Inhibition of early tumor growth requires Jα18-positive (natural killer T) cells

The role of natural killer T (NKT) cells in the immune response to tumor cells has been largely unexplored. As a model of adoptive tumor immunotherapy, cells from the draining lymph nodes of mice immunized with a tumor-specific or irrelevant antigen were transferred to naive recipients with established tumor. Inhibition of early tumor growth (day 4) required the transfer of both CD8(+) and Jalpha18(+) (NKT) cells from immunized animals without regard to immunogen. In contrast, CD8(+) cells, but not Jalpha18(+) cells, were necessary for the inhibition of late tumor growth (day 8). Thus, the developing tumor changes in sensitivity to NKT-mediated events and the role for NKT cells cannot be replaced by the presence of tumor-specific cells during early tumor growth. This suggests that recruitment/activation of Jalpha18(+) NKT cells is an important consideration during the immune therapy of early stage tumors.

A protective effect of early pregnancy factor on experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein

Experimental antoimmune encephalomyelitis (EAE) is an organ-specific autoimmune disease characterised by inflammation and demyelination of the central nervous system and is the best available animal model of multiple sclerosis (MS). Since previous studies have shown that EAE is less severe or is delayed in onset during pregnancy and that administration of the pregnancy hormone early pregnancy factor (EPF) down-regulates EAE, experiments in the present study were designed to explore further the role of EPF in EAE. By using the rosette inhibition test, the standard bioassay for EPF and, by semi-quantitative RT-PCR techniques, we have now shown that inflammatory cells from the spinal cord of rats with EAE can produce and secrete EPF, with production being greatest during recovery from disease. Administration of EPF to rats with EAE resulted in a significant increase in the expression of IL-4 and IL-10 mRNA and a significant decrease in IFN-gamma mRNA expression in spinal cord inflammatory cells. Encephalitogenic MBP-specific T cell lines were prepared from popliteal lymph nodes of rats with EAE. Proliferation assays using these cells demonstrated the ability of exogenous EPF to down-regulate the responses of T lymphocytes to MBP. (C) 2003 Elsevier B.V. All rights reserved.

Inheritance of early Archaean Pb-isotope variability from long-lived Hadean protocrust

Comparison of initial Pb-isotope signatures of several early Archaean (3.65-3.82 Ga) lithologies (orthogneisses and metasediments) and minerals (feldspar and galena) documents the existence of substantial isotopic heterogeneity in the early Archaean, particularly in the Pb-207/Pb-204 ratio. The magnitude of isotopic variability at 3.82-3.65 Ga requires source separation between 4.3 and 4.1 Ga, depending on the extent of U/Pb fractionation possible in the early Earth. The isotopic heterogeneity could reflect the coexistence of enriched and depleted mantle domains or the separation of a terrestrial protocrust with a U-238/Pb-204 (mu) that was ca. 20-30% higher than coeval mantle. We prefer this latter explanation because the high-p signature is most evident in metasediments (that formed at the Earth's surface). This interpretation is strengthened by the fact that no straightforward mantle model can be constructed for these high-mu lithologies without violating bulk silicate Earth constraints. The Pb-isotope evidence for a long-lived protocrust complements similar Hf-isotope data from the Earth's oldest zircons, which also require an origin from an enriched (low Lu/Hf) environment. A model is developed in which greater than or equal to3.8-Ga tonalite and monzodiorite gneiss precursors (for one of which we provide zircon U-Pb data) are not mantle-derived but formed by remelting or differentiation of ancient (ca. 4.3 Ga) basaltic crust which had evolved with a higher U/Pb ratio than coeval mantle in the absence of the subduction process. With the initiation of terrestrial subduction at, we propose, ca. 3.75 Ga, most of the greater than or equal to3.8-Ga basaltic shell (and its differentiation products) was recycled into the mantle, because of the lack of a stabilising mantle lithosphere. We argue that the key event for preservation of all greater than or equal to3.8-Ga terrestrial crust was the intrusion of voluminous granitoids immediately after establishment of global subduction because of complementary creation of a lithospheric keel. Furthermore, we argue that preservation of !3.8-Ga material (in situ rocks and zircons) globally is restricted to cratons with a high U/Pb source character (North Atlantic, Slave, Zimbabwe, Yilgarn, and Wyoming), and that the Pb-isotope systematics of these provinces are ultimately explained by reworking of material that was derived from ca. 4.3 Ga (i.e. Hadean) basaltic crust.

