Josef Müller-Höcker

Ludwig-Maximilians-University of Munich | LMU · Faculty of Medicine

Background/purpose of the study: Despite tremendous progress in therapy, about 30 % of patients with hepatoblastoma still succumb to the disease. Thus, the development of improved therapies as well as the identification of prognostic factors are urgently needed. Methods: In the present study, expression and promoter methylation of the N-myc down...

Arteriogenesis is strongly dependent on the recruitment of leukocytes, especially monocytes, into the perivascular space of growing collateral vessels. On the basis of previous findings that platelets are central players in inflammatory processes and mediate the recruitment of leukocytes, the aim of this study was to assess the role of platelets in...

Oxyphil cell transformation of epithelial cells due to the accumulation of mitochondria occurs often during cellular aging. To understand the pathogenic mechanisms, we studied mitochondrial DNA (mtDNA) alterations in the three cell types of the parathyroids using multiplex real-time PCR and next-generation sequencing. mtDNA was analyzed from cytoch...

Key Points MK promotes PMN recruitment during the acute inflammatory response. MK and β2 integrins (CD11/CD18) cooperate in mediating PMN adhesion during acute inflammation.

Activation of Wnt signaling plays a central role in the formation of hepatoblastoma (HB), the most common pediatric liver cancer. Blocking this pathway with specific inhibitors is currently the target of various research endeavours. This study provides evidence that the naturally occurring flavonoid epigallocatechin-3-gallate (EGCG) is highly effec...

Aberrant expression of imprinted genes, such as those coding for the insulin-like growth factor 2 (IGF2) and neuronatin (NNAT), is a characteristic of a variety of embryonic neoplasms, including Wilms tumor (WT). In case of IGF2, it is generally accepted that loss of imprinting in a differentially methylated region of the IGF2/H19 locus results in...

Background: Medical stimulation of endogenous progenitor cell circulation may serve as a new therapeutic tool for treatment of acute myocardial infarction. We analyzed the effects of antidiabetic gliptins plus GCSF (granulocyte colony stimulating factor) on myocardial regeneration after myocardial infarction in a mouse model. Methods and results:...

Patients with Hermansky-Pudlak syndrome type 2 (HPS2) present with oculocutaneous albinism, nystagmus, prolonged bleeding time, and increased susceptibility to infections. Twelve HPS2 patients with mutations in the β3A-subunit of the cytosolic adaptor-related protein complex 3 (AP3B1, also called HPS2) have been described so far. Here, we report on...

Nested stromal epithelial tumor of the liver is a rare neoplasm of early childhood and adolescence with a characteristic nested morphology of spindle and epithelioid cells. Histogenesis and pathogenesis of this neoplasm are, however, still unclear. Because the characteristic nested morphology with spindle mesenchymal and epithelioid cells is sugges...

Hepatoblastoma (HB) is an embryonal liver neoplasm of early childhood with a poor prognosis for patients with distant metastases and vascular invasion. We and others have previously shown that the overexpression of insulin-like growth factor 2 (IGF2), loss of imprinting at the IGF2/H19 locus, and amplification of pleomorphic adenoma gene 1 (PLAG1)...

Parathyroid hormone (PTH) administration after myocardial infarction (MI) is known to attenuate ischaemic cardiomyopathy. This effect mainly resulted from an increase in mobilization and homing of CD34+/CD45+ cells into the ischaemic myocardium. PTH-related stem cell mobilization was shown to be related to endogenous granulocyte-colony stimulating...

Two sons of a consanguineous marriage developed biventricular cardiomyopathy. One boy died of severe heart failure at the age of 6 years, the other was transplanted because of severe heart failure at the age of 10 years. In addition, focal palmoplantar keratoderma and woolly hair were apparent in both boys. As similar phenotypes have been described...

