tbuckley/cabot-search huggingface dataset:
Thrombosis and Hemorrhage
Authors: Shirley Parker Levine
Journal: JAMA (1995)

This is the first edition of a multiauthored text on hemostasis and clinical disorders of blood clotting and thrombosis. The first third of the book is divided into three major sections: coagulation and fibrinolysis, platelets, and the vessel wall. Each chapter in these sections is an indepth discussion of a specific aspect of physiologic hemostasis and includes the molecular biology, biology, and biochemistry of clotting factors, platelets, and endothelial cells. The information is very detailed and could be used as a definitive reference on the structure and function of all important molecules and cells that support or inhibit hemostasis. The text is supported by excellent diagrams and tables. There are good-quality color plates of megakaryocytes but minimal scanning or transmission electron micrographs. One of the major deficits of this basic section of the book is the absence of an initial detailed overview of both primary and secondary hemostasis, including endothelial
Factors Involved in Homograft Tolerance
Authors: J. Bradley Aust, Ronald D. Guttmann
Journal: JAMA (1963)

FOLLOWING THE EXAMPLE of Billingham et al,<sup>1</sup>it has been possible to produce acquired tolerance of homologous tissues between many strains of mice in the newborn period. It is accepted that the rejection of homografts is an immunological reaction mediated by cells derived from the reticuloendothelial system. Tolerance is most easily produced in fetal life or in the newborn period when the animal is still immunologically immature. The greater the genetic disparity between graft and host, the more difficult it is to produce tolerance. The larger the antigen dose, the more readily tolerance is effected. Owen's<sup>2</sup>model of the dizygotic twin cattle, who throughout life each circulated red blood cell genotypes derived from both partners, led Burnet and Fenner<sup>3</sup>to postulate that an animal challenged with antigen during fetal life prior to development of immunological competence would thereafter be unable to respond to further challenge with
Key risks to children's health are socioeconomic, says global health report
Authors: A. Gulland
Journal: BMJ (2013)

Specific calls for global action on health and other social issues can have a major effect on children’s life chances, concludes a report that compared data on laws and public policies affecting children in 191 countries.

Children’s Chances looked at policies in a range of areas, including health, education, discrimination, and labour laws.1 It aimed to look quantitatively at what steps governments could take to improve children’s chances, said its author, Jody Heymann, dean of the Fielding School of Public Health at the University of California.

Paid maternity leave of 14 weeks or more was one example of a global call to action, made by the International Labour Organisation in 2000, and has had a dramatic effect on governments’ policies, she …
Restructuring health care in the Third World
Authors: M. Carpenter
Journal: JAMA (1982)

The delegates to a World Health Organization (WHO) conference on primary health care (PHC) came to a general agreement that in Third World hospitals research should focus on community needs rather than on technical subjects; education should focus on preparing and sending physicians in the community rather than in specialized settings; and patient care should focus on creating health services away from the hospital as well as effective referral systems.  Western-style hospitals tend to be unsuited to the PHC needs of Third World peoples such as sanittation potable water food and other services.  An important area of health service research is role reallocation or the ways in which much medical care can be routinized so that health workers could take on much of the responsibility usually delegated to physicians.  In this way widespread health problems such as diarrhea marasmus and neonatal tetanus can be handled first on the community level so that the hospital is not overloaded with cases that could have been prevented much earlier.  Health services research should define 1) what type of knowledge is needed for community health; 2) how patient data collection can be used to improve quality of service; 3) how to prevent shortages in the drug supply due to inefficiency poor transportation and hot weather; and 4) how to use appropriate technology.  Medical education should be reoriented to allow medical students to get a balanced exposure to clinical medicine epidemiology and family and community health.  Programs should allow physicians to experience community practice and to learn how to use volunteer health workers to their advantage.  Patient care is difficult in Third World hospitals because of small staff shortages of drugs and lack of beds.  The problems villagers have reaching the hospital and adjusting to an unfamiliar urban atmosphere might be lessened if the rural areas were linked to the hospital through referral systems.  A group of local research centers is needed to adapt integrated program principles to local conditions.
Pathway-Based Analysis Tools for Complex Diseases: A Review
Authors: Lv Jin, Xiao-Yu Zuo, Wei-Yang Su, Xiao-Lei Zhao, Man-Qiong Yuan, Li-Zhen Han, Xiang Zhao, Ye-Da Chen, Shao-Qi Rao
Journal: Genomics Proteomics & Bioinformatics (2014)

