Pathway of inactivation of cholecystokinin octapeptide (CCK-8) by synaptosomal fractions

Cholecystokinin octapeptide (CCK-8) was degraded by peptidases present in intact synaptosomes isolated from rat cortex and hypothalamus. Most of the degrading activity was present in the cytoplasmic fraction although a small amount (7%) was membrane-bound. Products of the degradation were isolated by HPLC and characterized by amino acid analysis. The Met³-Gly⁴ bond was the main primary site of cleavage giving rise to Asp-Tyr(SO₃H)-Met and Gly-Trp-Met-Asp-Phe-NH₂. These products appeared to be further degraded by sequential removal of amino-terminal residues. The Asp¹-Tyr² and Asp⁷-Phe⁸ bonds were also sites of cleavage. p-Chloromercuribenzoate was the most effective inhibitor (90% inhibition) of CCK-8 degradation by synaptosomal peptidases at the concentrations tested.This peptidase activity in synaptosomes may be important in the regulation of levels of the neuropeptide CCK-8 at the synapse. Identification of the sites of cleavage of CCK-8 on incubation with synaptosomes will assist in the isolation and characterization of the enzymes involved.     

Nogo-A, -B, and -C are found on the cell surface and interact together in many different cell types

Nogo-A, -B, and -C are generated from the Nogo/RTN-4 gene and share a highly conserved C-terminal domain. They lack an N-terminal signal sequence and are predominantly localized to the endoplasmic reticulum (ER). We found the N terminus of endogenous Nogo-A exposed on the surface of fibroblasts, DRG neurons, and myoblasts. Surface-expressed Nogo-A was also present on presynaptic terminals of the neuromuscular junction and on DRG neurons in vivo. Surface biotinylations confirmed the presence of all Nogo isoforms on the surface. To search for proteins that interact with Nogo-A and suggest a function for the large intracellular pool of Nogo-A, immunoprecipitations were performed. Surprisingly, the most predominant proteins that interact with Nogo-A are Nogo-B and Nogo-C as seen with radiolabeled lysates and as confirmed by Western blotting in multiple cell lines. Nogo-A, -B, and -C share a 180-amino acid C-terminal domain with two highly conserved hydrophobic stretches that could form a channel or transporter in the ER and/or on the cell surface.     

Distribution of NHS funds between fundholding and non-fundholding practices.

OBJECTIVES--To estimate the amount spent on specific hospital care by health agencies in 1993-4 and compare it with the resources allocated to patients registered with fundholding practices for the same type of care. To investigate whether fundholding practices and health agencies pay different amounts for inpatient care. DESIGN--Examination of hospital episode statistics, 1991 census data, and family health services authority and health agency records. SETTING--Health agencies and fundholding practices in the former North West Thames Regional Health Authority. MAIN OUTCOME MEASURES--Amount per capita allocated to inpatient and outpatient care for patients registered with fundholding and non-fundholding practices. Average specialty cost per finished consultant episode for health agencies and fundholding practices. RESULTS--The ratio of per capita funding for patients in non-fundholding practices to those in fundholding practices ranged from 59% to 87% for inpatient and day case care and from 36% to 106% for outpatient care. Average specialty costs per episode were similar for fundholding practices and health agencies. CONCLUSIONS--Fundholding practices seem to have been funded more generously than non-fundholding practices in North West Thames.     

A chemical-modification approach to the olfactory code. Studies with a thiol-specific reagent

