tbuckley/cabot-search huggingface dataset:
Development of Endothelium-Dependent Relaxation in Canine Coronary Collateral Arteries
Authors: Julie A. Rapps, Paul R. Myers, Qiao Zhong, Janet L. Parker
Journal: Circulation (1998)

Background —Little information exists regarding development of vasomotor control mechanisms during coronary collateral artery maturation. Therefore, we studied endothelium-dependent relaxation of canine collateral arteries isolated 2, 4, and 9 months after placement of an ameroid occluder around the proximal left circumflex coronary artery. Results —Collateral arteries isolated after 2 months exhibited markedly reduced endothelium-dependent relaxation in response to acetylcholine (ACh; 10 −10 to 10 −4 mol/L) and bradykinin (BK; 10 −11 to 10 −6 mol/L) compared with relaxation of noncollateral coronary arteries ( P &lt;0.01). In contrast, endothelium-independent relaxation of collateral arteries to nitroprusside was only slightly reduced compared with relaxation of noncollateral arteries ( P &lt;0.05). Endothelium-dependent relaxation of collateral arteries isolated after 4 and 9 months was increased significantly, to the extent that relaxation to ACh and BK was not significantly different between collateral and noncollateral arteries at these periods. Inhibition of nitric oxide synthesis with N Τ -nitro- l -arginine methyl ester (L-NAME; 100 μmol/L) markedly inhibited ACh-induced relaxation in all noncollateral arteries and in collateral arteries isolated after 9 months. However, neither L-NAME nor indomethacin (5 μmol/L) alone inhibited ACh-mediated relaxation of collateral arteries isolated after 4 months. ACh-induced relaxation of these collateral arteries was only inhibited when arteries were preconstricted with 30 mmol/L K + and pretreated with L-NAME and indomethacin (ie, when synthesis/effects of nitric oxide, prostaglandins, and endothelium-derived hyperpolarizing factor were inhibited). Conclusions —Development of endothelium-dependent relaxation in canine coronary collateral arteries is not complete after 2 months. After 4 months, endothelium-dependent relaxation of collateral arteries is similar to relaxation of noncollateral arteries, but the relaxation exhibits decreased dependence on synthesis of nitric oxide and increased involvement of prostaglandins and endothelium-derived hyperpolarizing factor(s). After 9 months of development, collateral arteries exhibit normal nitric oxide–dependent relaxation, similar to noncollateral arteries.
Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology
Authors: Vered Molho-Pessach, Jonathan J. Rios, Chao Xing, Kenneth D.R. Setchell, Jonathan C. Cohen, Helen H. Hobbs
Journal: Hepatology (2011)

The most common inborn error of bile acid metabolism is 3β-hydroxy-Δ(5)-C(27)-steroid oxidoreductase (3β-HSD) deficiency, a disorder that usually presents in early childhood with hepatic dysfunction. Timely diagnosis of this disorder is crucial because it can be effectively treated with primary bile acid replacement. Here we describe a 24-year-old woman from Iran with cirrhosis of unknown etiology. Her sister and a first cousin died of cirrhosis (ages 19 and 6 years) and another 32-year-old first cousin had a self-limited liver disorder in childhood that resolved at age 9 years. The family history suggested that the affected family members were homozygous for a mutant allele inherited identical-by-descent. A genome-wide analysis of 2.4 million single nucleotide polymorphisms was performed to identify regions of homozygosity that were present in the proband and the 32-year-old first cousin, but not in a healthy relative. One of these regions contained the gene encoding 3β-HSD (HSD3B7). Sequence analysis of HSD3B7 revealed that the proband and her 32-year-old cousin were homozygous for a frameshift mutation (c.45_46del AG, p.T15Tfsx27) in exon 1. The diagnosis of 3β-HSD deficiency was confirmed by documenting high levels of 3β-hydroxy-Δ(5) bile acids in the serum of the proband and the 32-year-old first cousin using mass spectrometry. To our knowledge, the 32-year-old relative in this family represents the oldest asymptomatic patient with this disorder.This study highlights the clinical utility of homozygosity mapping in diagnosing autosomal recessive metabolic disorders. This family illustrates the wide variation in expressivity that occurs in 3β-HSD deficiency and underscores the need to consider a bile acid synthetic defect as a possible cause of liver disease in adults.
Doctors in The Human Comedy (Guillaume Dupuytren, Jean Baptiste Bouillaud, Francois Joseph Victor Broussais, Francois Magendie)
Authors: F. N. Poynter
Journal: JAMA (1968)