Social and behavioural determinants of early childhood caries

Background: To investigate the association between selected social and behavioural (infant feeding and preventive dental practices) variables and the presence of early childhood caries in preschool children within the north Brisbane region. Methods: A cross sectional sample of 2515 children aged four to five years were examined in a preschool setting using prevalence (percentage with caries) and severity (dmft) indices. A self-administered questionnaire obtained information regarding selected social and behavioural variables. The data were modelled using multiple logistic regression analysis at the 5 per cent level of significance. Results: The final explanatory model for caries presence in four to five year old children included the variables breast feeding from three to six months of age (OR=0.7, CI=0.5, 1.0), sleeping with the bottle (OR=1.9, CI=1.5, 2.4), sipping from the bottle (OR=1.6, CI=1.2, 2.0), ethnicity other than Caucasian (OR=1.9, CI=1.4, 2.5), annual family income $20,000-$35,000 (OR = 1.7, CI=1.3, 2.3) and annual family income less than $20,000 (OR=2.1, CI=1.5, 2.8). Conclusion: A statistical model for early childhood caries in preschool children within the north Brisbane region has been constructed using selected social and behavioural determinants. Epidemiological data can be used for improved public oral health service planning and resource allocation within the region.

Echocardiographic detection of early diabetic myocardial disease

OBJECTIVES We sought to determine whether disturbances of myocardial contractility and reflectivity could be detected in diabetic patients without overt heart disease and whether these changes were independent and incremental to left ventricular hypertrophy (LVH). BACKGROUND Left ventricular (LV) dysfunction is associated with diabetes mellitus, but LVH is common in this population and the relationship between diabetic LV dysfunction and LVH is unclear. METHODS We studied 186 patients with normal ejection fraction and no evidence of CAD: 48 with diabetes mellitus only (DM group), 45 with LVH only (LVH group), 45 with both diabetes and LVH (DH group), and 48 normal controls. Peak strain and strain rate of six walls in apical four-chamber, long-axis, and two-chamber views were evaluated and averaged for each patient. Calibrated integrated backscatter (113) was assessed by comparison of the septal or posterior wall with pericardial IB intensity. RESULTS All patient groups (DM, DH, LVH) showed reduced systolic function compared with controls, evidenced by lower peak strain (p < 0.001) and strain rate (p = 0.005). Calibrated 113, signifying myocardial reflectivity, was greater in each patient group than in controls (p < 0.05). Peak strain and strain rate were significantly lower in the DH group than in those in the DM alone (p < 0.03) or LVH alone (p = 0.01) groups. CONCLUSIONS Diabetic patients without overt heart disease demonstrate evidence of systolic dysfunction and increased myocardial reflectivity. Although these changes are similar to those caused by LVH, they are independent and incremental to the effects of LVH. (C) 2003 by the American College of Cardiology Foundation.

Characterisation of early Archaean chemical sediments by trace element signatures

