Relationship between transmitter release and presynaptic calcium influx when calcium enters through discrete channels.

We have used a three-dimensional diffusion model of calcium entering the presynaptic nerve terminal through discrete channels to simulate experiments relating transmitter release to presynaptic calcium current. The relationship will be less than linear, or will curve downward, if calcium channels are well separated. It will resemble a power-law function with exponent less than the cooperativity of calcium action if channels are clustered closer together. Large presynaptic depolarizations elicit more release than small depolarizations admitting the same calcium influx. This occurs because large pulses open more channels near each other, with the result that the calcium concentration near release sites is greater, due to overlap of calcium diffusing from adjacent channels.     

Inhibin and renin in follicular fluids of patients with one or two ovaries stimulated with a GnRH agonist and gonadotrophins

Follicular fluids from eight patients with one ovary and from ten patients with two ovaries were investigated for bioactive inhibin, total renin, oestradiol (E2) and progesterone (P4) concentrations. Four follicular fluids were pooled per patient before assessment. All women had been stimulated similarly using a protocol including a GnRH agonist, HMG and HCG. Renin levels were significantly lower and P4 significantly higher in pools of follicular fluid from patients with one ovary, whereas inhibin and E2 concentrations were similar in both patient groups. A significant negative correlation was found in the pools of follicular fluid between inhibin and E2 in both groups. These results suggest a role for inhibin and renin in the paracrine and autocrine control of stimulated follicular development.     

Peripheral T-cell lymphoma in childhood. A clinicopathological study of six cases

A review of the pathological material from 42 children with non-Hodgkin's lymphoma seen over a 44 month period revealed 10 large cell tumours. Of these, six were classified as peripheral T-cell lymphoma, an entity rarely reported in childhood. Three patients were boys and three girls (median age 9.5 years), and extranodal presentation was a feature of two patients. Five had high-grade tumours; of these, three were classified as large cell anaplastic, Ki-1 positive and two as pleomorphic large cell. The remaining patient had a low-grade tumour of angioimmunoblastic type. T-cell subsets were examined in three cases and showed the following phenotypes: CD4-, CD8-; CD4+, CD8-; CD4-, CD8+. Three of the patients with high-grade tumours died, with a mean survival of 22 weeks. The remaining patients are alive and clinically disease-free for between 10 and 24 months after treatment.     

Potential roles of protease inhibitors in Alzheimer's disease

Recently, protease inhibitors have been recognized as potential contributors to the pathogenesis of Alzheimer's disease. In this role, they could mediate an exaggerated regenerative response in the brain, participate as acute phase reactants, or be involved in the aberrant proteolytic processing of the amyloid proteins. Protease inhibitors are, therefore, attractive targets for drug intervention in Alzheimer's disease.     

Cytoskeletal rearrangement by oxidative stress

The cytoskeleton is susceptible to oxidative stress and this occurs prior to membrane blebbing and cell lysis. Vimentin intermediary filaments in rheumatoid synoviocytes are more susceptible than in normal synoviocytes and this may have pathological significance. They are however no more susceptible to heat shock than other cell types.     

Localization of phospholipids in human catecholamine neurons with Baker''s acid haematein

Summary Protein bodies in catecholamine neurons of the normal human brain contain arginine-rich proteins similar to those present in the core of Lewy bodies in Parkinsonian brains. Lewy bodies are known also to contain phospholipids in their core, demonstrable with Baker's acid haematein. We used Baker's procedure on catecholamine neurons of normal brains to test whether the protein bodies also contain phospholipids. Postmortem tissues of three control individuals were used in this study. Locus coeruleus and substantia nigra were dissected out from the fresh brains and two sets of blocks were made from each area. One set was fixed in formol-calcium for the preservation of lipids, the second was fixed in Bouin's solution and treated with hot pyridine for the extraction of lipids. Finally, both sets were subjected to the same chroming and staining procedure according to Baker. In catecholamine neurons the protein bodies were stained with acid haematein, indicating the presence of phospholipids. Since this staining resisted pyridine extraction we conclude that these phospholipids are firmly bound to the basic proteins. Thus, protein bodies in healthy catecholamine neurons give the same positive reaction for phospholipids as that reported for the core of Lewy bodies in damaged neurons in Parkinsonism.     

TRH-induced reflex changes in patients with ALS

A trial of Thyrotropin Releasing Hormone (TRH) 5.0 mg/kg body weight subcutaneously every other day for two weeks produced transient increased tone in muscles, along with other (side-) effects in patients with Amyotrophic Lateral Sclerosis (ALS). One patient's extensor plantar transiently changed to a flexor plantar reflex after injection, probably due to disproportionate increase in tone of the calf muscles. No significant changes in F-waves or H-reflexes were seen. No increase in useful voluntary strength, or in strength measured by Medical Research Council (MRC) testing or strain gauge isometric strength testing was seen. However, dyspnea was seen within 10 minutes of TRH injection.     

Structural modeling of functional neural pathways mapped with 2-deoxyglucose: effects of acoustic startle habituation on the auditory system

This paper describes the first application of structural modeling to neuroscience. Structural modeling (also known as path analysis) is a method to assess the relative impact of directional links in a system and how these interrelations may change under different conditions. The objective was to demonstrate how structural modeling can be used to determine the functional interrelationships between brain structures that form the auditory system. Using structural modeling, changes in auditory system 2-DG uptake were examined during long- and short-term habituation of the acoustic startle reflex. Models were based on the anatomical connections between central auditory system structures. Using functional 2-DG data, the correlations between these structures were calculated and numerical weights were computed for each anatomical link. The analysis revealed that the lemniscal path was dominant during short-term habituation, while during long-term habituation this influence was modified through extra-lemniscal pathways. The models are discussed in the context of previous findings to demonstrate how structural modeling can not only complement, but also extract more information from 2-DG mapping experiments.