It was in 1833 that Honoré de Balzac first had the idea of a great series of novels which would present a complete picture of the human scene, depicting the character of man and society in all its aspects and in every situation. But this grandiose plan was not meant to be merely descriptive, for it was inspired throughout by a unifying philosophy which claimed to show<i>why</i>man is as he is and why the social structure takes the form it does. He had already worked out the number of volumes—48— needed to present this panoramic view of mankind, but it was six years later that he first invited comparison, or contrast, with Dante's great epic by giving the series the title<i>La Comédie Humaine</i>. Balzac was living and writing in Paris, the city which is still for all Frenchmen<i>le monde</i>, as it certainly was in 1833. If
The future of general practice. Caring for larger lists.
Authors: G N Marsh
Journal: BMJ (1991)

To investigate the immunomodulating effects of IL-15 in vivo on mycobacterial infection, we used IL-15-transgenic (Tg) mice, which were recently constructed with cDNA-encoding secretable isoform of IL-15 precursor protein under the control of a MHC class I promoter. The IL-15-Tg mice exhibited resistance against infection with <i>Mycobacterium bovis</i> bacillus Calmette-Guérin (BCG), as assessed by bacteria growth. IFN-γ level in serum was significantly higher in IL-15-Tg mice than in non-Tg mice after BCG infection. NK cells were remarkably increased, and Ag-specific T cytotoxic 1 response mediated by CD8<sup>+</sup> T cells producing IFN-γ was significantly augmented in the IL-15-Tg mice following BCG infection. Neutralization of endogenous IFN-γ by in vivo administration of anti-IFN-γ mAb deteriorated the clearance of the bacteria. Depletion of of NK cells or CD8<sup>+</sup> T cells by invivo administration of anti-asialo-GM<sub>1</sub> Ab or anti-CD8 mAb hampered the exclusion of bacteria. Thus, overexpression of IL-15 in vivo enhanced protection against BCG infection via augmentation of NK and T cytotoxic 1 responses.
Altered proopiomelanocortin gene expression in adrenocorticotropin-producing nonpituitary tumors. Comparative studies with corticotropic adenomas and normal pituitaries.
Authors: Y de Keyzer, X Bertagna, F Lenne, F Girard, J P Luton, A Kahn
Journal: Journal of Clinical Investigation (1985)

In order to assess the mechanisms of proopiomelanocortin (POMC) gene expression in human ACTH-producing tumors, we performed the simultaneous evaluation of POMC products and messenger RNA (mRNA) in tissue fragments obtained from two corticotropic adenomas, five nonpituitary tumors, and two normal human pituitaries. The POMC products were examined using a combination of gel exclusion chromatography and four different radioimmunoassays directed against gamma 3 melanocyte stimulating hormone (gamma 3MSH), ACTH, gamma-lipotropin (gamma LPH), and beta-endorphin. The POMCmRNA was detected and analyzed by dot and northern blot hybridization using a single-stranded genomic DNA probe corresponding to the coding region of the human POMC gene. Tissue concentrations of POMC products and mRNA showed parallel distributions. Immunoreactive gamma 3MSH and gamma LPH patterns revealed only 16-kD fragment- and gamma LPH-like peptides in normal and tumoral pituitaries; additional gamma 3MSH- and/or beta MSH-like peptides were found in all five nonpituitary tumors. A single POMCmRNA of approximately 1,200 bases (b) was detected in normal and tumoral pituitaries; a single identical POMCmRNA was also found in four nonpituitary tumors. A thymic carcinoid tumor, in addition to the 1,200-b POMCmRNA, contained equal amounts of a second larger POMCmRNA of approximately 1,450 b. It is concluded that POMC gene expression appears qualitatively unaltered in corticotropic adenomas. In nonpituitary tumors, in contrast, abnormal POMC processing is frequent; in addition, an extra POMCmRNA was detected in a thymic tumor with a greater length than the normal mRNA; the mechanisms and pathophysiological implications of these modifications remain to be elucidated.
Separate Associations Between Visceral and Subcutaneous Adipose Tissue Distribution, Insulin and Glucose Levels in Obese Women
Authors: R Ross, L Fortier, R Hudson
Journal: Diabetes Care (1996)

