다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

J. Appl. Cryst.の発刊に際して

The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Results Baseline levels of IL-6 (P,001) and CRP (P,001) were significantly higher among cases than among controls The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 75 for IL-6 (95% confidence interval [CI], 37-154) and 157 for CRP (95% CI, 65-379) Positive associations persisted after adjustment for body mass index, family history of diabetes, smoking, exercise, use of alcohol, and hormone replacement therapy; multivariate relative risks for the highest vs lowest quartiles were 23 for IL-6 (95% CI, 09-56; P for trend=07) and 42 for CRP (95% CI, 15-120; P for trend=001) Similar results were observed in analyses limited to women with a baseline hemoglobin A1c of 60% or less and after adjustment for fasting insulin level

https://jamanetwork.com/journals/jama/articlepdf/1150732/JOC10096.pdf

C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus

Microalgae represent an exceptionally diverse but highly specialized group of micro-organisms adapted to various ecological habitats. Many microalgae have the ability to produce substantial amounts (e.g. 20-50% dry cell weight) of triacylglycerols (TAG) as a storage lipid under photo-oxidative stress or other adverse environmental conditions. Fatty acids, the building blocks for TAGs and all other cellular lipids, are synthesized in the chloroplast using a single set of enzymes, of which acetyl CoA carboxylase (ACCase) is key in regulating fatty acid synthesis rates. However, the expression of genes involved in fatty acid synthesis is poorly understood in microalgae. Synthesis and sequestration of TAG into cytosolic lipid bodies appear to be a protective mechanism by which algal cells cope with stress conditions, but little is known about regulation of TAG formation at the molecular and cellular level. While the concept of using microalgae as an alternative and renewable source of lipid-rich biomass feedstock for biofuels has been explored over the past few decades, a scalable, commercially viable system has yet to emerge. Today, the production of algal oil is primarily confined to high-value specialty oils with nutritional value, rather than commodity oils for biofuel. This review provides a brief summary of the current knowledge on oleaginous algae and their fatty acid and TAG biosynthesis, algal model systems and genomic approaches to a better understanding of TAG production, and a historical perspective and path forward for microalgae-based biofuel research and commercialization.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-313X.2008.03492.x

Microalgal triacylglycerols as feedstocks for biofuel production: perspectives and advances

Bone marrow harbors cells that have the capacity to differentiate into cells of nonhematopoietic tissues of neuronal, endothelial, epithelial, and muscular phenotype. Here we demonstrate that bone marrow-derived cells populate pancreatic islets of Langerhans. Bone marrow cells from male mice that express, using a CRE-LoxP system, an enhanced green fluorescent protein (EGFP) if the insulin gene is actively transcribed were transplanted into lethally irradiated recipient female mice. Four to six weeks after transplantation, recipient mice revealed Y chromosome and EGFP double-positive cells in their pancreatic islets. Neither bone marrow cells nor circulating peripheral blood nucleated cells of donor or recipient mice had any detectable EGFP. EGFP-positive cells purified from islets express insulin, glucose transporter 2 (GLUT2), and transcription factors typically found in pancreatic beta cells. Furthermore, in vitro these bone marrow-derived cells exhibit - as do pancreatic beta cells - glucose-dependent and incretin-enhanced insulin secretion. These results indicate that bone marrow harbors cells that have the capacity to differentiate into functionally competent pancreatic endocrine beta cells and that represent a source for cell-based treatment of diabetes mellitus. The results generated with the CRE-LoxP system also suggest that in vivo cell fusion is an unlikely explanation for the "transdifferentiation" of bone marrow-derived cells into differentiated cell phenotypes.

/pdf/in-vivo-derivation-of-glucose-competent-pancreatic-endocrine-4h2kzr36ge.pdf

In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion

The modulation of voltage-dependent calcium channels by hormones and neurotransmitters has important implications for the control of many Ca2+-dependent cellular functions including exocytosis and contractility1–7. We made use of electrophysiological techniques, including whole-cell patch-clamp recordings from dorsal root ganglion (DRG) neurones, to demonstrate a role for GTP-binding proteins (G-proteins) as signal transducers in the noradrenaline- and γ-aminobutyric acid (GABA)-induced inhibition of voltage-dependent calcium channels8–11. This action of the transmitters was blocked by: (1) preincubation of the cells with pertussis toxin (a bacterial exotoxin catalysing ADP-ribosylation of G-proteins12); or (2) intracellular administration of guanosine 5′-O-(2-thiodiphosphate) (GDP-β-S), a non-hydrolysable analogue of GDP that competitively inhibits the binding of GTP to G-proteins13. Our findings provide the first direct demonstration of the G-protein-mediated inhibition of voltage-dependent calcium channels by neurotransmitters. This mode of transmitter action may explain the ability of noradrenaline and GABA to presynaptically inhibit Ca2+-dependent neurosecretion from DRG sensory neurones4,5.

