tbuckley/cabot-search huggingface dataset:
Estrogen attenuates the adventitial contribution to neointima formation in injured rat carotid arteries
Authors: S Oparil
Journal: Cardiovascular Research (1999)

Objective: This study tested, in ovariectomized rats, whether (1) adventitial activation plays a role in the vascular injury response, and (2) inhibition of adventitial activation and the subsequent wave of cell proliferation moving from adventitia to neointima contributes to the estrogen-induced attenuation of neointima formation in balloon injured carotid arteries. Methods: Ovariectomized Sprague-Dawley rats were treated with either 17β-estradiol or vehicle beginning 72 h prior to balloon injury of the right common carotid artery and were sacrificed at 0, 3, 7, 14 and 28 days after injury. BrdU was administered 18 h and 12 h prior to sacrifice in order to quantitate mitotic activity in adventitia, media and neointima of the damaged vessel at specified times post injury. Results: Adventitial activation, evidenced by positive BrdU staining, was evident on the day of injury, peaked on day 3 and was resolved by day 7, thus preceding neointima formation. Numbers of BrdU labeled cells in adventitia on day 3 were significantly reduced in estrogen treated rats compared to controls. BrdU labeled cells were undetectable in media on the day of injury, appeared at day 3 and disappeared by day 14. Neointima appeared at day 7 and increased in area throughout the period of observation. Neointimal area and numbers of BrdU labeled cells in neointima were significantly reduced in estrogen treated rats compared to controls. These findings suggest that there is a wave of cell proliferation moving in an adventitia-to-lumen direction following endoluminal injury of the rat carotid artery and that estrogen modulates this proliferative response to injury. Conclusion: These results support the hypothesis that adventitial activation contributes to the vascular injury response and that estrogen reduces this contribution.
Evaluation of test immunisation in the assessment of antibody deficiency syndromes.
Authors: A D Webster, A A Latif, M K Brenner, D Bird
Journal: BMJ (1984)

Antibody responses after immunisation with pneumococcal polysaccharide did not correlate with the severity and frequency of infections in 22 patients with severe hypogammaglobulinaemia, when these were measured by a Farr radioimmunoassay. Five "healthy" patients with severe hypogammaglobulinaemia not only failed to make antipneumococcal polysaccharide antibody, when measured by radioimmunoassay, but also had very low or unrecordable antibody responses to Escherichia coli and failed to produce antibody when immunised with tetanus toxoid. Some of these subjects, however, did make small amounts of IgM antipneumococcal polysaccharide antibody when this was measured by an enzyme linked immunosorbent assay, while others retained some ability to produce IgM or IgA or both in their saliva. These findings show that the measurement of serum antibody responses after immunisation, with the possible exception of IgM antibodies to polysaccharides, is unlikely to be helpful in assessing the requirement for gammaglobulin replacement therapy in patients with hypogammaglobulinaemia.
Prospective Study of Body Mass Index and Risk of Stroke in Apparently Healthy Women
Authors: Tobias Kurth, J. Michael Gaziano, Kathryn M. Rexrode, Carlos S. Kase, Nancy R. Cook, JoAnn E. Manson, Julie E. Buring
Journal: Circulation (2005)

Obesity is an escalating pandemic in the United States, and its association with coronary heart disease is well understood. Several studies have found positive associations between body mass index (BMI) and stroke in men, but the association with stroke and its subtypes is less clear in women.This was a prospective cohort study among 39 053 women participating in the Women's Health Study. BMI was measured as self-reported weight (in kilograms) divided by height (in meters) squared. Incident stroke was self-reported and confirmed by medical record review. We used the Cox proportional hazards model to evaluate the association between BMI and stroke. After a mean follow-up of 10 years, a total of 432 strokes (347 ischemic, 81 hemorrhagic, and 4 undefined) occurred. We found a statistically significant trend for increased risk of total and ischemic stroke across 7 BMI categories. With World Health Organization criteria, women who were obese (BMI > or =30 kg/m2) had hazard ratios of 1.50 (95% CI 1.16 to 1.94) for total stroke, 1.72 (95% CI 1.30 to 2.28) for ischemic stroke, and 0.82 (95% CI 0.43 to 1.58) for hemorrhagic stroke compared with women with BMI <25 kg/m2. Additional control for history of hypertension, diabetes, and elevated cholesterol substantially attenuated the hazard ratios for total and ischemic stroke. There was no effect modification for age, exercise, or smoking.In this large prospective cohort study among women, BMI was a strong risk factor for total and ischemic stroke but not for hemorrhagic stroke. The association was highly mediated by hypertension, diabetes, and elevated cholesterol.
A FAMILY OF SQUINTERS
Authors: Frank H. Rodin
Journal: JAMA (1926)

