tbuckley/cabot-search huggingface dataset:
Mechanisms of abnormal uterine bleeding
Authors: M. Livingstone
Journal: Human Reproduction Update (2002)

Over the past 10 years there has been an upsurge of interest in the mechanisms underlying normal and disturbed menstrual bleeding. These studies have particularly focused on the mechanisms underlying the common problems of menorrhagia associated with ovulatory and anovulatory dysfunctional uterine bleeding (DUB) and of unpredictable breakthrough bleeding during hormonal contraceptive use. A wide range of abnormalities of endometrial morphology and function have been demonstrated, but it is still not clear how all the pieces of this complex jigsaw puzzle fit together. Ovulatory DUB is predominantly associated with decreased endometrial vasoconstriction and vascular haemostatic plug formation, leading to defective control of the volume of blood which is lost during menstruation. By contrast, breakthrough bleeding is associated with a wide range of molecular disturbances which appear to result in unpredictable vessel breakdown through disturbed endometrial angiogenesis, increased vascular fragility and loss of the integrity of the endothelial, epithelial and stromal supporting structures. Anovulatory DUB is very poorly understood, but may be associated with disturbed angiogenesis, fragile vessels and defective haemostatic processes. Little is known about the actual mechanisms of the common problem of abnormal bleeding associated with specific genital tract pathologies such as uterine myomata.
Modifier loci condition autoimmunity provoked by Aire deficiency
Authors: Wenyu Jiang, Mark S. Anderson, Roderick Bronson, Diane Mathis, Christophe Benoist
Journal: The Journal of Experimental Medicine (2005)

Loss of function mutations in the autoimmune regulator (Aire) gene in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients and mutant mice lead to autoimmune manifestations that segregate as a monogenic trait, but with wide variation in the spectrum of organs targeted. To investigate the cause of this variability, the Aire knockout mutation was backcrossed to mice of diverse genetic backgrounds. The background loci strongly influenced the pattern of organs that were targeted (stomach, eye, pancreas, liver, ovary, thyroid, and salivary gland) and the severity of the targeting (particularly strong on the nonobese diabetic background, but very mild on the C57BL/6 background). Autoantibodies mimicked the disease pattern, with oligoclonal reactivity to a few antigens that varied between Aire-deficient strains. Congenic analysis and a whole genome scan showed that autoimmunity to each organ had a distinctive pattern of genetic control and identified several regions that controlled the pattern of targeting, including the major histocompatibility complex and regions of Chr1 and Chr3 previously identified in controlling type 1 diabetes.
Preference for hot drinks is associated with peptic disease.
Authors: R C Pearson, R F McCloy
Journal: Gut (1989)

The temperature at which people chose to take a hot drink was measured in 59 patients with endoscopically proven peptic disorders of the upper gastrointestinal tract and 65 asymptomatic controls. The patients in the disease group drank significantly hotter tea or coffee than the control group (medians 62 degrees and 56 degrees Celsius respectively, P less than 0.0001). The median temperatures of choice for subgroups of patients with oesophageal, gastric or duodenal disease were significantly higher than the control group (63.5 degrees, 63 degrees, 60.5 degrees C respectively). There was no relationship between a preference for hotter drinks with either the sex or smoking habits of the patient. In the control group the temperature of choice tended to decrease with age though linear regression just failed to reach statistical significance (p = 0.06); this trend was not apparent in the disease group (p = 0.64). Thermal injury as a result of drinking hot fluids may be a causative factor in some peptic disorders.
Tumor Growth Suppression in Pancreatic Cancer by a Putative Metastasis Suppressor Gene <i>Cap43/NDRG1/Drg-1</i> through Modulation of Angiogenesis
Authors: Yuichiro Maruyama, Mayumi Ono, Akihiko Kawahara, Toshiro Yokoyama, Yuji Basaki, Masayoshi Kage, Shigeaki Aoyagi, Hisafumi Kinoshita, Michihiko Kuwano
Journal: Cancer Research (2006)

