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Biomedical subjects

D Neureiter

Publications and source records attributed to D Neureiter.

At least 19 recordsLinked to original sources

Eosinophil infiltration and degranulation in oesophageal mucosa from adult patients with eosinophilic oesophagitis: a retrospective and comparative study on pathological biopsy.

AIM: To examine eosinophil infiltration and degranulation in 50 oesophageal biopsy specimens from 30 patients (21 men, 9 women; mean 39 years) with eosinophilic oesophagitis, by haematoxylin and eosin staining and immunohistochemistry. METHODS: Immunohistochemistry was carried out using a monoclonal antibody for human eosinophilic major basic protein (MBP). Eosinophils were counted in three high power fields (x40) and degranulation, as quantified by extracellular MBP immunostaining, was scored on a scale of 1-4. Morphological changes (basal cell hyperplasia, elongation of papillae and dilatation of intercellular spaces) were scored on a 1-4 scale on sections stained with haematoxylin and eosin. RESULTS: Numbers of intraepithelial eosinophils were significantly higher with MBP immunostaining than with haematoxylin and eosin staining (mean 109.6 v 80.6; p<0.001), whereas numbers of eosinophils were considerably correlated (r = 0.794). Eosinophil degranulation was higher in the distal oesophagus. Additionally, basic morphological changes were markedly associated with eosinophil infiltration. Extracellular deposition of eosinophil-MBP and eosinophil infiltration in subepithelial connective tissue, present in the biopsy specimens, were detected by immunohistochemistry. CONCLUSION: Numbers of eosinophils and degranulation are underestimated by haematoxylin and eosin staining. Immunohistochemistry detected up to two times more eosinophils than routine haematoxylin and eosin staining. Moreover, eosinophil-MBP immunoreactivity in extracellular regions indicates the release of toxic eosinophil granule proteins and gives further evidence for a causative role of eosinophils with regard to structural changes in eosinophilic oesophagitis. Immunohistochemistry may serve as a useful diagnostic tool to support the morphological differential diagnosis of eosinophilic oesophagitis and gastro-oesophageal reflux disease.

Adult↗

Atherosclerosis and vascular calcification in chronic renal failure.

Cardiovascular complications are a major clinical problem in patients with chronic kidney disease and end-stage renal failure; cardiac death accounts for approximately 40-50% of all deaths in these patients. Death from cardiovascular causes is up to 20 times more common in uremic patients than in the general population with the risk being even higher than in patients with diabetes mellitus. A high rate of myocardial infarction and excessive cardiac mortality have repeatedly been documented in patients with kidney disease and renal failure. Not only is the prevalence of myocardial infarction high, but also the case fatality rate is significantly higher in uremic patients with and without diabetes, respectively, compared to nonuremic patients. This is of particular interest since the prevalence of coronary atheroma in uremic patients was shown to be approximately 30% by autopsy and coronary angiography studies. Thus, coronary factors, i.e. atherosclerosis, and non-coronary factors may play an important role in the genesis of cardiac complications in the renal patient. In addition, renal failure recently has also be identified as a predictor of mortality in different stages of peripheral vascular disease. In particular, marked differences in the pathogenesis, morphology and course of atherosclerosis and arteriosclerosis under the conditions of renal failure have been documented. Among others increased plaque formation and particularly higher proportion and intensity of vascular calcification have been found in clinical and autopsy studies. In addition to the so-called classical or traditional risk factors, an important role for nonclassical risk factors such as microinflammation, hyperphosphatemia and oxidative stress has been documented in patients with renal failure and is discussed in detail.

Animals↗

[Alpha 1-proteinase inhibitor deficiency and isolated liver cirrhosis without pulmonary emphysema in a 53-year-old female patient].

