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J Müller-Höcker

Publications and source records attributed to J Müller-Höcker.

At least 19 recordsLinked to original sources
PubMed2003

Chief cell proliferation of the gastric mucosa mimicking early gastric cancer: an unusual variant of fundic gland polyp.

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 gastric cancer. The exact classification of the alteration remains unresolved. The presence of microcysts suggests that the lesion is a variant of fundic gland polyp formation.

Aged↗
PubMed2003

Chloroquine-induced phospholipidosis of the kidney mimicking Fabry's disease: case report and review of the literature.

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 angionephrosclerosis. Electron microscopy showed accumulations of lamellated myelinoid material and occasionally also of curvilinear bodies, especially in the glomerular podocytes and to a lesser extent in vascular myothelial and endothelial cells. In the tubular system, mainly protein droplets were stored. Activity of alpha-galactosidase A was normal in isolated leukocytes (56 nmol/mg; range, 33.2 to 109 nmol/mg), ruling out Fabry's disease. Clinical, morphological, and biochemical findings were consistent with chloroquine-associated deterioration of renal function that improved considerably after discontinuation of chloroquine treatment. Adverse effects of chloroquine may aggravate preexisting renal disease. Electron microscopy is a worthwhile tool for establishing the correct diagnosis.

Chloroquine↗
PubMed2002

Monoclonal gammopathy after low-grade MALT lymphoma: evidence for a second neoplasm.

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 gammopathy and infiltration of the bone marrow with neoplastic cells. Initially, the patient had received chemotherapy with different protocols (including etoposide, cyclophosphamide, fludarabin, methotrexate, and vincristine), none of which induced a lasting response. Therapy with rituximab (chimeric anti-CD20 monoclonal antibody) finally led to partial remission. Eighteen months after rituximab, progressive lymphoma in the abdomen and a monoclonal gammopathy developed. The bone marrow showed infiltration by lymphoplasmacytoid cells (monoclonal expression of the light-chain type lambda, positive for CD20, heterogeneous expression of CD45). The patient achieved another short clinical response with 4 cycles of the CHOP-protocol, but soon the lymphoma progressed again. Five years and 8 months after the initial diagnosis, the patient died from septicemia and progressive lymphoma. By polymerase chain reaction (PCR) for the IgH gene it was shown that lymphoma cells were initially oligoclonal in the salivary gland and, later, biclonal in the bone marrow. Sequencing of two bands of apparently same length showed that these manifestations of lymphoma were not identical. Taken together, our data show that the initial low-grade oligoclonal MALT lymphoma was no longer present and a more aggressive biclonal lymphoma with plasmacytoid differentiation had developed. The new lymphoma was clonally distinct and produced high amounts of monoclonal IgG lambda by immunoelectrophoresis. The relationship of the second lymphoma to the initial MALT lymphoma is discussed.

Antibodies, Monoclonal↗
PubMed2002

De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy.

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 identified in a constitutively expressed exon of TPM3 in a nemaline myopathy patient, but is similar to recently described mutations in beta-tropomyosin (TPM2) associated with nemaline myopathy and mutations in fast alpha-tropomyosin (TPM1) which cause hypertrophic cardiomyopathy.

Adenosine Triphosphatases↗
PubMed2002

[26-year-old female patient with elevated liver enzymes].

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 ultrastructurally identified as large deposits of membrane-bound glycogen. The morphological findings prompted biochemical investigations which showed an excess of muscle glycogen. Acid maltase activity was reduced to < 10 % of normal, leading together with the clinical findings to the diagnosis of glycogenosis type II (Pompe's disease) of the adult type. Because of the modest impairment of the patient and the limited therapeutic possibilities, the patient remained thus untreated for.

Adult↗
PubMed2002

A case of idiopathic nodular glomerulosclerosis mimicking diabetic glomerulosclerosis (Kimmelstiel-Wilson type).

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, had been excluded both by extensive clinical and by laboratory investigation. The differential diagnosis also included amyloidotic and non-amyloidotic fibrillary glomerulopathy, light chain glomerulopathy, collagen type III disease, immunotactoid glomerulopathy, and the sclerosing variant of membranoproliferative glomerulonephritis. Immunohistochemistry and ultrastructural investigations, however, excluded these entities, and the diagnosis of idiopathic nodular glomerulosclerosis was made. This variant has to be included in the differential diagnosis of nodular glomerulopathy associated with nephrotic syndrome.

Amyloidosis↗
PubMed2001

Cytochrome c oxidase deficiency due to mutations in SCO2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts.