Abstract Cap43 has been identified as a nickel- and calcium-induced gene, and is also known as N-myc downstream-regulated gene 1 (NDRG1), Drg-1 and rit42. It is also reported that overexpression of Cap43 suppresses metastasis of some malignancies, but its precise role remains unclear. In this study, we asked how Cap43 could modulate the tumor growth of pancreatic cancer. Stable Cap43 cDNA transfectants of pancreatic cancer cells with Cap43 overexpression showed similar growth rates in culture as their control counterparts with low Cap43 protein level. By contrast, Cap43 overexpression showed a marked decrease in tumor growth rates in vivo. Moreover, a marked reduction in tumor-induced angiogenesis was observed. Gelatinolytic activity by matrix metalloproteinase-9 and invasive ability in Matrigel invasion activity were markedly decreased in pancreatic cancer cell lines with high Cap43 expression. Cellular expression of matrix metalloproteinase-9 and two major angiogenic factors, vascular endothelial growth factor and interleukin-8, were also significantly decreased in cell lines with Cap43 overexpression as compared with their parental counterparts. Immunohistochemical analysis of specimens from 65 patients with pancreatic ductal adenocarcinoma showed a significant association between Cap43 expression and tumor microvascular density (P = 0.0001) as well as depth of invasion (P = 0.0003), histopathologic grading (P = 0.0244), and overall survival rates for patients with pancreatic cancer (P = 0.0062). Thus, Cap43 could play a key role in the angiogenic on- or off-switch of tumor stroma in pancreatic ductal adenocarcinoma. (Cancer Res 2006; 66(12): 6233-42)
Relationship between the Rate of H+ Transport and Pathways of Glucose Metabolism by Turtle Urinary Bladder
Authors: L. H. Norby, John H. Schwartz
Journal: Journal of Clinical Investigation (1978)

The urinary bladder of the fresh-water turtle acidifies its contents by actively transporting H(+) ions across the luminal membrane. It is known that the H(+) transport system is dependent upon oxidative metabolism and the substrate glucose; however, the specific biochemical events resulting in H(+) translocation have not been identified. This study examines the relationship between active H(+) transport and a specific oxidative pathway of glucose metabolism, the pentose phosphate shunt. To investigate this relationship the metabolic and transport rates were simultaneously measured under several well-defined conditions. When H(+) transport was inhibited by either the application of an opposing pH gradient or by acetazolamide, glucose metabolism by the pentose phosphate shunt declined. Conversely, stimulation of H(+) transport by either imposing a more favorable pH gradient or by CO(2) addition resulted in an increase in pentose phosphate shunt metabolism. Glycolytic activity, in contrast, was invariant with the maneuvers which altered the rate of H(+) transport. Additional experiments localized pentose phosphate shunt enzyme activity to the mucosal fraction of the bladder which is the cell layer responsible for acid secretion. The finding that the rate of glucose metabolism by the pentose phosphate shunt is related to the rate of H(+) transport suggests but does not prove that the pentose phosphate shunt may be an important metabolic pathway for H(+) transport by the turtle urinary bladder.
Localisation of neuroendocrine tumours of the upper gastrointestinal tract.
Authors: T Zimmer, K Ziegler, M Bader, U Fett, B Hamm, E O Riecken, B Wiedenmann
Journal: Gut (1994)

