Parasite immunity and the major histocompatibility complex

Parasite infestations offer fertile ground for investigation of the relationship between immunity, disease and the major histocompatibility complex (MHC). However, due to the complexities of parasite life cycles and the success of parasites in evading the immune response, immune reactions against the parasite often do not parallel protective immunity, and immunity does not imply lack of disease. — An additional level of complexity is introduced in some forms of parasite immunity by accessory effector cells, e. g., macrophages and eosinophils, that need to be activated for maximal effectiveness, and the activated form of these cells may partly compensate for a deficiency in specific immune responses. — It is not surprising, therefore, that polygenic effects operate in parasite immunity and reports linking non-MHC genes with parasite immunity far out number those linking MHC genes with it. From the reports that do link MHC genes with parasite immunity, two areas emerge that are interesting. First, the increased incidence of certainHLA genes in people with schistosomiasis who develop hepatosplenic disease may pinpoint individuals at risk of morbidity and direct early treatment to them. Second, mechanisms that intimately involve MHC products but are not linked to a particular MHC haplotype, may indicate newer areas in the investigation of parasite immunity.     

The effects of different horticultural practices on the chemical flavour composition of some cabbage cultivars

Variations in the chemical flavour composition of three cultivars of cabbage were determined for plants of different horticultural histories. In some i     

On the massive legs of a Moa (Pachyornis elephantopus, Dinornithes)

Pachyornis , which is extinct, was a huge bird with massively thick leg bones. These have been measured, to assess their strength. A mathematical model is used to calculate the forces that must have acted on them, when Pachyornis ran. Hence it is shown that the stresses likely to have acted on them are similar in magnitude to the stresses experienced (in stenuous activities) by bones of modem birds and mammals. The femur and tarsometatanus, however, seem disproportionately strong in comparison with the tibiotanus.     

Targeted disruption of the tissue inhibitor of metalloproteinases gene increases the invasive behavior of primitive mesenchymal cells derived from embryonic stem cells in vitro.

The metalloproteinase family of proteolytic enzymes can degrade extracellular matrix and facilitate invasive migration. This class of enzymes is specifically inhibited by the tissue inhibitor of metalloproteinases (TIMP-1). Using homologous recombination, we have disrupted the gene encoding TIMP-1 in pluripotent embryonic stem cells. Because the TIMP-1 gene is X linked and is hemizygous in embryonic stem cells, we have been able to study the effect of this mutation in culture. Using a basement membrane invasion assay, we found that the mutant cells, differentiated in low concentrations of serum with retinoic acid, were more invasive than their normal cell counterparts, and that this was specifically reversed by adding exogenous TIMP-1 protein. The invasive cell population had characteristics of an early population of primitive mesenchymal cells, including expression of vimentin and a transient period of invasiveness from 4-8 d after initiation of differentiation. Therefore, metalloproteinase activity can be rate limiting for cell invasion.     

Central peptidergic mechanisms controlling reproductive hormone secretion: novel methodology reveals a role for the natriuretic peptides.

A variety of neural factors can influence reproductive hormone secretion by neuromodulatory actions within the hypothalamus or neuroendocrine actions within the anterior pituitary gland. Passive immunoneutralization and antagonist administration protocols have suggested physiological roles for a number of these factors; however, both experimental approaches have severe technical limitations. We have developed novel methodology utilizing cytotoxin cell targeting with neuropeptides linked to the toxic A chain of the plant cytotoxin ricin. With this methodology we can target and destroy in vivo or in vitro cells bearing receptors for that peptide. Ricin A chain conjugated to atrial natriuretic peptide (ANP), a neuropeptide known to pharmacologically inhibit luteinizing hormone-releasing hormone (LHRH) release, was injected into the cerebroventricular system of intact, cycling rats and ovariectomized rats. Cytotoxin conjugate treatment significantly lengthened the estrous cycle. In ovariectomized rats the luteinizing hormone surge induced by steroid priming was completely inhibited. LHRH content of the median eminences of these rats was not significantly altered. These data suggest that ANP binding to clearance receptors in the hypothalamus displaces the C-type natriuretic peptide (CNP) from the shared clearance receptor, making more CNP available to inhibit LHRH release. In the absence of cells bearing the clearance receptor all available CNP binds to the ANPR-B receptor and exerts its effect via an inhibitory interneuron, since LHRH fibers are spared by this treatment.     

Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial.

OBJECTIVE--To see whether intravenous acetylcysteine would improve outcome in patients with fulminant hepatic failure after paracetamol overdose. DESIGN--A prospective randomised controlled study. SETTING--The Institute of Liver Studies, King''s College Hospital, London. PATIENTS--50 consecutive patients (21 male) aged 16-60 with fulminant hepatic failure after paracetamol overdose who had not previously received acetylcysteine. INTERVENTIONS--Conventional intensive liver care plus either acetylcysteine (25 patients) in the same dose regimen as used early after a paracetamol overdose, except that the infusion was continued until recovery from encephalopathy or death, or an equivalent volume of 5% dextrose (25 patients). MAIN OUTCOME MEASURES--Survival; incidence of cerebral oedema, renal failure, and hypotension requiring inotropic support; liver function as assessed by prolongation of the prothrombin time; and degree of encephalopathy. RESULTS--The rate of survival was significantly higher in the acetylcysteine treated group than in the controls (48% (12/25 patients) v 20% (5/25); p = 0.037, 95% confidence interval for difference in proportions surviving 3% to 53%). Acetylcysteine treated patients had a lower incidence of cerebral oedema (40% (10/25) v 68% (17/25); p = 0.047, 95% confidence interval for difference in incidence 2% to 54%), and fewer developed hypotension requiring inotropic support (48% (12/25) v 80% (20/25); p = 0.018, 95% confidence interval 7% to 57%). Rates of deterioration and recovery of liver function, however, were similar in the two groups. No adverse reactions to acetylcysteine were seen. CONCLUSIONS--Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose.     

Anaerobic Oxidation of Acetylene by Estuarine Sediments and Enrichment Cultures

Acetylene disappeared from the gas phase of anaerobically incubated estuarine sediment slurries, and loss was accompanied by increased levels of carbon dioxide. Acetylene loss was inhibited by chloramphenicol, air, and autoclaving. Addition of ¹⁴C₂H₂ to slurries resulted in the formation of ¹⁴CO₂ and the transient appearance of ¹⁴C-soluble intermediates, of which acetate was a major component. Acetylene oxidation stimulated sulfate reduction; however, sulfate reduction was not required for the loss of C₂H₂ to occur. Enrichment cultures were obtained which grew anaerobically at the expense of C₂H₂.