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  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  27. Deutscher Krebskongress; 20060322-20060326; Berlin; DOCOP487 /20060320/
    Publication Date: 2006-04-21
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 377 (1978), S. 157-174 
    ISSN: 1432-2307
    Keywords: Pancreatic diabetes ; Endocrine pancreas ; Islet composition ; Immunocytochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The endocrine pancreatic tissue from patients with severe primary chronic pancreatitis (n=6), secondary chronic pancreatitis due to duct obstruction by carcinoma (n=6) and non-diabetic, non-pancreatitic controls (n=4) was studied qualitatively and quantitatively using specific immunocytochemistry and electron microscopy. Grouping of variously sized islets in the sclerotic tissue (sclerosis islets), islet neoformation by ductuloinsular proliferation, and intrainsular fibrosis were the main qualitative findings. Immunocytochemical quantitation of the distribution of insulin (B), glucagon (A), somatostatin (D) and pancreatic polypeptide (PP) producing cells revealed a significant relative increase in the number of A cells and a decrease in the number of B cells of the sclerosis islets in primary chronic pancreatitis (B-44.1±9.3%:A-38.3±2.4%:D-8.6±5.1%:PP-4.6±4.1%) as well as in secondary chronic pancreatitis (B-38.0±14.3%:A-38.4±19.0%:D-9.1±5.8%:PP-14.5±23.4%) compared with controls (B-71.1±8.1%:A-24.3±5.5%:D-8.0±2.8%:PP-0.5±0.4%). The number of PP cells was significantly increased in primary chronic pancreatitis only. It is suggested that scarring of the exocrine pancreas affects islet composition, probably by impairment of the local circulation and of glucose diffusion, thus leading to reduction of the number and glucose sensitivity of B cells. The hyperplasia of A and PP cells appears to be a secondary phenomenon due to the loss of B cells.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 379 (1978), S. 203-217 
    ISSN: 1432-2307
    Keywords: B cell calcium in vitro ; Calcium ultracytochemistry ; Biphasic insulin secretion ; Glucose stimulation ; Cyproheptadine inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using the ultracytochemical pyroantimonate technique different patterns of calcium containing precipitates were found in the B cells of the isolated perfused rat pancreas under conditions of stimulated and inhibited insulin secretion. The calcium specificity of the ultracytochemical method was assessed by perfusion with a EGTA containing calcium-free medium, which markedly reduced the extent of precipitation. Perfusion with 20 mM D-glucose over a period of 30 min resulted in calcium distribution patterns which could be related to the biphasic insulin release. The calcium patterns differed significantly in their quality and quantitative morphometry from those after 5 mM D-glucose or cyproheptadine (CPH) perfusion (20 mM D-glucose plus 0.1 mM CPH). After 3–5 min of 20 mM glucose perfusion there was an increased calcium precipitation along the inner side of the B cell membranes. After 20–30 min an additional increase in precipitation was found in the cytoplasmic matrix and in the secretory granules. B cells in a CPH-inhibited state of secretion and also after perfusion with 5 mM glucose lacked these findings. The data suggest that an increase in the membrane associated calcium may induce the first phase of insulin secretion by triggering the exocytosis of peripheral granules, while the cytoplasmic calcium may be involved in long term regulation of insulin release.
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  • 4
    ISSN: 1432-2307
    Keywords: Oral carcinoma ; Squamous cell carcinoma ; Cytostatic therapy ; Bleomycin ; Macrophages ; Giant cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei Bleomycin-Therapie von verhornenden Plattenepithelcarcinomen werden diese unter zunehmender Verhornung devitalisiert, während einfache Tumornekrosen eine geringere Rolle spielen. Dabei findet sich eine ausgedehnte resorptive, granulomatöse Entzündung mit Makrophagen und schließlich eine bindegewebige Organisation. Im Randbereich der verhornenden Tumorareale treten zahlreiche mehrkernige Riesenzellen auf. Die Natur dieser Riesenzellen war bisher umstritten. Die enzymhistochemischen, elektronenmikroskopischen und ultrahistochemischen Untersuchungen an 3 Fällen mit fortgeschrittenen Careinomen der Mundhöhle zeigen, daß die unter der Bleomycinbehandlung auftretenden Riesenzellen keine Tumorriesenzellen, sondern durch Verschmelzung von einkernigen (monocytogenen) Makrophagen entstehende mehrkernige Makrophagen sind. Dabei ergeben sich Hinweise für eine funktionelle Genese der Riesenzellen. Eine zusätzliche immunologische Funktion der Makrophagen und der Riesenzellen ist möglich und wird durch die häufige Assoziation von Riesenzellen mit Lymphocyten nahegelegt. Die Bedeutung dieser Tatsache für eine Bewertung der Bleomycinwirkung und für den therapeutischen Einsatz des Bleomycins wird diskutiert.