OBJECTIVE The primary purpose of this study was to determine the separate associations between visceral (VAT) and subcutaneous adipose tissue (SAT) distribution, skeletal muscle (SM), and plasma insulin and glucose levels, and. A second objective was to determine whether anthropometric methods could be used to identify those women who are at increased metabolic risk. RESEARCH DESIGN AND METHODS Whole-body SAT, SM, and VAT volume were measured (in liters), using a multislice magnetic resonance imaging (MRI) protocol in 40 premenopausal obese women. Plasma insulin and glucose levels were measured after an overnight fast and in response to a 75-g oral glucose tolerance test (OGTT). RESULTS With the exception of fasting glucose, VAT was positively correlated with all insulin and glucose variables (P &amp;lt; 0.01). This observation remained true whether VAT was derived from multiple MR images (i.e., VAT volume [in liters]) or from a single MR image (i.e., VAT area [in squared centimeters]). Furthermore, the segmentation of intraperitoneal adipose tissue (portally drained adipose tissue) from VAT did not improve the observed relationships. VAT remained a significant (P &amp;lt; 0.05) correlate of insulin and glucose area after adjusting for either SAT or abdominal SAT (ASAT). SAT, ASAT, and SM volume were not related to any metabolic variable. Waist circumference (WC) was the single strongest anthropometric correlate for fasting insulin and insulin area (P &amp;lt; 0.05). Because it has been reported that disturbances in insulin-glucose homeostasis are more likely associated with a WC value &amp;gt; 1 m, in subjects matched for total adiposity, we compared the glucose and insulin area values for those with a WC above (n = 17) and below (n = 15) this value. The group with a WC &amp;gt; 1 m had significantly higher values for both insulin and glucose areas (P &amp;lt; 0.05). CONCLUSIONS The primary observation is that VAT is associated with plasma insulin and glucose variables independent of whole-body SAT, ASAT, and SM in obese women. In addition, the findings provide support for the utility of WC as an anthropometric tool that may be used to identify a subgroup of obese patients at increased metabolic risk.
Carcinoma In Situ Of the Uterine Cervix
Authors: James M. Ovens
Journal: JAMA (1973)

<h3>To the Editor.—</h3> In the Oct 30 issue ofThe Journal, the question was asked about how much time can safely elapse from the diagnosis of carcinoma in situ of the uterine cervix until a hysterectomy is done. The reply by the consultant indicated that hysterectomy could be done immediately, or a certain length of time up to six to eight weeks could be allowed. There is another very definite possibility in the treatment of carcinoma of the cervix not mentioned by the consultant. With a suspicious result for a Papanicolaou smear, quadrant biopsies, or Schiller's stains being used, a cold conization of the cervix can be done. Examination of the specimen removed at the cold cone may show carcinoma of the cervix in situ surrounded by normal tissue. If the coned site of the cervix is then allowed to heal, which it will do in about six weeks, Papanicolaou
Subdural Hematoma Following Administration of Urea for Diagnosis of Hypertension
Authors: Sumner Marshall, Frank Hinman
Journal: JAMA (1962)

THE INTRAVENOUS ADMINISTRATION of hypertonic urea solution has been advocated by Stamey in the diagnosis of unilateral renal disease by differential renal function studies. Its purpose is to promote maximal relative reabsorption of water in the ischmic kidney, and it also serves as an osmotic diuretic to assure satisfactory flow rates for the procedure. However, an additional effect of the infusion of urea solution is the decrease in cellular volume. When this occurs in the brain, intracranial hemorrhage may be precipitated. Report of a Case A 54-year-old male with known hypertension of many years duration, suffered a cerebrovascular accident in 1954 with resultant right hemiparesis. His hypertension was unsatisfactorily controlled by medical therapy. Physical examination revealed a blood pressure of 230/120 mm. Hg and a right hemiparesis marked by muscle atrophy and spasticity of the extremities on that side. A positive Babinski sign was noted on the right side. The
Chronic ethanol consumption stimulates hepatitis B virus gene expression and replication in transgenic mice
Authors: Jonathan Larkin, Marcia M. Clayton, Jie Liu, Mark A. Feitelson
Journal: Hepatology (2001)