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases.
Adenosine and adenosine antagonism in asthma
Authors: C. PERSSON;, S. T HOLGATE
Journal: Thorax (1998)

The antinociceptive effect of (±)-3-α-tropanyl-(2-Cl)-acid phenoxybutyrate (SM-21) (10–40 mg kg<sup>−1</sup> s.c., 10–30 mg kg<sup>−1</sup> i.p., 20–60 mg kg<sup>−1</sup> p.o., 3–20 mg kg<sup>−1</sup> i.v. and 5–20 μg per mouse i.c.v.) was examined in rodents and guinea pigs by using the hot-plate, abdominal constriction, tail-flick and paw-pressure tests. The antinociception produced by (±)-SM-21 was prevented by atropine, pirenzepine and hemicholinium-3 but not by quinpirole, R-(α)-methylhistamine, [1-[2(methylsufonyl)amino]ethyl]-4-piperidinyl]methyl-5-floro-2-methoxy-1H-indole-3-carboxylate hydrochloride, N<sup>6</sup>-cyclopentyladenosine, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide, naloxone, 3-aminopropyl-diethoxy-methyl-phosphinic acid or reserpine. On the basis of the above data, it can be postulated that (±)-SM-21 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. Affinity profiles of (±)-SM-21 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M<sub>1</sub>, guinea pig atrium for M<sub>2</sub>, guinea pig ileum for M<sub>3</sub> and immature guinea pig uterus for putative M<sub>4</sub>) have shown a selectivity ratio M<sub>2</sub>/M<sub>1</sub> of 4.6 that, although very low, might be responsible for the antinociception induced by (±)-SM-21 through an increase in ACh extracellular levels. In the antinociceptive dose range, (±)-SM-21 did not impair mouse performance evaluated by the rota-rod and hole-board tests.
Different Body-Fat Distributions in IDDM and NIDDM
Authors: Arye Lev-Ran, L Robert Hill
Journal: Diabetes Care (1987)

Stepwise logistic regression was used for the analysis of the following anthropometric parameters in 146 adult patients with diabetes: waist/hips ratio, waist/thighs ratio, ratio of the arms-to-thighs circumferences, and ratio of the subscapular-to-triceps skinfolds. After adjustment for age and body mass index, only the waist/thighs ratio was found to have an independent discriminating value between insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. The correlation of type of diabetes with the waist/thighs ratio was especially strong in women, exceeding even the role of age and body mass index. Other anthropometric parameters were related to type of diabetes through their correlation with waist/thighs ratio and had no independent discriminating value. The study shows that IDDM and NIDDM belong to different anthropometric types, which probably reflects their different pathogenesis.
The Challenge of Medical-Care Insurance
Authors: C. Marshall Lee
Journal: New England Journal of Medicine (1960)

Many years, and perhaps centuries, must pass before the current will acquire a settled direction. Our hopes... for sudden tranquility ought not to be too sanguine. Fanaticism and superstition will still be selfish, subtle, intriguing... despotism will still struggle for domination;... democracy will envy all, contend with all, endeavor to pull down all... These and other elements will yet, for a long time, continue a fermentation.... (Part of a letter from John Adams to Thomas Jefferson, July 16, 1814.†)IN the United States people like to believe that the fundamental social and economic structure is predicated on the assumption . . .
Preference and resistance to change do not always covary
Authors: Masaharu Takahashi
Journal: Behavioral and Brain Sciences (2000)