In order to localise neuroendocrine tumours of the foregut type (that is, of the stomach, duodenum, and pancreas), 18 patients were studied prospectively by endoscopic ultrasonography, computed tomography, transabdominal ultrasonography, magnetic resonance imaging, and somatostatin receptor scintigraphy. These 18 patients had a total of 25 primary tumour lesions which were verified histologically in tissue obtained by surgery or by ultrasound or endoscopy guided biopsy. Tumours were found in the stomach (n = 1), duodenum (n = 6), pancreas (n = 17), and liver (n = 1). Endoscopic ultrasonography had the highest sensitivity for tumour detection, followed by somatostatin receptor scintigraphy, computed tomography, transabdominal ultrasonography, and magnetic resonance imaging (88%, 52%, 36%, 32%, and 24% respectively). Endoscopic ultrasonography was especially sensitive in tumours smaller than 2 cm in diameter (88% v somatostatin receptor scintigraphy 35%; computed tomography 12%; transabdominal ultrasonography 6%; and magnetic resonance imaging 0%). Of 17 tumours located in the pancreas, endoscopic ultrasonography showed a sensitivity of 94% (somatostatin receptor scintigraphy 47%; computed tomography 47%; transabdominal ultrasonography 41%; and magnetic resonance imaging 29%). Of eight extrapancreatic tumours, six were identified by endoscopic ultrasonography, five by somatostatin receptor scintigraphy, and only one by computed tomography, transabdominal ultrasonography, and magnetic resonance imaging. One neuroendocrine tumour that was not detected by endoscopic ultrasonography was correctly identified by somatostatin receptor scintigraphy. Endoscopic ultrasound allowed correct determination of the tumour size and tumour spread into parapancreatic structures, especially the large vessels (T stage), in all 14 patients operated upon. The lymph node stage (N stage) was correctly determined in 10 of these 14 patients. In summary, endoscopic ultrasonography and somatostatin receptor scintigraphy were the most sensitive imaging methods for the localisation of these tumours and should be used as early diagnostic procedures to accurately stage neuroendocrine tumours of the foregut type.
Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.
Authors: R P Hebbel, J W Eaton, R S Kronenberg, E D Zanjani, L G Moore, E M Berger
Journal: Journal of Clinical Investigation (1978)

To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude.
Prostaglandin I<sub>2</sub>analogues enhance already exuberant Th17 cell responses in systemic sclerosis
Authors: Marie-Elise Truchetet, Yannick Allanore, Elisa Montanari, Carlo Chizzolini, Nicolò Costantino Brembilla
Journal: Annals of the Rheumatic Diseases (2012)

Among pleiotropic effects, the capacity of prostaglandin I(2) (PGI(2)) analogues to affect adaptive immunity remains poorly characterised. The purpose of this study was to assess whether PGI(2) analogues could affect T helper (Th) cell responses in patients with systemic sclerosis (SSc) and healthy donors (HD).Peripheral blood mononuclear cells (PBMC) were obtained from 33 patients with SSc and 29 HD. Cytokine levels in PBMC and monocyte/CD4 T cell cultures were quantified by immunoassays. The frequencies of interleukin (IL)-17A, IL-22, interferon γ (IFNγ) and IL-4-producing CD4 T cells were assessed by multiparametric flow cytometry. Selective receptor antagonists, cytokine blocking antibodies and signalling protein inhibitors were used to identify the receptors and signalling pathways mediating PGI(2) analogue effects.Th17 and Th22 cells were more abundant in individuals with SSc than in HD. PGI(2) analogues (iloprost, treprostinil and beraprost) significantly increased IL-17A and IL-22 in vitro while decreasing IFNγ production both in SSc and HD PBMC. These effects relied on the specific expansion of Th17 and Th22 and inhibition of Th1 cells. The enhanced Th17 cell responses depended on increased IL-23 production by monocytes, involved the IP prostacyclin receptor and required protein kinase A activation. Importantly, in vivo administration of iloprost in individuals with SSc presenting with digital ulcers resulted in a significant increase in the frequency of Th17 cells.These findings demonstrate that PGI(2) analogues affect Th cell differentiation/expansion programmes, favouring Th17 and inhibiting Th1 cell responses in SSc. The impact of these changes on the disease course needs to be taken into consideration and further exploited to improve SSc.
Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis
Authors: CHRISTINE JAWORSKY, A.M. KLIGMAN, G.F. MURPHY
Journal: British Journal of Dermatology (1992)

