New Approach to Information Handling in General Practice

In this paper we describe the use of punched feature cards in a general practice for 18 months. Its advantages are the low cost, speed of information retrieval, visible statistics, computer compatibility, accuracy, confidentiality, flexibility, and simplicity of setting up and collection of information. The system encourages the doctor to ask questions about his practice, and could readily be adopted in other practices.     

Results of Treatment of Thyrotoxicosis after Postoperative Relapse

Ninety patients who had a recurrence of thyrotoxicosis after thyroidectomy have been reviewed. All 10 patients who had a second operation and 18 out of 20 patients treated with a full course of antithyroid drugs relapsed. These results differ greatly from the results of treatment of the first episode of thyrotoxicosis, whether by thyroidectomy or antithyroid drugs. Radioiodine is the treatment of choice in this group of patients, despite the high incidence of hypothyroidism.     

Dichotomous effects of IFN-γ on dendritic cell function determine the extent of IL-12-driven antitumor T cell immunity

Sustained intratumoral delivery of IL-12 and GM-CSF can overcome tumor immune suppression and promote T cell-dependent eradication of established disease in murine tumor models. However, the antitumor effector response is transient and rapidly followed by a T suppressor cell rebound. The mechanisms that control the switch from an effector to a regulatory response in this model have not been defined. Because dendritic cells (DC) can mediate both effector and suppressor T cell priming, DC activity was monitored in the tumors and the tumor-draining lymph nodes (TDLN) of IL-12/GM-CSF-treated mice. The studies demonstrated that therapy promoted the recruitment of immunogenic DC (iDC) to tumors with subsequent migration to the TDLN within 24-48 h of treatment. Longer-term monitoring revealed that iDC converted to an IDO-positive tolerogenic phenotype in the TDLN between days 2 and 7. Specifically, day 7 DC lost the ability to prime CD8(+) T cells but preferentially induced CD4(+)Foxp3(+) T cells. The functional switch was reversible, as inhibition of IDO with 1-methyl tryptophan restored immunogenic function to tolerogenic DC. All posttherapy immunological activity was strictly associated with conventional myeloid DC, and no functional changes were observed in the plasmacytoid DC subset throughout treatment. Importantly, the initial recruitment and activation of iDC as well as the subsequent switch to tolerogenic activity were both driven by IFN-γ, revealing the dichotomous role of this cytokine in regulating IL-12-mediated antitumor T cell immunity.     

Guanine nucleotide-dependent pertussis-toxin-insensitive stimulation of inositol phosphate formation by carbachol in a membrane preparation from human astrocytoma cells.

The efficacy of muscarinic-receptor agonists for stimulation of inositol phosphate formation and Ca2+ mobilization in intact 1321N1 human astrocytoma cells is correlated with their capacity for formation of a GTP-sensitive high-affinity binding complex in membranes from these cells [Evans, Hepler, Masters, Brown & Harden (1985) Biochem. J. 232, 751-757]. These observations prompted the proposal that a guanine nucleotide regulatory protein serves to couple muscarinic receptors to the phospholipase C involved in phosphoinositide hydrolysis in 1321N1 cells. Inositol phosphate (InsP) formation was measured in a cell-free preparation from 1321N1 cells to provide direct support for this idea. The formation of InsP3, InsP2 and InsP1 was increased in a concentration-dependent manner (K0.5 approximately 5 microM) by guanosine 5'-[gamma-thio]triphosphate (GTP[S]) in washed membranes prepared from myo-[3H]inositol-prelabelled 1321N1 cells. Both GTP[S] and guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG) stimulated InsP formation by 2-3-fold over control; GTP, GDP and GMP were much less efficacious. Millimolar concentrations of NaF also stimulated the formation of inositol phosphates in membrane preparations from 1321N1 cells. In the presence of 10 microM-GTP[S], the muscarinic cholinergic-receptor agonist carbachol stimulated (K0.5 approximately 10 microM) the formation of InsP above that achieved with GTP[S] alone. The effect of carbachol was completely blocked by atropine. The order of potency of nucleotides for stimulation of InsP formation in the presence of 500 microM-carbachol was GTP[S] greater than p[NH]ppG greater than GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate Gi (the inhibitory guanine nucleotide regulatory protein), had no effect on InsP formation in the presence of GTP[S] or GTP[S] plus carbachol. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not Gi is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells.     