/pdf/gtp-binding-proteins-mediate-transmitter-inhibition-of-3o2nz6xbbn.pdf

GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels.

Non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes) is a disorder of glucose homeostasis characterized by hyperglycaemia, peripheral insulin resistance, impaired hepatic glucose metabolism, and diminished glucose-dependent secretion of insulin from pancreatic beta-cells. Glucagon-like-peptide-1(7-37) (GLP-1) is an intestinally derived hormone that may be useful for the treatment of NIDDM because it acts in vivo to increase the level of circulating insulin, and thus lower the concentration of blood glucose. This therapeutic effect may result from the ability of GLP-1 to compensate for a defect in the glucose signalling pathway that regulates insulin secretion from beta-cells. In support of this concept we report here that GLP-1 confers glucose sensitivity to glucose-resistant beta-cells, a phenomenon we term glucose competence. Induction of glucose competence by GLP-1 results from its synergistic interaction with glucose to inhibit metabolically regulated potassium channels that are also targeted for inhibition by sulphonylurea drugs commonly used in the treatment of NIDDM. Glucose competence allows membrane depolarization, the generation of action potentials, and Ca2+ influx, events that are known to trigger insulin secretion.

/pdf/pancreatic-beta-cells-are-rendered-glucose-competent-by-the-qwfkqgc794.pdf

Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37)

In the genetic mutant mouse models ob/ob or db/db , leptin deficiency or resistance, respectively, results in severe obesity and the development of a syndrome resembling NIDDM. One of the earliest manifestations in these mutant mice is hyperinsulinemia, suggesting that leptin may normally directly suppress the secretion of insulin. Here, we show that pancreatic islets express a long (signal-transducing) form of leptin-receptor mRNA and that β-cells bind a fluorescent derivative of leptin (Cy3-leptin). The expression of leptin receptors on insulin-secreting β-cells was also visualized utilizing antisera generated against an extracellular epitope of the receptor. A functional role for the β-cell leptin receptor is indicated by our observation that leptin (100 ng/ml) suppressed the secretion of insulin from islets isolated from ob/ob mice. Furthermore, leptin produced a marked lowering of ]Ca 2+ ] i in ob/ob β-cells, which was accompanied by cellular hyperpolarization and increased membrane conductance. Cell-attached patch measurements of ob/ob β-Cells demonstrated that leptin activated ATP-sensitive potassium channels (K ATP ) by increasing the open channel probability, while exerting no effect on mean open time. These effects were reversed by the sulfonylurea tolbutamide, a specific inhibitor of K ATP . Taken together, these observations indicate an important physiological role for leptin as an inhibitor of insulin secretion and lead us to propose that the failure of leptin to inhibit insulin secretion from the β-Cells of ob/ob and db/db mice may explain, in part, the development of hyperinsulinemia, insulin resistance, and the progression to NIDDM.

https://diabetes.diabetesjournals.org/content/diabetes/46/6/1087.full.pdf

Leptin Suppression of Insulin Secretion by the Activation of ATP-Sensitive K + Channels in Pancreatic β-Cells

Recently published studies of islet cell function reveal unexpected features of glucagon-like peptide-1 (GLP-1) receptor-mediated signal transduction in the pancreatic beta-cell. Although GLP-1 is established to be a cAMP-elevating agent, these studies demonstrate that protein kinase A (PKA) is not the only cAMP-binding protein by which GLP-1 acts. Instead, an alternative cAMP signaling mechanism has been described, one in which GLP-1 activates cAMP-binding proteins designated as cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs, also known as Epac). Two variants of Epac (Epac1 and Epac2) are expressed in beta-cells, and downregulation of Epac function diminishes stimulatory effects of GLP-1 on beta-cell Ca(2+) signaling and insulin secretion. Of particular note are new reports demonstrating that Epac couples beta-cell cAMP production to the stimulation of fast Ca(2+)-dependent exocytosis. It is also reported that Epac mediates the cAMP-dependent mobilization of Ca(2+) from intracellular Ca(2+) stores. This is a process of Ca(2+)-induced Ca(2+) release (CICR), and it generates an increase of [Ca(2+)](i) that may serve as a direct stimulus for mitochondrial ATP production and secretory granule exocytosis. This article summarizes new findings concerning GLP-1 receptor-mediated signal transduction and seeks to define the relative importance of Epac and PKA to beta-cell stimulus-secretion coupling.

/pdf/epac-a-new-camp-binding-protein-in-support-of-glucagon-like-5a9jtkgbhi.pdf

George G. Holz

Papers

In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion

GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels.

Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37)

Leptin Suppression of Insulin Secretion by the Activation of ATP-Sensitive K + Channels in Pancreatic β-Cells

Epac: A New cAMP-Binding Protein in Support of Glucagon-Like Peptide-1 Receptor-Mediated Signal Transduction in the Pancreatic β-Cell