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 mechanism of action remains unclear. To investigate the molecular basis of pathogenesis of Sco2 defects in humans we performed genetic and biochemical studies on tissues, myoblasts and fibroblasts from affected patients, as well as on a recombinant human C-terminal Sco2 segment (22 kDa), bearing the putative CxxxC metal-binding motif. Recombinant Sco2 was shown to bind copper with a 1:1 stoichiometry and to form homomeric complexes in vitro, independent of the metal-binding motif. Immunohistochemistry using antibodies directed against different COX subunits showed a marked tissue-specific decrease in the Cox II/III subunits that form part of the catalytic core, consistent with the differential tissue involvement, but a more uniform distribution of Cox Vab, a nuclear-encoded subunit. Sco2 was severely reduced in patient fibroblasts and myoblasts by immunoblot analysis. Patient fibroblasts showed increased (64)Cu uptake but normal retention values and, consistent with this, the copper concentration was four times higher in Sco2-deficient myoblasts than in controls. COX activity in patient myoblasts was completely rescued by transduction with a retroviral vector expressing the human SCO2 coding sequence, and more interestingly by addition of copper-histidine (300 microM) to the culture medium. Whether the latter is accomplished by the very low residual levels of Sco2 in the patient cells, direct addition of copper to the Cu(A) site, or by another copper-binding protein remains unknown. Whatever the mechanism, this result suggests a possible therapy for the early treatment of this fatal infantile disease.

Amino Acid Motifs↗
PubMed2001

Deregulated expression of cell cycle-associated proteins in solid pseudopapillary tumor of the pancreas.

Solid pseudopapillary tumor of the pancreas was studied in a 20-year-old woman and a 54-year-old woman. In the younger patient, the tumor had metastasized to the liver 8 years after distal pancreatectomy. In both neoplasms, the distinct histologic pattern of solid, pseudopapillary, and degenerative cystic areas was present. Analysis by means of immunohistochemistry revealed a diffuse expression for vimentin, neuron-specific enolase, and a focal positivity for al-antitrypsin, whereas epithelial markers were negative in the tumor of the older patient and only focally expressed in the tumor of the younger patient. Immunohistochemical analysis of cell cycle-associated proteins provided an overexpression of cyclin D1 and cyclin D3 in both tumors, although to varying degrees. In addition, the cyclin-dependent kinase inhibitors p21, and to a lesser extent p27, were up-regulated just as mdm2. There was no accumulation of p53 protein, and Ki67-positive cells were extremely scarce. Analysis of the liver metastases showed an immunoreactive profile similar to that of the primary tumor. The results show a deregulation of the cell cycle with overexpression of cell cycle-activating proteins D1 and D3 and a probably counterbalancing upregulation of the cyclin-dependent kinase inhibitors p21 and p27. The findings may explain the low pool of Ki67-reactive tumor cells and the generally good clinical outcome of these tumors. Whether a more profound dysbalance of the cell cycle regulation is responsible for the development of metastatic disease remains to be clarified.

Biomarkers, Tumor↗
PubMed2001

Immunocytochemical localization of mitochondrial single-stranded DNA-binding protein in mitochondria-rich cells of normal and neoplastic human tissue.

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 has been detected in various tissues and particularly in mitochondria-rich tissues such as external eye muscles and parietal cells of the stomach and in mitochondria-rich tumors (oncocytomas) of various origins. Ultraimmunocytochemistry disclosed the specific distribution of immunoreactive mtSSB over the mitochondria. The staining intensity was heterogeneous. Forty-five percent had a labeling index (silver grains/microm2) greater than 1 and less than 3, approximately 20% had an index of 3 or greater, and 15% of mitochondria remained unstained. The mean labeling index was 1.83. Immunolabeling showed a linear correlation with the mitochondrial profile area (r = 0.82). In conclusion, mtSSB is regularly expressed in normal and neoplastic human tissue of different origin, function, and differentiation. The heterogeneous staining pattern most probably reflects the functional heterogeneity of mitochondria.

DNA, Mitochondrial↗
PubMed2001

Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies.

OBJECTIVE: To evaluate the frequency of pathogenic mtDNA transfer RNA mutations and deletions in biochemically demonstrable respiratory chain (RC) deficiencies in paediatric and adult patients. METHODS: We screened for deletions and sequenced mitochondrial transfer RNA genes in skeletal muscle DNA from 225 index patients with clinical symptoms suggestive of a mitochondrial disorder and with biochemically demonstrable RC deficiency in skeletal muscle. RESULTS: We found pathogenic mitochondrial DNA mutations in 29% of the patients. The detection rate was significantly higher in adults (48%) than in the paediatric group (18%). Only one pathogenic mutation was detected in the neonatal group. In addition, we describe seven novel transfer RNA sequence variations with unknown pathogenic relevance (six homoplasmic and one heteroplasmic) and 13 homoplasmic polymorphisms. One heteroplasmic transfer RNA(Leu(UUR)) A>G mutation at position 3274 is associated with a distinct neurological syndrome. CONCLUSIONS: We provide an estimation of the frequency of mitochondrial transfer RNA mutations and deletions in paediatric and adult patients with respiratory chain deficiencies.

Adolescent↗
PubMed2001

Expression of glucose transporter 1 in human endometrial and decidual tissue.

