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Biomedical subjects

H U Kasper

Publications and source records attributed to H U Kasper.

At least 19 recordsLinked to original sources
PubMed2006

Induction of early murine cytomegalovirus infection by different reporter gene-associated recombinant viruses.

Murine cytomegalovirus (MCMV) has provided useful models for acute, chronic and latent CMV infection because of its similarities in structure and biology with human CMV. We report the induction of acute MCMV hepatitis with different bacterial artificial chromosome (BAC)-cloned virus constructs [MCMV-SEAP which includes the gene for secreted alkaline phosphatase (SEAP) under Rous sarcoma virus (RSV)-promoter control, MCMV-GFP which includes the gene for enhanced green fluorescent protein (eGFP) under HCMV-ie promoter control, MCMV-HBs includes the gene for hepatitis B surface antigen (HBsAg) under simian virus (SV)40-promoter control and the DeltaMC95.21 virus in which the m152 gene was deleted and substituted by the reporter gene lacZ] in order to elucidate the histopathological changes together with different reporter-gene products in the liver tissue and the effect of the deletion of a certain gene. All the virus constructs induced a similar mild acute hepatitis which had its climax from days 3 to 5 post-infection in immunocompetent mice. In situ, the reporter-gene products beta-galactosidase and secreted alkaline phosphatase could be visualized in relation to the inflammatory changes. The composition of the invading cell populations did not change even in the absence of the m152 gene. Additionally discrete inflammatory changes were seen in kidney and serosa while the other organs were not involved. This model helps us understand the immunological and histopathological mechanisms of the CMV-induced hepatitis, which plays an important role especially in the immunocompromised patient. The morphological changes can be analysed while the respective reporter gene product is expressed by the virus construct.

Acute Disease↗
PubMed2005

Experimental bile duct protection by intraductal cooling during radiofrequency ablation.

BACKGROUND: The use of radiofrequency ablation (RFA) for liver tumours is limited by the proximity of large bile ducts to the targeted lesion. The aim of this randomized study was to evaluate intraductal cooling as a mean of protecting the bile ducts during RFA. METHODS: Twelve pigs underwent RFA adjacent to the right bile duct. After placement of an intraductal cooling catheter and a RFA probe, pigs were randomized to cooling or no cooling. Intraductal temperature was measured in all animals. The bile ducts were assessed by magnetic resonance imaging (MRI) and cholangiography 1 and 28 days after the procedure. RESULTS: Intraductal cooling abolished the increase of intraductal temperature seen in the absence of cooling. Concurrent cholangiography and MRI showed a biliary lesion in one of six pigs subjected to intraductal cooling and in five of six without cooling (P = 0.040). The biliary injuries were barely visible by MRI on day 1 but were clearly visible on day 28. CONCLUSION: Intraductal cooling can prevent biliary injury induced by RFA. The exact parameters for intraductal cooling require further investigation to establish the best compromise between bile duct protection and complete ablation of surrounding tissue.

Animals↗
PubMed2005

[Clear cell tumor of the lung].

Clear cell tumors of the lung are rare tumors composed of epithelioid HMB45 positive tumor cells. It has been proposed that clear cell tumors generate from perivascular epithelioid cells which are also found in renal angiomyolipoma. Due to its morphologic epithelioid features with clear cytoplasm the distinction from either primary or metastatic clear cell carcinoma is difficult. Usually clinical investigations do not lead to the final diagnosis so that only subsequent histological examination and immunophenotyping can establish the correct tumor classification. We describe the case of a 52 year old woman who underwent exploratory thoracotomy because of a lung mass in the right lower lobe. In frozen sections a solid trabecular tumor was diagnosed, paraffin histology and immunohistochemistry revealed a clear cell tumor of the lung. The difficulty of the correct diagnosis of the clear cell tumor of the lung in frozen sections is discussed as well as the differential diagnosis.

Adenocarcinoma, Clear Cell↗
PubMed2005

Successful use of sirolimus in a patient with bulky ovarian metastasis of hepatocellular carcinoma after liver transplantation.

This 44-year-old woman developed multifocal hepatocellular carcinoma (HCC) within hepatitis B-induced liver cirrhosis. At the time of listing for transplantation the HCC had progressed beyond the Milan criteria. Due to her young age, high grade of histological differentiation according to biopsy, and lack of therapeutic alternatives, she was listed for transplantation. She received an organ from the Eurotransplant marginal liver list. Immunosuppression was reduced to tacrolimus monotherapy within 4 months. Five months after transplantation bilateral bulky ovarian metastases were seen on computed tomography (CT) scan. A bilateral salphingo-oophorectomy was performed and immunosuppression switched to sirolimus monotherapy. Fourteen months after this procedure and 19 months after transplantation, the patient is asymptomatic with stable liver function. She is free of recurrence as judged by CT scan, bone scan, and alpha-fetoprotein. In conclusion, radical surgical treatment and immunosuppression using sirolimus may achieve tumor-free survival in selected patients with advanced or recurrent HCC.

