Stress and immunity: an integrated view of relationships between the brain and the immune system

The old notion that stress exacerbates the progression of physical illness via its corticosteroid-mediated immunosuppressive effects must be revised. Experimental and clinical studies demonstrate that both laboratory and natural stressors alter the activities of lymphocytes and macrophages in a complex way that depends on the type of immune response, the physical and psychological characteristics of the stressor and the timing of stress relative to the induction and expression of the immune event. The influences of stress on immunity are mediated not only by glucocorticoids but also by catecholamines, endogenous opioids and pituitary hormones such as growth hormone. Sensitivity of the immune system to stress is not simply fortuitous but is an indirect consequence of the regulatory reciprocal influences that exist between the immune system and the central nervous system. The immune system receives signals from the brain and the neuroendocrine system via the autonomic nervous system and hormones and sends information to the brain via cytokines. These connections appear to be part of a long-loop regulatory feedback system that plays an important role in the coordination of behavioral and physiological responses to infection and inflammation.     

Beta-oxidation of long-chain fatty acids by human fibroblasts: evidence for a novel long-chain acyl-coenzyme A dehydrogenase.

Fibroblasts from patients with long-chain acyl-CoA dehydrogenase deficiency were found to oxidize [1-14C]linoleate at an average rate of 60% of normal but [9,10(n)-3H]myristate at an average rate of only 37% of normal, a relationship reverse from that predicted by the chain-length specificities of the three known straight-chain mitochondrial acyl-CoA dehydrogenases. The residual long-chain beta-oxidative activity was found to be mitochondrial and associated with the accumulation of tetradecadienoate (C14:2w6) when the mutant fibroblasts were incubated with 100 mumol/L linoleate (C18:2w6) or eicosadienoate (C20:2w6). The results suggest the presence in human fibroblasts of a novel acyl-CoA dehydrogenase with activity toward 15 to 20 carbon-length fatty acids.     

Using patient and general practice characteristics to explain variations in cervical smear uptake rates.

OBJECTIVES--To produce practice and patient variables for general practices from census and family health services authority data, and to determine the importance of these variables in explaining variation in cervical smear uptake rates between practices. DESIGN--Population based study examining variations in cervical smear uptake rates among 126 general practices using routine data. SETTING--Merton, Sutton, and Wandsworth Family Health Services Authority, which covers parts of inner and outer London. MAIN OUTCOME MEASURE--Percentage of women aged 25-64 years registered with a general practitioner who had undergone a cervical smear test during the five and a half years preceding 31 March 1992. RESULTS--Cervical smear uptake rates varied from 16.5% to 94.1%. The estimated percentage of practice population from ethnic minority groups correlated negatively with uptake rates (r = -0.42), as did variables associated with social deprivation such as overcrowding (r = -0.42), not owning a car (r = -0.41), and unemployment (r = -0.40). Percentage of practice population under 5 years of age correlated positively with uptake rate (r = 0.42). Rates were higher in practices with a female partner than in those without (66.6% v 49.1%; difference 17.5% (95% confidence interval 10.5% to 24.5%)), and in computerised than in non-computerised practices (64.5% v 50.5%; 14.0% (6.4% to 21.6%)). Rates were higher in larger practices. In a stepwise multiple regression model that explained 52% of variation, five factors were significant predictors of uptake rates: presence of a female partner; children under 5; overcrowding; number of women aged 35-44 as percentage of all women aged 25-64; change of address in past year. CONCLUSIONS--Over half of variation in cervical smear uptake rates can be explained by patient and practice variables derived from census and family health services authority data; these variables may have a role in explaining variations in performance of general practices and in producing adjusted measures of practice performance. Practices with a female partner had substantially higher uptake rates.     

Proportional processing of a visual mate choice signal in the green swordtail,Xiphophorus hellerii

During mate choice, receivers often assess the magnitude (duration, size, etc.) of signals that vary along a continuum and reflect variation in signaller quality. It is generally assumed that receivers assess this variation linearly, meaning each difference in signalling trait between signallers results in a commensurate change in receiver response. However, increasing evidence shows receivers can respond to signals non-linearly, for example through Weber's Law of proportional processing, where discrimination between stimuli is based on proportional, rather than absolute, differences in magnitude. We quantified mate preferences of female green swordtail fish, Xiphophorus hellerii, for pairs of males differing in body size. Preferences for larger males were better predicted by the proportional difference between males (proportional processing) than the absolute difference (linear processing). This demonstration of proportional processing of a visual signal implies that receiver perception may be an important mechanism selecting against the evolution of ever-larger signalling traits.     

Febrile Gastroenteritis Due to Salmonella thompson—Report of an Outbreak

Salmonella thompson, a common pathogen of poultry, has received scant attention as a cause of human gastroenteritis. At least 45 persons were infected with S thompson in Sacramento, California, after eating at a chicken restaurant and 38 became symptomatic. Ten required admission to hospital, and all were treated with antibiotics and improved. In 19 cases cultures of stool specimens for S thompson over a 60-day period showed slower but statistically insignificant differences in salmonellal elimination in 7 patients who received antibiotics when compared with 12 who were untreated. We report this outbreak to increase awareness of the virulence and prevalence of gastroenteritis due to S thompson.     