Two juxtaglomerular cell tumors (JGCTs) were investigated in comparison with 14 endocrine tumors of the pancreas (ETPs), focusing on the cell cycle, apoptosis, and cytogenetic changes. JGCTs revealed nuclear accumulation of Cyclin D(1), together with the cyclin-dependent kinase inhibitors p21(Cip1/Waf1) and p27(Kip1). In contrast, no accumulation o...

G-CSF based stem cell mobilization and stabilization of cardiac SDF-1 by DPP-IV-inhibition (dual stem cell therapy) improve heart function and survival after myocardial infarction. However, it is barely understood whether this new approach acts specifically through the SDF-1/CXCR4 axis, stimulation of resident cardiac stem cells and improved myocar...

Overexpression of insulin-like growth factor 2 (IGF2), an imprinted gene located on chromosome 11p15, has been reported as a characteristic feature in various embryonal tumors, including Wilms tumor (WT). Recent studies specified loss of imprinting (LOI) in a differential methylated region (DMR) of the IGF2/H19 cluster or loss of heterozygosity (LO...

E-cadherin is a major component of adherens junctions. Impaired expression of E-cadherin in the small intestine and colon has been linked to a disturbed intestinal homeostasis and barrier function. Down-regulation of E-cadherin is associated with the pathogenesis of infections with enteropathogenic bacteria and Crohn's disease. To genetically clari...

Clinical studies suggest that transplantation of total bone marrow (BM) after myocardial infarction (MI) is feasible and potentially effective. However, focusing on a defined BM-derived stem cell type may enable a more specific and optimized treatment. Multilineage differentiation potential makes BM-derived multipotent adult progenitor cells (MAPCs...

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy and usually follows an autosomal dominant trait. Clinically, FSHD affects facial muscles and proximal upper limb and girdle muscles, but may present with variable clinical phenotypes even within the same family. Most genetically confirmed FSHD patients exhibit...

Mutations in alpha-B crystallin gene (CRYAB) have been described to cause congenital cataracts, dilated cardiomyopathy and myofibrillar myopathy. For skeletal myopathy, only three different mutations have been reported within the last decade. Here we describe for the first time the missense mutation p.Gly154Ser to be associated with a late-onset di...

The frequently observed de-endothelialization of venous coronary bypass grafts prepared using standard methods exposes subendothelial prothrombotic cells to blood components, thus endangering patients by inducing acute thromboembolic infarction or long-term proliferative stenosis. Our aim was to gain deeper histological and physiological insight in...

The aim of this study is to evaluate a non-invasive method for measuring myocardial perfusion defect size in mice using a clinical single-photon emission computed tomography system equipped with pinhole collimators (pinhole SPECT). Thirty days after ligation of the left anterior descending coronary artery, 13 mice (C57BL/6J) were imaged following i...

Combined morphological, immunocytochemical, biochemical and molecular genetic studies were performed on skeletal muscle, heart muscle and liver tissue of a 16-months boy with fatal liver failure. The pathological characterization of the tissues revealed a severe depletion of mtDNA (mitochondrial DNA) that was most pronounced in liver, followed by a...

Ischemic cardiomyopathy is one of the main causes of death, which may be prevented by stem cell-based therapies. SDF-1alpha is the major chemokine attracting stem cells to the heart. Since SDF-1alpha is cleaved and inactivated by CD26/dipeptidylpeptidase IV (DPP-IV), we established a therapeutic concept--applicable to ischemic disorders in general-...

Renal cell carcinoma (RCC) is a rare tumor in the pediatric population. Recently, a phenotypically and genetically distinct kidney carcinoma, mainly prevalent in children and associated with an Xp11.2 translocation or TFE3 gene fusion, has been described. It has been advanced that in this subtype of RCC, there is an accumulation of cyclin D1, cycli...

