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Biomedical subjects

Hans H Jung

Publications and source records attributed to Hans H Jung.

11 recordsLinked to original sources
PubMed2007

Phenotypic variation among brothers with the McLeod neuroacanthocytosis syndrome.

McLeod syndrome is an X-linked multisystem disorder affecting red blood cells, the peripheral and central nervous systems, and skeletal and cardiac muscle. No clear correlations of the clinical findings with the genotype of XK mutations have yet been uncovered. Here, we report the clinical features and progression in 10 affected brothers from 4 families with McLeod syndrome. There is significant variation in clinical presentation within families, including in causes of morbidity and mortality. This phenotypic variation, despite shared mutations, suggests the action of disease-modifying factors that may explain some of the difficulties with genotype-phenotype correlation in McLeod syndrome.

Adult↗
PubMed2006

Cerebral metabolic alterations in McLeod syndrome.

The X-linked McLeod neuroacanthocytosis syndrome is a multisystem disorder with central nervous system manifestations resembling Huntington's disease. We examined 5 McLeod patients and 5 asymptomatic heterozygous females with fast multiple spin-echo spectroscopic imaging. Three patients with pronounced psychiatric or cognitive manifestations had pathological N-acetyl aspartate/(creatine + choline) ratios in frontal, temporal, and insular areas, with an individual pattern. Two patients with a severe choreatic movement disorder had unilateral thalamic alterations. One patient with moderate movement disorder and personality disorder had bilateral occipital alterations. One female heterozygote had unilateral insular metabolic alterations, possibly indicating subclinical cerebral involvement. Although the prominent psychiatric and cognitive manifestations in McLeod patients suggest significant and widespread cortical abnormalities, previous neuroradiological and histopathological data had not revealed definite extrastriatal pathology. Our findings demonstrating metabolic abnormalities in different brain regions of McLeod patients might either reflect neuronal dysfunction due to impaired basal ganglia-thalamo-cortical circuits or subtle structural alterations in the particular cerebral areas.

Adult↗
PubMed2006

Developments in neuroacanthocytosis: expanding the spectrum of choreatic syndromes.

As with other neurodegenerative disorders, research into the group of diseases known under the umbrella term of "neuroacanthocytosis" has greatly benefited from the identification of causative genes. The distinct and unifying aspect of these disorders is the presence of thorny deformations of circulating erythrocytes. This may be due to abnormal properties of red cell membranes, which could lead to insights into mechanisms of neurodegeneration. Research approaches in this field, in addition to examining functions and protein interactions of the affected proteins with particular respect to neurons, have also drawn upon the expertise of hematologists and red cell membrane biologists. In this article, recent developments in the field are presented.

Animals↗
PubMed2005

Neuroacanthocytosis: new developments in a neglected group of dementing disorders.

Neurological abnormalities associated with spiculated, "acanthocytic" red cells in blood have been summarized as neuroacanthocytosis. This is a heterogeneous group of conditions that can now be clearly subdivided on the basis of genetic discoveries. The core neuroacanthocytosis syndromes are autosomal recessive chorea-acanthocytosis (ChAc) and the X-linked McLeod syndrome (MLS). Huntington's disease-like 2 (HLD2) and pantothenate kinase associated neurodegeneration (PKAN) can now also be included. All of these share dyskinesias, cognitive deterioration and progressive neurodegeneration mainly of the basal ganglia, but they are sufficiently distinct to permit a specific working diagnosis on the basis of clinical, laboratory and imaging findings. In addition, the VPS13A (formerly called CHAC), XK, JPH3 and PANK2 genes, respectively, may be examined for mutations. Unfortunately, little is yet known about the normal and abnormal physiology of the protein products of these genes, but they appear to be involved in membrane function and intracellular protein sorting. Since no cures are yet available, development and study of disease models in experimental animals (mouse, C. elegans) is a priority for current research. From a clinical point of view, the common occurrence of cardiomyopathy in MLS, the transfusion hazards due to the McLeod Kell phenotype and the possibility of improving the violent trunk spasms and orofacial dyskinesias typical for ChAc (with subsequent lip or tongue mutilations and feeding dystonia) by deep brain surgery or stimulation should be considered in patient management.

Amino Acid Sequence↗
PubMed2003

Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42.

