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Biomedical subjects

A Hoorens

Publications and source records attributed to A Hoorens.

17 recordsLinked to original sources
PubMed2000

Acute onset of type I diabetes mellitus after severe echovirus 9 infection: putative pathogenic pathways.

Enterovirus infections have been implicated in the development of type I diabetes mellitus. They may cause beta cell destruction either by cytolytic infection in the pancreas or indirectly by contributing to autoimmune reactivity. We sought evidence for these 2 mechanisms in a case of acute-onset diabetes mellitus that occurred during severe echovirus 9 infection. The virus was isolated and administered to cultured human beta cells. No viral proliferation was observed, and no beta cell death was induced, while parallel exposure to Coxsackie B virus serotype 3 resulted in viral proliferation and massive beta cell death. Although the viral protein 2C exhibited a sequence similar to that of the beta cell autoantigen glutamic acid decarboxylase (GAD(65)), no cross-reactive T cell responses were detected. The patient did not develop antibodies to GAD(65) either. Absence of evidence for direct cytolytic action or an indirect effect through molecular mimicry with GAD(65) in the present case raises the possibility of another indirect pathway through which enteroviruses can cause diabetes mellitus.

Acute Disease↗
PubMed2000

Endocytosis of low-density lipoprotein by human pancreatic beta cells and uptake in lipid-storing vesicles, which increase with age.

Studies with I(125)-labeled low-density lipoproteins (LDLs) have shown the presence of high-affinity LDL receptors on insulin-producing beta cells but not on neighboring alpha cells. By using gold-labeled lipoproteins, we demonstrate receptor-mediated endocytosis of LDLs and very low-density lipoproteins in rat and human beta cells. Specific for human beta cells is the fusion of LDL-containing endocytotic vesicles with lipid-storing vesicles (LSVs; diameter, 0.6-3.6 microm), which are absent in rodent beta cells. LSVs also occur in human pancreatic alpha and duct cells, but these sequester little gold-labeled LDL. In humans <25 years old, LSVs occupy 1% of the cytoplasmic surface area in beta, alpha, and duct cells. In humans >50 years old, LSV surface area in beta cells (11 +/- 2% of cytoplasmic surface area) is fourfold higher than in alpha and duct cells and 10-fold higher than in beta cells at younger ages (P < 0.001); the mean LSV diameter in these beta cells (1.8 +/- 0.04 microm) is larger than at younger ages (1.1 +/- 0.2 microm; P < 0.005). Oil red O staining on pancreatic sections confirms that neutral lipids accumulate in beta cells of older donors. We conclude that human beta cells can incorporate LDL and very low-density lipoprotein material in LSVs. The marked increase in the LSV area of aging human beta cells raises the question whether it is caused by prolonged exposure to high lipoprotein levels such as occurs in Western populations and whether it is causally related to the higher risk for type 2 diabetes with aging.

Adolescent↗
PubMed1999

Nicotinamide protects human beta cells against chemically-induced necrosis, but not against cytokine-induced apoptosis.

Nicotinamide intervention trials are presently undertaken to prevent Type I (insulin-dependent) diabetes in high risk subjects. They are based on studies in rodents reporting nicotinamide protection against beta-cell injury in vitro and in vivo. This study examines whether nicotinamide can protect human beta cells in vitro. At concentrations (2 and 5 mmol/l) to protect rat beta cells against necrosis by streptozotocin or hydrogen peroxide, nicotinamide prevents hydrogen peroxide-induced necrosis of human beta cells. As with rat beta cells, nicotinamide fails to protect human beta cells against apoptosis induced by a combination of the cytokines interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha. In rat beta cells, nicotinamide (2 to 20 mmol/l) was also found to induce apoptosis, in particular during the days following its protection against necrosis; this cytotoxic effect was not observed with human beta cells. These data demonstrate that nicotinamide can protect human beta cells against radical-induced necrosis, but not against cytokine-induced apoptosis. This effect is not associated with a delayed apoptosis as in rat beta cells.

Animals↗
PubMed1999

Subperiosteal ganglion cyst of the tibia. A communication with the knee demonstrated by delayed arthrography.

We report a patient with a subperiosteal ganglion cyst of the tibia which was imaged by radiography, arthrography, CT and MRI. The images were correlated with the arthroscopic surgical and histological findings. Spiculated formation of periosteal new bone on plain radiographs led to the initial suspicion of a malignant tumour. Demonstration of the cystic nature of the tumour using cross-sectional imaging was important for the precise diagnosis. Communication between the ganglion cyst and the knee was shown by a delayed arthrographic technique, and the presence of this communication was confirmed at arthroscopy and surgically.

Arthrography↗
PubMed1998

Undifferentiated carcinoma of the pancreas: analysis of intermediate filament profile and Ki-ras mutations provides evidence of a ductal origin.