Fragestellung: Altern ist in Gehirn und Skelettmuskel mit einer Akkumulation von Mutationen und Deletionen der mitochondrialen DNA (mtDNA) assoziiert, die uber eine Storung der zellularen Energiebereitstellung letztlich zu einer Dysfunktion der betroffenen Gewebe fuhrt. Fur die auseren Augenmuskeln ist ein derartiger Zusammenhang bislang nicht unte...

Kidney biopsies in 2 females with nephrotic syndrome were suggestive of membranous nephropathy at routine light microscopy and immunohistochemistry. Electron microscopy on re-embedded paraffin tissue, however, revealed that the light microscopic pattern was due to a fibrillary glomerulonephritis with a dominant membranous manifestation. These findi...

We report the case of a 13-year-old boy with a longstanding history of unspecific hepatomegaly. The morphological investigations were diagnostic of a cholesterol ester storage disease (CESD), a rare autosomal recessive inherited disease with deficient activity of lysosomal acid lipase (LAL). The combination of hepatomegaly with accumulation of macr...

Unlabelled: Recent evidence has indicated that Hedgehog (Hh) signaling significantly contributes to liver development and regeneration and that activation of the pathway may contribute to growth of hepatocellular carcinoma (HCC) in adults. However, the role of Hh signaling in pediatric liver tumors remains to be elucidated. In this study, we show...

We report the case of a 13-year-old boy with a longstanding history of unspecific hepatomegaly. The morphological investigations were diagnostic of a cholesterol ester storage disease (CESD), a rare autosomal recessive inherited disease with deficient activity of lysosomal acid lipase (LAL). The combination of hepatomegaly with accumulation of macr...

The aim of this study was to determine the effects of HIV type-1 (HIV-1) infection and antiretroviral therapy (ART) on placental mitochondria. HIV-1-infected pregnant women and HIV-1-uninfected controls were enrolled prospectively. Placental mitochondrial DNA (mtDNA) copy numbers were determined by quantitative PCR, subunits II and IV of cytochrome...

We report on clinicopathological and whole body MRI analyses of the index patient of a large nonconsanguineous German-Ukraine family with homozygous and heterozygous AGL gene mutations at position p.W1327X (c.3980G > A). There are only limited reports on this phenotype with a homozygous genotype. The index patient, a 49-year-old woman presented wit...

A case of low-grade intraosseous fibrosarcoma of the mandible in a 9-year-old girl is described. The patient underwent pre-surgical chemotherapy which was abandoned as unsuccessful after two cycles. Radical tumour resection and mandibular reconstruction with a titanium bar were performed 3 months after diagnosis. No adjuvant therapy was given and l...

Mobilization of bone marrow-derived stem cells (BMCs) was shown to have protective effects after myocardial infarction (MI). However, the classical mobilizing agent, granulocyte-colony stimulating factor (G-CSF) relapsed after revealing an impaired homing capacity. In the search for superior cytokines, erythropoietin (EPO) appears to be a promising...

We describe a 15-year-old boy and his 19-year-old sister with progressive dilated cardiomyopathy and mild non-progressive proximal lower limb myopathy, secondary to the accumulation of amylopectin-like fibrillar glycogen, (polyglucosan) bodies, in heart and skeletal muscle. Evidence of idiopathic amylopectinosis or polysaccharidosis was demonstrate...

A pathological increase of the permeability of the mitochondrial membranes may culminate in the irreversible rupture of the mitochondrial outer membrane. Such a permeability transition is lethal because it results in the release of death-inducing molecules from mitochondria and/or metabolic failure. Current methods to assess this outer membrane dam...

Cytokine-mediated mobilization of hematopoietic stem cells has become an established method in the field of autologous and allogenic stem cell transplantation. Furthermore, it presents a new concept in tissue repair and regenerative medicine. In the present study, we explored the potency of parathyroid hormone (PTH) compared to granulocyte colony-s...

ES-cell-based cardiovascular repair requires an in-depth understanding of the molecular mechanisms underlying the differentiation of cardiovascular ES cells. A candidate cardiovascular-fate inducer is the bHLH transcription factor MesP1. As one of the earliest markers, it is expressed specifically in almost all cardiovascular precursors and is requ...

