Kerneinschl�sse und Amitose

Schiller, Erich

doi:10.1007/bf00541095

Cited by 13 publications

(5 citation statements)

References 8 publications

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“…Nuclear inclusions were first described in light microscopy more than 100 years ago [1][2][3]. Since then they have been detected in many normal and neoplastic tissues [6][7][8].…”

Section: Discussionmentioning

confidence: 99%

“…In 1883 the later Nobel laureate Paul Ehrlich described inclusions in the protoplasma of cells in diabetic patients, which he designated as vacuoles . In the 1940s Schiller et al investigated nuclear inclusions in hepatocytes and noted that their occurrence in the liver was associated with certain cell criteria, such as enlarged nuclei . Until that time, all investigations and observations were limited to the mere description of morphological aspects of nuclear inclusions in light microscopy.…”

Section: Introductionmentioning

confidence: 99%

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Intranuclear inclusions in hepatocellular carcinoma contain autophagy‐associated proteins and correlate with prolonged survival

Schwertheim

Westerwick

Jastrow

et al. 2019

The Journal of Pathology CR

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For decades, intranuclear inclusions in many normal and neoplastic cells have been considered to be mere invaginations of cytoplasm into the nucleus without any notable function or influence on disease. We investigated such inclusions in 75 specimens of hepatocellular carcinoma (HCC). In this context we demonstrate that these inclusions are true inclusions, completely closed and delimited by the nuclear membrane, containing degenerate cell organelles and lysosomal proteins. Moreover, their occurrence was positively associated with patient survival but not with tumour grade or stage. In a standardised area a mean of 124 inclusions per specimen was present in the tumorous liver tissue in contrast to 5 inclusions in the non‐tumorous adjacent section and 89% of all scrutinised HCC showed at least one membrane‐bound nuclear inclusion. Ultrastructural characterisation by transmission electron microscopy revealed degenerative materials such as residues of lysosomes, endoplasmic reticulum and Golgi apparatus within the inclusions. Due to the fact that the content of the inclusions appears to be more condensed than cytoplasm and contains fewer intact cell organelles, we assume that they are not mere invaginations of cytoplasm. Three dimensional (3D) reconstruction of isolated and immunofluorescence stained nuclei showed that the inclusions are completely located within the nucleus without any connection to the cytoplasm. The limiting membrane of the inclusions contained lamin B suggesting nuclear membrane origin. The content of the inclusions stained for the autophagy‐associated proteins p62, ubiquitin, LC3B, cathepsin B and cathepsin D. Triple immunofluorescence staining followed by 3D reconstruction revealed co‐localisation of p62, ubiquitin and LC3B in the same inclusion. Our observations uncover that these inclusions are real inclusions completely surrounded by the nucleus. We propose that the presence of autophagy‐associated proteins and proteases within the inclusions contribute to beneficial survival.

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“…Nuclear inclusions were first described in light microscopy more than 100 years ago [1][2][3]. Since then they have been detected in many normal and neoplastic tissues [6][7][8].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intranuclear inclusions in hepatocellular carcinoma contain autophagy‐associated proteins and correlate with prolonged survival

Schwertheim

Westerwick

Jastrow

et al. 2019

The Journal of Pathology CR

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“…Altmann (3) has presented structural forms of the nucleus said to represent a functional cycle ("Funktionsformwechsel") of the nucleus of the exocrine cells of the mouse pancreas, which can be correlated with a "functional cycle" of the cytoplasm. Schiller thinks that the extrusion of nuclear material is the beginning of amitotic cell division (43).…”

Section: The Incidence Of Nuclear "Blebbing"--manymentioning

confidence: 99%

Electron Microscope Studies of Nuclear Extrusions in Pancreatic Acinar Cells of the Rat

