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Biomedical subjects

G Klöppel

Publications and source records attributed to G Klöppel.

At least 19 recordsLinked to original sources
PubMed1992

The epidermal growth factor receptor in human pancreatic cancer.

The epidermal growth factor receptor (EGFR) and its ligands are thought to be important in the control of proliferation of many epithelial systems, including the exocrine pancreas. Abnormalities in expression of two of the known ligands of the EGFR, transforming growth factor alpha and epidermal growth factor, occur frequently in ductal adenocarcinoma of the human pancreas. We have examined an archival series of cases of pancreatic pathology for expression of the EGFR using the anti-EGFR antiserum 12E and found that there is almost ubiquitous overexpression of EGFR in pancreatic cancer and in chronic pancreatitis. Southern blot analysis showed no evidence of amplification or rearrangement of the EGFR gene. We conclude that an autocrine loop involving the EGFR system may be involved in the genesis of both neoplasia and reactive hyperplasia of pancreatic ductal epithelium.

Adenocarcinoma↗
PubMed1992

The erbB-3 gene in human pancreatic cancer.

Abnormalities of the type 1 growth factor receptor family have been implicated in the pathogenesis of pancreatic cancer. There is evidence for a potential autocrine loop involving overexpression of the epidermal growth factor (EGF) receptor and its ligands, as well as overexpression of the erbB-2 receptor. A third member of this receptor family, erbB-3, has recently been recognized and found to be abnormally expressed in some types of human cancer. In this study we show that overexpression of the erbB-3 protein occurs very frequently in carcinoma of the exocrine pancreas and also in chronic pancreatitis. We found no evidence of amplification or rearrangement of the erbB-3 gene by Southern blot analysis of DNA from pancreatic cancer cells lines.

Amino Acid Sequence↗
PubMed1992

Islet amyloid polypeptide immunoreactivity in the human fetal pancreas.

Islet amyloid polypeptide is known to localize to the adult human Beta cell. We analysed the immunoreactivity for islet amyloid polypeptide in a series of 29 human fetal pancreata (9-24 weeks of gestation) with respect to age dependency and cellular localization using an antibody raised against synthetic rat islet amyloid polypeptide 12-37. Cells immunoreactive for islet amyloid polypeptide were demonstrated in low numbers from week 13 onwards while insulin positivity was already present at 9 weeks of gestation. In the age group 13-16 gestational weeks, cells positive for insulin were 20-fold more frequent than cells positive for islet amyloid polypeptide. This difference gradually disappeared with age, reaching parity in the adult gland. Double immunostaining demonstrated that all islet amyloid polypeptide immunoreactivity co-localized with insulin. Co-expression of insulin and islet amyloid polypeptide was more frequent in Beta-cell clusters (greater than or equal to 10 cells) than in single Beta cells; islet amyloid polypeptide positivity was present in 58 +/- 9% (mean +/- SEM; n = 4) of fetal, 88 +/- 9% (n = 3) of neonatal and 100% (n = 3) of adult clustered Beta cells, and only 8-18% of the single Beta cells. The results suggest that the developing fetal Beta cells, dependent on age and localization, differ in their capacity to express detectable amounts of immunoreactive islet amyloid polypeptide. Beta-cell maturation might therefore be associated with islet amyloid polypeptide expression.

Adult↗
PubMed1992

Immunocytochemistry in adrenocortical tumours: a clinicomorphological study of 72 neoplasms.

Surgical specimens of 72 adrenocortical tumours (ACTs) were investigated. Histologically, 57 tumours were classified as adenomas and 15 as carcinomas. In 9 of the latter cases, distant metastases and/or lethal outcome of disease was recorded. Immunocyto-chemistry showed only 2 ACTs to be positive for cytokeratin and 6 for vimentin. None of the 72 tumours showed argyrophilia or immunoreactivity for epithelial membrane antigen (EMA), S-100 protein, chromogranin A, Leu 7 or Leu-M1, while 31 cases exhibited positivity on immunostaining with a polyclonal antiserum against synaptophysin. All 72 ACTs were immunoreactive with the recently described antibody D11. Thus the panel of antibodies described here could not discriminate between adenomas and carcinomas or between carcinomas with aggressive and indolent behaviour. Immunostaining with D11 and for EMA and Leu-M1 may help to distinguish ACTs from phenotypically similar lesions of different histogenesis.

Adrenal Cortex Neoplasms↗
PubMed1992

Human cytomegalovirus in the pancreas of patients with type 2 diabetes: is there a relation to clinical features, mRNA and protein expression of insulin, somatostatin, and MHC class II?