An ongoing concept is that stem cells have the potential to regenerate the injured myocardium. In addition to direct vasorelaxing effects on the vasculature, which are mediated by an increased cAMP production leading to a decreased calcium influx in smooth muscle cells, parathyroid hormone (PTH) was recently shown to facilitate stem cell mobilizati...

Cardiomyocytes in pulmonary veins (PVs) have been reported in rodents and humans. In humans they were related to atrial arrhythmias, including atrial fibrillation (AF). To investigate histological similarities and differences in PV cardiomyocyte localization and distribution, we performed comparative light and electron microscopic studies on humans...

Renal carcinomas harboring the TFE-3 translocation are rare and occur predominately in children and adolescents. Here, we report a case of infantile renal carcinoma with TFE3 translocation and show that the cell cycle is deregulated in this type of carcinoma. It is characterized by nuclear accumulation of cyclin D1 and D3 in combination with high l...

Cardiomyocytes in pulmonary veins (PVs) have been reported in rodents and humans. In humans they were related to atrial arrhythmias, including atrial fibrillation (AF). To investigate histological similarities and differences in PV cardiomyocyte localization and distribution, we performed comparative light and electron microscopic studies on humans...

Naxos disease is an autosomal recessively inherited familial syndrome that is characterized by woolly hair, palmoplantar keratoderma, and a cell adhesion cardiomyopathy, specifically an arrhythmogenic right ventricular dysplasia.1 This cardiocutaneous syndrome was first reported in the Hellenic island of Naxos. Cases also have been reported in othe...

The mammalian-target-of-rapamycin/mTOR-inhibitor sirolimus as a component of the immunosuppressive strategy after solid organ transplantation is effective at preventing allograft rejection. However, recent reports indicate that sirolimus is associated with altered sex hormone levels and impaired sperm quality parameters. Herein, we report on a case...

The need for clinical awareness and diagnostic precision of glycogen storage disease type 2 (GSD2) has increased, as enzyme replacement therapy has become available. So far, only small series have reported the muscle pathology of late-onset GSD2. We reassessed 43 muscle biopsies of 38 GSD2 patients. In all patients the diagnosis of GSD2 has been es...

Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and wer...

Benign symmetric lipomatosis, also called Madelung's disease, is characterized by lipomata and fatty infiltrations. Involvement of the nervous system has occasionally been described, mitochondrial dysfunctions have been suggested. We report a 55 year old male suffering from benign symmetric lipomatosis with associated axonal neuropathy and hyperlip...

Granulocyte-colony stimulating factor (G-CSF) has been shown to improve cardiac function after myocardial infarction (MI) by bone marrow cell mobilization and by protecting cardiomyocytes from apoptotic cell death. However, its role in collateral artery growth (arteriogenesis) has not been elucidated. Here, we investigated the effect of G-CSF on ar...

Chondroblastoma is a benign bone tumor, accounting for approximately one percent of all benign bone tumors. It mostly occurs in typical locations such as long bones. Malignant transformation including metastasis has been described in only a few cases. Therefore, we report a unique case of chondroblastoma with tumor manifestation in the 7th decade o...

Three unrelated, sporadic patients with muscle coenzyme Q10 (CoQ10) deficiency presented at 32, 29, and 6 years of age with proximal muscle weakness and elevated serum creatine kinase (CK) and lactate levels, but without myoglobinuria, ataxia, or seizures. Muscle biopsy showed lipid storage myopathy, combined deficiency of respiratory chain complex...

We report on clinical, histological and genetic findings in two patients carrying novel heteroplasmic mutations in the mitochondrial cytochrome c oxidase subunit genes COII and COIII. The first patient, a 35 year-old man had a multisystemic disease, with clinical symptoms of bilateral cataract, sensori-neural hearing loss, myopathy, ataxia, cardiac...