Undifferentiated carcinomas and osteoclast-like giant cell tumours of the pancreas commonly contain foci of neoplastic ductal glands. To test the hypothesis that undifferentiated carcinomas and osteoclast-like giant cell tumours have a ductal origin, the immunocytochemical cytokeratin pattern and the frequency and type of Ki-ras mutations at colon 12 were studied in a series of 17 undifferentiated carcinomas and two osteoclast-like giant cell tumours. The cytokeratin features of undifferentiated carcinomas and osteoclast-like giant cell tumours were compared with those found in 10 ductal adenocarcinomas, 20 acinar cell carcinomas, 25 neuroendocrine tumours, and 15 solid-pseudopapillary tumours. All undifferentiated carcinomas and osteoclast-like giant cell tumours stained with at least one cytokeratin antibody, and 13/19 of them with antibodies against cytokeratins 7, 8, 18, and 19. The latter cytokeratins were expressed in all ductal adenocarcinomas, but only in 15/20 acinar cell carcinomas, 2/25 neuroendocrine tumours, and 1/15 solid-pseudopapillary tumours. In addition to cytokeratin, 15/19 undifferentiated carcinomas/osteoclast-like giant cell tumours were positive for vimentin. Ki-ras mutations at codon 12 were found in 10 undifferentiated carcinomas and one osteoclast-like giant cell tumour from which DNA could be successfully amplified. The Ki-ras mutation patterns were analysed in six tumours and corresponded to those typical of ductal adenocarcinomas. In tumours with ductal and anaplastic components, both components revealed identical mutation patterns. From these findings, it is concluded that both undifferentiated carcinomas and osteoclast-like giant cell tumours belong to the pancreatic tumours that show a ductal phenotype. Since undifferentiated carcinomas and osteoclast-like giant cell tumours share the same cytokeratin and Ki-ras features, they are probably derived from the same cell lineage.

Adenocarcinoma↗
PubMed1998

Multiple focal nodular hyperplasia.

Focal nodular hyperplasia (FNH) is a benign lesion of the liver which usually presents with one or two localizations. We report a patient with history of resection of a biliary cyst, and who had been taking oral contraceptives for the past 18 years, who had multiple localizations of FNH (more than 30 lesions). The largest lesion measured 10.5 x 11 x 12cm. The imaging characteristics of our patient were atypical. A central scar could be demonstrated only in the largest lesion, in an eccentric location. In the other lesions, no scar formations could be detected. Furthermore, imaging characteristics suggested that several of the lesions contained fat. This was confirmed by biopsy. The patient had an associated inflammatory syndrome which could not be otherwise explained. The patient was advised to stop taking the oral contraceptives. Follow-up after 2 years showed that the lesions were unchanged; the inflammatory syndrome persisted. Multiple localizations of FNH are very rare. Sometimes they are associated with malformations in other organs (vascular malformations and neoplasia, mostly of the brain). Often they occur as isolated cases, however. Usually their prognosis seems to be good.

Adult↗
PubMed1997

Cytokines induce deoxyribonucleic acid strand breaks and apoptosis in human pancreatic islet cells.

We have previously observed that a 6-day exposure of human pancreatic islets to a combination of cytokines (interleukin-1beta 50 U/ml + tumour necrosis factor-alpha 1000 U/ml + interferon-gamma 1000 U/ml) severely impairs beta-cell functions. In the present study, we examined whether this condition affects DNA integrity and viability of human islet cells. Cells were studied after 3, 6, and 9 days of cytokine treatment by both single cell gel electrophoresis (the "comet assay," a sensitive method for detection of DNA strand breaks) and by a cytotoxicity assay using the DNA binding dyes Hoechst 33342 and propidium iodide as indices for the number of viable, necrotic, and apoptotic cells. Cytokine treatment for 6 and 9 days resulted in a 50% increase in comet length (P < 0.01 vs. controls), indicating DNA strand breaks, as well as in a significant increase in the number of apoptotic cells (P < 0.02 vs. controls), but not in the number of necrotic cells. The arginine analogs N(G)-nitro-L-arginine and N(G)-monomethyl-L-arginine prevented nitric oxide formation by the cytokines but did not interfere with cytokine-induced DNA strand breaks and apoptosis. The present data suggest that prolonged (6-9 days) exposure of human pancreatic islets to a mixture of cytokines induces DNA strand breaks and cell death by apoptosis. These deleterious effects of cytokines appear to be independent of nitric oxide generation.

Analysis of Variance↗
PubMed1996

Glucose promotes survival of rat pancreatic beta cells by activating synthesis of proteins which suppress a constitutive apoptotic program.