HISTORY: A 53 year-old woman presented with an elevated serum aminotransferase and cirrhosis of the liver of unknown cause. She reported neither alcohol nor drug abuse and had no previous serious illness. She had smoked about 10 pack years of cigarettes in the past. INVESTIGATIONS: Serological markers were negative for infectious agents, hemochromatosis, Wilson's disease and autoimmune diseases. Serum electrophoresis showed a decrease of the alpha1-globulin fraction (1 %; normal: 1.5 - 4.0); serum alpha1-antitrypsin was very low at 0.25 ng/l (normal: 0.9 - 2.0). The histology revealed liver cirrhosis due to alpha1-proteinase-inhibitor deficiency. Genetic testing proved a PiZZ type of proteinase-inhibitor deficiency. The patient had normal lung functions. Because of the increased risk of hepatocellular carcinoma, future sonographic monitoring and alpha-fetoprotein measurements every 6 months were recommended. TREATMENT AND COURSE: As lung functions were normal there was no indication for administering alpha1-antitrypsin. CONCLUSION: Although proteinase-inhibitor deficiency is a rare cause of liver cirrhosis, especially without any sign of emphysema, it should be considered when other, more common causes of liver cirrhosis are excluded.

Alpha-Globulins↗

Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic cancer.

BACKGROUND AND AIMS: Pancreatic cancer remains a devastating diagnosis with only limited therapeutic options. Specific inhibition of expression of target genes has become possible using small interfering (si) RNAs. We therefore investigated how far siRNA specific for bcl-2 may serve as a therapeutic option for pancreatic cancer in vitro and in vivo. METHODS: siRNAs targeting two different regions in the bcl-2 gene were transfected to YAP C and DAN G pancreatic carcinoma cells and human foreskin fibroblasts. Permutations were generated by changing 3' and 5' overhangs and varying the length of the paired RNA duplex. Transfection efficacy was determined using FITC labelled siRNAs and fluorescence microscopy. Cell survival and apoptosis were quantified at 24-120 hours. Pancreatic cancer xenografts in male nude mice were treated intraperitoneally with siRNAs daily for 24 days. siRNA pharmacokinetics in vivo were assessed using radioactively labelled siRNAs. Total protein and RNA were extracted for western Blot analysis and quantitative polymerase chain reaction. RESULTS AND CONCLUSIONS: Bcl-2 specific siRNAs specifically inhibited expression of the target gene in vitro and in vivo. Antiproliferative and proapoptotic effects were observed in tumour cells but not in fibroblasts or non-malignant tissues. siRNA permutations and diverse overhangs influenced gene silencing efficacy. siRNA was quickly distributed to all organs and excreted via the kidney and liver. Bcl-2 specific siRNA is a promising adjunctive treatment for pancreatic carcinoma.

3' Untranslated Regions↗

[Central giant cell granuloma and osteitis fibrosa cystica of hyperparathyroidism. A challenge in differential diagnosis of patients with osteolytic jawbone lesions and a history of cancer].

BACKGROUND: Giant cell lesions of the bone present similar histological features. The differential diagnosis comprises central giant cell granuloma, giant cell tumor of bone, and osteitis fibrosa cystica (brown tumor) in combination with hyperparathyroidism. Since these lesions may mimic metastatic bone disease in patients with a history of cancer, a malignant process has to be considered. Since the treatment and prognosis of these entities-benign versus malignant osteolytic bone processes-differ greatly, definitive differential diagnosis is of utmost importance. CASE REPORT: Two patients presenting with osteolytic lesions of the maxilla are reported here. In both cases a history of cancer (breast and prostate) suggested bone spreading of these malignant tumors. The clinical and histological findings were similar in both patients. One lesion was diagnosed as central giant cell granuloma, the other was found to be brown tumour in osteitis fibrosa cystica as an initial manifestation of hyperparathyroidism. DISCUSSION: The presented cases demonstrate the difficulties in establishing the correct diagnosis of patients found to have osteolytic lesions of the jawbones which is critical for the appropriate management of these patients. The article discusses the different entities of osteolytic lesions of the jawbones and the necessary diagnostic and therapeutic approach.

Adenoma↗

Mesenchymal chondrosarcoma: an immunohistochemical study of 10 cases examining prognostic significance of proliferative activity and cellular differentiation.