Human cytomegalovirus (HCMV) was recently demonstrated in the pancreas of about half the patients with type 2 diabetes mellitus in the absence of mumps, rubella or Coxsackie B virus. The present study addresses the question as to whether type 2 diabetes with an HCMV-positive pancreas differs from those with HCMV-negative pancreases with respect to age, sex, treatment, duration of disease, volume densities of B-cells and D-cells, mRNA levels of insulin and somatostatin, islet amyloid peptide deposits and major histocompatibility complex (MHC) class I and class II gene transcription, and protein expression. HCMV-positive type 2 diabetic patients showed a tendency towards a shorter duration of disease and significantly increased levels of MHC class II on RNA. In addition, expression of MHC class II product (HLA-DR) was identified in duct epithelial cells and/or islet cells in 9 diabetic pancreases and in 2 non-diabetic glands. No MHC class I expression could be detected. No other clinical differences between HCMV-positive and HCMV-negative glands were found. All 10 HCMV-positive diabetics showed a strong expression of MHC class II mRNA in the pancreas. By immunocytochemistry, 4 of 10 demonstrated expression on the islets; three of ten also expressed MHC DR beta on ductal cells. This finding might be related to the viral infection, as only 2 of the 9 HCMV-negative patients were HLA-DR beta positive and none of the non-diabetic controls showed increased levels of MHC class II mRNA. These data suggest that HCMV infection in the pancreas is associated with type 2 diabetes. However, no conclusions as to a role of this virus in the aetiopathology of type 2 diabetes can be drawn at present.

Aged↗
PubMed1992

Distribution patterns of proinsulin and insulin in human insulinomas: an immunohistochemical analysis in 76 tumors.

The distribution of proinsulin and insulin immunoreactivity was studied in 76 human insulinomas and in normal pancreas. One trabecular and two solid insulinomas showed the staining pattern of normal beta cells. A "near normal" staining pattern (perinuclear proinsulin and diffuse or polarized insulin staining) existed in 10 of 27 trabecular and 11 of 44 solid insulinomas. An "intermediate" staining pattern (intense perinuclear as well as weaker diffuse proinsulin staining with diffuse or polarized insulin staining) was observed in 10 of 27 trabecular and 20 of 44 solid insulinomas. Different "abnormal" staining patterns were found in 6 of 27 trabecular and 6 of 44 solid insulinomas. Of the 5 glandular insulinomas, 4 exhibited a "near normal" and one an "abnormal" staining pattern. No correlation was found between any particular staining pattern and the multihormonality or malignancy of the insulinomas. The diffuse labeling for proinsulin in about 50% of the insulinomas is suggestive of abnormal prohormone processing.

Antibodies, Monoclonal↗
PubMed1992

Hypersensitivity with hepatotoxicity to mesalazine after hypersensitivity to sulfasalazine.

A 21-year-old woman with Crohn's disease of the colon developed a skin rash after 3 weeks of treatment with sulfasalazine. Administration of sulfasalazine was discontinued. When mesalazine was instituted 1 week later, she developed a severe hypersensitivity reaction characterized by fever, diarrhea, skin rash with subsequent desquamation, marked atypical lymphocytosis, and severe hepatotoxicity. Recovery was complete. The clinical and biological features as well as liver pathology of this case bear a striking resemblance to earlier reports of hypersensitivity reaction with severe hepatotoxicity to sulfasalazine. The authors urge caution when mesalazine is given to a patient with known hypersensitivity to sulfasalazine.

Adult↗
PubMed1992

Ki-ras oncogene activation in preinvasive pancreatic cancer.

Activation of the Ki-ras oncogene by specific point mutations at codon 12 occurs at a remarkably high frequency in pancreatic ductal adenocarcinoma and is likely to be an important event in the pathogenesis of this cancer. To determine whether ras activation also occurs in noninvasive proliferative lesions of the pancreas, a series of cases of ductal papillary hyperplasia, intraductal papillary neoplasia, and intraduct extensions of ductal adenocarcinoma were examined for activating mutations of Ki-ras at codons 12, 13, and 61 using polymerase chain reaction amplification. Specific mutations at Ki-ras codon 12 were found in 5 of 6 cases (83%) of intraduct extensions of carcinomas and in 12 of 16 (75%) invasive carcinomas. In cases with both intraductal and invasive components, the same mutation was identified in each. No mutations were found in 5 intraductal papillary neoplasms and 9 cases of ductal papillary hyperplasia. The authors conclude that Ki-ras activation at codon 12 is important in the tumorigenesis of ductal adenocarcinoma of the pancreas but is not required in the pathogenesis of ductal papillary hyperplasia or intraductal papillary neoplasm.

Adult↗
PubMed1992

Pseudotuberculous pyelonephritis associated with nephrolithiasis.

This report describes a 40-year-old man with an unusual form of granulomatous pyelonephritis, associated with nephrolithiasis, resulting in end-stage kidney disease and right pretransplant nephrectomy. The kidney specimen contained a staghorn calculus and showed chronic inflammation with confluent caseating granulomas and multinucleated giant cells, resembling renal tuberculosis. However, neither tubercle bacilli nor other microorganisms were demonstrated in the renal tissue or in urine cultures. Because these findings do not support a tuberculous etiology of the granulomatous pyelonephritis, we conclude that this patient had a pseudotuberculous reaction as a consequence of nephrolithiasis.

