No abstract

The peripheral anionic site of acetylcholinesterase lies at the entrance to the active site gorge. It is composed of five residues (Tyr 70, Asp 72, Tyr 121, Trp 279 and Tyr 334; Torpedo numbering); associated with it are a number of surface loops, conferring a high degree of conformational flexibility on the area. The site is involved in the allosteric modulation of catalysis at the active centre and is the target of various anti-cholinesterases. It is also implicated in a number of non-classical functions, in particular, amyloid deposition, cell adhesion and neurite outgrowth. A number of peptide and protein ligands for the site have been identified. In this review, the structure and multiple functions of the peripheral anionic site are discussed, together with its potential as a target in rational drug design for the development of novel and improved inhibitors and of therapeutics for the treatment of neural cancers, nerve regeneration and neurodegenerative disorders such as Alzheimer's disease.

Chronic cervical lymphadenopathy is a common clinical problem frequently requiring surgical biopsy. To evaluate the characteristics of surgically excised cervical lymph nodes (LN) in children in a developing country, we studied 1,332 children less than 15 years old (1,877 surgically removed cervical LNs) over a 23-year period (1976-1999). Indications for biopsy included failure to respond to antibiotic therapy, rapid increase in size, hard, matted LNs in the preauricular, supraclavicular, and posterior triangle of the neck, and difficulty in diagnosis. Clinical and pathological characteristics investigated included age, malignancy, and granulomatous disease such as tuberculosis (tbc). The mean age was 7 years (tbc 5.8/neoplastic disease 8.5 years). Twenty LNs (1.5%) were histologically normal. There were 637 (47.8%) with nonspecific reactive lymphoid hyperplasia and 484 with chronic granulomatous changes (36.3%). Tuberculous lymphadenitis was confirmed in 332 of these (25%). In 181 (54.5%) Mycobacterium tuberculosis was cultured and a further 149 had acid-fast bacilli. Other granulomatous diseases identified included sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfmann disease) (3), syphilis (4), yaws (2), and toxoplasmosis (1). No mycobacteria other than M. tuberculosis were encountered. More than two-thirds (108) of 154 patients with neoplastic LN involvement had a lymphoma; in a further 10 lymphadenopathy was associated with leukemia. Pyogenic organisms were identified in 32, and 5 were positive for human immunodeficiency virus, 1 of whom had Kaposi's sarcoma. A second pathology was identified in 18 of the 637 cases of reactive lymphoid hyperplasia (3 with tuberculosis); in 15 (1.3%) a diagnosis of lymphoma was made from other sites (pleural fluid, etc.) within 6 months of initial biopsy. This represents a diagnostically difficult subgroup requiring further investigation. Chronic lymphadenopathy in children in developing countries has a high incidence of infective causes, including a significant incidence of M. tuberculosis. The incidence of serious pathology in more than one-half of the cervical LNs examined justifies aggressive surgical investigation.

No abstract