AIMS: Mesenchymal chondrosarcoma is a rare malignant chondrogenic neoplasm that tends to affect young adults and teenagers. The prognosis is unpredictable, and the identification of prognostic markers that could aid in determining the behaviour of this tumour would be helpful. There are few studies in the literature that have attempted to address this issue. METHODS AND RESULTS: In this study, we explored the prognostic significance of three different parameters: (1) tissue morphology of small cell areas, (2) the expression of tumour differentiation marker genes, and (3) the proliferation rate. Our results did not show a correlation of prognosis with the histological features of the neoplastic small cell areas or the expression of tumour differentiation genes. However, the proliferative activity of the tumour cells appeared to have some prognostic significance as related to patient survival. CONCLUSION: Mesenchymal chondrosarcoma is a rare tumour with a wide clinical range of behaviour. Therefore, it is difficult to obtain reliable prognostic parameters. Nevertheless, our study suggests that proliferative activity may be a useful prognostic parameter for mesenchymal chondrosarcomas.

Adolescent↗

[Detection of liver metastases--comparison of contrast--enhanced ultrasound using first versus second generation contrast agents].

AIM: To compare detection rates for liver metastases for conventional ultrasound, US using tissue harmonic imaging (THI), echo-enhanced pulse inversion harmonic imaging using Optison and Levovist. METHOD: In 73 patients with histologically proven gastrointestinal tumors spiral CT (S-CT), conventional US, US in the THI-mode, echo-enhanced ultrasound in the portal venous phase (ECI Optison ) and in the liver specific late phase (ECI Levovist) were performed and reviewed by blinded readers. RESULTS: 73 patients (25 female, 48 male, age 63 +/- 11) were included. S-CT detected 158 liver metastases. Conventional US detected 117, THI 119, ECI Optison 169 and ECI Levovist 166 liver metastases. Especially for small (< 2 cm) liver metastases and metastases near the diaphragm echo-enhanced ultrasound exceeded conventional US (p < 0.001). Between both echo enhancers there was no significant difference. CONCLUSION: Using echo enhancers increases the ultrasound detection rate significantly. Examination in the portalvenous phase using a second generation enhancer (Optison) is equal to a late-phase examination using Levovist.

Contrast Media↗

Pseudomembranous tracheobronchitis due to Bacillus cereus.

We present a case of a rapidly progressive pseudomembranous tracheobronchitis and pneumonia in a 52-year-old woman with severe aplastic anemia. Bacillus cereus was isolated from bronchoalveolar lavage fluids, blood cultures, and pseudomembrane biopsy specimens; despite intensive antibiotic treatment, the patient's condition deteriorated rapidly. To our knowledge, this is the first report of a B. cereus infection that has caused pseudomembranous tracheobronchitis, possibly because of the production of bacterial toxins.

Anti-Bacterial Agents↗

Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritis human articular knee cartilage: a study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage.

OBJECTIVE: Chondrocytes are crucial for adequate matrix balance and function. Cell proliferation and, recently, extensive apoptotic cell death have been reported in osteoarthritic (OA) cartilage. Apoptotic cell death would be an obvious central factor in the initiation and progression of OA, since there is no potential for replacing articular chondrocytes in the adult. Therefore, we studied the occurrence of apoptotic cell disintegration and cell proliferation in OA and normal articular cartilage obtained from the knees of adult donors of all ages. METHODS: Following immunostaining for cellular proteins as well as staining for nuclear DNA, we performed triple-channel confocal laser scanning microscopy on thick cartilage slices to evaluate lacunar emptying and cell viability. Cell proliferation and apoptotic cell death were evaluated morphologically, by immunodetection of the proliferation-associated Ki-67 antigen, and by the TUNEL reaction. RESULTS: With the exception of the calcified layer, we were not able to detect any major (apoptotic or nonapoptotic) cell disintegration in normal young or aged articular knee cartilage. Single apoptotic cells were detected in OA articular knee cartilage. A significant increase in lacunar emptying was observed in late-stage specimens with higher Mankin scores compared with age-matched normal control cartilage specimens, but not in low-grade lesions. A significant (but lesser) increase in empty lacunae was also observed with age in normal cartilage. Cell proliferation was rarely detected in OA cartilage samples and was not detected at all in normal cartilage samples. CONCLUSION: Our results confirm the findings of previous studies showing that cell proliferation occurs in OA cartilage. They also show that, contrary to previous suggestions, apoptotic cell death is not a widespread phenomenon in aging or OA cartilage.