    Notes: Summary During treatment of keratinizing squamous cell carcinomas with bleomycin tumor cells are devitalized by keratinization, while simple necrosis plays a minor role. Connected with this process is a marked resorptive granulomatous inflammation with numerous macrophages which is followed by a fibrous organization. In the border region of the keratinized tumor areas many multinucleated giant cells appear. The nature of these giant cells was the subject of controversy. Enzyme histochemical, electronmicroscopic, and ultrahistochemical investigations in three cases of advanced sqnamous cell carcinoma of the oral cavity prove that the giant cells which are formed during bleomycin treatment are not multinucleated tumor cells, but multinucleated macrophages. The enzymatic pattern is similar to macrophages with a high content of acid phosphatase and aminopeptidase. The ultrastructure of the giant cells is characterized by lysosomes with acid phosphatase activity, pinocytotic vesicles, and cytoplasmic projections on the cell surface with signs of macroendocytosis. The tumor cells show an epithelial differentiation with desmosomes, tonofibrils, and keratohyaline granula. The giant cells are formed by fusion of mononucleated (monocytogenic) macrophages. The fusions seem to be related to the functional status of the cells. It is possible, that the macrophages and the giant cells have an additional immunologic function. This is suggested by the frequent association of giant cells with lymphocytes. The importance of these facts for the evaluation of the action of bleomycin and the consequences for its therapeutic use are discussed. A combination with methods causing a dedifferentiation of the tumor or suppression of the immunologic defense seems to be problematic.
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  • 5
    ISSN: 1432-2307
    Keywords: Pancreatic duct proliferations ; Normal pancreas ; Pancreatic carcinoma ; Chronic pancreatitis ; Pancreatic carcinogenesis in man and animals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 21 patients who had undergone total pancreatectomy for pancreatic head carcinoma, the uninvolved pancreas was examined with regard to the type, incidence and regional distribution of duct epithelial proliferation. The results were compared with those in 37 operative specimens from patients with chronic pancreatitis, in 46 normal pancreases from autopsies and with findings in experimental pancreatic carcinogenesis. While the incidence of squamous metaplasia and non-papillary epithelial hypertrophy varied little in the different groups, papillary epithelial hyperplasia was found three times more often in cases of carcinoma, with associated mild duct obstruction. Atypical epithelial proliferation was only detected in the vicinity of carcinomas. Unequivocal transition from papillary hyperplasia to atypical proliferation was not observed. In hamsters treated with dihydroxy-di-n-propylnitrosamine (DHPN) for induction of pancreatic duct carcinomas, the early duct lesions closely resembled atypical epithelial proliferation of human pancreas. It is concluded that (1) papillary epithelial hyperplasia is probably only indicative of early duct obstruction and/or a general neoplastic stimulus, (2) intraductal epithelial proliferation with atypia is a true precursor of duct carcinoma, and (3) chronic pancreatitis lacks atypical duct lesions.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 387 (1980), S. 319-331 
    ISSN: 1432-2307
    Keywords: Endocrine pancreas ; PP cells ; Immunocytochemistry ; Distribution ; Normal pancreas ; Chronic pancreatitis ; Pancreatic carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The endocrine pancreatic tissue from 13 patients with severe chronic pancreatitis, 5 patients with pancreatic duct carcinoma and 4 non-diseased pancreases was analysed by immunocytochemistry and morphometry. The controls revealed two distinct islet types with different regional distribution. The lower dorsal part of the pancreatic head contained islets with irregular outlines and a high number of PP cells (PP-cells 60.4±4.1%; B-cells 29.4±4.6%; A-cells 7.4±1.5%; D-cells 2.8±0.6%). The other parts of the pancreas contained compact islets with only a few PP cells (PP-cells 1.0±0.4%; B-cells 69.3±3.0%; A-cells 24.1±2.1%; D-cells 5.8±0.5%). In chronic pancreatitis the sclerotic tissue of the body and the tail region contained compact islets with altered cell inter-relationships when compared with controls. While the number of B-cells was diminished (48.5%), A and PP cells appeared to be increased in number (42.7 and 4.1%, respectively). Furthermore, ductulo-insular proliferations were conspicuous (nesidioblastosis) with budding-off of small endocrine cell clusters made up predominantly of A and PP cells. In 3 patients with pancreatic carcinoma increased numbers of PP cells and of A cells were found along the advancing edge of the carcinoma. The data emphasize the necessity of taking into consideration regional PP cell distribution in each case in which an increase of PP cells is observed. True hyperplasia is found in chronic pancreatitis and, focally, in some cases with pancreatic carcinoma.
