Broad spectrum of hepatocyte inclusions in humans, animals, and experimental models.

We focus on hepatic inclusions, which are defined as intracellular aggregates of stainable substances. They represent established hallmarks of their respective human disorders, but unlike aggregates found in neurodegenerative disorders are often not well studied. Hepatic inclusions can be subdivided into primary liver aggregates and aggregates found in multiple tissues. The former ones consist of inclusions found in endoplasmic reticulum storage diseases such as α 1-antitrypsin aggregates or ground-glass hepatocytes, p62-containing (Mallory-Denk bodies and intracellular hyaline bodies) and porphyrin-containing inclusions. p62-containing aggregates are not restricted to the liver but are found in multiple other disorders such as Parkinson or Alzheimer disease. Inclusions such as pale bodies or intracellular hyaline bodies are typical for malignant disorders while others (ground-glass hepatocytes and α1-antitrypsin aggregates) are predominantly seen in non-neoplastic tissues. The inclusions, which are not restricted to the liver, are often due to a systemic viral infection, but also due to disruption of glycogen metabolism or systemic inclusion-forming diseases such as polyglutamine disorders or sarcoidosis. Despite their heterogeneity, inclusions share several pathogenic principles such as an imbalance between protein damage/misfolding on one side and repair/degradation on the other side. This is why hepatic aggregates represent a valuable tool to study the aggregation process in general and to improve our understanding of inclusions found in multiple human disorders.

delta-Endotoxin proteins associated with spherical parasporal inclusions of the four Lepidoptera-specific Bacillus thuringiensis strains.

Four Lepidoptera-specific reference strains of Bacillus thuringiensis, belonging to serovars sumiyoshiensis (H3a:3d), fukuokaensis (H3a:3d:3e), darmstadiensis (H10a:10b) and japonensis (H23), which produce spherical parasporal inclusions, were examined for comparative characterization of delta-endotoxins. SDS-PAGE profiles of the alkali-solubilized parasporal inclusions revealed the presence of single major protein bands of 130 kDa in the four strains. Chymotrypsin and trypsin treatment of the proteins gave profiles different from those of the strains HD-1 (serovar kurstaki, H3a:3b:3c) and T84 A1 (serovar sotto, H4a:4b). Also, minor variations were observed in proteolysis profiles among the four strains. The LC50 values of purified parasporal inclusions for the silkworm (Bombyx mori) larvae were 7.35, 6.45, 3.08 and 2.63 micrograms g-1 diet, respectively, showing that their toxicity levels were 5-15 times lower than that of the strain HD-1 (0.49 microgram g-1 diet). Analysis by immunodiffusion and immunoblotting with polyclonal antisera revealed that parasporal inclusion proteins of the four strains are highly related, whereas they shared few or no common antigens with those of the strains HD-1, T84 A1 and Buibui (serovar japonensis).

The development of the osmiophilic inclusion bodies within the granular pneumocyte of chicken lung.

The origin and development of osmiophilic inclusion bodies (OIB) type A of granular pneumocytes were morphologically studied in chicken lungs. The OIB type A were formed by a process of twisting and progressive spiraling of profiles of the rough endoplasmic reticulum (RER). No evidence has been found in favor of a mitochondrial or Golgi-related origin of OIB.

Ultrastructural study of intracytoplasmic deposits in human hepatocellular carcinoma.

Twenty-three cases of human hepatocellular carcinoma were examined electron microscopically, and intracytoplasmic deposits were detected and classified as follow: (1) inclusion bodies such as Mallory bodies, (2) fat droplets, (3) secondary lysosomal changes such as alpha- or beta-glycogen particle accumulations surrounded by a single membrane layer, myelin figure and lipofuscin granules, (4) abnormal changes in organellae such as alpha- or beta-glycogen particle accumulations, the hyperplasia of smooth endoplasmic reticulum, finger prints, glycogen bodies, larger peroxisomes and hypertrophy of bile canaliculus-like structures, (5) degenerative changes in cytoplasm evidenced by debris, focal cytoplasmic degradation and autophagic vacuoles. These intracytoplasmic deposits seem to play important roles in the pathogenesis of hepatocellular carcinoma, but the relation to carcinogenesis is still unclear.

[Crystalline morphology of trihexosylceramide deposits characteristic of Fabry's disease (notably the rheumatic form)]. / Morphologie cristalline des dépôts de trihexosylcéramides caractéristiques de la maladie de Fabry (forme rhumatismale notamment).

This paper deals with the various crystalline aspects of the ceramide trihexoside (CTH) inclusions, in the synovial tissue essentially. A basic classification is proposed and uncommon examples are illustrated. Image processing confirms the membrane-like structure of CTH inclusions and corroborates the proposed classification.

Ultrastructural classification of paracrystalline inclusions in untreated and estrogen treated human Leydig cells.

Ultrastructural examination of untreated and estrogen-treated human testes revealed for the first time five types of paracrystalline inclusions in the cytoplasm of Leydig cells. The distinctions between each type of inclusion were based on longitudinal and cross-sectional ultrastructure. The inclusions were not found in Leydig cells containing Reinke crystals, nor were different types of inclusions found in the cytoplasm of the same cell. One form of inclusion or Reinke crystals were occasionally found in the nucleus. Some Leydig cells with intranuclear inclusions contained the same or a different type of inclusion in the cytoplasm. The present study revealed five types of paracrystalline inclusion in contrast to the one or two types described in previous reports. A possible explanation for this difference is that earlier investigators based their observations on small pieces of tissue obtained from biopsy, while the present data were obtained by studying many regions of each testis. All five types of paracrystalline inclusions were found in relatively normal as well as azoospermic (estrogen-treated) testes.