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Biomedical subjects

H Herbst

Publications and source records attributed to H Herbst.

At least 19 recordsLinked to original sources
PubMed2003

Focal overexpression of insulin-like growth factor 2 by hepatocytes and cholangiocytes in viral liver cirrhosis.

Insulin-like growth factor (IGF)-2 is overexpressed in hepatocellular carcinoma and accompanying dysplastic lesions. IGF-2 signalling is mediated through IGF-1 receptor (IGF-1R), while mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF-2R) controls pericellular levels of free IGF-2. We studied, by in situ hybridisation and immunohistology, 18 liver specimens with cirrhosis of different aetiology without neoplastic or dysplastic lesions. Immunohistology was also performed for insulin receptor IGF-1R and IGF-binding proteins 3 and 4. High focal levels of IGF-2 RNA were found in some hepatocytes of all livers with HBV- or HCV-induced cirrhosis (n=10), but in only one of the cirrhoses with nonviral aetiology (n=8). IGF-2 was overexpressed in biliary duct epithelial cells in one case. Compared with noncirrhotic liver, all cirrhotic specimens showed reduced hepatocellular expression of M6P/IGF-2R protein, which contrasted with enhanced expression in perisinusoidal cells. Immunostaining for the other antigens did not reveal significant differences. Upregulation of IGF-2 in some hepatocytes may lead to high focal IGF-2 levels sufficient to saturate local IGF-2 binding capacities, and may result in an increased susceptibility to cellular dedifferentiation and, ultimately, liver cancer. Downregulation of hepatocellular M6P/IGF-2R and upregulation of IGF-2 seem to be early events in hepatocarcinogenesis prior to the appearance of morphologically distinct dysplastic lesions. Elevated focal IGF-2 transcript levels may therefore indicate an increased risk for hepatocellular and cholangiocellular carcinomas.

Bile Ducts↗
PubMed2003

Intraoral sebaceous carcinoma.

Sebaceous carcinoma in the oral cavity is extremely rare, and we have found only four previously reported cases. We describe a fifth case. A wide surgical excision seems to be the correct treatment and estimation of serum carcinoembryonic antigen (CEA) may be a useful tumour marker in the follow-up of intraoral sebaceous carcinomas.

Adenocarcinoma, Sebaceous↗
PubMed2003

Eruption cyst formation associated with cyclosporin A.

BACKGROUND: Cyclosporin A (CyA) is a potent immunomodulatory agent with a wide range of applications. Despite its therapeutic value, multiple adverse effects of CyA have been identified. This case report describes eruption cyst formation as a possible adverse effect of CyA administration during tooth eruption in a boy treated with CyA as a consequence of a cardiac transplantation. The clinical diagnosis of eruption cyst was confirmed by histopathological examination. TREATMENT: The periodontal treatment consisted of supragingival and subgingival scaling, followed by surgical removal of the tissues overlying the crowns of the teeth associated with eruption cysts, and flap surgery in the region of gingival overgrowth. The patient was then placed on quarterly periodontal supportive therapy and his immunosuppressive medication was switched from CyA to tacrolimus. RESULTS: Twenty months after therapy, neither new cyst formation nor recurrence of gingival overgrowth was registered. CONCLUSION: Formation of an eruption cyst may be an adverse effect of CyA in children with erupting teeth.

Child↗
PubMed2003

[Neuroendocrine tumors of the gastroenteropancreatic system--reevaluation using the Capella classification].

INTRODUCTION: Neuroendocrine tumors of the gastroenteropancreatic system (GEP) are heterogeneous regarding hormone production, localisation and biological behaviour making the prognostic evaluation of these rare tumors difficult. Capella et al. proposed a new classification that combines for the first time both biological and prognostic characteristics. This study aimed to evaluate the prognostic value of Capella's classification in the patients treated at our hospital. METHODS: 86 from 1975-1999 surgically treated and histologically confirmed neuroendocrine tumors were retrospectively classified as benign (B), uncertain behavior (UB), low grade malignant (LG) or high grade malignant (HG) following the Capella classification. These data were correlated with the long-term outcome of the patients 8.5 (range: 1-24) years after surgery. RESULTS: 43 % of tumors were localised in the pancreas, the others were equally distributed in the remaining GEP. Most tumors were classified as B (42 %) or LG (41 %), few were UB (10 %) or HG (7 %). 61 patients survived free of disease, 25 patients died, 13 of them not tumor related. Tumor related deaths were only observed in 6 patients with inoperable LG- and 6 patients with HG-neuroendocrine tumors within 3 years after surgery. CONCLUSION: The Capella classification reliably reflects the heterogeneity and the biological behaviour of GEP-neuroendocrine tumors and can therefore be recommended for clinical use.