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  • 7
    ISSN: 1432-2307
    Keywords: Glucagonomas ; Morphological features ; Immunocytochemistry ; Review of literature ; Classification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In five patients single or multiple glucagonomas were characterized by immunocytochemistry. Two large single glucagonomas were associated with the glucagonoma syndrome, which completely dissappeared after removal of the tumours. The morphologic findings in these patients are compared with 48 others collected from literature. In the other three patients, the glucagonomas were not associated with a clinical syndrome and were detected by chance (one accompanying an insulinoma; the other in pancreases of patients suffering from multiple endocrine neoplasia I; MEN I). These tumours appeared by their histological, immunocytochemical and ultrastructural features better organized than the glucagonomas with syndrome. Glucagonomas not producing a syndrome can be classified into (a) solitary, often malignant endocrine pancreatic tumours, (b) glucagonomas associated with insulinomas and other tumours, (c) multiple glucagonomas in MEN I and (d) single microglucagonomas in elderly patients. It is emphasized that only immunohistology allows clear identification of these tumours as glucagonomas.
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  • 8
    ISSN: 1432-2307
    Keywords: Inhibition of insulin secretion ; Diazoxide ; Diphenylhydantoin ; B cell morphology ; Crinophagy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The action of diazoxide, an antidiuretic agent, and diphenylhydantoin, an antiepileptic (DPH), both with strong hyperglycemic side effects on the pancreatic B cells, was examined by electron microscopy and cytochemistry, with the following findings. 1. Effects on secretory apparatus: the severe hyperglycemic syndrome following a single injection of diazoxide (200 mg/kg) or DPH (150 mg/kg) did not change the granularity of the B cells. Ultrastructurally a marked increase of lysosomal digestion of secretory granules (crinophagy) was observed in almost all B cells. Crinophagy may be regarded as a result of an impaired discharge of secretory granules during simultaneous maintenance of biosynthesis. It is also possible that changes of the electrophysical properties of the granule surfaces may play an additional role in crinophagy. 2. Effect on synthesizing apparatus: in B cells subtotally degranulated by the injection of anti-insulin serum (AIS), regranulation occurred more rapidly after the additional administration of diazoxide or DPH than without these compounds. This fact may imply that, under the hyperglycemic conditions tested, diazoxide or DPH have no effect on the synthesizing capacity of the B cells.
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  • 9
    ISSN: 1432-0428
    Keywords: Mouse pancreatic islets ; β-cells ; stimulation anti-insulin serum ; diabetic syndrome ; enzymehisto-chemical studies ; α-glycerophosphate oxydase ; acid phos-phatase ; glucose-6-phosphate dehydrogenase ; glucose-6-phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On a procédé à l'examen histochimique enzymatique d'îlots de Langerhans sur des souris ayant un syndrome diabétique après injection unique, ou répétée, de sérum anti-insuline, et on les a comparés avec des résultats normaux. Les variations de l'activité des enzymes des cellules-B se sont trouvées en accord avec les résultats histopathologiques de dégranulation importante et de variations hypersécrétoires des cellules-B. L'α-glycérophosphate-oxydase (GPOX) a montré la diminution d'activité la plus sensible et la plus forte. Par contre la diminution de l'activité de la phosphatase acide (ACPase) était moins forte. La glucose-6-phosphatedéshydrogénase (G-6-P-DH) a accusé une activité de même intensité que dans un cas normal. La glucose-6-phosphatase (G-6-Pase) fut le seul enzyme à faire preuve d'une accroissement d'activité. Les activités de la cytochrome-oxydase (CCOX), de la lactico-déshydrogénase (LDH), de la succino-déshydrogénase (SDH), de la phosphatase alcaline (AP), ainsi que de l'adénosine-triphosphatase (ATPase) sont restées sans changement. — Le rôle du cycle du pentose phosphate (enzyme indicateur: G-6-P-DH), du cycle du glycérophosphate (enzyme indicateur: GPOX) et de la phosphorylation du glucose (enzyme indicateur G-6-Pase) est discuté en ce qui concerne le mécanisme de synthèse et de libération de l'insuline.