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare hereditary disease characterised by recurrent transient ischaemic attacks, strokes, and vascular dementia. Pathological studies reveal multiple small infarcts and diffuse white matter changes as well as vascular alterations most prominent...

This case report deals with an, in our regions, unusual diagnosis of coincidence of a genital schistosomiasis of a 30-year-old woman, coming from Africa. The female patient presented herself by a specialist because of longer lasting hypermenorrhoe. After clinical examination the patient underwent an operation because of an uterus myomatosus. The hi...

This case report deals with an, in our regions, unusual diagnosis of coincidence of a genital schistosomiasis of a 30-year-old woman, coming from Africa. The female patient presented herself by a specialist because of longer lasting hypermenorrhoe. After clinical examination the patient underwent an operation because of an uterus myomatosus. The hi...

Deficiencies of different proteins involved in copper metabolism have been reported to cause human diseases. Well-known syndromes, for example, are Menkes and Wilson diseases. Here we report a patient presenting with congenital cataract, severe muscular hypotonia, developmental delay, sensorineural hearing loss and cytochrome-c oxidase deficiency w...

................ ................ ................ ................ ................ ................ ................ ............... ongenital myopathies (CM) are neuromuscular disorders classified by characteristic histopathological findings in muscle fibers. Areas devoid of oxidative enzyme activity (core lesions) are pathological hallmarks of...

Patients with Wilson's disease (WD), Indian childhood cirrhosis (ICC), and idiopathic copper toxicosis (ICT) develop severe liver disease morphologically characterized by ballooning of hepatocytes, inflammation, cytoskeletal alterations, and Mallory body (MB) formation, finally leading to mostly micronodular cirrhosis. The pathogenesis of MBs in co...

Edema formation is the first manifestation of acute pancreatitis. Microcirculatory derangements like leukocyte-endothelial cell interaction and perfusion failure result in enhancement of microvascular permeability to large molecules playing a pivotal role in the progression of the acutely altered pancreatic tissue. Due to the lack of suitable metho...

An adult-onset hereditary inclusion body myopathy with sparing of the quadriceps muscle was originally described in Iranian Jews and assigned to a locus on chromosome 9p12-p13. Recently, mutations of the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene were reported to cause hereditary inclusion body myopathy and one type o...

Mutations in the human dysferlin gene ( DYSF) cause autosomal recessive muscular dystrophies characterized by degeneration and weakness of proximal and/or distal muscles: limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). Recently, an interaction between caveolin-3 and dysferlin in normal and dystrophic muscle (primary caveo...

Background: Overt metastasis from solid tumors to the thyroid gland is a rare finding. Carcinomas that metastasize most often originate from kidney, breast and lung. Only single cases of metastasis from the gastrointestinal tract have been reported. We describe a rare case of metastasis to the thyroid gland from a rectal adenocarcinoma which had b...

More than 100 pathogenic mitochondrial (mt) DNA mutations have been described in the past decade in association with different neuromuscular disorders. Apart from large scale mtDNA rearrangements and common point mutations in mt tRNA genes, pathogenic mutations affecting structural genes of mtDNA encoded respiratory chain subunits have been reporte...

We describe a hitherto unknown lesion of gastric chief cell proliferation mimicking structurally mucosal gastric cancer. The unremarkable cytology of the cells, their very low Ki-67 index, the inclusion of occasional parietal cells and especially ultrastructural evidence of chief cell differentiation proved helpful in the differentiation from early...

A 46-year-old female patient with Sjögren's syndrome, hypertension, and stable chronic renal insufficiency (creatinine [CR], 1.9 to 2.1 mg/dL) had a progressive worsening of renal function (CR, 5.0 mg/dL) after 11 months of chloroquine therapy (155 mg/day; cumulative dose of approximately 51 g). Light microscopy revealed nonspecific angionephroscle...