Nevin &amp; Grace's primary argument against theory and research on behavioral momentum is that preference and resistance to change may not covary. The method for evaluating preference and resistance to change seems problematic. Moreover, the theory fails to account convincingly for effects of average overall time to primary reinforcement on choice and preference for unsegmented schedules.
Molecular Variant of Angiotensinogen Gene Is Associated With Coronary Atherosclerosis
Authors: Tomoaki Ishigami, Satoshi Umemura, Tamio Iwamoto, Kouichi Tamura, Kiyoshi Hibi, Satoshi Yamaguchi, Nobuo Nyuui, Kazuo Kimura, Naomichi Miyazaki, Masao Ishii
Journal: Circulation (1995)

Background A positive association was previously reported between angiotensin-converting enzyme (ACE) gene polymorphism and several cardiovascular diseases, such as myocardial infarction, left ventricular hypertrophy, and restenosis after percutaneous transluminal coronary angioplasty. Plasma ACE activity and carotid-wall thickening measured by ultrasonography were related, and it was postulated that long-term exposure to high levels of plasma ACE could be involved in structural changes of the arterial wall. In addition, angiotensinogen gene mutation was recently reported to be associated with essential hypertension and preeclampsia. There exists a possibility that the renin-angiotensin system plays an important role in the progress of cardiovascular diseases in humans. Therefore, we examined the association between the molecular variant of the angiotensinogen gene and coronary atherosclerosis. Methods and Results This study included 82 patients who had coronary atherosclerosis and 160 control subjects; all study participants were Japanese. All patients with coronary atherosclerosis had at least one coronary artery with &gt;25% luminal diameter obstruction on average according to multiple coronary angiographic views. Angiotensinogen gene molecular variants were designated AA , Aa , and aa . The a allele indicated thymine-cytosine transition at nucleotide 704 in exon 2. Genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction was performed to amplify the concerned region of the angiotensinogen gene. After restriction enzyme digestion, it was possible to distinguish the molecular variant of the angiotensinogen gene. The frequencies of these genotypes were 7.3%, 26.8%, and 65.9% in the patients and 18.8%, 31.9%, and 49.3% in the control subjects for the AA , Aa , and aa allelles, respectively. There was an excess in the a allele among patients ( P &lt;.01). Conclusions We found a significant association between coronary atherosclerosis and a molecular variant of the angiotensinogen gene. The results suggested that the molecular variant of the angiotensinogen gene could be a new risk factor for coronary atherosclerosis.
Necrotic ulcerations on the back of the hands in a patient with chronic renal failure: An uncommon presentation of calciphylaxis
Authors: Maider Pretel Irazabal, Laura Marques Martin, Miguel Ángel Idoate Gastearena, Tania Labiano Miravalles, Nuria García Fernández
Journal: Journal of the American Academy of Dermatology (2012)
Neuronal SH2B1 is essential for controlling energy and glucose homeostasis
Authors: Decheng Ren, Yingjiang Zhou, David Morris, Minghua Li, Zhiqin Li, Liangyou Rui
Journal: Journal of Clinical Investigation (2007)

SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (α, β, γ, and/or δ) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1β was specifically expressed in neural tissue in SH2B1-transgenic (SH2B1Tg) mice. SH2B1Tg mice were crossed with SH2B1-knockout (SH2B1KO) mice to generate SH2B1TgKO mice expressing SH2B1 only in neural tissue but not in other tissues. Systemic deletion of the SH2B1 gene resulted in metabolic disorders in SH2B1KO mice, including hyperlipidemia, leptin resistance, hyperphagia, obesity, hyperglycemia, insulin resistance, and glucose intolerance. Neuron-specific restoration of SH2B1β not only corrected the metabolic disorders in SH2B1TgKO mice, but also improved JAK2-mediated leptin signaling and leptin regulation of orexigenic neuropeptide expression in the hypothalamus. Moreover, neuron-specific overexpression of SH2B1 dose-dependently protected against high-fat diet–induced leptin resistance and obesity. These observations suggest that neuronal SH2B1 regulates energy balance, body weight, peripheral insulin sensitivity, and glucose homeostasis at least in part by enhancing hypothalamic leptin sensitivity.
Use of Arterial Transfer Functions for the Derivation of Central Aortic Waveform Characteristics in Subjects With Type 2 Diabetes and Cardiovascular Disease
Authors: Sarah A. Hope, David B. Tay, Ian T. Meredith, James D. Cameron
Journal: Diabetes Care (2004)