The effects of thiol-specific reagents on the amplitude of the electro-olfactogram (E.O.G.) responses elicited from frog olfactory mucosa by pulses of odorant vapours was studied. The impermeant thiol-specific reagent mersalyl [(3-{[2-(carboxymethoxy)-benzoyl]amino}-2-methoxypropyl)hydroxymercury monosodium salt] brings about a rapid decrease in the E.O.G. signal obtained with the odorant pentyl acetate. The extent of the decrease is proportional to the concentration of the mersalyl applied and the effect of the reagent is partially but incompletely reversed by treatment of the labelled mucosa with dithiothreitol. The sites labelled by mersalyl can be protected by pretreating the mucosa with a dilute solution of the odorant pentyl acetate and leaving the solution in contact with the tissue after the addition of mersalyl. When the protecting odorant is washed out of the tissue, the original E.O.G. amplitude is regained. Pentyl acetate applied to the mucosa protected the E.O.G. response to vapour pulses of the following odorants from the effects of mersalyl: n-butyric acid, n-butyl acetate, phenylacetaldehyde and cineole (1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane). The pentyl acetate applied to the mucosa failed to protect the E.O.G. response to vapour pulses of the following odorants from the effects of mersalyl: butan-1-ol, benzyl acetate, nitrobenzene, beta-ionone and linalyl acetate. The significance of the differential protection effects for the odour-quality-coding mechanism in the olfactory primary neurons is discussed. It is suggested that the olfactory code at this level of the olfactory system may be elucidated by chemical-modification methods.     

Aspects of early arthritis. Definition of disease states in early arthritis: remission versus minimal disease activity

With regard to rheumatoid arthritis, remission as currently used in the literature can have two meanings: either a state with persistent absence of clinical and radiological signs of disease activity without being treated for a specific time period, or it may point to a disease state with minimal disease activity during antirheumatic treatment. A risk factor for the first is absence of autoantibodies, with the anti-CCP-antibodies as best predictors, whereas risk factors for achieving a drug-induced state of minimal disease activity are not well defined. These definitions of remission refer to different disease states; therefore, we propose that the term remission is reserved for patients that are not treated with antirheumatic drugs.     

Cerebral oxidized and reduced nicotinamide-adenine dinucleotide phosphate and glucose 6-phosphate dehydrogenase in mice during exposure to high oxygen pressure.

NADP+, NADPH and glucose 6-phosphate dehydrogenase were determined in the cerebral cortex of mice exposed to high O2 pressure for 0, 8 and 16 min. These time intervals corresponded to 0, 50 and 100% of the CT50 (the time taken for 50% of the mice to convulse). Cerebral NADP+, NADPH and glucose 6-phosphate dehydrogenase also were determined in O2-exposed mice exhibiting hyperactivity, convulsions, and in mice killed 10s after convulsions. Similar increases in cortical NADP+ and decreases in NADPH were found in mice exposed to 610kPa (6 atm.) of 100% O2 for 0, 50 and 100% of the CT50, during hyperactivity, onset of seizure and 10s after convulsions. The NADP+/NADPH ratio increased approx. 25% at 0% of the CT50, and remained at this increased value at all O2-exposure periods including the hyperactive state, onset of seizure and 10s after convulsions. Identical changes in cerebral NADP+ , NADPH and the NADP+/NADPH ratio were found in mice exposed for 16min to 100% O2 at 100, 350 or 610kPa. No change in cerebral glucose 6-phosphate dehydrogenase was found in mice exposed to 610kPa of 100% O2 during the various stages of O2 toxicity. Only in the 10s post-convulsive group was a statistically significant decrease in glucose 6-phosphate dehydrogenase observed. Disulfiram [bis(diethylthiocarbamoyl) disulphide], an effective O2-protective agent, did not prevent the O2-induced increase in cerebral NADP+ and the NADP+/NADPH ratio, or decrease in NADPH.     

Biometrical variability of foliage and cone characters inCupressus bakeri (Cupressaceae)

Biometrical variability of foliage, cones, and seeds were analyzed in 8 native populations (throughout the range) of a relictual species,Cupressus bakeriJeps. (Cupressaceae) from California and Oregon. The partition of variation within and among populations for this rare plant was investigated and the justification for subspecies status was reviewed. Morphological characters varied significantly, with more of the variation among populations than at the population level. Multivariate analyses indicated close affinities among populations on serpentine sites suggesting the presence of a serpentine race. However, the high degree of variation among populations did not permit their clear separation into the two subspecies described byWolf (1948). We conclude thatC. bakeri should be treated as a monotypic species.