Adolescent↗
PubMed2003

Demystified...tissue microarray technology.

Several "high throughput methods" have been introduced into research and routine laboratories during the past decade. Providing a new approach to the analysis of genomic alterations and RNA or protein expression patterns, these new techniques generate a plethora of new data in a relatively short time, and promise to deliver clues to the diagnosis and treatment of human cancer. Along with these revolutionary developments, new tools for the interpretation of these large sets of data became necessary and are now widely available. Tissue microarray (TMA) technology is one of these new tools. It is based on the idea of applying miniaturisation and a high throughput approach to the analysis of intact tissues. The potential and the scientific value of TMAs in modern research have been demonstrated in a logarithmically increasing number of studies. The spectrum for additional applications is widening rapidly, and comprises quality control in histotechnology, longterm tissue banking, and the continuing education of pathologists. This review covers the basic technical aspects of TMA production and discusses the current and potential future applications of TMA technology.

Animals↗
PubMed2002

Signet-ring cell carcinoma of unknown primary location. Metastatic to lower back musculature - remission following FU/FA chemotherapy.

The detection of gastrointestinal signet-ring cell carcinoma by endoscopy can be a diagnostic challenge. The main clinical features include atypical metastasis and a poor prognosis. We present a case of a metastasizing signet-ring cell carcinoma with unknown primary location arising in 71-year-old female. Following 6 cycles of a routine intravenous FU/FA chemotherapy, an almost complete remission could be observed. After 2 years of follow up, metastatic recurrence was detected to the lower back musculature. This case report emphasizes the difficulties in diagnosing signet-ring cell carcinoma by endoscopy and demonstrates an unusual clinical course.

Abdominal Neoplasms↗
PubMed2001

Auxiliary partial orthotopic liver transplantation: treatment of acute liver failure in a new rat model.

BACKGROUND AND AIMS: Liver regeneration and functional interaction between native liver and graft after auxiliary partial orthotopic liver transplantation (APOLT) are not entirely understood and, therefore, require an experimental model simulating the clinical features of acute liver failure (ALF) and the surgical technique of APOLT. MATERIALS AND METHODS: ALF was induced by subtotal hepatectomy in 50 Lewis rats (200-250 g). Sham operation (I), ALF without treatment (II), ALF with portocaval shunt for decreasing blood flow of the remnant liver (III), and ALF treated by APOLT (IV) were performed. The auxiliary graft represented a left donor liver lobe which was orthotopically implanted using a microsurgical technique including reconstruction of the graft artery and internal biliary drainage. Operative outcomes, serum chemistry and histopathological findings were examined up to the 14th day. RESULTS: ALF without treatment (groups II and III) led to a small droplet fatty degeneration in the hepatocytes and a significant increase of liver parameters until the death of the animals within the first two postoperative days ( P<0.05). After APOLT (group IV), 80% of the animals survived up to the 14th day, revealing significantly decreased liver parameters ( P<0.05), a well-perfused graft and an up to five times increased native liver size with normal architecture. CONCLUSION: This new rat model simulates the clinical features of an ALF treated by APOLT and is especially interesting for further basic research on the interaction between native liver and auxiliary graft after APOLT.

Animals↗
PubMed2001

Collagen type XVIII/endostatin is differentially expressed in primary and metastatic colorectal cancers and ovarian carcinomas.

Collagen type XVIII (C18) is a nonfibrillar collagen of basement membranes. Its C-terminal fragment, endostatin, has been identified as an inhibitor of angiogenesis. C18 is predominantly expressed by hepatocytes of normal, cirrhotic and neoplastic liver. We compared the patterns of C18 RNA-expression in colonic adenocarcinoma metastases, which represent the most frequently occurring liver tumours, to normal colon mucosa, to primary colon cancers and to ovarian cancers which are often morphologically similar to colonic cancer or metastasis. Two C18-specific RNA-probes were generated to perform in situ hybridization combined with immunohistochemistry for cytokeratin, vimentin and the endothelial marker CD31, in order to characterize the C18-expressing cells. C18/endostatin protein was localized by immunohistology. In colorectal carcinomas and their liver metastases high levels of C18 transcripts were observed in endothelial cells and fibroblasts/myofibroblasts, whereas C18 RNA was virtually absent from carcinoma cells. Ovarian carcinomas displayed high C18 RNA expression both in carcinoma and stromal cells, indicating that induction of C18 transcription in tumour stromal cells is independent of the ability of carcinoma cells to express C18. While the role of tumour cell derived C18 in cancer growth regulation remains unknown, stimulation of proteolysis of the locally strongly expressed C18 to endostatin could offer an attractive approach for a targeted antineoplastic therapy.