Reconciling Carbon-cycle Concepts, Terminology, and Methods

Recent projections of climatic change have focused a great deal of scientific and public attention on patterns of carbon (C) cycling as well as its controls, particularly the factors that determine whether an ecosystem is a net source or sink of atmospheric carbon dioxide (CO₂). Net ecosystem production (NEP), a central concept in C-cycling research, has been used by scientists to represent two different concepts. We propose that NEP be restricted to just one of its two original definitions—the imbalance between gross primary production (GPP) and ecosystem respiration (ER). We further propose that a new term—net ecosystem carbon balance (NECB)—be applied to the net rate of C accumulation in (or loss from [negative sign]) ecosystems. Net ecosystem carbon balance differs from NEP when C fluxes other than C fixation and respiration occur, or when inorganic C enters or leaves in dissolved form. These fluxes include the leaching loss or lateral transfer of C from the ecosystem; the emission of volatile organic C, methane, and carbon monoxide; and the release of soot and CO₂ from fire. Carbon fluxes in addition to NEP are particularly important determinants of NECB over long time scales. However, even over short time scales, they are important in ecosystems such as streams, estuaries, wetlands, and cities. Recent technological advances have led to a diversity of approaches to the measurement of C fluxes at different temporal and spatial scales. These approaches frequently capture different components of NEP or NECB and can therefore be compared across scales only by carefully specifying the fluxes included in the measurements. By explicitly identifying the fluxes that comprise NECB and other components of the C cycle, such as net ecosystem exchange (NEE) and net biome production (NBP), we can provide a less ambiguous framework for understanding and communicating recent changes in the global C cycle.     

Signal Integration by Shadow Enhancers and Enhancer Duplications Varies across the Drosophila Embryo

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The response of soil organic carbon of a rich fen peatland in interior Alaska to projected climate change

It is important to understand the fate of carbon in boreal peatland soils in response to climate change because a substantial change in release of this carbon as CO₂ and CH₄ could influence the climate system. The goal of this research was to synthesize the results of a field water table manipulation experiment conducted in a boreal rich fen into a process‐based model to understand how soil organic carbon (SOC) of the rich fen might respond to projected climate change. This model, the peatland version of the dynamic organic soil Terrestrial Ecosystem Model (peatland DOS‐TEM), was calibrated with data collected during 2005–2011 from the control treatment of a boreal rich fen in the Alaska Peatland Experiment (APEX). The performance of the model was validated with the experimental data measured from the raised and lowered water‐table treatments of APEX during the same period. The model was then applied to simulate future SOC dynamics of the rich fen control site under various CO₂ emission scenarios. The results across these emissions scenarios suggest that the rate of SOC sequestration in the rich fen will increase between year 2012 and 2061 because the effects of warming increase heterotrophic respiration less than they increase carbon inputs via production. However, after 2061, the rate of SOC sequestration will be weakened and, as a result, the rich fen will likely become a carbon source to the atmosphere between 2062 and 2099. During this period, the effects of projected warming increase respiration so that it is greater than carbon inputs via production. Although changes in precipitation alone had relatively little effect on the dynamics of SOC, changes in precipitation did interact with warming to influence SOC dynamics for some climate scenarios.     

Turkey erythrocyte membranes as a model for regulation of phospholipase C by guanine nucleotides

Phosphoinositides of human, rabbit, rat, and turkey erythrocytes were radiolabeled by incubation of intact cells with [32P]Pi. Guanosine 5'-O-(thiotriphosphate) (GTP gamma S) and NaF, which are known activators of guanine nucleotide regulatory proteins, caused a large increase in [32P]inositol phosphate release from plasma membranes derived from turkey erythrocytes, but had no effect on inositol phosphate formation by plasma membranes prepared from the mammalian erythrocytes. High performance liquid chromatography analysis indicated that inositol bisphosphate, inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate all increased by 20-30-fold during a 10-min incubation of turkey erythrocyte membranes with GTP gamma S. The increase in inositol phosphate formation was accompanied by a similar decrease in radioactivity in phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2). GTP gamma S increased inositol phosphate formation with a K0.5 of 600 nM; guanosine 5'-(beta, gamma-imido)trisphosphate was 50-75% as efficacious as GTP gamma S and expressed a K0.5 of 36 microM. Although GTP alone had little effect on inositol phosphate formation, it blocked GTP gamma S-stimulated inositol phosphate formation, as did guanosine 5'-O-(2-thiodiphosphate). Turkey erythrocytes were also shown to express phosphatidylinositol synthetase activity in that incubation of cells with [3H] inositol resulted in incorporation of radiolabel into phosphatidylinositol, PIP, and PIP2. Incubation of membranes derived from [3H]inositol-labeled erythrocytes with GTP gamma S resulted in large increases in [3H] inositol phosphate formation and corresponding decreases in radiolabel in PIP and PIP2. The data suggest that, in contrast to mammalian erythrocytes, the turkey erythrocyte expresses a guanine nucleotide-binding protein that regulates phospholipase C, and as such, should provide a useful model system for furthering our understanding of hormonal regulation of this enzyme.