Faculty Bibliography

Lewy bodies (LB) are intraneuronal, cytoplasmic inclusion bodies. They are invariably present in Parkinson's and diffuse LB diseases. Their composition by direct biochemical methods is unknown, although LBs are immunoreactive with a number of antibodies, including anti-ubiquitin and anti-neurofilament antibodies. Familial amyloidosis, Finnish type (FAF), is an autosomal-dominant form of systemic amyloidosis. The authors have isolated and partially sequenced the amyloid. The protein has significant sequence identity with gelsolin, an actin-modulating protein. Rabbit polyclonal antibodies raised to the FAF amyloid not only immunostain the amyloid but also LBs in the cortex and substantia nigra of Parkinson's and diffuse LB disease brains. Immunoreactivity is absorbed by the purified amyloid but is unaffected by ubiquitin. This provides a link between the LB and one of the human amyloidoses, FAF

The present report documents a family with three cases in two successive generations of pigmentary orthochromatic leukodystrophy (POLD). The clinical features of these cases and histochemical and ultrastructural investigations of two of the brains from successive generations are discussed. A review of the familial cases of POLD reported in the literature is also presented. Transmission of these cases was by a dominant inheritance. Onset of the clinical symptoms occurred at 42 to 54 years of age; duration of the disease was from 2-11 years, and death occurred at 45 to 57 years of age. Clinical manifestations of all three cases were severe headaches; bilateral pyramidal, pseudobulbar, cerebellar, and frontal release signs; gait disturbances; euphoria, or apathy; epileptic seizures; and dementia. The neuropathological pattern consists of slight cerebral atrophy, brownish discoloration of the cerebral white matter with demyelination and severe gliosis, sparing the sub-cortical U fibers; presence in the macrophages of lipid pigment granules that are sudanophilic, non metachromatic, and PAS and iron positive. The electron microscopic pattern of the lipid pigment in the macrophages is that of ceroid: electron-dense, membrane-bound intracytoplasmic lysosomes with curvilinear and/or fingerprint profiles

We report a rare occurrence of intraparenchymal plasmacytoma and review the literature. The clonal nature of the neoplasm is demonstrated by immunohistochemical and molecular techniques. The importance of the latter techniques in ruling out other pathological entities is stressed

This report describes a case of symptomatic pituitary hemorrhage into a Rathke's cleft cyst in a 25-year-old woman. The literature on pituitary hemorrhage in nonadenomatous sellar tumors is reviewed

A retrospective review of 16 consecutive patients with pituitary apoplexy treated over a 10-year period is reported. Eight men and 8 women (mean age, 48 years) underwent transsphenoidal decompression after an average duration of symptoms of 19 days. The diagnosis of pituitary apoplexy was made by the sudden onset of headache (88%), nausea (56%), or meningismus (13%), with or without visual disturbances (75%), in the setting of a sellar tumor on computed tomographic or magnetic resonance imaging scans. Thirteen of 16 patients showed significant improvement of symptoms after surgery (average follow-up, 2.5 years). In addition, 5 patients with clinically silent yet extensive pituitary hemorrhage were treated. Although extensive pituitary hemorrhage often produced fulminant apoplexy, it also presented insidiously over many days with few, if any, clinical signs. Rapid diagnosis, endocrine replacement, and transsphenoidal decompression constituted effective therapy. Magnetic resonance imaging (after at least 12 hours of symptoms) was superior to computed tomography in detecting hemorrhage

The storage pigment in neuronal ceroid lipofuscinoses (NCL) has a close similarity to age pigment lipofuscin. We studied immunoreactivity of isolated neuronal pigments from the juvenile form of NCL and aging control, using monoclonal antibodies (mAbs) against amyloid beta-protein. Ultrastructural localization of the immunoreactivity demonstrated that in NCL the epitopes are distributed mainly in curvilinear multilamellar arrays of the storage pigments and less in fingerprint profiles, while in aging control they are more homogeneously distributed on age pigment lipofuscin. The different distribution of the epitopes may reflect some catabolic as well as morphologic differences in lysosomes. A unique 31-kDa polypeptide detected on Western blots in NCL possibly derives from the same precursor, amyloid beta-protein precursor (ABPP). ABPP processing may be aberrant in NCL brains, and this can be detected as a 31-kDa polypeptide reactive with the mAbs

The 200,000-dalton neurofilament subunit (P200) and the 160,000-dalton (P160) and 78,000-dalton (P78) neurofilament subunits were partially purified from bovine brain. Intact neurofilaments were prepared by high-speed and sucrose-zone centrifugation. The crude neurofilament was solubilized in 8 M urea solution containing pyridine, formic acid, and 2-mercaptoethanol. The solubilized neurofilament was purified by carboxymethyl (CM) cellulose column and hydroxylapatite column chromatography. The P200 was purified as separate from P160 and P78, but the P160 and P78 subunits were copurified on CM cellulose, hydroxylapatite, Bio-Gel A150m, and Sephadex G-150 column chromatography. Electron microscopy of these purified neurofilament subunits revealed the P200 subunit as a globular structure, and the P160 and P78 subunits as a rod-shaped structure extending up to 120 nm with a 8- to 12-nm width. In the presence of 200 mM KCl, 15 mM MgCl2, and 1 mM ATP, the purified subunits assembled into long filaments. Under the assembly condition, P160 and P78 subunits elongated up to 500 nm, but the longer filament formation required the presence of P200 subunits. The filaments formed in vitro were of two types: long straight filaments and intertwined knobby-type filaments. From these results, we have suggested that P160 and P78 form the neurofilament backbone structure and P200 facilitates the assembly of the backbone units into longer filaments