Adenocarcinoma↗
PubMed2001

[Fulminant liver failure after administration of the herbal antidepressant Kava-Kava].

HISTORY AND CLINICAL FINDINGS: A 60 year-old woman was admitted to hospital because of jaundice, fatigue, weight loss over several months and icteric skin. Because of progressive liver failure, concomitant renal failure and progressive encephalopathy she was transferred to an intensive care unit. INVESTIGATIONS: Biochemical tests revealed acute liver failure with high levels of total and conjugated bilirubin (30 mg/dl) as well as aspartate aminotransferase (921 IU/l) and alanine aminotransferase (1350 IU/l) concentrations. Prothrombin time was less than 10 %. Serological tests could rule out viral hepatitis, metabolic or autoimmune causes of liver failure. On abdominal computed tomography and ultrasonography no pathological changes were detected. Above all portal vein thrombosis, ascites, focal lesions of the liver and extrahepatic cholestasis could be excluded. Liver histology showed extensive hepatocellular necrosis with intrahepatic cholestasis. TREATMENT AND CLINICAL COURSE: The patient's physical condition deteriorated. She had to be intubated because of respiratory insufficiency and encephalopathy stage IV. Because of progressive liver failure under conservative treatment the patient received an orthotopic liver transplant 11 days after admission. CONCLUSIONS: The exclusion of other causes and the histological diagnosis made Kava-Kava as the cause of acute liver failure most likely. This is the 18th case of Kava-Kava induced liver failure reported to the European regulatory authorities.

Alanine Transaminase↗
PubMed2001

Remodeling of extracellular matrix in gastric ulceration.

The quality of ulcer repair remains crucial for the stability of the injured tissue and for preventing recurrence. Therefore, we studied the temporo-spatial expression of the fibrillar and basement membrane collagens (types I, III, and IV), the collagenase MMP-2 as well as its inhibitor TIMP-1 before and after oral administration of basic fibroblast growth factor (b-FGF) over 30 days in acetic acid-induced rat gastric ulcers. The alterations and the exact location of the mRNA transcripts and their precipitated proteins were visualized by means of radioactive in situ hybridization and immunohistochemistry. Our data show that hybridization signals of procollagen I could first be identified 2 hours after ulcer induction. After 12 hours the ulcer was established and the mRNA was enhanced at the ulcer margin. After 24-48 hours the other procollagen transcripts were detected and all were further upregulated over the mesenchymal cells of all gastric layers up to 21 days, then declined at 30 days. In contrast, MMP-2 became prominent after 48 hours and up to 21 days. TIMP-1 was enhanced at 72 hours. After oral administration of b-FGF the transcriptional activity of the procollagens and MMP-2 was not significantly altered, while ulcer diameter was significantly reduced. We conclude that the early onset and long duration of collagens' expression points to their central structural and functional role in gastric ulcer healing. MMP-2 seems to be involved in both active ulceration and ECM remodeling. The timing of TIMP/MMP expression may be critical for proper restoration of gastric wall integrity.

Animals↗
PubMed2001

Low prevalence of latently Epstein-Barr virus-infected cells in chronic gastritis.

The association of Epstein-Barr virus (EBV) with a proportion of gastric carcinomas is well established. The role of EBV in conditions predisposing to carcinoma such as chronic gastritis has remained undefined, however. We used in situ hybridization with radioactive and nonradioactive single-stranded RNA probes specific for the EBV small latent nuclear transcripts, EBER1 and EBER2, to analyze biopsy specimens from 242 patients with mild to severe chronic gastritis of Sydney classification types A, B, and C. A small number of EBV infected lymphocytes was detected in only nine cases, even in biopsies investigated with radioactive probes. Labeling of epithelial or stromal cells was not observed. The paucity of latently EBV-infected cells in chronic gastritis biopsies differs from the previously reported higher prevalence of virus carrying cells in inflammatory conditions at other sites of the gastrointestinal tract. These findings argue against a direct involvement of EBV in the pathogenesis of chronic gastritis. The low prevalence of EBV-positive cells suggests that local factors do not favor the entry and retention of circulating EBV-infected lymphocytes in gastric mucosa. Moreover, our findings indicate that EBV infection of gastric epithelial cells is not an early event in gastric carcinogenesis.

Adolescent↗
PubMed2001

Expression of cytokine and chemokine genes in Epstein-Barr virus-associated nasopharyngeal carcinoma: comparison with Hodgkin's disease.

Nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD) are characterized by their association with Epstein-Barr virus (EBV) and the presence of an intense lymphoid stroma, consisting of T lymphocytes and other reactive cells. In both entities, the tumour cells express viral proteins known to provide target epitopes for cytotoxic T-cells (CTLs), yet in vivo, the tumour cells appear to escape CTL recognition. A comparative in situ hybridization study of cytokine and chemokine gene expression in NPC and HD has been undertaken, focusing on cytokines which are known to be inducible by EBV in vitro. Hodgkin and Reed-Sternberg (HRS) cells expressed interleukin (IL)-6, IL-8, and IL-10, and the thymus and activation regulated chemokine (TARC) in 15/22, 0/22, 5/22, and 16/21 cases, respectively. In NPC, the epithelial tumour cells showed expression of IL-6 in 3/43 cases and of IL-8 in 2/40 cases. There was no detectable expression of IL-10 and TARC in these cases. These data confirm that HRS cells frequently express cytokine and chemokine genes and suggest that this may enable HRS cells to modulate the immune response in their microenvironment and to escape CTL detection. In contrast, NPC tumour cells show only rare expression of IL-6 and IL-8 and no detectable expression of IL-10 and TARC. Thus, the results suggest that the mechanisms employed by the EBV-positive tumour cells to escape immune recognition and destruction differ between HD and NPC.

Carcinoma↗
PubMed2001

Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high-molecular-weight cytokeratin expression patterns.

According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (n=14), papilloma (n=22), tubular adenoma (n=3), and adenosis (n=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5/6-expressing basal-type cells within the proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS.

Adenoma↗
PubMed2001

Proliferating bile duct epithelial cells are a major source of connective tissue growth factor in rat biliary fibrosis.

Connective tissue growth factor (CTGF) is a downstream mediator of transforming growth factor-beta1 (TGF-beta1) and thus a potential target for antifibrotic treatment strategies. CTGF is up-regulated in disorders such as atherosclerosis, scleroderma, and fibrosis of kidneys and lungs. We investigated the temporospatial expression patterns of CTGF and TGF-beta1 mRNA in rat livers with acute fibrogenesis (after a single dose of CCl(4)) and with advanced fibrosis (6 weeks after complete bile duct occlusion). Multiprobe ribonuclease protection assay revealed increasing TGF-beta1 and CTGF mRNA levels 6 hours after injection of CCl(4), with peak levels after 72 hours. In biliary fibrosis TGF-beta1 and CTGF mRNA levels increased fourfold and sevenfold, respectively (P: < 0.001). In situ hybridization combined with cell-specific markers revealed CTGF transcripts in desmin-positive cells after a single dose of carbon tetrachloride, whereas no transcripts were found in normal livers. In biliary fibrosis, however, proliferating bile duct epithelial cells were the predominant source of CTGF mRNA. We conclude that in rat liver fibrogenesis CTGF is up-regulated in close association with TGF-beta1 and that, contrary to a previous report, not solely hepatic stellate cells but activated bile duct epithelial cells are the main source of this profibrogenic factor.

Acute Disease↗
PubMed2001

Modulation of collagen XVIII/endostatin expression in lobular and biliary rat liver fibrogenesis.

BACKGROUND/AIMS: The liver is the major source of collagen XVIII (C18), the precursor of the angiogenesis inhibitor endostatin. In human liver C18 is mainly expressed by hepatocytes. However, its quantitative and temporospatial expression patterns during liver fibrogenesis are unknown. METHODS: We used RNA quantification and in situ hybridization combined with cell-specific markers to study C18 compared to procollagen alpha1(I) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA expression in acute (single dose of CCl4) and chronic (biliary) rat liver fibrogenesis. RESULTS: C18 transcripts were only found in hepatocytes and bile duct epithelia of normal and fibrotic livers, and occasionally in arterial myocytes and hepatic stellate cells. 72 h after CCl4 injection, C18 mRNA levels remained unchanged, while procollagen alpha1(I) mRNA was increased at 72 h and TIMP-1 mRNA peaked at 12 h (P < 0.05). In biliary fibrosis C18 mRNA levels increased 1.8-fold, contrasting with 20- and 4-fold elevated procollagen alpha1(I) and TIMP-1 transcript levels, respectively. CONCLUSIONS: Hepatocytes and bile duct epithelia are the predominant sources of C18 in normal and fibrotic rat liver. Contrary to procollagen alpha1(I) and TIMP-1, C18 expression remains constant in acute fibrogenesis and is upregulated in biliary fibrosis. Modulation of epithelial C18 expression and its processing to endostatin could allow a liver-specific anticancer therapy.

Animals↗