Adult↗

Tenascin: a sensitive and specific diagnostic marker of minimal collagenous colitis.

Collagenous colitis is a rare cause of chronic watery diarrhea. In this condition, endoscopic findings are usually normal. Currently, the diagnosis relies on the histological presence of thick subepithelial bands of collagen deposits and an inflammatory infiltrate within the mucosa. However, these subepithelial bands may be developed only focally and may be too subtle to allow a definitive diagnosis upon routine hematoxylin and eosin (HE) and van Gieson's stainings. Recently, we and others were able to show a prominent staining of tenascin and type-VI collagen in the subepithelial band-like structures. In this study, we tested the diagnostic value of tenascin staining and type-VI collagen immunolocalization for the identification of collagenous colitis and compared it with conventional histology and histochemical detection of collagens. The analysis was based on 434 biopsy specimens of collagenous colitis, other forms of colitis, and normal mucosa. We were able to show that the immunohistochemical detection of increased amounts of tenascin, selectively in the subepithelial zone, is a specific test for collagenous colitis, with a sensitivity superior to conventional histological and histochemical detection, especially in minimal collagenous colitis (P<0.001). Of note, tenascin staining also allows the diagnosis of collagenous colitis in biopsies obtained only from the rectum and sigmoid colon, thus avoiding the need for colonoscopic investigations. Tenascin immunostaining is a simple and safe tool to complement conventional histological diagnostics in clinically and histopathologically unclear cases of diarrhea.

Adolescent↗

Association between infection with Helicobacter pylori and Chlamydia pneumoniae and risk of ischemic stroke subtypes: Results from a population-based case-control study.

BACKGROUND AND PURPOSE: Helicobacter pylori and Chlamydia pneumoniae have been associated epidemiologically and pathogenetically with coronary atherosclerosis. However, population-based data on chronic infection and stroke are lacking. Therefore, we investigated the association of both bacterial pathogens and ischemic stroke subtypes in a population-based case-control study. METHODS: Patients with first ischemic stroke in the population-based Erlangen Stroke Project were collected as cases. Neighborhood controls were drawn from the study population, matched for age, sex, and place of residence. IgG antibodies to H pylori were measured by enzyme immunoassay, and IgG antibodies to C pneumoniae were measured by microimmunofluorescence technique. Conditional logistic regression was used. Analyses were stratified for etiologic stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: A total of 145 case and 260 control subjects were included. Chronic H pylori infection was associated with a higher risk of stroke caused by small-artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71). Overall, elevated H pylori as well as elevated C pneumoniae antibodies were not associated with ischemic stroke. CONCLUSIONS: Our population-based study does not provide evidence of any strong association between the immune response to C pneumoniae as a marker of prior infection and ischemic stroke. Further studies are required to reveal the role of chronic H pylori infection as an independent risk factor for the subgroup small-artery occlusion.

Aged↗

Cell populations involved in pigmented villonodular synovitis of the knee.