OBJECTIVE—Optimal blood pressure control in subjects with diabetes reduces cardiovascular complications. There is theoretical benefit in the assessment of central aortic waveforms including the augmentation index, which is taken as a putative index of stiffness. Transfer functions may be used to reconstruct aortic from radial pressure waveforms; however, a single generalized transfer function may not be appropriate for all patients. We aimed to evaluate the technique in subjects with diabetes. RESEARCH DESIGN AND METHODS—Simultaneous invasive central aortic and noninvasive radial waveforms were acquired in 19 subjects with type 2 diabetes, and a diabetes-specific transfer function was derived. Similar data were acquired from 38 age- and sex-matched subjects without diabetes. Central waveforms were reconstructed using a generalized transfer function in all patients and the diabetes-specific transfer function in individuals with diabetes. RESULTS—There was no difference between groups in measured central pressures. The error in generalized transfer function-derived systolic pressure was greater in individuals with diabetes (6 ± 7 mmHg) (mean ± SD) than without diabetes (2 ± 8 mmHg) (P &amp;lt; 0.05). Errors in other parameters were no different. The diabetes-specific transfer function reduced the error in derived systolic pressure to 0 ± 7 mmHg in individuals with diabetes—no different than that with the generalized transfer function in individuals without diabetes. The central augmentation index reconstructed by either transfer function was unrelated to that directly measured. CONCLUSIONS—A generalized transfer function is inappropriate for the derivation of central waveforms in subjects with type 2 diabetes. Errors in subjects with diabetes might be reduced with a diabetes-specific transfer function.
MS-31 * INTRACRANIAL MENINGIOMAS COMPLICATED BY HYPERTENSION: FOUR CASE REPORTS
Authors: H. Zhen, W. Zhao, X. Yang, J. Wang, J. Zhao, J. Huo, X. Zhang, Z. Fei
Journal: Neuro-Oncology (2014)

BACKGROUND: The etiology and mechanism of both meningioma and hypertension are still not fully understood, and their diagnosis and treatment still need to be improved. The phenomenon that some meningiomas can directly lead hypertension was never reported previously. Here we reported four consecutive cases with hypertension secondary to intracranial meningiomas. CASE PRESENTATION: Case 1 was a 62-year-old woman with a meningioma (size: about 2.0 cm × 1.6 cm × 1.5 cm) at left frontal lobe and with a medical history of hypertension for 10 years; Case 2 was a 50-year-old woman with a meningioma (size: about 1.5 cm × 1.2 cm × 1.1 cm) at right parietal lobe and with a medical history of hypertension for 4 years; Case 3 was a 42-year-old woman with a meningioma (size: about 2.7 cm × 2.6 cm × 2.3 cm) in trigonum of left lateral ventricle and with a medical history of hypertension for 3 months; Case 4 was a 56-year-old woman with a meningioma (size: about 2.0 cm × 1.8 cm × 1.5 cm) at bilateral falx of frontal lobe and with a medical history of hypertension for 8 years. All the four cases were treated in our hospital from April to June in 2013. After surgical resection of the tumors, blood pressure of all the patients returned to normal level in a short term, and it remained stable for 10 to 12 months of postoperative follow-up period. CONCLUSION: These four cases may present a new clinical syndrome and provide important clinical insights, and also should attract the attention of clinicians, i.e. in patients with hypertension, coexisting intracranial meningiomas should be suspected, and appropriate diagnosis and aggressive surgical treatment should be provided; for patients with hypertension secondary to meningiomas, their hypertension can be cured after surgical removal of the tumors.
Ex Vivo Cryoimaging for Plaque Characterization
Authors: Ali Faramarzalian, David Prabhu, Ahmad Abdul-Aziz, Wei Wang, Daniel Chamie, Hirosada Yamamoto, Yusuke Fujino, Sami Hawwa, Nicholas P. Ziats, Andrew M. Rollins, David L. Wilson, Marco A. Costa, Hiram G. Bezerra
Journal: JACC. Cardiovascular imaging (2014)
Triglyceride Storage Disease: A Disorder of Lipolysis in Adipose Tissue in Two Patients
Authors: C. Gilbert, D. J. Galton, J. Kaye
Journal: BMJ (1973)