    Abstract: Zusammenfassung Es wurden enzymhistochemische Untersuchungen an den Langerhansschen Inseln von Mäusen mit einem diabetischen Syndrom nach einmaliger und wiederholter Injektion von Anti-Insulin-Serum durchgeführt und mit Normalbefunden verglichen. Analog zu den pathohistologischen Befunden einer starken Degranulierung und hypersekretorischer Alterationen der B-Zellen fanden sich Aktivitätssteigerungen bei einigen Enzymen im Bereich der Inseln. — Die empfindlichste und stärkste Aktivitätsminderung ließ die α-Glycerophosphatase (GPOX) erkennen. Weniger stark war die Aktivitätsabnahme der sauren Phosphatase (SP). Eine gleichstarke Aktivität wie im Normalfall wies die Glucose-6-Phosphat Dehydrogenase (G-6-P-DH) auf. Als einziges Enzym zeigte die Glucose-6-Phosphatase (G-6-Pase) eine Aktivitätssteigerung. Die Aktivität der Cytochromoxydase (CCOX), Lactat-Dehydrogenase (LDH), Succino-Dehydrogenase (SDH), alkalischen Phosphatase (AP) und Adenosintriphosphatase (ATPase) blieb unverändert. Die Befunde werden im Zusammenhang mit den hypothetischen Beziehungen des Pentosephosphatcyclus (Indikatorenzym: G-6-P-DH), des Glycerophosphatcyclus (Indikatorenzym: GPOX) und der Glucosephosphorylierung (Indikatorenzym: G-6-Pase) zur Insulinsynthese und -Sekretion diskutiert.
    Notes: Summary Islets of Langerhans in white mice with a diabetic syndrome after single and repeated injections of anti-insulin serum were studied by enzymehistochemical methods and compared with controls. Changes in activity of some enzymes were noted in the islet area in accordance with the histopathological findings of severe degranulation and hypersecretory changes of the beta cells. — The α-glycerophosphate oxidase (GPOX) showed the most sensitive and severe decrease of activity whereas the acid phosphatase (ACPase) was only slightly decreased. Compared with the enzyme activity in normal mice, no significant changes of glucose-6-phosphate dehydrogenase (G-6-PD) could be observed. The only enzyme showing an increased activity was the glucose-6-phosphatase (G-6-Pase). The studies of the cytochrome oxidase (CCOX), lactic dehydrogenase (LDH), succinic dehydrogenase (SDH), acid phosphatase (ACPase), alkaline phosphatase (APase) and adenosine triphosphatase (ATPase) revealed no alterations of the enzyme patterns under these experimental conditions. The findings are discussed with regard to the hypothetical relations between the pentose phosphate shunt (indicator enzyme: G-6-PD), the glycerophosphate cycle (indicator enzyme: GPOX) and the phosphorylation of glucose (indicator enzyme: G-6-Pase) to insulin synthesis and release.
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  • 10
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Ein rezidiviertes und metastasiertes Hämangioperizytom meningealen Ursprungs führte nach 10jähriger Krankheitsdauer terminal bei einem 40jährigen Patienten zu einem Hypoglykämiesyndrom. Das Gesamtgewicht der Tumoren betrug 1800 g. Elektronenmikroskopisch fanden sich organellenreiche Tumorzellen mit einem stark entwickelten Ergastoplasma, prominenten Golgi-Komplexen, umgeben von vielen Mikrovesikeln, runde bis ovale elektronendichte Körper sowie feine Fibrillenstrukturen. Perikapillär und interzellulär war reichlich Basalmembran-ähnliches Material abgelagert. Auf Grund dieser strukturellen Merkmale einer ausgeprägten Syntheseleistung wird ein erhöhter Glucosebedarf der Tumorzellen als pathogenetisch wichtiger Faktor bei der Entstehung der Hypoglykämie angenommen. Die Frage nach der Sekretion einer tumoreigenen Substanz, bei der es sich um den vermuteten Inhibitor der hepatischen Gluconeogenese und/oder Glycogenolyse handeln könnte, kann anhand der Tumorfeinstruktur nicht eindeutig beantwortet werden. Typische Granula wie bei polypeptidhormon-sezernierenden Zellen wurden nicht beobachtet. Die Möglichkeit, daß die nachgewiesenen elektronendichten Körper atypische Sekretgranula repräsentieren, wird diskutiert.
    Notes: Summary A recurred and metastasized hemangiopericytoma of menigeal origin caused a terminal hypoglycemia syndrome in a 40 year old man. The disease had been observed over a period of 10 years. The total weight of the tumour metastases was 1800 g. Electron microscopical examination of the tumour cells revealed, in particular, a markedly developed ergastoplasm, prominent Golgi complexes surrounded by many microvesicles, round to ovoid electron dense bodies and fine fibrillar structures. Furthermore, large deposits of basement membrane-resembling material were found in the pericapillary and intercellular spaces. On the basis of the structural characteristics which indicate distinct synthesizing capacity of the cells, an excessive glucose consumption by the tumour is suggested to be an important factor in the pathogenesis of tumour hypoglycemia. The question whether the ultrastructure of the tumour also exhibits secretory processes, which may be related to the release of a presumed inhibitor of hepatic gluconeogenesis and/or glycogenolysis, remains open. Typical granules as in polypeptide hormon secreting cells were not observed. The possibility that the demonstrated electron dense membrane limited bodies represent atypical secretory granules is discussed.
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