Journal Article Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis Get access CHRISTINE JAWORSKY, CHRISTINE JAWORSKY Duhring Research Laboratories, Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA. U.S.A Dr C. Jaworsky, Clinical Research Building, 422 Curie Boulevard, Philadelphia, PA 19104‐6065. U.S.A. Search for other works by this author on: Oxford Academic Google Scholar A.M. KLIGMAN, A.M. KLIGMAN Duhring Research Laboratories, Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA. U.S.A Search for other works by this author on: Oxford Academic Google Scholar G.F. MURPHY G.F. MURPHY Duhring Research Laboratories, Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA. U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 3, 1 September 1992, Pages 239–246, https://doi.org/10.1111/j.1365-2133.1992.tb00121.x Published: 01 September 1992
Acute and Chronic Regulation of Thick Ascending Limb Endothelial Nitric Oxide Synthase by Statins
Authors: Marisela Varela, Jeffrey L. Garvin
Journal: Journal of the American Society of Nephrology (2004)

Statins, 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, acutely increase endothelial nitric oxide synthase (eNOS) activity and chronically increase eNOS expression in endothelial cells. NO decreases transport in thick ascending limbs (TAL). We hypothesized that statins inhibit TAL transport by acutely activating eNOS, thereby increasing NO production and chronically enhancing eNOS expression. Oxygen consumption (QO(2)) by TAL suspensions from Sprague-Dawley rats was used as a measure of active NaCl reabsorption. Na/K ATPase activity was assessed by measuring ATP hydrolysis in the presence and absence of ouabain. eNOS expression was measured by Western blot. A total of 50 micro M pravastatin decreased QO(2) by 18.6 +/- 3.4% (P < 0.01). In the presence of 500 micro M furosemide and 200 micro M amiloride, transport blockers, QO(2) remained the same after pravastatin was added. Na/K ATPase activity was not different from controls and TAL treated with 50 micro M pravastatin (0.33 +/- 0.07 versus 0.29 +/- 0.04 nmol P(i)/ micro g protein/min, where P(i) is inorganic phosphate). Nystatin stimulated QO(2) to 178 +/- 13.7 in pravastatin-treated TAL and 195 +/- 11.5 in furosemide-treated TAL. The inhibitory effect of pravastatin on QO(2) was blocked by L-nitroarginine methyl ester, an NOS inhibitor. In addition, pravastatin increased NO production as measured by the fluorescent dye DAF-2A. Pravastatin at a dose of 10 mg/kg per d had no effect on eNOS protein at 1 d (24.1 +/- 2.7 versus 25.5 +/- 1.1 arbitrary units [AU]) or 7 d (24.1 +/- 2.7 versus 20.9 +/- 1.3 AU). Similarly, at 1 d, 50 mg/kg per d had no effect on expression (24.1 +/- 2.7 versus 21.2 +/- 3.6 AU). At 7 d, this dose decreased eNOS protein from 24.1 +/- 2.7 to 11.8 +/- 4.4 AU. It is concluded that pravastatin acutely decreases NaCl entry into the TAL by releasing NO. Pravastatin does not chronically increase eNOS expression in TAL.
Accelerated Decline of Aerobic Fitness With Healthy Aging
Authors: Philip A. Ades, Michael J. Toth
Journal: Circulation (2005)

s we get older, even if we are healthy, we become less fit.At the extreme, we become disabled and eventually die.Although this deterioration in physical work capacity is widely accepted, few studies have characterized changes in aerobic capacity across the age span.Instead, the majority of studies have utilized cross-sectional designs.These studies are limited, however, by selective survival-ie, older participants, as a group, are inherently healthier than younger individuals, as evidenced by their survival.Thus, the 5% to 10% drop in aerobic fitness per decade, defined from cross-sectional studies, may well be an underestimate.
Co-existent Total Anomalous Pulmonary Venous Drainage into Portal Vein, Drainage of Left-sided Inferior Vena Cava into Left Atrium, and Splenic Agenesis
Authors: C. S. Muir, K. Prathap
Journal: Thorax (1965)