Adult↗
PubMed2005

[Report of a spindle cell myoepithelialioma of the minor salivary glands with extensive lipomatous component].

Myoepitheliomas of the salivary glands are rare benign tumors composed of spindle-shaped myoepithelial cells, but may show plasmacytoid, epitheloid and clear cell-types that principally exhibit myoepithelial but not ductal differentiation. These tumors are mainly located in the major salivary glands and have sometimes abundant, acellular, mucoid or hyaline stroma but lack chondroid and myxochondroid foci, probably representing the one end of the spectrum of pleomorphic adenoma. Lipomatosis in the form of isolated small islands or scattered single lipocytes, is quite uncommon, and a large amount of adipose tissue in a pleomorphic adenoma and myoepithelioma is a rarity and only described in major salivary glands. We present the case report of a 38-year old man with a myoepithelioma of the minor palatinal salivary glands with extensive lipomatosis as an example of this rare phenomena.

Adipose Tissue↗
PubMed2003

Underestimation of nodules while staging hepatocellular carcinoma prior to neoadjuvant treatment on waiting list for transplantation.

Neoadjuvant therapy of hepatocellular carcinoma (HCC) has increasing importance for patients awaiting liver transplantation, as waiting time increases. The therapeutic options (ethanol injection, radiofrequency ablation, chemoembolization) are only effective locally. Therefore, occult carcinomas can overcome the efficacy of these therapies. To evaluate the impact of occult nodules, we analyzed the staging results and histology from 21 HCC patients. The average pretransplant waiting time was 5.2 +/- 3.2 months. The staging before transplantation was reliable concerning the maximum diameter of the HCC. The number of HCC nodules increased from 30 at the time of clinical staging to 59 in histology, hence from 1.4 +/- 1.5 to 2.8 +/- 1.9 per patient. Patients with pT1/2 HCCs experienced an even larger increase (from 1.3 to 3.2 nodules) than patients suffering of pT3/4 HCCs (2.6 to 3.4 nodules). All occult HCCs were less than 2 cm in diameter and showed no prognostically negative histological features such as vascular invasion. The 3-year survival of the patients with small HCCs was 86% compared to 34% for those with advanced cancer. The survival of patients with small HCCs was similar to the survival of patients receiving a transplant for a nonmalignant indication. Only after neoadjuvant therapy with radiofrequency ablation or ethanol injection but not with chemoembolization, was significant necrosis of HCC observed. Considering the current average waiting time, repetitive staging and treatment of new nodules seems justified to achieve a low dropout rate during the waiting time.

Carcinoma, Hepatocellular↗
PubMed2002

[Deposition of keinoid fibers in gastrointestinal stromal tumors of the small intestine. Report of two cases and review of the literature].

Skeinoid fibers are interstitial collections of a pathological collagen, most often seen in gastrointestinal stromal tumors. They were first described in 1991. We report two cases of intestinal stromal tumors, one in an exceptionally young patient with excessive skeinoid fiber deposition. The microscopic as well as the ultrastructural findings of skeinoid fibers are demonstrated and their role is discussed considering the newest literature.

Adult↗
PubMed2001

Expression of thrombospondin-1 in pancreatic carcinoma: correlation with microvessel density.

Thrombospondin-1 (TSP-1) is a multifunctional platelet and extracellular matrix protein that is involved in angiogenesis. Under certain pathological conditions, e.g., malignant tumors, high concentrations of TSP-1 work as an angiogenic agonist. Here we examined 98 pancreatic carcinomas with respect to TSP-1 immunoreactivity and its correlation to intratumoral microvessel density (MVD), a representation of the overall degree of angiogenesis in carcinomas. Northern blot analysis for TSP-1 mRNA was performed in seven additional cases. Eighty-seven tumors showed strong TSP-1 immunoreactivity, nine carcinomas were only weakly positive, and two lesions were negative for TSP-1. TSP-1 immunoreactivity was detected in the extracellular matrix, mostly at the invasion front of the tumor. Using Northern blot analysis, we observed high levels of TSP-1 mRNA in three out of seven pancreatic carcinomas. The mean MVD in pancreatic carcinoma was 38.8 vessels per mm2. Tumors with a high expression of TSP-1 showed a higher MVD and the correlation between TSP-1 immunoreactivity and microvessel density was highly significant (P=0.003). As a modulator of angiogenesis, TSP-1 is strongly expressed in most pancreatic adenocarcinomas and is likely to contribute to the extensive neovascularization and spread of this highly aggressive tumor.