BACKGROUND: The antemortem diagnosis of Alzheimer disease (AD) requires time-consuming and costly procedures. Therefore, biochemical tests that can direct the physician rapidly to the correct diagnosis are highly desirable. Measurement of single biochemical markers in cerebrospinal fluid (CSF), such as total tau protein and beta-amyloid peptide42 (Abeta42), shows robust alterations that highly correlate with the clinical diagnosis of AD but generally lack sufficient diagnostic accuracy. OBJECTIVE: To study the combination of CSF phosphorylated tau protein (phospho-tau) and Abeta42 as biochemical markers for AD. METHODS: We combined CSF measurements of phospho-tau and Abeta42 in 100 consecutive patients who under-went diagnostic workup for dementia and in 31 healthy control subjects. RESULTS: We found that the calculated ratio of phospho-tau to Abeta42 was significantly increased in patients with AD and provided high diagnostic accuracy in distinguishing patients with AD from healthy control subjects (sensitivity, 86%; specificity, 97%), subjects with non-AD dementias (sensitivity, 80%; specificity, 73%), and subjects with other neurological disorders (sensitivity, 80%; specificity, 89%). CONCLUSION: The diagnostic usefulness of the CSF ratio of phospho-tau to Abeta42 is superior to either measure alone and can be recommended as an aid to evaluating individuals suspected of having dementia.

Adult↗
PubMed2003

McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement.

BACKGROUND: The X-linked McLeod neuroacanthocytosis syndrome is a multisystem disorder with hematologic, neuromuscular, and central nervous system (CNS) manifestations. All carriers of the McLeod blood group phenotype examined so far had at least subclinical signs of systemic involvement. STUDY DESIGN AND METHODS: Evaluation of two brothers carrying the McLeod phenotype with neurologic examination, immunohematology, RBC membrane protein Western blotting, analysis of XK DNA sequence and RNA levels, muscle histology including XK/Kell immunohistochemistry, cerebral magnetic resonance imaging (MRI), and quantified positron emission tomography (PET). RESULTS: Immunohematology and Western blotting confirmed presence of the McLeod blood group phenotype. No acanthocytosis or other hematologic anomalies were found. XK gene sequence analysis revealed a missense mutation in exon 3 (E327K). WBC XK RNA levels were not decreased. There were no neuromuscular and CNS signs or symptoms. In addition, no subclinical involvement was discovered on the basis of normal muscle histology with a physiologic pattern of XK and Kell immunohistochemistry, normal cerebral MRI, and quantified PET. CONCLUSION: Known disease-causing XK gene mutations comprised deletions, nonsense, or splice-site mutations predicting absent or truncated XK protein devoid of the Kell-protein binding site. Although the E327K missense mutation was associated with the immunohematologic characteristics of McLeod syndrome, the mutated XK protein seemed to be largely functional. These findings contribute to the understanding of the physiology of XK and Kell proteins, and the pathogenetic mechanisms of acanthocytosis, myopathy, and striatal neurodegeneration in McLeod syndrome.

Amino Acid Transport Systems, Neutral↗
PubMed2002

Malignant McLeod myopathy.

Mild myopathy is a common manifestation of the X-linked McLeod neuroacanthocytosis syndrome. We present a patient with McLeod syndrome and a primarily subclinical myopathy, who developed severe rhabdomyolysis with renal insufficiency after a prolonged period of excessive motor restlessness due to an agitated psychotic state and a single dose of clozapine. Other possible causes for rhabdomyolysis such as prolonged immobility, trauma, hyperthermia, generalized seizures, toxin exposure, or metabolic changes were excluded. Clinical course was favorable, with persistent slight elevation of serum creatine kinase levels caused by the underlying myopathy. Our findings suggest that McLeod myopathy is a predisposing factor for severe rhabdomyolysis. This possibly life-threatening condition should be added to the clinical spectrum of McLeod syndrome, and serum creatine kinase levels should be carefully monitored in patients with this syndrome, particularly if a hyperkinetic movement disorder is present or neuroleptic medication is used.

Acanthocytes↗
PubMed2002

Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease.

Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP 1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP 1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-1 levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP 1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD.

5' Untranslated Regions↗
PubMedDate not supplied

ABCA1 modulates CSF cholesterol levels and influences the age at onset of Alzheimer's disease.

Increased formation of the beta-amyloid peptide (Abeta) is a central event in the pathogenesis of Alzheimer's disease (AD). High cellular cholesterol load promotes Abeta formation. The ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux from cells. We hypothesized that genetic variability in ABCA1 may influence cholesterol metabolism in the central nervous system (CNS) and, thus, interfere with the development of AD. Healthy elderly carriers of the A allele of a non-synonymous (R219K) single nucleotide polymorphism (SNP) in the ABCA1 gene (rs2234884) had on average 33% lower total cholesterol in cerebrospinal fluid (CSF) than non-carriers. In 169 patients with late onset, sporadic AD, this allele was associated with delayed age at onset of the disease by 1.7 years on average. Rs2234884 and another non-synonymous SNP (R1587K) in ABCA1 (rs2234886) failed to show significant association with the risk for AD. We conclude that genetic variability of ABCA1 influences the development of AD, possibly by interfering with CNS cholesterol homeostasis.

ATP Binding Cassette Transporter 1↗