Incidence of autoantibodies in cancer patients

A review of the incidence of autoantibodies to normal tissue constituents in 250 patients with malignant disease has shown positive tests in 15% compared with 24% in patients with general non-neoplastic disorders and 8% in normal blood donors. In patients with lymphoma or leukaemia, the incidence of anti-smooth muscle antibodies was 15% compared with 4% in the control population; there was no increase in the incidence of anti-smooth muscle antibodies in patients with other malignant conditions. The incidence of anti-smooth muscle antibody in 4000 sera submitted for the investigation of possible autoimmune disorders is also reviewed.     

The identification and characterization of excitotoxic nerve-endings in Alzheimer disease

Regionally specific neuronal loss is a distinguishing feature of Alzheimer disease (AD). Excitotoxicity is a mechanism commonly invoked to explain this. We review the accumulating evidence for such a hypothesis, particularly the altered expression and pharmacology of glutamate receptors and transporters in pathologically susceptible regions of the AD brain. Loss of neurons would be expected to lead to the retrograde degeneration of their afferents, which should be reflected in a loss of presynaptic markers such as synaptophysin. We discuss the possibility that neurons may be destroyed locally, but that glutamatergic presynaptic terminals may remain, or even re-proliferate. The reduced glutamate uptake site density in AD brain may signify a loss of the transporters on otherwise intact terminals, rather than the loss of glutamatergic afferents. Neuronal death may follow if cells are exposed to excessive amounts of glutamate; the loss of transporters from functioning, but defective, glutamate terminals would mean they could continue to release glutamate to exacerbate excitotoxicity. We discuss experimental methods to quantitate synapses, which are crucial for deciding between the various possibilities.     

Ätiologie und Pathogenese

Ohne Zusammenfassung     

Central neurocytoma.

One case of central neurocytoma is presented. A review of the literature suggests that the condition is more common than previously recognised. The pathological features are discussed and the role of surgery and radiotherapy in the management of the condition is discussed.     

Reizwirkungen

Ohne Zusammenfassung     

Upregulation of beta-catenin levels in superior frontal cortex of chronic alcoholics

Background: Chronic and excessive alcohol misuse results in neuroadaptive changes in the brain. The complex nature of behavioral, psychological, emotional, and neuropathological characteristics associated with alcoholism is likely a reflection of the network of proteins that are affected by alcohol‐induced gene expression patterns in specific brain regions. At the molecular level, however, knowledge remains limited regarding alterations in protein expression levels affected by chronic alcohol abuse. Thus, novel techniques that allow a comprehensive assessment of this complexity will enable the simultaneous assessment of changes across a group of proteins in the relevant neural circuitry. Methods: A proteomics analysis was performed using antibody microarrays to determine differential protein levels in superior frontal cortices between chronic alcoholics and age‐ and gender‐matched control subjects. Seventeen proteins related to the catenin signaling pathway were analyzed, including α‐, β‐, and δ‐catenins, their upstream activators cadherin‐3 (type I cadherin) and cadherin‐5 (type II cadherin), and 5 cytoplasmic regulators c‐Src, CK1ε, GSK‐3β, PP2A‐Cα, and APC, as well as the nuclear complex partner of β‐catenin CBP and 2 downstream genes Myc and cyclin D1. ILK, G_α1, G_β1, and G_β2, which are activity regulators of GSK‐3β, were also analyzed. Results: Both α‐ and β‐catenin showed significantly increased levels, while δ‐catenin did not change significantly, in chronic alcoholics. In addition, the level of the β‐catenin downstream gene product Myc was significantly increased. Average levels of the catenin regulators c‐Src, CK1ε, and APC were also increased in chronic alcoholics, but the changes were not statistically significant. Conclusion: Chronic and excessive alcohol consumption leads to an upregulation of α‐ and β‐catenin levels, which in turn increase downstream gene expressions such as Myc that is controlled by β‐catenin signaling. This study showed that the β‐catenin signal transduction pathway was upregulated by chronic alcohol abuse, and prompts further investigation of mechanisms underlying the upregulation of α‐ and β‐catenins in alcoholism, which may have considerable pathogenic and therapeutic relevance.