Rare earth element (REE) plus yttrium (Y) patterns of modem seawater have characteristic features that can be used as chemical fingerprints. Reliable proxies for marine REE + Y chemistry have been demonstrated from a large geological time span, including Archaean banded iron formation (BIF), stromatolitic limestone, Phanerozoic reef carbonate and Holocene microbialite. Here we present new REE + Y data for two distinct suites of early Archaean (ca. 3.7-3.8 Ga) metamorphosed rocks from southern West Greenland, whose interrelationships, if any, have been much debated in recent literature. The first suite comprises mangetite-quartz BIF, magnetite-carbonate BIF and banded magnetite-rich quartz rock, mostly from the Isua Greenstone Belt (IGB). The REE + Y patterns, particularly diagnostic anomalies (Ce/Ce*, Pr/Pr*), are closely related to those of published seawater proxies. The second suite includes banded quartz-pyroxene-amphibole +/- garnet rocks with minor magnetite from the so-called Akilia Association enclaves (in early Archaean granitoid gneisses) of the coastal region, some 150 km southwest of the IGB. Rocks of this type from one much publicised and highly debated locality (the island of Akilia) have been identified by some workers [Nature 384 (1996) 55; Geochim. Cosmochim. Acta 61 (1997) 2475] as BIF-facies, and their C-13-depleted signature in trace graphite interpreted as a proxy for earliest life on Earth. However, REE + Y patterns of the Akilia Association suite (except for one probably genuine magnetite-rich BIF from Ugpik) are inconsistent with a seawater origin. We agree with published geological and geochemical (including REE) work [Science 296 (2002) 1448] that most of the analysed Akilia rocks are not chemical sediments, and that C-isotopes in such rocks therefore cannot be used as biological proxies. Application of the REE + Y discriminant for the above two rock suites has been facilitated in this study by the use of MC-ICP technique which yields a more complete and precise REE + Y spectrum than was available in many previous studies. (C) 2004 Elsevier B.V. All rights reserved.

Effect of early marine diagenesis on coral reconstructions of surface-ocean 13C/12C and carbonate saturation state

Recent research suggests that future decreases in the carbonate saturation state of surface seawater associated with the projected build-up of atmospheric CO2 could cause a global decline in coral reef-building capacity. Whether significant reductions in coral calcification are underway is a matter of considerable debate. Multicentury records of skeletal calcification extracted from massive corals have the potential to reconstruct the progressive effect of anthropogenic changes in carbonate saturation on coral reefs. However, early marine aragonite cements are commonly precipitated from pore waters in the basal portions of massive coral skeletons and, if undetected, could result in apparent nonlinear reductions in coral calcification toward the present. To address this issue, we present records of coral skeletal density, extension rate, calcification rate, δ13C, and δ18O for well preserved and diagenetically altered coral cores spanning ∼1830-1994 A.D. at Ningaloo Reef Marine Park, Western Australia. The record for the pristine coral shows no significant decrease in skeletal density or δ13C indicative of anthropogenic changes in carbonate saturation state or δ13C of surface seawater (oceanic Suess effect). In contrast, progressive addition of early marine inorganic aragonite toward the base of the altered coral produces an apparent ∼25% decrease in skeletal density toward the present, which misleadingly matches the nonlinear twentieth century decrease in coral calcification predicted by recent modeling and experimental studies. In addition, the diagenetic aragonite is enriched in 13C, relative to coral aragonite, resulting in a nonlinear decrease in δ13C toward the present that mimics the decrease in δ13C expected from the oceanic Suess effect. Taken together, these diagenetic changes in skeletal density and δ13C could be misinterpreted to reflect changes in surface-ocean carbonate saturation state driven by the twentieth century build-up of atmospheric CO2. Copyright 2004 by the American Geophysical Union.

Petrology and geochemistry of early cretaceous bimodal continental flood volcanism of the NW Etendeka, Namibia. Part 2: Characteristics and petrogenesis of the high-Ti latite and high-Ti and low-Ti voluminous quartz latite eruptives

As a result of their relative concentration towards the respective Atlantic margins, the silicic eruptives of the Parana (Brazil)-Etendeka large igneous province are disproportionately abundant in the Etendeka of Namibia. The NW Etendeka silicic units, dated at similar to132 Ma, occupy the upper stratigraphic levels of the volcanic sequences, restricted to the coastal zone, and comprise three latites and five quartz latites (QL). The large-volume Fria QL is the only low-Ti type. Its trace element and isotopic signatures indicate massive crustal input. The remaining NW Etendeka silicic units are enigmatic high-Ti types, geochemically different from low-Ti types. They exhibit chemical affinities with the temporally overlapping Khumib high-Ti basalt (see Ewart et al. Part 1) and high crystallization temperatures (greater than or equal to980 to 1120degreesC) inferred from augite and pigeonite phenocrysts, both consistent with their evolution from a mafic source. Geochemically, the high-Ti units define three groups, thought genetically related. We test whether these represent independent liquid lines of descent from a common high-Ti mafic parent. Although the recognition of latites reduces the apparent silica gap, difficulty is encountered in fractional crystallization models by the large volumes of two QL units. Numerical modelling does, however, support large-scale open-system fractional crystallization, assimilation of silicic to basaltic materials, and magma mixing, but cannot entirely exclude partial melting processes within the temporally active extensional environment. The fractional crystallization and mixing signatures add to the complexity of these enigmatic and controversial silicic magmas. The existence, however, of temporally and spatially overlapping high-Ti basalts is, in our view, not coincidental and the high-Ti character of the silicic magmas ultimately reflects a mantle signature.