Clark

1960

The Journal of Cell Biology

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This paper describes "blebs" protruding from the surface of the nucleus into the cytoplasm. The "blebs" are separated from the cytoplasm by 2 membranes which are continuous with the outer and inner nuclear membranes. The "blebs" contain 3 structurally distinct substances. Two of these substances (13 and 7 substances) are similar to extranucleolar karyoplasm and nucleolar material. The other substance (a substance) is present in every "bleb," but it cannot be readily compared to a recognizable nuclear structure. Cytoplasmic vesicles are described that are apparently different from the Golgi vesicles or the vesicular component of the ergastoplasm. It is suggested that these vesicles may be of nuclear "bleb" origin.A dark karyoplasmic zone extending from the region of the nucleolus into the nuclear "bleb" is shown. This zone may be similar in some respects to the preformed pathway ("Leitbahn") described by Altmann (3) and Hertl (28) and could reflect movement of nuclear material from the nucleolar region into the cytoplasm.The "blebs" are thought to be homologous to structures described by many light microscopists, but they are considerably larger than the nuclear "blebs" described previously by electron microscopists.The transfer of microscopically visible material from the nucleus into the cytoplasm has been described from time to time for many years and has been suggested as one of the possible mechanisms whereby the interphase nucleus could bring its influence to bear on cytoplasmic function. Observations described in this paper of vesicular structures, apparently budding out from the nucleus into the cytoplasm, provide further evidence of possible transfer of nuclear material into the cytoplasm. The size and morphology of these nuclear extrusions indicate that they correspond to the structures described by m a n y light microscopists (3-5, 7, 8, 21, 27, 28, 30, 31, 33, 34, 39, 43, 51), but the extrusions seem to be much larger than those described previously by electron microscopists (1,2,6,17,23,24,37,53).

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“…The existence of intranuclear inclusions (NI) in many normal and neoplastic tissues has been known for a long time, in diabetic patients [1] in hepatocytes [2, 3] and particularly in thyroid carcinoma [4, 5], where its presence is one of the diagnostic criteria for papillary thyroid carcinoma [4, 5]. Ultrastructural studies of hepatocytes revealed that the inclusions contained cytoplasmic structures, often with degenerative changes.…”

Section: Introductionmentioning

confidence: 99%

New insights into intranuclear inclusions in thyroid carcinoma: Association with autophagy and with BRAFV600E mutation

et al. 2019

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BackgroundIntranuclear inclusions (NI) in normal and neoplastic tissues have been known for years, representing one of the diagnostic criteria for papillary thyroid carcinoma (PTC). BRAF activation is involved among others in autophagy. NI in hepatocellular carcinoma contain autophagy-associated proteins. Our aim was to clarify if NI in thyroid carcinoma (TC) have a biological function.MethodsNI in 107 paraffin-embedded specimens of TC including all major subtypes were analyzed. We considered an inclusion as positive if it was delimited by a lamin AC (nuclear membrane marker) stained intact membrane and completely closed. Transmission electron microscopy (TEM), immunohistochemistry (IHC), immunofluorescence (IF) and 3D reconstruction were performed to investigate content and shape of NI; BRAFV600E mutation was analyzed by next generation sequencing.ResultsIn 29% of the TCs at least one lamin AC positive intranuclear inclusion was detected; most frequently (76%) in PTCs. TEM analyses revealed degenerated organelles and heterolysosomes within such NI; 3D reconstruction of IF stained nuclei confirmed complete closure by the nuclear membrane without any contact to the cytoplasm. NI were positively stained for the autophagy-associated proteins LC3B, ubiquitin, cathepsin D, p62/sequestosome1 and cathepsin B in 14–29% of the cases. Double-IF revealed co-localization of LC3B & ubiquitin, p62 & ubiquitin and LC3B & p62 in the same NI. BRAFV600E mutation, exclusively detected in PTCs, was significantly associated with the number of NI/PTC (p = 0.042) and with immunoreactivity for autophagy-associated proteins in the NI (p≤0.035). BRAF-IHC revealed that some of these BRAF-positive thyrocytes contained mutant BRAF in their NI co-localized with autophagy-associated proteins.ConclusionsNI are completely delimited by nuclear membrane in TC. The presence of autophagy-associated proteins within the NI together with degenerated organelles and lysosomal proteases suggests their involvement in autophagy and proteolysis. Whether and how BRAFV600E protein is degraded in NI needs further investigation.

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Kerneinschl�sse und Amitose

Cited by 13 publications

References 8 publications

Intranuclear inclusions in hepatocellular carcinoma contain autophagy‐associated proteins and correlate with prolonged survival

Intranuclear inclusions in hepatocellular carcinoma contain autophagy‐associated proteins and correlate with prolonged survival

Electron Microscope Studies of Nuclear Extrusions in Pancreatic Acinar Cells of the Rat

New insights into intranuclear inclusions in thyroid carcinoma: Association with autophagy and with BRAFV600E mutation

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