Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease

Over the past decade, neurotrophic factors have generated much excitement for their potential as therapy for neurological disorders. In this regard, nerve growth factor (NGF), the founding member of the neurotrophin family, has generated great interest as a potential target for the treatment of Alzheimer's disease (AD). This interest is based on the observation that cholinergic basal forebrain (CBF) neurons which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus undergo selective and severe degeneration in advanced AD and that these neurons are dependent upon NGF and its receptors for their survival. In fact, NGF transduces its effects by binding two classes of cell surface receptors, TrkA and p75(NTR), both of which are produced by CBF neurons. This review focuses on NGF/receptor binding, signal transduction, regulation of specific cellular endpoints, and the potential use of NGF in AD. Alterations in NGF ligand and receptor expression at different stages of AD are summarized. Recent results suggest that cognitive deficits in early AD and mild cognitive impairment (MCI) are not associated with a cholinergic deficit. Thus, the earliest cognitive deficits in AD may involve brain changes other than simply cholinergic system dysfunction. Recent findings indicate an early defect in NGF receptor expression in CBF neurons; therefore treatments aimed at facilitating NGF actions may prove highly beneficial in counteracting the cholinergic dysfunction found in end-stage AD and attenuating the rate of degeneration of these cholinergic neurons.     

Prolonged survival in a patient with sinonasal teratocarcinosarcoma with cranial extension. Case report

Sinonasal teratocarcinosarcoma is a rare malignant neoplasm characterized by the combined histological features of carcinosarcoma and teratoma. The primary symptoms of this tumor are usually nasal obstruction and epistaxis, and a nasal cavity mass is the most common clinical finding. The authors describe an exceptionally rare case in which the patient presented with massive intracranial extension and exhibited confusion as an initial symptom. He subsequently underwent combined radical surgery and radiation therapy and has remained free of disease for 31 months. The surgical approach to the lesion, histological features, and clinical course are detailed.     

Multiple phosphorylation of chicken protein tyrosine phosphatase 1 and human protein tyrosine phosphatase 1B by casein kinase II and p60c-src in vitro

The objectives of this study were to evaluate milk choline as an indicator of choline absorption and to use milk choline to evaluate the efficacy of a rumen-protected choline supplement. In a preliminary 4-wk experiment, two Holstein cows in early lactation were abomasally infused with either 0 or 60 g/d of choline chloride in 2 L of water, which was used as a carrier. Choline infusion increased milk choline secretion from 1.95 to 3.95 g/d during the 2-wk choline infusion period. In Experiment 2, four Holstein cows in early lactation were abomasally infused with 0, 25, 50, and 75 g/d of choline chloride in 2 L of water using a 4 x 4 Latin square design with 1-wk experimental periods. Milk choline secretion was 2.56, 3.62, 3.72, and 3.82 g/d for the respective choline treatments. In Experiment 3, 10 Holstein cows in midlactation were fed either 0 or 50 g/d of choline using an experimental rumen-protected choline supplement during a 2-wk experiment. Milk choline secretion was increased from 2.12 to 2.99 g/d with the supplemental choline. Results of these experiments demonstrated that milk choline is responsive to postruminal choline supply and can be used as a qualitative indicator of choline absorption.     

Conservation of baculovirus inhibitor of apoptosis repeat proteins (BIRPs) in viruses, nematodes, vertebrates and yeasts

The purpose of this study was to compare striatal D2 dopamine receptor occupancy of various typical neuroleptics and clozapine in relation to the occurrence of extrapyramidal side effects (EPS). Forty-four inpatients with schizophrenia, including 12 patients with schizodominant schizoaffective disorder, were evaluated using 123I-iodobenzamide (IBZM) and single photon emission computed tomography. Striatal D2 dopamine receptor occupancy was estimated by use of a striatal/frontal cortex ratio (ST/FC) of IBZM binding. Fourteen patients were neuroleptic-free and served as controls. Six patients were treated with clozapine and 24 patients were treated with various typical neuroleptics. ST/FC ratios in patients taking typical neuroleptics were significantly lower than those who were neuroleptic free or treated with clozapine. Patients with EPS had lower ST/FC ratios than those without EPS. A significant linear relationship between ST/FC ratios and severity of EPS estimated by the Simpson-Angus-Scale was established (r=-0.51, p=0.041).     

Biological impact of small air ions

The thrust of the experimental data presented here is that small air ions are biologically active. There is convincing evidence that both negative and positive ions (i) inhibit growth of bacteria and fungi on solid media; (ii) exert a lethal effect on vegetative forms of bacteria suspended in water when opportunity is provided for contact of cells and ions; and (iii) reduce the viable count of bacterial aerosols. Through physical action, ions of either charge upset the stability of aerolosized bacterial suspensions and, in addition, have a direct lethal effect which is more prominent with negative ions than with positive ions. With regard to the serotonin hypothesis of air ions action, the situation is more complex. The essential fact is that mice and rats display a charge-related metabolic response to air ions and this phenomenon also occurs in humans. Because serotonin is such a potent hormone, the ultimate functional changes incident to air ion action are impressive and account for the signs of symptoms of the sharav syndrome. Alterations in the cumulative mortality rate with three experimental respiratory disease in the mouse also are charge-dependent, positive ions routinely exercising a detrimental effect. Further, in the case of mice infected with influenza virus, ion-deprivation increases the cumulative mortality rate. Since ion depletion is a constant concomitant of modern urban life, one reasonably may speculate about comparable inimical effects on humans.     

Processes to increase the yields of normal serum albumin

By heating in the presence of a stabilizer, albumin can be recovered from Cohn fraction IV-4 and also pyrogen-free from pyrogenic albumin.     

Stereospecific actions of the inhalation anesthetic isoflurane at the GABAA receptor complex

To overcome problems associated with Western blotting of denatured proteins, we have used quantitative immunoelectrophoretic techniques to perform functional analysis of the Neisseria gonorrhoeae common antigen. Using these techniques, we show (a) that Neisseria gonorrhoeae expresses an antigen that is cross-reactive with the common antigen of Pseudomonas aeruginosa and Legionella micdadei and with the GroEl-like protein of Chlamydia, and (b) that this N. gonorrhoeae common antigen has lectin-like activity and can be precipitated with three different sugars immobilized on agarose beads: alpha-D-glucosamine, maltose and fucose.