1989-1990: The Jeremiah

Alan Mixon as ThomasThe Jeremiah;Grayscal

1989-1990: The Jeremiah

From left: Alan Mixon as Thomas and Jen Jones as ConstanceThe Jeremiah;Grayscal

1989-1990: The Jeremiah

Foreground: Alan Mixon as Thomas. Background, from left: James Fletcher as Joe, Jen Jones as Constance, and Carrie Hitchcock as AliceThe Jeremiah;Grayscal

1989-1990: The Jeremiah

From left: Alan Mixon as Thomas and Carrie Hitchcock as AliceThe Jeremiah;Grayscal

Neuropathology provides clues to the pathophysiology of Gaucher disease

To better understand the pathogenesis of brain dysfunction in Gaucher disease (GD), we studied brain pathology in seven subjects with type 1 GD (four also exhibited parkinsonism and dementia), three with type 2 GD and four with type 3 GD. Unique pathologic patterns of disease involving the hippocampal CA2-4 regions and layer 4b of the calcarine cortex were identified. While these findings were common to all three GD phenotypes, the extent of the changes varied depending on the severity of disease. Cerebral cortical layers 3 and 5, hippocampal CA2-4, and layer 4b were involved in all GD patients. Neuronal loss predominated in both type 2 and type 3 patients with progressive myoclonic encephalopathy, whereas patients classified as type 1 GD had only astrogliosis. Adjacent regions and lamina, including hippocampal CA1 and calcarine lamina 4a and 4c were spared of pathology, highlighting the specificity of the vulnerability of selective neurons. Elevated glucocerebrosidase expression by immunohistochemistry was found in CA2-4. Hippocampal ⁴⁵Ca²⁺ uptake autoradiography in rat brain was performed demonstrating that hippocampal CA2-4 neurons, rather than CA1 neurons, were calcium-induced calcium release sensitive (CICR-sensitive). These findings match recent biochemical studies linking elevated glucosylceramide levels to sensitization of CA2-4 RyaR receptors and 300% potentiation of neuronal CICR sensitivity. In two patients with type 1 GD and parkinsonism, numerous synuclein positive inclusions, similar to brainstem-type Lewy bodies found in Parkinson disease, were also found hippocampal CA2-4 neurons. These findings argue for a common cytotoxic mechanism linking aberrant glucocerebrosidase activity, neuronal cytotoxicity, and cytotoxic Lewy body formation in GD

Neuropathology provides clues to the pathophysiology of Gaucher disease

To better understand the pathogenesis of brain dysfunction in Gaucher disease (GD), we studied brain pathology in seven subjects with type 1 GD (four also exhibited parkinsonism and dementia), three with type 2 GD and four with type 3 GD. Unique pathologic patterns of disease involving the hippocampal CA2-4 regions and layer 4b of the calcarine cortex were identified. While these findings were common to all three GD phenotypes, the extent of the changes varied depending on the severity of disease. Cerebral cortical layers 3 and 5, hippocampal CA2-4, and layer 4b were involved in all GD patients. Neuronal loss predominated in both type 2 and type 3 patients with progressive myoclonic encephalopathy, whereas patients classified as type 1 GD had only astrogliosis. Adjacent regions and lamina, including hippocampal CA1 and calcarine lamina 4a and 4c were spared of pathology, highlighting the specificity of the vulnerability of selective neurons. Elevated glucocerebrosidase expression by immunohistochemistry was found in CA2-4. Hippocampal ⁴⁵Ca²⁺ uptake autoradiography in rat brain was performed demonstrating that hippocampal CA2-4 neurons, rather than CA1 neurons, were calcium-induced calcium release sensitive (CICR-sensitive). These findings match recent biochemical studies linking elevated glucosylceramide levels to sensitization of CA2-4 RyaR receptors and 300% potentiation of neuronal CICR sensitivity. In two patients with type 1 GD and parkinsonism, numerous synuclein positive inclusions, similar to brainstem-type Lewy bodies found in Parkinson disease, were also found hippocampal CA2-4 neurons. These findings argue for a common cytotoxic mechanism linking aberrant glucocerebrosidase activity, neuronal cytotoxicity, and cytotoxic Lewy body formation in GD

How Race Affects Dismissals of College Football Coaches

We employ a discrete-time hazard model and a Blinder-decomposition approach to explore the possibility of racial discrimination in the dismissal and retention of college-football coaches by university administrations. A rich data set consisting of 81 institutions over an 11-year period (1990-2000) that contains, in addition to a coach\u27s race, variables on cumulative winning records, annual on-the-field improvements, and pre-/post-season game participation by institutions and their coaches is employed. Our study finds that black coaches, on average, face a dismissal probability that is 9.6 percentage points below that of their nonblack counterparts, ceteris paribus, suggesting that black head coaches may be the beneficiaries of favorable treatment by university administrators. Such a result likely stems from universities\u27 approach to social concerns involving race and gender issues. This finding also fits a construct that considers workplace discrimination as multi-dimensional. For example, black representation in the college football coaching ranks may be disproportionately low, possibly as a result of discrimination. However, once hired, black coaches are given more time to succeed than nonblacks, other things constant