Attack and defensive behaviour in the albino rat

Attack of dominant colony males of an albino rat (Rattus norvegicus) strain, on introduced strangers, produced a non-random distribution of bites, with ventral trunk virtually never bitten. Also, vibrissae-contact of attacker and defender interfered with bites to the defender's head and upper back. The specific agonistic reactions of attacking and defending rats appeared to involve strategies based on these limitation on attack: defenders utilized 'boxing' and lying 'on-the-back' behaviour, which interposed ventral trunk and vibrissae between attacker and defender. In turn, the 'lateral display' permitted attackers to circumvent the defender's behaviour. Limitations on attack therefore appeared to underlie the specific agonistic behaviour of both attacking and defending rats.     

Conformational changes induced by integration host factor at origin gamma of R6K and copy number control.

We have investigated the role of integration host factor (IHF) in the replication of plasmid R6K by studying the maintainance of the plasmid in a strain of Escherichia coli that lacks both subunits of IHF and in an isogenic wild type strain and found that all three origins, alpha, beta, and gamma, were functional in the absence of IHF; however, loss of IHF reduced the copy number of those replicons initiating solely from ori gamma by 5-fold. Concomitant loss of direct repeats within the origin that bind the R6K replication initiator protein, Pi, resulted in a further reduction in copy number. Using gel mobility shift analysis, we showed that IHF bound specifically only to one site within the A/T rich region of the minimal origin adjacent to the Pi binding sites. The origin region possessed no intrinsic DNA curvature although IHF induced a strong bend upon binding. Combination footprinting with different orders of addition of Pi and IHF suggested that there was no cooperativity between the two proteins with regard to DNA binding. Hydroxyl-radical footprinting revealed hypersensitive asymmetric periodic cleavage sites within the origin region in the presence of IHF that extended over 200 base pairs and a localized perturbation of cleavage chemistry. The presence of periodic cleavages was dependent upon the presence of the wild type R6K origin sequence and was not observed when the IHF binding site was positioned adjacent to a heterologous sequence. We observed that the conformational changes induced by IHF upon binding to the R6K origin were negatively correlated with the observed decrease in copy number, and therefore, origin conformation altered by protein-DNA interaction may play an important role in the regulation of replication initiation.     

Clearance and fate of leukemia-inhibitory factor (LIF) after injection into mice

Leukemia-inhibitory factor (LIF) elicits effects on a broad range of cell types, including cells of the monocytic and megakaryocytic series, embryonal stem cells, hepatocytes, adipocytes, and osteoblasts. Native and recombinant LIF, injected intravenously into adult mice, had an initial half-life of 6-8 min and a more prolonged second clearance phase. Clearance of 125I-LIF from the circulation was paralleled by a rapid accumulation in the kidneys, liver, lungs, and spleen and a more gradual accumulation in the thyroid gland. Labeling of the renal glomerular tufts, parenchymal hepatocytes, splenic red pulp, alveolar pneumocytes, and thyroid follicular cells as well as of megakaryocytes and osteoblasts in the bone cavities, placental trophoblasts, and cells of the choroid plexus was demonstrable autoradiographically. The appearance of a large amount of nonprecipitable 125I in the urine suggested that the kidneys were the major route of LIF clearance from the body.     

Identification of insulin-like growth factor-binding proteins in the circulation of four teleost fish species.

Insulin-like growth factor-binding proteins (IGF-BPs) were demonstrated in the circulation of four teleost fish species. In the coho salmon (Oncorhynchus kisutch), serum binding of 125I-labelled human IGF-I (125I-hIGF-I) was competitively inhibited by addition of excess recombinant bovine IGF-I (rbIGF-I) in a manner similar to that when rat serum was used. Western-ligand blot procedure using the same labelled hormone identified at least three major forms of IGF-BPs in the plasma of all four teleost species investigated: coho salmon, striped bass (Morone saxatilis), tilapia (Oreochromis mossambicus), and longjawed mudsucker (Gillichthys mirabilis). The first form is around 40-50 kDa, may be regulated by growth hormone (GH), and seems to be a good candidate for the fish version of mammalian IGF-BP3 (which is in the same size range and is GH-regulated). The second and third forms are 29 kDa and 31 kDa and are good candidates for the fish versions of mammalian IGF-BP1 and IGF-BP2, respectively, as they appear to be regulated by insulin and are in the same size range as their mammalian counterparts. Functionally different classes of circulating IGF-BPs may be conserved between fish and mammal.     

Phenice's visual sexing technique for the os pubis: a critique

Innominate bones from 362 California Indians were sexed with Phenice's three non-metrical features of the os pubis. The frequencies of marked, intermediate, and absent cases of these three morphological features were tabulated in males and females to see if unambiguous and reliable distinctions were consistently available. The results suggest that Phenice's technique offered extremely reliable sex evaluations in this material.