Epidemiologic observations show a higher frequency of hepatitis B virus (HBV) serologic markers in chronic alcoholics compared with the general population. This may be the result of an increased susceptibility of alcoholics to infection and/or to an ethanol-mediated stimulation of HBV gene expression and replication. To test the latter hypothesis, HBV transgenic SCID mice, which support consistent levels of virus replication, were fed with a standard Lieber-DiCarli or isocaloric diet for 5 weeks. In ethanol-fed mice, the levels of hepatitis B surface antigen (HBsAg) and viral DNA in serum increased by up to 7-fold compared with mice fed the control diet. Ethanol-treated mice also had elevated HBV-RNA levels, and increased expression of surface, core, and X antigens in the liver, especially in the pericentral regions. None of these changes were observed in transgenic mice fed isocaloric diets. Thus, chronic alcohol consumption alters the patterns of HBV gene expression and replication in the serum and liver of HBV transgenic SCID mice, and may provide a partial explanation for the increased frequency of HBV markers among alcoholics.
Integrins induce expression of monocyte chemoattractant protein-1 via focal adhesion kinase in mesangial cells
Authors: Yujiro Watanabe, Masahito Tamura, Akihiko Osajima, Hirofumi Anai, Narutoshi Kabashima, Ryota Serino, Yasuhide Nakashima
Journal: Kidney International (2003)
Calcium and Secretin-Stimulated Gastrin Release in the Zollinger-Ellison Syndrome
Authors: B. E. KOLTS
Journal: Annals of Internal Medicine (1974)

Serum gastrin and calcium concentrations were measured and compared before and after calcium and secretin infusions in three patients with the Zollinger-Ellison syndrome and three control subjects. Calcium infusion induced marked increases in serum gastrin concentrations in the patients with Zollinger-Ellison syndrome (increases 3100 to 19 000 pg/ml) and modest increases in the control subjects (mean increase, 29 pg/ml). In each patient with Zollinger-Ellison syndrome who received calcium infusion there was a significant (P < 0.001) positive correlation (r from +0.91 to +0.95) between serum gastrin and calcium levels. Intravenous secretin also produced increases in both serum gastrin and calcium in each patient with Zollinger-Ellison syndrome; however, there was not a positive correlation between serum gastrin and calcium. These studies affirm secretin-induced paradoxical augmentation of serum gastrin in patients with Zollinger-Ellison syndrome. Failure to show positive correlation between serum gastrin and calcium with secretin administration, as is readily demonstrable with calcium infusion, provides no support for serum calcium increases as the mechanism by which serum gastrin is increased after secretin infusion in patients with Zollinger-Ellison syndrome.
Unfinished Business — Expanding HIV Testing in Developing Countries
Authors: Kevin M De Cock, Rebecca Bunnell, Jonathan Mermin
Journal: New England Journal of Medicine (2006)

Knowledge of serologic status is required for the appropriate targeting of services and interventions. Drs. Kevin De Cock, Rebecca Bunnell, and Jonathan Mermin discuss how the increased resources available for combating HIV and AIDS, the strong emphasis on treatment, and the commitment of the G8 to universal access necessitate a massive expansion of HIV testing.
Estimating the financial requirements of health care
Authors: R. Klein
Journal: BMJ (2001)