We describe an atypical case of nemaline myopathy with an unusual distribution of muscle weakness who presented at 14 years of age with kyphoscoliosis. In this patient, we demonstrate heterozygosity for a de novo CGT-CAT (Arg167His) mutation in a constitutively expressed exon (exon 5) of slow alpha-tropomyosin (TPM3). This is the first mutation ide...

More than 100 mitochondrial (mt) DNA mutations have been described in association with different complex neurological disorders and with respiratory chain (RC) deficiency in the past decade.1 Aside from more frequently reported mt tRNA mutations and deletions, a growing list of pathogenic mutations affecting structural genes of mtDNA encoded respir...

A 26-year-old woman presented with elevated liver enzymes, which were diagnosed two months ago. Examination revealed mild proximal muscle weakness, though the patient herself did not realise any impairment. The abdominal ultrasound and the histology of the liver remained unsuspicious. Muscle biopsy showed vacuolar degeneration, which could be ultra...

Crystal-storing histiocytosis (CSH) is a rare event in disorders associated with monoclonal gammopathy. The intracellular crystal formation is almost always accompanied by the expression of kappa light chains. However, the exact mechanism for the storage has not been clarified until now. We report a case of generalized CSH in a 73-year-old man who...

A 26-year-old woman presented with elevated liver enzymes, which were diagnosed two months ago. Examination revealed mild proximal muscle weakness, though the patient herself did not realise any impairment. The abdominal ultrasound and the histology of the liver remained unsuspicious. Muscle biopsy showed vacuolar degeneration, which could be ultra...

DOI 10.1016/S0022-510X(02)80024-7

We report the case of a patient with lymphoma of the salivary gland, at first diagnosed as lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) but later found to infiltrate the bone marrow. At diagnosis, the patient had a polyclonal increase of gamma-globulins. Five years after initial diagnosis, the patient presented with monoclonal gamm...

A boy presented with lactic acidosis, hepatomegaly, hypoglycemia, generalised icterus, and muscle hypotonia in the first weeks of life. At the age of 2 months, neonatal giant cell hepatitis was diagnosed by light microscopy. Electron microscopy of the liver revealed an accumulation of abnormal mitochondria and steatosis. Skeletal muscle was normal...

A case of idiopathic nodular glomerulosclerosis mimicking diabetic Kimmelstiel-Wilson glomerulopathy is reported. The patient was a 45-year-old man suffering from nephrotic syndrome. Light and electron microscopy revealed diffuse and nodular glomerulosclerosis indistinguishable from diabetic nodular glomerulosclerosis. Diabetes mellitus, however, h...

Mutations in SCO2, a cytochrome c oxidase (COX) assembly gene, have been reported in nine infants with early onset fatal cardioencephalomyopathy and a severe COX deficiency in striated muscle. Studies on a yeast homolog have suggested that human Sco2 acts as a copper chaperone, transporting copper to the Cu(A) site on the Cox II subunit, but the me...

To evaluate the frequency of pathogenic mtDNA transfer RNA mutations and deletions in biochemically demonstrable respiratory chain (RC) deficiencies in paediatric and adult patients. We screened for deletions and sequenced mitochondrial transfer RNA genes in skeletal muscle DNA from 225 index patients with clinical symptoms suggestive of a mitochon...

Mitochondrial single-stranded DNA-binding protein (mtSSB) is necessary for mtDNA replication. So far the protein has been studied mainly in Escherichia coli and in cell cultures of lower mammals. In this investigation, the authors studied the expression of mtSSB in normal and neoplastic human tissue by light and electron immunocytochemistry. mtSSB...

Regulation of endometrial glucose transport is important for the decidualization process. Therefore, we have examined the expression of the glucose transporter protein isoform 1 (GLUT1) in endometrial samples during the menstrual cycle and in decidual tissue by immunohistochemistry, and GLUT1 mRNA by RNase protection assays. GLUT1 protein was not d...