rather than by mitochondrial injury.
Animals↗
Mitochondrial encephalomyopathy: correlation of P-31 exercise MR spectroscopy with clinical findings.
PURPOSE: To evaluate the sensitivity of standardized exercise phosphorus-31 magnetic resonance (MR) spectroscopy in screening for subclinical muscle involvement in mitochondrial encephalomyopathy and to estimate if changes seen at biopsy have functional consequences. MATERIALS AND METHODS: Exercise MR spectroscopy was performed in 52 examinations of 18 healthy volunteers and 14 patients with defects of mitochondrial respiratory chain enzymes. Calculation and kinetic analysis of the phosphocreatine (PCr) index and pH time courses were standardized with a microcomputer program. RESULTS: PCr index scores and conventional test scores matched in 10 of 14 cases. No obvious correlation existed between pH parameters and clinical score. Muscle affection, according to pH parameter score, was rated moderate (n = 3), severe (n = 1), or maximum (n = 2) in six of 14 cases in which clinical test scores showed only mild affection. CONCLUSION: Exercise MR spectroscopic PCr index parameters provide diagnostic information on skeletal muscle involvement in patients with mitochondrial encephalopathy. The sensitivity of the PCr index parameter seems equal or superior to that of conventional diagnostic tests. The role of pH parameters, however, has yet to be defined.
Adult↗
Cerebral MR in ophthalmoplegia plus.
PURPOSE: To evaluate MR patterns in ophthalmoplegia plus and correlate them with clinical symptoms. METHODS: MR was performed on a 1.5-T whole-body scanner with T2-weighted gradient-echo and spin-echo images. The retrospective analysis included 19 patients with clinically established diagnoses of ophthalmoplegia plus. RESULTS: Two types of cerebral MR abnormalities were found in ophthalmoplegia plus: brain atrophy and hyperintensities restricted to the white matter and basal ganglia, which appeared as either focal or diffuse areas of high signal intensity and were of strictly supratentorial location. No specific distribution was found. These findings differ markedly from infarction-like lesions found in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. CONCLUSIONS: MR is sensitive for the detection of central nervous system involvement in ophthalmoplegia plus, but findings are nonspecific. However, cerebral MR in ophthalmoplegia plus is different from other mitochondrial encephalomyopathies and underlines the clinical differentiation of mitochondrial encephalomyopathies.
Adolescent↗
Myocardial respiratory chain enzyme activities in idiopathic dilated cardiomyopathy, and comparison with those in atherosclerotic coronary artery disease and valvular aortic stenosis.
Mitochondrial respiratory chain enzyme activities were measured in biopsies of left ventricular myocardium from 25 adults in 3 groups: cardiac transplant recipients with atherosclerotic coronary artery disease (CAD), transplant recipients with idiopathic dilated cardiomyopathy (IDC), and patients with compensatory left ventricular hypertrophy due to aortic valve stenosis (AS). Specific activities of complexes I + III and II + III were 21 +/- 12 and 58 +/- 21 nmol/min/mg of noncollagen protein, respectively, in CAD, and 56 +/- 21 and 96 +/- 57 nmol/min/mg, respectively, in IDC (p < 0.004 and < 0.03, respectively). Specimens from patients with AS had enzyme activities that were intermediate between those from patients with CAD and IDC. Myocardium of patients with transvalvular pressure gradients between 50 and 79 mm Hg showed low activities of complexes I + III and II + III (17 +/- 5 and 62 +/- 17 nmol/min/mg of noncollagen protein, respectively), whereas those with higher pressure gradients between 80 and 100 mm Hg had enzyme activities of complexes I + III and II + III equal to those in IDC (37 +/- 11 and 73 +/- 18 nmol/min/mg, respectively). The same results were obtained when enzyme activities were normalized for the activity of the mitochondrial matrix enzyme citrate synthase. The data suggest that a compensatory metabolic adaptation of the mitochondrial respiratory chain enzymes occurs in both AS and IDC. A reduction in enzyme activities that is observed in heart failure due to CAD and that may explain the contractile dysfunction in these patients cannot be confirmed in IDC. In IDC, the enzyme activities are sustained until very late in the disease.
Aged↗
Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNALeu(UUR) gene.
A heteroplasmic point mutation (transition A-to-G at nucleotide position 3,243 in the mitochondrial tRNALeu(UUR) gene) is found in a family suffering from a syndrome with diabetes, deafness and cardiomyopathy as the predominant clinical features.
Adolescent↗