OBJECTIVE: Pigmented villonodular synovitis (PVNS) of the knee is a tumor-like process of uncertain nature. We analyzed the involved cell populations, iron deposition, and cell proliferation in PVNS to propose a pathogenetic concept of this still elusive disease entity. METHODS: The study was performed on a series of 14 cases of localized PVNS of the knee. Histology and histochemistry were used to evaluate basic morphology and iron deposit distribution. Immunohistochemistry was performed to characterize the inflammatory cell infiltrate and to identify the proliferating cell compartments. In situ hybridization analysis using a cDNA probe against type I collagen was utilized to further characterize the mononuclear cell infiltrate. RESULTS: In addition to the classic features (mononuclear cell infiltrate, multinuclear giant cells, iron deposits, and stromal fibrosis) we observed a chronic inflammatory cell infiltrate in all PVNS samples, in which CD8 positive T cells were conspicuous. A high portion of non-phagocytotic cells resorbed iron and became CD68 positive. A proportion of mononuclear cells expressed type I collagen, thus resembling B synoviocytes. CONCLUSION: Our results suggest that preexisting chronic inflammation plays an important pathogenetic role in the PVNS disease process. Chronic inflammation increases the risk of articular bleeding and probably deranges the iron processing capacity of local synovial macrophages. The resulting iron overload could lead to a shift of iron storing cells from synovial macrophages to B synoviocytes and fibroblasts. A perpetuated proliferation and activation of these cells can explain why PVNS behaves like a neoplastic process.

Adult↗

[Digital ischemia as paraneoplastic marker of metastatic endometrial carcinoma].

Digital ischemia with gangrene of one or several fingertips has been described as a paraneoplastic syndrome associated with various malignant tumors, especially adenocarcinomas. Most often this paraneoplastic syndrome represents the first symptom of an occult neoplasia in an advanced stage. We present the case of an 83 year-old patient with digital ischemia and gangrenous fingertips in association with a latent adenocarcinoma of the uterus and metastatic involvement of the paraaortal lymph nodes. Acute occurrence of digital ischemia and gangrene without pathological laboratory findings and negative past medical history concerning cardiovascular-induced emboli, arteriosclerotic occlusion, or rheumatologic and autoimmune diseases should suggest this paraneoplastic syndrome and lead to thorough search for an underlying tumor.

Aged↗

Late manifestation of Indian childhood cirrhosis in a 3-year-old German girl.

UNLABELLED: We report on a 3.8-year-old German girl who presented with signs of subacute liver failure based on a 4-month history. Investigations done before admission excluded infectious, metabolic and immunological diseases. Laboratory findings were increased values of aminotransferases, hyperbilirubinaemia, hyperammonaemia and deteriorated plasmatic coagulation. Caeruloplasmin and serum copper concentrations were normal; however, urinary copper excretion was elevated (80 microg/l). Liver biopsy showed a micronodular liver cirrhosis and an extremely high liver copper concentration (1400 microg/g dry weight). Epidemiological investigations revealed an elevated copper concentration (8645 microg/l, normal: <2000) and a low pH value (6.3) of the drinking water supplied by copper pipes. The girl had been exposed to copper-contaminated drinking water since the age of 2 years. CONCLUSION: Laboratory, histopathological findings and a proven chronic copper intoxication lead to the diagnosis of Indian childhood cirrhosis in a German girl. Whereas this disease is mostly described in patients with increased copper intake in infancy, our patient developed toxic liver cirrhosis with relatively late copper exposure. Indian childhood cirrhosis should be considered in the differential diagnosis of early childhood liver cirrhosis.

Child, Preschool↗

Pleomorphic adenomas of the parotid express different mesenchymal phenotypes: demonstration of matrix gene expression products characteristic of the fibroblastic and chondrocytic cell lineages.

AIMS: Pleomorphic adenomas of the salivary glands are characterized by their high tissue diversity. Many studies have explored the derivation and differentiation of the neoplastic cells. We investigated the composition of the collagenous extracellular tumour matrix and could show a specific biochemical composition pattern in the different tumour areas. METHODS AND RESULTS: In epithelially differentiated acinar and ductal areas there was positive staining for basement membrane collagen type IV and no, or only scarce, staining for collagen types I, II, III, or VI. Solid areas mostly lacked any extracellular matrix. In areas with fibrous tissue-like appearance, the fibroblast-typical interstitial collagen types I, III and VI were seen. Chondroid areas showed abundantly the characteristic cartilage components, collagen type II and, pericellularly, type VI collagen. CONCLUSIONS: Our data show the presence of fibroblastic and chondrocytic cell differentiation in pleomorphic adenomas. Thus, they confirm that these neoplasms display, besides epithelial cell types, also real mesenchymal cell and tissue types. Differences in the abundance and the biochemical composition of the extracellular tumour matrix account largely for the morphological heterogeneity of pleomorphic adenomas of the salivary glands.