in can linings.These are issues of major interest, not least because of the possible exposure of infants to these chemicals at critical stages of development.Sharpe has argued that, until appropriate in vivo experiments are done, phthalates and similar chemicals will continue to cause concern for testicular development. 12 Meanwhile the debate about phytoestrogens and women's health continues: on the one hand there is concern that any hormonally active substance can induce or exacerbate breast and uterine cancer, and on the other is the knowledge that these substances can be used as alternatives to hormone replacement therapy in the treatment of postmenopausal symptoms and osteoporosis. 13 This is a fascinating area with important repercussions, and it is appropriate to investigate environmental causes of disease.Research is now being undertaken that will establish baselines for some key indices of reproductive health, which should allow future researchers to resolve the current uncertainties and determine the impact of endocrine disrupters on our health.
Reliability of Inspiratory Capacity for Estimating End-expiratory Lung Volume Changes during Exercise in Patients with Chronic Obstructive Pulmonary Disease
Authors: SHENG YAN, DARIUSZ KAMINSKI, PAWEL SLIWINSKI
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The inspiratory capacity (IC) maneuver is increasingly used to monitor exercise-induced dynamic hyperinflation in patients with COPD. However, the reliability of this method in patients with COPD exercising to symptom limitation has not been systematically studied and presented. The purpose of the present study was therefore to evaluate the reliability of the IC maneuver in assessing changes in end-expiratory lung volume (EELV) by assessing the pressure developed during IC maneuvers, in patients with COPD during incremental bicycle exercise to exhaustion. Fifteen patients with stable COPD performed bicycle exercise to symptom limitation. During the experiment, the patients performed IC efforts during resting breathing and at the end of each exercise work load. Esophageal pressure (Pes) measured at peak inspired volume plateau (zero flow) was − 13.5 ± 1.9 and − 13.4 ± 1.9 cm H2O (p = 0.79) during IC maneuvers at resting breathing and during the final exercise work load, respectively. When the Pes values at the peak inspired volume plateau during IC efforts at each exercise level were expressed as a percentage of those during resting breathing, the great majority of the ratios were above 90% with the lowest at 84%, and these ratios were independent of exercise intensity. Despite a constant Pes during IC, there was a progressive decrease in IC with increasing exercise work load in most patients, suggesting an increase in EELV. At the highest exercise work load achieved, Δ EELV calculated as the decrease in IC was 0.26 ± 0.06 L (p < 0.001). We conclude that repeated IC maneuver is a simple and reliable method for estimating EELV changes during exercise to exhaustion in patients with COPD.
Patient-Centered Care Model Demands Better Physician-Patient Communication
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

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Abstract 624: Synergistic effects of combining the Akt inhibitor triciribine with erlotinib in EGFR TKI-resistant NSCLC
Authors: Joell J. Gills, Betsy Morrow, Shigeru Kawabata, Jose Mercado, Bryan Hennessy, Ajaikumar B. Kunnumakkara, William Pao, Phillip A. Dennis
Journal: Cancer Research (2010)

Abstract EGFR tyrosine kinase inhibitors (TKIs) are clinically useful agents for the treatment of NSCLC, yet resistance ultimately develops. In an effort to develop strategies to combat resistance and prolong patient benefit, EGFR TKIs were combined with the Akt inhibitor triciribine in a panel of EGFR TKI-resistant NSCLC cell lines. The combination synergistically reduced proliferation in cells that expressed a variety of resistance mechanisms, including intrinsic EGFR T790M mutations, K-Ras mutations, and Met amplification. The combination of erlotinib and triciribine significantly increased apoptosis in H1975 and H1650 cells. It also decreased the phosphorylation of Akt and PRAS40, C-Raf, MEK, and ERK to a greater extent than either drug alone. Unbiased analysis using reverse phase lysate arrays confirmed decreased activation of PI3K/Akt pathway components as well as ERK. The effect of the combination appeared to depend on downregulation of Akt, since a constitutively active form of Akt abrogated the decreased proliferation and increase in cell death caused by the combination. In vivo, the combination inhibited the growth of H1975 xenografts to a greater extent than either drug alone. When tested in an invariably progressive, transgenic model of EGFR-driven lung tumorigenesis (EGFR L858R/T790M), the combination did not cause regression of tumors but stabilized disease in approximately 80% of mice. We conclude the combination of triciribine with EGFR TKIs is promising and should be explored clinically, and that combining inhibitors of the PI3K/Akt pathway with EGFR TKIs may be a useful strategy to overcome EGFR TKI resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 624.