Petrology and geochemistry of early cretaceous bimodal continental flood volcanism of the NW Etendeka, Namibia. Part 1: Introduction, mafic lavas and re-evaluation of mantle source components

The bimodal NW Etendeka province is located at the continental end of the Tristan plume trace in coastal Namibia. It comprises a high-Ti (Khumib type) and three low-Ti basalt (Tafelberg, Kuidas and Esmeralda types) suites, with, at stratigraphically higher level, interstratified high-Ti latites (three units) and quartz latites (five units), and one low-Ti quartz latite. Khumib basalts are enriched in high field strength elements and light rare earth elements relative to low-Ti types and exhibit trace element affinities with Tristan da Cunha lavas. The unradiogenic Pb-206/Pb-204 ratios of Khumib basalts are distinctive, most plotting to the left of the 132 Ma Geochron, together with elevated Pb-207/Pb-204 ratios, and Sr-Nd isotopic compositions plotting in the lower Nd-143/Nd-144 part of mantle array (EM1-like). The low-Ti basalts have less coherent trace element patterns and variable, radiogenic initial Sr (similar to0.707-0.717) and Pb isotope compositions, implying crustal contamination. Four samples, however, have less radiogenic Pb and Sr that we suggest approximate their uncontaminated source. All basalt types, but particularly the low-Ti types, contain samples with trace element characteristics (e.g. Nb/Nb-*) suggesting metasediment input, considered source-related. Radiogenic isotope compositions of these samples require long-term isolation of the source in the mantle and depletions (relative to unmodified sediment) in certain elements (e.g. Cs, Pb, U), which are possibly subduction-related. A geodynamic model is proposed in which the emerging Tristan plume entrained subducted material in the Transition Zone region, and further entrained asthenosphere during plume head expansion. Mixing calculations suggest that the main features of the Etendeka basalt types can be explained without sub-continental lithospheric mantle input. Crustal contamination is evident in most low-Ti basalts, but is distinct from the incorporation of a metasedimentary source component at mantle depths.

A cohort study of early neurological consultation by telemedicine on the care of neurological inpatients

Objectives: To find out the effect of early neurological consultation using a real time video link on the care of patients with neurological symptoms admitted to hospitals without neurologists on site. Methods: A cohort study was performed in two small rural hospitals: Tyrone County Hospital (TCH), Omagh, and Erne Hospital, Enniskillen. All patients over 12 years of age who had been admitted because of neurological symptoms, over a 24 week period, to either hospital were studied. Patients admitted to TCH, in addition to receiving usual care, were offered a neurological consultation with a neurologist 120 km away at the Neurology Department of the Royal Victoria Hospital, Belfast, using a real time video link. The main outcome measure was length of hospital stay; change of diagnosis, mortality at 3 months, inpatient investigation, and transfer rate and use of healthcare resources within 3 months of admission were also studied. Results: Hospital stay was significantly shorter for those admitted to TCH (hazard ratio 1.13; approximate 95% Cl 1.003 to 1.282; p = 0.045). No patients diagnosed by the neurologist using the video link subsequently had their diagnosis changed at follow up. There was no difference in overall mortality between the groups. There were no differences in the use of inpatient hospital resources and medical services in the follow up period between TCH and Erne patients. Conclusions: Early neurological assessment reduces hospital stay for patients with neurological conditions outside of neurological centres. This can be achieved safely at a distance using a real time video link.