Total anomalous drainage of the pulmonary veins into the portal venous system is rare.Burroughs and Edwards (1960) noted 17 such cases in the 188 examples of total anomalous pulmonary venous drainage which they collected from the literature.Rarer still is the presence of a left-sided inferior vena cava emptying into the left atrium or into the left side of a common atrium.We have traced five such cases.A review of the literature by Gilbert, Nishimura, and Wedum (1958) revealed only 81 cases of coexistent splenic agenesis and cardiac malforma- tion.In three of these the pulmonary veins drained into the portal circulation.The simultaneous presence of all three congenital abnormalities-total anomalous drainage of the pulmonary veins into the portal system, drainage of a left-sided inferior vena cava into the left atrium, and splenic agenesis-must be exceedingly rare.We report such a case, the like of which we have not been able to trace. CASE REPORTT. C. H., a 27-day-old Chinese male infant, was admitted to the General Hospital, Singapore, on 2 May 1964 with a one-week history of breathlessness and cough.He was found to be generally cyanosed: a systolic murmur was heard all over the praecordium, and a few crepitations and wheezes were heard in the lungs.The child died four days after admission.Although congenital heart disease was diagnosed, the nature of the defects was in doubt.
Randomized Trial of Adjunctive Interleukin-2 in Adults with Pulmonary Tuberculosis
Authors: John L. Johnson, Emmanuel Ssekasanvu, Alphonse Okwera, Harriet Mayanja, Christina S. Hirsch, Joseph G. Nakibali, Dana Drzayich Jankus, Kathleen D. Eisenach, W. Henry Boom, Jerrold J. Ellner, Roy D. Mugerwa
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Interleukin (IL)-2 has a central role in regulating T cell responses to Mycobacterium tuberculosis. Adjunctive immunotherapy with recombinant human IL-2 was studied in a randomized, placebo-controlled, double-blinded trial in 110 human immunodeficiency virus-seronegative adults in whom smear-positive, drug-susceptible pulmonary tuberculosis was newly diagnosed. Patients were randomly assigned to receive twice-daily injections of 225, 000 IU of IL-2 or placebo for the first 30 days of treatment in addition to standard chemotherapy. Subjects were followed for 1 year. The primary endpoint was the proportion of patients with sputum culture conversion after 1 and 2 months of treatment. After 1 month, the proportion of patients for whom sputum culture converted to negative was 17% for the IL-2 group compared with 30% in the control group (p = 0.14; chi2). After 2 months, 77% in the IL-2 group were culture negative compared with 85% of those receiving placebo (p = 0.29, chi2). Results were similar when patients with isoniazid monoresistance were included in the analysis. There were no differences in weight gain and no improvement in fever, cough, and chest pain between groups. One patient in each arm relapsed. IL-2 did not enhance bacillary clearance or improvement in symptoms in human immunodeficiency virus-seronegative adults with drug-susceptible tuberculosis.
The myriad functions and metaphors of memory
Authors: Asher Koriat, Morris Goldsmith
Journal: Behavioral and Brain Sciences (1997)

Glenberg provides a new and exciting view that is especially useful for capturing some functional aspects of memory. However, memory and its functions are too multifarious to be handled by any one conceptualization. We suggest that Glenberg's proposal be restricted to its own “focus of convenience.” In addition, its value will ultimately depend on its success in generating detailed and testable theories.
You can't always get what you want: Evolution and true beliefs
Authors: Jeffrey P. Schloss, Michael J. Murray
Journal: Behavioral and Brain Sciences (2009)

Abstract McKay &amp; Dennett (M&amp;D) convincingly argue against many proposals for adaptively functioning misbelief, but the conclusion that true beliefs are generally adaptive does not follow. Adaptive misbeliefs may be few in kind but many in number; maladaptive misbeliefs may routinely elude selective pruning; reproductively neutral misbeliefs may abound; and adaptively grounded beliefs may reliably covary with but not truthfully represent reality.