Adult↗
PubMed1992

Incidence and morphology of liver metastasis from extrahepatic malignancies to cirrhotic livers.

Incidence and morphologic pattern of liver metastasis from extrahepatic cancer in cirrhosis were studied in 2162 consecutive autopsies performed during a 12.5 year period. The cirrhotic liver was less frequently affected by metastasis than the noncirrhotic liver (33.3% versus 46.4%). The incidence of extrahepatic malignancies and their hematogenous metastasis was lower (though statistically not significant) in patients with cirrhosis than in patients without cirrhosis (20% versus 32%). Patients with cirrhosis but without cancer died at a younger age (63.5 years) than patients with both cancer and cirrhosis (69.5 years). In cirrhotic livers, metastases from neuroendocrine tumors were predominantly localized within the parenchymal nodules, while nonendocrine carcinomas metastasized to the fibrotic septa. The results suggest (1) that patients with cirrhosis develop less frequently extrahepatic malignancies and hepatic metastasis than patients without cirrhosis, probably because of a shorter life expectancy due to the complications of liver cirrhosis; (2) microscopic localization of metastases in cirrhotic livers depend on tumor type.

Age Factors↗
PubMed1991

Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy.

Specimens from the pancreas and duodenum of 26 patients with sporadic Zollinger-Ellison syndrome (ZES) and 18 patients with multiple endocrine neoplasia type 1 (MEN-1) and hypergastrinemia (17 with ZES) were screened immunocytochemically for gastrinomas. Location, size, multicentricity, and malignancy of the gastrinomas were evaluated. The MEN-1 patients had gastrinomas in the duodenum (nine of 18), pancreas (one of 18), and periduodenal lymph nodes (two of 18). No gastrinoma was identified in six patients. Most duodenal gastrinomas were multiple (five of nine) and smaller than 0.6 cm (six of nine). Lymph node metastases were present in eight of 12 patients. All 26 patients with sporadic ZES had a solitary gastrinoma; 14 were found in the pancreas and had a diameter greater than 2 cm. Ten patients had a duodenal gastrinoma, two with a diameter less than 0.6 cm. In two patients, only periduodenal "lymph node gastrinomas" were detected. Eighteen of the sporadic gastrinomas were malignant. These results suggest that duodenal location and multicentricity of gastrinomas are associated with the MEN-1 syndrome, and solitary gastrinomas, either in the pancreas or the duodenum, are predominantly seen in sporadic ZES.

Duodenal Neoplasms↗
PubMed1991

Immunohistochemical demonstration of villin in the normal human pancreas and in chronic pancreatitis.

Human pancreatic tissue was investigated by immunohistochemistry using a polyclonal antibody against the actin binding protein villin, which participates in the formation of actin filament bundles in the microvilli. In cells of the different parts of the pancreatic duct system as well as in the acinar cells villin immunoreactivity was located mainly at the apical cell surface. This was confirmed by the ultrastructural demonstration of microvilli on the surface of duct and acinar cells, which exhibited the typical actin bundles. In chronic pancreatitis the staining for villin in duct-like structures of degenerative pancreatic tissue was irregular or even absent. This correlated with the electron microscopic observation of duct-like structures known as tubular complexes composed of cells devoid of microvilli at the apical cell surface. At the light microscopical level degenerative structures without lumen and of unknown origin showed a strong staining for villin at their basal cell surface.

Carrier Proteins↗
PubMed1991

Transplantation of purified islet cells in diabetic BB rats.

The ability to prepare purified islet Beta-cell aggregates was used to examine the survival of this cell type after allotransplantation in diabetic BB rats. The aggregates were intraportally implanted in numbers that were previously found to correct a streptozotocin-induced diabetic state in syngeneic or allogeneic Brown Norway recipients. When the grafts were prepared from RT1u/l donors, which shared the MHC-class I antigen with the BB recipients (RT1u/u), their implant sites became diffusely infiltrated by inflammatory cells and their metabolic function was completely lost within 5 weeks. MHC-class I incompatible islet Beta-cell allografts (RT1n/n) exhibited a longer survival, in particular when combined with other islet endocrine cells and/or when covered by a 5-week cyclosporin treatment. In the latter combination, 10 of 12 BB rat recipients remained normoglycaemic over the 10-week observation period, their liver implants presenting a comparable insulin reserve and similarly discrete mononuclear cell infiltration as streptozotocin-diabetic Brown Norway rats receiving this treatment. However, administration of cyclosporin to diabetic BB rats was associated with a morbidity that was not observed in drug-treated streptozotocin-diabetic Brown Norway animals or in untreated diabetic BB rats. It is concluded that MHC-incompatible islet Beta cells can induce a long-term normalization in diabetic BB rats provided that they are implanted under conditions which allow allograft acceptance. The standardized preparation of purified islet Beta-cell grafts can help assessing the conditions for successful transplantations in diabetes with an autoimmune origin.

Animals↗