Why type streptococci? The epidemiology of group A streptococci in Oxfordshire 1976-1980.

The results of typing all group A streptococci isolated in one laboratory in 5 years were reviewed to see if the collected information showed epidemiological patterns. The great majority of the 5858 streptococci typed came from patients seen in general practice: 72% from throat swabs and 11% from skin lesions. Eight types, M types 1, 2, 3, 4, 6, 12, 22 and type 28 R accounted for 65% of strains. These eight types had different patterns: types 2 and 6 caused small circumscribed outbreaks and were uncommon between epidemics; types 3, 4 and 12 caused larger, wider epidemics, whereas types 1, 22 and 28 R had a more stable pattern. Type 4 was more commonly resistant to tetracycline than most other types, a finding which affected the apparent incidence of tetracycline resistance in group A streptococci. Streptococci from superficial sites were more likely to have serum opacity factor and to lack a detectable M-antigen than strains isolated from the throat. Routine typing of streptococci helped to detect outbreaks of infection in special groups. It is concluded that regular streptococcal typing should be continued in some places.     

The configuration of beta-eucaine and beta-isoeucaine

The configurations of the two isomers, β-eucaine (benzamine hydrochloride B.P.C. 1954) and β-isoeucaine have been deduced. As a result of a study of the nuclear magnetic resonance spectra and of catalytic hydrogenation and oxidation, the α-form has been assigned an equatorial hydroxyl group on C-4 and the β-form an axial hydroxyl group in this position.     

Differential interactions between IGFBP-3 and transforming growth factor-beta (TGF-beta) in normal vs cancerous breast epithelial cells

In addition to modulating insulin-like growth factors action, it is now clear that insulin-like growth factor-binding protein-3 also has intrinsic effects on cell growth and survival. We have compared the effects of insulin-like growth factor-binding protein-3 and transforming growth factor-beta on cell proliferation and death of Hs578T cells and the normal breast epithelial cell line, MCF-10A. The growth of MCF-10A cells was inhibited at low concentrations of insulin-like growth factor-binding protein-3 but stimulated at high concentrations. These differential effects were unaffected in the presence of an insulin-like growth factor-I receptor antagonist. A synthetic peptide corresponding to the serine phosphorylation domain of insulin-like growth factor-binding protein-3 (that does not bind to insulin-like growth factors) also mimicked these differential actions. The growth of both cell lines was significantly inhibited by transforming growth factor-beta, this was associated with a 14-fold increase of insulin-like growth factor-binding protein-3 secreted by the Hs578T cells but a five-fold decrease of insulin-like growth factor-binding protein-3 secreted by MCF-10A cells. Replacement doses of exogenous insulin-like growth factor-binding protein-3 overcame the transforming growth factor-beta-induced growth inhibition in the MCF-10A cells. Cell death induced by ceramide was significantly reduced by insulin-like growth factor-binding protein-3 in the MCF-10A cells and depleting insulin-like growth factor-binding protein-3 with transforming growth factor-beta in these cells consequently increased their susceptibility to ceramide. In contrast, insulin-like growth factor-binding protein-3 enhanced apoptosis induced by ceramide in the Hs578T cells but transforming growth factor-beta treated Hs578T cells were resistant to apoptosis. The addition of anti-sense mRNA to insulin-like growth factor-binding protein-3 significantly abrogated this effect of transforming growth factor-beta. These data indicate that insulin-like growth factor-binding protein-3 has intrinsic activity capable of inhibiting or enhancing the growth and survival of breast epithelial cells depending on the cell line and exposure to other cytokines.     

The association between meconium and the production and reabsorption of lung liquid and lactate loss by in vitro lungs from fetal guinea pigs

OBJECTIVE: We sought to use an in vitro approach to determine relationships between meconium and fetal lung liquid production and to relate meconium to possible problems in lung liquid removal at birth. STUDY DESIGN: Near-term fetal guinea pigs were divided according to the level of spontaneously occurring meconium (no meconium, light meconium, or heavy meconium). Their lungs were maintained in vitro in Krebs-Henseleit saline solution for 3 hours. Lung liquid production or reabsorption was measured by a dye-dilution method, and loss of lactate to the lung liquid and outer Krebs-Henseleit solution was monitored. Reabsorptions were investigated by activating powerful responses with dinitrophenol during the middle hour. RESULTS: During the first hour, lungs from meconium-free fetuses produced liquid at 1.25 +/- 0.12 mL/kg(-1) body weight. h(-1); rates from light or heavy meconium groups were not significantly different (n = 18). Similarly, total lactate loss was not significantly different between the meconium-free and light-meconium groups but was twice as high in heavy-meconium preparations (73.68 +/- 10.60 micromol/L. g(-1) dry lung tissue. h(-1); P <.025, analysis of variance). The meconium-free and heavy-meconium groups continued to produce fluid, with no significant change throughout the 3 hours of incubation; lactate losses fell slightly. Therefore there were no problems with fluid production with meconium present, but the high-lactate losses with heavy meconium suggested long-term intrauterine hypoxia. Dinitrophenol produced powerful reabsorptions in lungs from meconium-free fetuses (-0.85 +/- 0.35 mL. kg(-1) body weight. h(-1); P <.005, analysis of variance; P <.0005, regression analysis) but failed to do so in heavy-meconium fetuses (n = 36). Lactate losses rose 2-fold in both groups (P <.005 to P < 0.0005, analysis of variance and regression analysis), despite already elevated losses with heavy meconium (n = 12). Therefore, in heavy-meconium fetuses, dinitrophenol affected metabolic pathways but did not activate fluid reabsorption, suggesting damage to reabsorptive mechanisms. CONCLUSION: Unless major airways are blocked, meconium is not associated with reduced fetal lung liquid production, which can cause poor lung development, but there may well be poor fluid removal after birth because of compromised reabsorptive mechanisms, which are unlikely to be helped by possible hormonal intervention.     

Early-life exposure to endotoxin alters hypothalamic-pituitary-adrenal function and predisposition to inflammation

We have investigated whether exposure to Gram-negative bacterial endotoxin in early neonatal life can alter neuroendocrine and immune regulation in adult animals. Exposure of neonatal rats to a low dose of endotoxin resulted in long-term changes in hypothalamic-pituitary-adrenal (HPA) axis activity, with elevated mean plasma corticosterone concentrations that resulted from increased corticosterone pulse frequency and pulse amplitude. In addition to this marked effect on the development of the HPA axis, neonatal endotoxin exposure had long-lasting effects on immune regulation, including increased sensitivity of lymphocytes to stress-induced suppression of proliferation and a remarkable protection from adjuvant-induced arthritis. These findings demonstrate a potent and long-term effect of neonatal exposure to inflammatory stimuli that can program major changes in the development of both neuroendocrine and immunological regulatory mechanisms.