Intranuclear inclusions

Muscle biopsy with full histochemical and ultrastructural investigation is necessary for the confirmation of a diagnosis of IBM. The inclusions which are the hallmark of this disorder are to be found in three locations (a) basophilic granular inclusions are found at the periphery of vacuoles within the cytoplasm of muscle fibers (b) eosinophilic hyaline inclusions are also found in the cytoplasm but are not associated with vacuoles and (c) intranuclear inclusions consisting of aggregates of filamentous microtubules are found in a variable percentage of muscle nuclei. Inclusions of the first two types are visible at light microscope level, whereas the third type is detectable at the electron microscope level only. Ultrastructural... 

Davies SW, Beardsall K, Turmaine M, DiFiglia M, Aronin N, Bates GP. Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions Lancet 1998 351 131-133. 

Kim TW, Tanzi RE. Neuronal intranuclear inclusions in polyglutamine diseases nuclear weapons or nuclear fallout Neuron 1998 21 657-659. 

Gourfinkel AI, Cancel G, Duyckaerts C, Faucheux B, Hauw JJ, Trottier Y, Brice A, Agid Y, Hirsch EC. Neuronal distribution of intranuclear inclusions in Huntington s disease with adult onset. Neuroreport 1998 9 1823-1826. 

DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N. Aggregation of Huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997 277 1990-1993. 

Lieberman AP, Trojanowski JQ, Leonard DG, Chen KL, Barnett JL, Leverenz JB, Bird TD, Robitaille Y, Malandrini A, Fischbeck KH. Ataxin 1 and ataxin 3 in neuronal intranuclear inclusion disease. Ann Neurol 1999 46 271-273. 

Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997 90 537-548. 

Histopathological evidence of renal damage has been observed in lead-exposed workers. Renal ultrastructure and function were examined in five men with heavy occupational exposure to lead (Cramer et al. 1974). In addition, renal function was evaluated in two men from whom renal biopsies were not obtained. PbB levels ranged from 71 to 138 pg/dL. Renal function tests were normal in all except for a reduced glomerular filtration rate in one worker. Two subjects with relatively short exposure to lead (6 weeks and 8 months) and PbB levels of 89-129 pg/dL had intranuclear inclusions in the proximal tubules. Renal biopsies from workers with longer periods of lead exposure (4-20 years, PbB levels of 71-138 pg/dL) had diffuse interstitial or peritubular fibrosis. Glomeruli were normal in all subjects. 

Histopathological changes were noted in the kidneys of rats administered lead acetate in the drinking water for 76 weeks at lower doses (Roller et al. 1985). These changes, which were observed at a dose of 37 mg/kg/day, a dose much lower than that used by Vyskocil et al. (1989), included necrotic and dilated cortical tubules, tubular protein casts, areas with large nuclei and fibrous connective tissue, and large intranuclear inclusion bodies in the enlarged epithelial cells of the cortex near the cortical-medullary junction. 

Vicente-Ortega V, Martinez-Garcia AF, Cremades-Campos A, et al. 1996. Utrastructural investigation of lead-induced intranuclear inclusion bodies in mice. Ultrastructural Pathol 20 263-273. 

Adult males, age 16 weeks, fed pelleted commercial duck diet for 10 weeks diet formulated to contain 24% lead-contaminated sediment (3400 mg Pb/kg DW sediment = 816 mg Pb/kg DW total diet) 1 of 10 died vs. none in controls survivors had atrophied breast muscles, green staining of feathers around the vent, viscous bile green staining of the gizzard lining, and renal intranuclear inclusion bodies. Blood had 6.1 mg Pb/kg FW, liver had 2.8 mg Pb/kg FW, and feces had 1660 mg Pb/kg DW 61... 

Some deaths. Intranuclear inclusion bodies in cells of kidney proximal convoluted tubules... 

Locke, L.N., G.E. Bagley, and H.D. Irby. 1966. Acid-fast intranuclear inclusion bodies in the kidneys of mallards fed lead shot. Bull. Wildl. Dis. Assoc. 2 127-131. 

Figure 18.10 Characteristic inclusion bodies in neurodegenerative diseases, all labelled with antibodies (except (d)) as indicated, (a) and (b) HD intranuclear inclusion labelled for ubiquitin and huntingtin (cerebral cortex), (c) and (d) AD neuritic plaque labelled with AP (cerebral cortex) and silver stained, (e) and (f) PD, Lewy bodies labelled for ot-synuclein and phosphorylated a-synuclein (substantia nigra), (g) and (h) ALS labelled with ubiquitin and neurofilaments (medulla oblongata). (From Ross and Poirier, 2004. Reproduced by permission of Nature Publishing Group.)...

Floyd, J. A., Hamilton, B. A. 1999. Intranuclear inclusions and the ubiquitin-proteasome pathway digestion of a red herring Neuron 24 765-6. 

Cooper K, Haffajee Z, Taylor L. Comparative analysis of biotin intranuclear inclusions of gestational endometrium using the APAAP, ABC and PAP immunodetection systems. J. Clin. Pathol. 1997 50 153-156. 

HD Huntingtin with poly-glutamin expansion Striatum, basal ganglia, cortex Intranuclear inclusions and cytoplasmic aggregates... 

A broad array of human neurodegenerative diseases share strikingly similar histopathological features, e.g., the presence of insoluble protein deposits, such as the neurofibrillary tangles and neuritic plaques of Alzheimer s disease, the Lewy bodies of Parkinson s disease, and the intranuclear inclusions of Huntington s disease [42]. 

Saudou F, Finkbeiner S, Devys D, Greenberg ME (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. CeU... 

In birds, especially water fowl, lead toxicosis has been reported and lead shot may be found in the gizzard. The birds are generally emaciated with extensive muscle wasting and atrophy of the breast muscles. Changes in the kidneys are primarily renal tubular degeneration or necrosis (with or without intranuclear inclusions) (Locke and Thomas, 1996). Diagnosis is by analytical estimation and... 

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