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 detected in proliferative endometrial samples, but was highly expressed in decidual tissue. Placental tissue was highly positive. GLUT1 mRNA could be detected in endometrial samples with an increase in endometria of the late secretory phase (day 25-28) and maximum concentration in the decidua of the 9th-10th week of gestation. Our results show that GLUT1 is differentially expressed in the different phases of the human endometrium with a maximum in the human decidua. Therefore, GLUT1 may be an important marker for endometrial differentiation.

Adult↗
PubMed2000

IG-therasorb immunoapheresis in orthotopic xenotransplantation of baboons with landrace pig hearts.

BACKGROUND: The major problem of xenotransplantation is, that hyperacute xenograft rejection (HXR) causes graft failure within minutes or a few hours because of natural antibodies and activation of the complement system. As a preclinical model we transplanted pig hearts orthotopically into baboons. To prevent HXR after orthotopic xenotransplantation (oXHTx), the immunoglobulins (Ig) and natural antibodies were adsorbed to reusable Ig-Therasorb immunoadsorption (IA) columns. METHODS: We performed three oXHTx of landrace pig hearts into baboons (19+/-6.8 kg), using extracorporeal circulation (ECC) connected to the IA unit. After separating the recipient's blood into plasma and cellular fraction by a plasma filter, plasma flow was directed to the Ig-Therasorb column coated with polyclonal sheep-antibodies against human IgG, IgM, and IgA. Intraoperative treatment consisted of 4 cycles of IA. For a control, we transplanted one pig heart into a baboon (16.9 kg) without applying IA. Perioperatively, serum concentrations of Ig, anti-pig-antibodies, complement and cardiac enzymes were determined. Tissue samples of myocardium were collected at the end of the study for immunohistochemical examinations, light microscopic examination (LM) and electron microscopic examination (EM). For cardiac monitoring after oXHTx, we used ECG, echocardiography, and invasive measurement of cardiac output. To prevent a mismatch of donor and recipient heart size, the donor pig had a 30-40% lower body weight than the recipient baboon. RESULTS: Four cycles of IA removed >80% of IgG, IgM, and IgA from plasma. The graft of the control animal failed after 29 min. The first oXHTx with IA was intentionally terminated after 100 min, the second oXHTx after 11 hr and the third oXHTx after 21 hr. All xenografts showed no histological signs of HXR. After weaning off ECC, these donor hearts worked in sinus rhythm without electrocardiographic ST-segment elevation. An excellent cardiac output was measured by echocardiography and thermodilution (2 L/min). Serological parameters indicating cardiac damage were significantly lower after IA if compared with the control experiment. Macroscopically, the xenograft of the control animal showed massive hemorrhage in comparison with the almost inconspicuous grafts after IA. The myocardium of the IA group demonstrated fewer deposits of Ig and complement components compared with the control animal. CONCLUSION: Baboons do not hyperacutely reject a porcine xenograft after antibody depletion by the Ig-Therasorb column. In our experiment only 4 cycles of immunoapheresis effectively prevented HXR after oXHTx of baboons. The Ig-Therasorb column is a reusable device, which can be handled easily in combination with the ECC. IA must be tested in oXHTx longterm survival experiments, especially in combination with transgenic pig organs, which could be a reliable preclinical approach for future clinical xenotransplantation.

Animals↗
PubMed2000

Coincidence of Gaucher's disease due to a 1226G/1448C mutation and of an immunoglobulin G lambda multiple myeloma with Bence-Jones proteinuria.

We report about a 58-year-old female with coexisting type-I Gaucher's disease (GD) and multiple myeloma (MM). The diagnosis of GD was made in early childhood by means of bone marrow biopsy and was recently confirmed by analysis of the patient's genomic DNA for the underlying glucocerebrosidase mutations and the identification of the 1226G/1448C genotype. At the age of 24 years, the patient developed massive splenomegaly. Therefore, a splenectomy was performed. No further therapy was necessary for the next 34 years until 1999 when progressive anemia and thrombocytopenia occurred. Additional laboratory analysis revealed high serum protein and immunoglobulin (Ig) G levels and evidence of monoclonal gammopathy and lambda light-chain proteinuria, indicating plasma cell dyscrasia. This diagnosis was confirmed by the detection of osteolytic lesions in skeletal X-rays and a bone marrow biopsy showing an extensive infiltration with Gaucher cells and an increase of plasma cells, which expressed lambda light chains. When examined by means of electron microscopy, typical Gaucher cells, i.e., histiocytes containing tubular-structured cytoplasmatic material and spots of plasma cells with an increase of the endoplasmic reticulum, were found. GD associated with acquired MM has been described 13 times in the literature from 1968 to 1997. Only three of the patients were suffering from IgG myeloma. This distribution of the monoclonal component is in contrast to that of patients suffering from MM alone.

Bence Jones Protein↗