This study demonstrates that rat islet beta cells constitutively express an apoptotic program which is activated when mRNA or protein synthesis is blocked. Apoptotic beta cells were detectable by electron microscopy after treatment with actinomycin D or cycloheximide. With a fluorescence microscopic assay both agents were found to increase the number of apoptotic beta cells dose- and time-dependently, up to 70% after 1 wk of culture; virtually no apoptotic beta cells occurred in control preparations or in conditions leading to primary necrosis. Thus, survival of beta cells seems dependent on synthesis of proteins which suppress an endogenous suicide program. This mechanism explains earlier observed effects of glucose on survival of cultured beta cells. Glucose is known to dose-dependently increase the percentage of beta cells in active biosynthesis and the percentage that survives during culture. It is now demonstrated that the glucose-induced survival of beta cells cultured for 1 wk results from a dose-dependent reduction in the percentage of beta cells dying in apoptosis (49% at 3 mM glucose, 40% at 6 mM, 9% at 10 mM). Thus, intercellular differences in glucose sensitivity appear responsible for the heterogeneity in beta cell sensitivity to apoptotic conditions. These data indicate that glucose promotes survival of beta cells by activating synthesis of proteins which suppress apoptosis. The present model allows for further investigation of the regulation of apoptosis in beta cells and the identification of agents which induce or prevent beta cell death.

Animals↗
PubMed1996

[Fulminant or sub-fulminant hepatocellular failure caused by metastatic invasiveness of the liver: an other cause of hypoxic hepatitis?].

OBJECTIVES: The purpose of this retrospective study was to report a series of 9 new cases of fulminant hepatic failure due to metastatic liver disease and to identify signs to support a theory of hypoxia. METHODS: In these 9 cases and in 38 previously published cases of fulminant or subfulminant liver failure, we looked for clinical (shock, sepsis, and cutaneous signs of circulatory failure), laboratory (marked increase in serum aminotransferases levels) and histological (cell necrosis) parameters compatible with liver hypoxia. RESULTS: Cutaneous signs of circulatory failure or shock were observed in 3 of the 9 cases in this study, and were not due to cardiogenic or septic shock. A marked increase in serum aminotransferases levels, 10 times above the upper limit of normal, was observed in 8 of the 9 cases in the present study and in 23 of 37 cases of the literature. Liver cell necrosis was observed in 6 of the 7 autopsied patients in this series and in 20 of 34 cases in the literature. Generally, liver cell necrosis was more severe than tumor cell necrosis and was related to the degree of sinusoidal involvement by tumoral cells. In one case, hepatic blood flow was decreased despite a high level of cardiac blood flow suggesting impairment of circulation in the liver. CONCLUSIONS: These 9 cases and a review of the literature support the hypothesis of hypoxic liver cell necrosis leading to acute liver failure in cases of metastatic liver disease. However, liver hypoxia cannot explain all the reported cases and was never due to circulatory failure from cardiac or septic causes, but to the sinusoidal involvement by tumor cells.

Adult↗
PubMed1994

Pancreatoblastoma in an adult: its separation from acinar cell carcinoma.

Pancreatoblastomas are rare tumours, which usually occur in childhood. Here we describe a pancreatoblastoma in a 39-year-old woman. The tumour was located in the tail of the pancreas and consisted of cells forming well-differentiated acinar structures and scattered solid components ("squamoid corpuscles"). Immunocytochemically, the acinar components were positive for pancreatic enzymes and pancreatic stone protein, while the cells of the "squamoid corpuscles" lacked these markers. There was no p53 overexpression nor any mutation at codon 12 of the Ki-ras oncogene. The main differential diagnosis of this tumour was acinar cell carcinoma, because both tumours have a number of features in common (scattered solid components, positivity for pancreatic enzymes, lack of p53 overexpression and of Ki-ras mutation). Findings which distinguished the pancreatoblastoma and separated it from acinar cell carcinoma were the negativity of the solid components ("squamoid corpuscles") for neuroendocrine markers and their very weak keratin positivity. As the patient is alive and well 30 months after tumour resection, this pancreatoblastoma also differs in biology from the usual acinar cell carcinoma.

Adult↗
PubMed1993

Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Ki-ras mutation.

In a series of 22 pancreatic acinar cell carcinomas, including two acinar cystadenocarcinomas, cellular differentiation was analyzed by immunocytochemistry and electron microscopy. In addition, overexpression of p53 protein and Ki-ras codon 12 mutation was studied. Four of the 20 noncystic acinar cell carcinomas showed a pure acinar pattern, nine an acinar-solid, and seven a solid pattern. All tumors stained for at least one of the following pancreatic acinar markers: trypsin (21 of 22), lipase (19 of 22), chymotrypsin (13 of 22), phospholipase A2 (nine of 22), and pancreatic stone protein (19 of 22). One-third of the tumors expressed neuroendocrine markers (synaptophysin, eight of 22; chromogranin A, six of 21) and duct cell markers (CA19.9, nine of 21; B72.3, six of 21). Cellular coexpression of trypsin and synaptophysin was demonstrated in one tumor. Electron microscopy revealed zymogen granules (nine of nine). In only one of 16 tumors a Ki-ras mutation at codon 12 was found, whereas in none of 19 tumors could overexpression of p53 protein be demonstrated. The results suggest that acinar cell carcinomas show obvious capacity to differentiate into several directions, but nevertheless constitute an entity different from ductal adenocarcinomas or endocrine tumors.

Adolescent↗
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↗
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↗