Adenoma↗

Epithelial-mesenchymal transdifferentiation and extracellular matrix gene expression in pleomorphic adenomas of the parotid salivary gland.

Mesenchymal and epithelial cell differentiation are assumed to be dichotomic primary events in embryonic development. In this study, pleomorphic adenomas of the parotid gland were analysed as a model which shows morphological features of both epithelial and mesenchymal tissue types. Using matrix gene expression profiles as a supplementary criterion for the identification of cellular phenotypes, areas with unequivocal epithelial and mesenchymal differentiation could be demonstrated. Many areas displayed a transitional phenotype with cells showing both epithelial and mesenchymal features. The data provide evidence that epithelial-mesenchymal transitions represent the basic principle of the tisuse heterogeneity in pleomorphic adenomas. Thus, pleomorphic adenomas demonstrate the potential of adult (neoplastic) epithelial cells to transdifferentiate into mesenchymal cells in vivo.

Adenoma, Pleomorphic↗

Severe disturbance of the distribution and expression of type VI collagen chains in osteoarthritic articular cartilage.

OBJECTIVE: The aim of this study was to evaluate the messenger RNA (mRNA) expression and distribution of the major pericellular type VI collagen in normal and osteoarthritic (OA) cartilage. METHODS: Conventional and confocal laser scanning immunohistochemistry, as well as in situ hybridization experiments, were performed for all 3 collagen type VI chains in sections of normal and OA articular cartilage. RESULTS: Normal adult articular chondrocytes were surrounded by a type VI collagen-positive pericellular matrix and showed significant levels of mRNA expression for all 3 type VI collagen chains. In OA cartilage, the expression and overall distribution of type VI collagen was largely increased in the lower middle and upper deep zones. In contrast, the upper zones showed a significant loss of pericellular type VI collagen staining. CONCLUSION: Our results suggest that there is a significant basic turnover of type VI collagen in normal articular cartilage. In OA cartilage, the chondrocytes of the lower middle and upper deep zones account for a net increase in type VI collagen synthesis. The loss of type VI collagen staining in the upper zones is most likely the result of increased protein degradation rather than reduced synthetic activity.

Aged↗

De-differentiated chondrosarcoma is not a 'de-differentiated' chondrosarcoma.

AIMS: De-differentiated chondrosarcoma is characterized by the presence of two distinct chondroid and nonchondroid tumour portions. The aim of our study was to investigate the distribution of extracellular matrix components in this tumour entity and thus to shed light on its histogenetic origin. METHODS AND RESULTS: Histochemical and immunohistochemical analyses were performed for collagen subtypes I, II, III and VI and cartilage proteoglycans in three samples of de-differentiated as well as conventional chondrosarcomas (various grades). In the chondroid tumour areas of de-differentiated chondrosarcoma, typical cartilage matrix components could be detected similar to chondroid areas of grade 1 and 2 conventional chondrosarcomas. In contrast, the tumour matrix of the nonchondroid portions of de-differentiated chondrosarcomas contained matrix molecules which are typical for fibroblastic tissue. This matrix composition was not identical with less differentiated (nonchondroid) areas of grades 2 and 3 conventional chondrosarcomas. CONCLUSIONS: Our results confirm the chondroid nature of the differentiated portion of de-differentiated chondrosarcoma and indicate a nonchondrocytic nature of the nonchondroid portion. De-differentiated chondrosarcoma should not be considered as a 'de'-differentiated chondrosarcoma (grade 4 neoplasm), but as a tumour entity showing two types of mesenchymal differentiation.

Adult↗