An obese patient was studied whose adipose tissue showed a significant reduction in release of glycerol (P < 0.05) when stimulated by isoprenaline despite normal rises in tissue levels of cyclic-AMP. However, lipolysis was stimulated by a fast of 14 days as judged by weight loss and a rise in plasma fatty acids from 0.4 to 1.2 mM. The defect in this patient may be familial since her obese daughter also showed diminished release of glycerol from adipose tissue on three occasions when stimulated by isoprenaline, despite normal rises in levels of cyclic-AMP.
The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury.
Authors: M Takada, A Chandraker, K C Nadeau, M H Sayegh, N L Tilney
Journal: Journal of Clinical Investigation (1997)

Ischemia/reperfusion injury associated with organ retrieval and storage influences the development of chronic graft dysfunction, the major clinical problem in solid organ transplantation. The potential role of mononuclear cells (T cells and monocyte/macrophages) in this type of injury is unknown. Inbred male Lewis rats were uninephrectomized and the left kidney perfused in situ with 10 ml of iced University of Wisconsin solution. Immunohistological studies showed mononuclear cell infiltration of the ischemic organs associated with the upregulation of MHC class II antigen expression. Reverse transcriptase-PCR indicated that T cell associated cytokines and monocyte/macrophage activation markers/products are upregulated early after the ischemic insult. B7 expression occurred within 24 h and peaked at 3 d. Plasma creatinine levels rose transiently with complete recovery of renal function by 5 d. Animals began to develop progressive proteinuria after 8-12 wk, indicative of the long-term functional consequences of early ischemia/reperfusion injury. Blockade of T cell CD28-B7 costimulation with CTLA4Ig resulted in significant inhibition of T cell and macrophage infiltration and activation in situ. Treated animals did not exhibit transient renal dysfunction, nor developed proteinuria over time. This is the first demonstration that blocking T cell costimulatory activation in the absence of alloantigen can prevent the early and late consequences of ischemia/reperfusion injury.
Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury
Authors: Jon Cardinal, Pinhua Pan, Rajeev Dhupar, Mark Ross, Atsunori Nakao, Michael Lotze, Timothy Billiar, David Geller, Allan Tsung
Journal: Hepatology (2009)

The nuclear protein high mobility group box 1 (HMGB1) is an important inflammatory mediator involved in the pathogenesis of liver ischemia/reperfusion (I/R) injury. Strategies aimed at preventing its release from stressed or damaged cells may be beneficial in preventing inflammation after I/R. Cisplatin is a member of the platinating chemotherapeutic agents and can induce DNA lesions that are capable of retaining high mobility group proteins inside the nucleus of cells. In vitro studies in primary cultured rat hepatocytes show that nontoxic concentrations of cisplatin can sequester HMGB1 inside the nucleus of hypoxic cells. Similarly, the in vivo administration of nontoxic doses of cisplatin prevents liver damage associated with a well-established murine model of hepatic I/R as measured by lower circulating serum aminotransferase levels, lower hepatic inflammatory cytokine levels including tumor necrosis factor α and interleukin-6, lower inducible NO synthase expression, and fewer I/R-associated histopathologic changes. The mechanism of action in vivo appears to involve the capacity of cisplatin to prevent the I/R-induced release of HMGB1 as well as to alter cell survival and stress signaling in the form of autophagy and mitogen-activated protein kinase activation, respectively. Conclusion: Low, nontoxic doses of cisplatin can sequester HMGB1 inside the nucleus of redox-stressed hepatocytes in vitro and prevent its release in vivo in a murine model of hepatic I/R. Furthermore, cell survival and stress signaling pathways are altered by low-dose cisplatin. Therefore, platinating agents may provide a novel approach to mitigating the deleterious effects of I/R-mediated disease processes. (HEPATOLOGY 2009.)