Adenocarcinoma↗
PubMed2000

Mdm2 gene amplification in gastric cancer correlation with expression of Mdm2 protein and p53 alterations.

Mdm2, localized on chromosome 12, is considered a negative regulator of p53 function and seems to play a role in the pathogenesis of a variety of tumors. The mdm2 amplification in advanced-stage gastric carcinoma has not yet been investigated. Mdm2 amplification was determined in 43 gastric carcinomas, and the genetic results were correlated with mdm2 protein expression, p53 alterations, and clinicopathologic data. The tumors were classified according to Lauren: 20 intestinal-type tumors, 19 tumors of diffuse growth inclusive of a primary small cell carcinoma, and 4 carcinomas with mixed differentiation. Staging was based on the pTNM classification system. Mdm2 and p53 were demonstrated by immunohistology on formalin-fixed and paraffin-embedded tumor tissue. The mdm2 oncogene was amplified by nonradioactive hybridization of tumor DNA with an mdm2 cDNA probe. The Southern blots were evaluated densitometrically. For p53 mutation screening, we analyzed the highly conservative regions of the p53 gene (exons 4 to 8) with the use of the polymerase chain reaction-single-strand conformation polymorphism technique. Polymerase chain reaction products with band shifting were directly sequenced. Mdm2 amplification was demonstrated in 18 tumors (41.8%). The mdm2 gene was amplified more frequently in carcinomas with a diffuse growth pattern. Gastric carcinomas of the intestinal type, however, showed a higher frequency of p53 alterations. There was no statistical significance of the molecular genetic and immunohistologic results of the mdm2/p53 status to staging as well as to age and sex of the patients. The mdm2/p53 pathway is a part of the carcinogenesis of gastric carcinoma. Only approximately 20% of gastric carcinomas failed to show mdm2 and/or p53 alterations. The upregulation of the mdm2 oncogene and the accompanying inactivation of the tumor suppressor gene 53 seem to play a role above all in carcinomas of the diffuse type.

Adult↗
PubMed2000

[Lipoma-like liposarcoma of the tongue].

BACKGROUND: Liposarcomas of the tongue are rare. To date only 7 cases have been reported. PATIENT: We report a new case of a well differentiated lipoma-like liposarcoma of the body of the tongue in a 71-year old woman. Complete uneventful resection was performed. Histologically the tumor consisted of fat cells with occasional lipoblasts and spindle cell areas. There is no sign of recurrence of the tumor 2 years later. RESULTS AND CONCLUSIONS: Liposarcomas of the tongue are rare neoplasms. All cases reported were histologically well differentiated. Liposarcomas have to be considered in the differential diagnosis of solid masses of the tongue.

Aged↗
PubMed1999

Epithelial-myoepithelial carcinoma of the salivary gland--a low grade malignant neoplasm? Report of two cases and review of the literature.

Epithelial-myoepithelial carcinomas (EMC) are rare neoplasms of the salivary gland with an incidence of less than 1% arising predominantly in the parotid gland. Although they are thought to be of low grade malignancy, fatal courses are described. We report a case of EMC of the parotid gland in a 58-year-old woman with an unfavorable course of this disease in long term follow-up. The malignant potential of this tumor is discussed. In addition, we include another case of EMC of the submandibular gland.

Carcinoma↗
PubMed1999

P53-protein accumulation and MDM2-protein overexpression in gastric carcinomas. No apparent correlation with survival.

Forty-five cases of primary gastric carcinoma were investigated immunohistochemically for p53 protein accumulation and MDM2 protein overexpression. The results were correlated with pathological and clinical data. The incidence of p53 accumulation was 12 of 45 (26.7%) cases and that of MDM2 expression was 30 of 45 (66.7%). Eighteen of 45 (40%) cases showed MDM2 overexpression without p53 accumulation. All of the 12 p53-positive cases exhibited a co-expression of MDM2. Accumulation of p53 and MDM2 overexpression correlated with the grade of malignancy. MDM2 expression occurred more often in intestinal carcinomas than in the diffuse types. No correlation was found between p53 accumulation and the histopathology of gastric cancer. p53 accumulation and MDM2 overexpression did not correlate with tumor size, nodal status, presence of metastases, age or survival. p53 alteration, which seems to be a late step in gastric carcinogenesis, is a marker of higher grade tumors. MDM2 functions as a cofactor of p53 in late gastric carcinogenesis. An independent role of this oncoprotein in gastric carcinogenesis also seems possible. Neither p53 nor MDM2 is a useful prognostic indicator.

Adenocarcinoma↗
PubMed1998

Overexpression of platelet-derived growth factor (PDGF) B chain and type beta PDGF receptor in human chronic pancreatitis.

Platelet-derived growth factors (PDGF) are mitogenic polypeptides that are involved in cellular proliferation and tissue repair. The expression of PDGFs and type beta PDGF receptor was examined in the normal human pancreas and in chronic pancreatitis, a fibrotic disease associated with fibroblastic proliferation, atrophy, and acinar cell dedifferentiation. In the normal human pancreas, PDGF A chain mRNA levels were relatively abundant, whereas PDGF B chain mRNA levels were not detected, and type beta PDGF receptor mRNA transcripts were present at low levels. In the normal pancreas, PDGF immunoreactivity was present in islet cells, whereas type beta PDGF receptor immunoreactivity was present in acinar cells. In chronic pancreatitis, PDGF A chain mRNA transcripts were also abundant, and 11 of 19 samples exhibited the PDGF B chain mRNA transcript. In addition, there was a significant increase in the mRNA levels of type beta PDGF receptor in the pancreatitis samples by comparison with the normal pancreas (P < 0.001). In chronic pancreatitis tissues, PDGF and type beta PDGF receptor immunoreactivity were present in acinar, ductal, islet, and endothelial cells, fibroblasts, and leukocytes. The concomitant overexpression of PDGFs and of the type beta PDGF receptor points to the existence of autocrine and paracrine PDGF-dependent loops in human chronic pancreatitis.

Blotting, Northern↗
PubMed1998

Analysis of K-ras gene mutations in rare pancreatic and ampullary tumours.

OBJECTIVE: Mutation of the K-ras oncogene is a frequent event in pancreatic ductal carcinogenesis and it is believed to occur at an early stage in the development of pancreatic cancer. However, little is known of the role of K-ras mutations in rare pancreatic epithelial neoplasms, endocrine tumours or other non-epithelial tumours of the pancreas. Furthermore, limited data are available regarding the role of K-ras mutations in the pathogenesis of ampullary tumours. DESIGN AND METHODS: Using single-strand conformation polymorphism (SSCP) and direct sequencing of polymerase chain reaction (PCR)-amplified fragments, we analysed codons 12 and 13 for the presence of oncogenic mutations of the K-ras oncogene. Tissues were obtained from patients undergoing tumour resection for various rare pancreatic or ampullary neoplasms (number of cases in brackets): ampullary adenoma (1), neuro-endocrine tumour (3), malignant fibrous histiocytoma of the pancreas (1), pancreatic cystadenocarcinoma (1), serous cystadenoma (1), and primary and metastatic adenocarcinoma of the ampulla (5) and pancreas (3). RESULTS: K-ras gene mutations at codon 12 were detected in both pancreatic adenocarcinomas and in the metastatic lesion, whereas two ampullary cancers harboured a point mutation at codon 13: GGC-->GGG and GGC-->GGT. None of the other tumours exhibited a K-ras gene mutation at codons 12 or 13. CONCLUSION: Pancreatic tumours other than ductal adenocarcinoma of the pancreas do not harbour mutations of the K-ras oncogene. In addition, ampullary adenocarcinomas may present with codon 13 mutations; however, these mutations were not associated with amino acid substitution. Therefore, K-ras gene mutations seem to be a specific genetic alteration contributing to the pathogenesis of pancreatic ductal adenocarcinoma.

Adenocarcinoma↗
PubMed1998

P21 protein expression and ras-oncogene mutations in gastric carcinoma: correlation with clinical data.

Ras oncogenes coding for P21 protein are frequently involved in the carcinogenesis of various human tumours. For gastric carcinomas, the role of these oncogenes has not yet been fully understood. Forty-five primary gastric carcinomas were investigated for point mutations in the hot spot regions codon 12 and 13 of exon 1 and codon 61 of exon 2 of H-, K- and N-ras gene. PCR-SSCP technique followed by direct sequencing was used. The expression of P21 protein was analysed immunohistochemically. The results were correlated to clinicopathologic data. There were no point mutations in the genes of the ras family. The incidence of P21 protein expression was 66.7% (30 of 45 cases). This expression was more common in carcinomas of the intestinal type than in carcinomas of the diffuse type. There was no correlation with tumour size, metastasis, localisation of the tumour in the stomach, histologic type, grade of malignancy, gender, or clinical outcome of the disease. Overexpression of ras oncoproteins without point mutation seems to occur frequently in gastric carcinoma, particularly in tumours of the intestinal type. There is no prognostic impact. P21 protein expression cannot be used in a predictive staging system.

Adenocarcinoma↗