Four cases of strabismus in one family are sufficiently rare to justify this report. Mrs. C. S., aged 46, seen at Stanford University Eye Clinic, July 14, 1925, had had fourteen children, nine of whom were living. Her right eye had always turned out. The eldest six living children and her husband have straight eyes. The eyes of the youngest three children turn in. These children were of normal birth and always healthy. The mother had always enjoyed good health. As far as can be ascertained, there is no history of strabismus on either the maternal or the paternal side of the family. Retinoscopy of the mother and the children was done under atropine mydriasis. The examination of the fundi in all these cases was negative. Lenses did not improve their visions nor straighten out the eyes. Examination of the vision of Mrs. C. S. revealed: O. D.= hand movement;
Incidence and Prognosis of Syncope
Authors: Elpidoforos S. Soteriades, Jane C. Evans, Martin G. Larson, Ming Hui Chen, Leway Chen, Emelia J. Benjamin, Daniel Levy
Journal: New England Journal of Medicine (2002)

Little is known about the epidemiology and prognosis of syncope in the general population.We evaluated the incidence, specific causes, and prognosis of syncope among women and men participating in the Framingham Heart Study from 1971 to 1998.Of 7814 study participants followed for an average of 17 years, 822 reported syncope. The incidence of a first report of syncope was 6.2 per 1000 person-years. The most frequently identified causes were vasovagal (21.2 percent), cardiac (9.5 percent), and orthostatic (9.4 percent); for 36.6 percent the cause was unknown. The multivariable-adjusted hazard ratios among participants with syncope from any cause, as compared with those who did not have syncope, were 1.31 (95 percent confidence interval, 1.14 to 1.51) for death from any cause, 1.27 (95 percent confidence interval, 0.99 to 1.64) for myocardial infarction or death from coronary heart disease, and 1.06 (95 percent confidence interval, 0.77 to 1.45) for fatal or nonfatal stroke. The corresponding hazard ratios among participants with cardiac syncope were 2.01 (95 percent confidence interval, 1.48 to 2.73), 2.66 (95 percent confidence interval, 1.69 to 4.19), and 2.01 (95 percent confidence interval, 1.06 to 3.80). Participants with syncope of unknown cause and those with neurologic syncope had increased risks of death from any cause, with multivariable-adjusted hazard ratios of 1.32 (95 percent confidence interval, 1.09 to 1.60) and 1.54 (95 percent confidence interval, 1.12 to 2.12), respectively. There was no increased risk of cardiovascular morbidity or mortality associated with vasovagal (including orthostatic and medication-related) syncope.Persons with cardiac syncope are at increased risk for death from any cause and cardiovascular events, and persons with syncope of unknown cause are at increased risk for death from any cause. Vasovagal syncope appears to have a benign prognosis.
Activation of NF- κ B in <i>Mycobacterium tuberculosis</i>– induced Interleukin-2 Receptor Expression in Mononuclear Phagocytes
Authors: KAM-MENG TCHOU-WONG, OSAMU TANABE, CHUANXIANG CHI, TING-AN YIE, WILLIAM N. ROM
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Soluble interleukin-2 receptor- α (IL-2R α ) has been reported to be increased in the sera of patients with advanced tuberculosis, and levels decline after therapy in accordance with improvement of radiologic findings. We investigated expression of the IL-2R α in bronchoalveolar lavage (BAL) cells in active pulmonary tuberculosis, and evaluated the mechanism Mycobacterium tuberculosis induces in the IL-2R α using the THP-1 mononuclear phagocyte cell line. We found IL-2R α expression to be increased in BAL cells from involved sites of active pulmonary tuberculosis. Expression of the α -chain of IL-2R α on peripheral blood monocytes (PBM) was induced by M. tuberculosis by flow cytometry evaluation. Northern analysis demonstrated increased IL-2R α gene expression after stimulation with M. tuberculosis which was further induced by interferon- γ (IFN- γ ). The IL-2R α promoter containing the nuclear factor kappa B (NF- κ B) site was transcriptionally induced by M. tuberculosis and this NF- κ B site could confer inducibility to a heterologous herpes thymidine kinase (TK) promoter by M. tuberculosis. Electrophoretic mobility shift assays (EMSAs) revealed specific binding of nuclear protein to the NF- κ B site upon induction with M. tuberculosis. Using antibodies against the p50 and p65 subunits of NF- κ B in EMSAs, the involvement of both p50 and p65 proteins was further demonstrated. Functional expression of the IL-2R α on mononuclear phagocytes in M. tuberculosis infection may play an important immunomodulatory role in the host response.
Glycogen synthase kinase 3-mediated voltage-dependent anion channel phosphorylation controls outer mitochondrial membrane permeability during lipid accumulation
Authors: Cecile Martel, Maya Allouche, Davide Degli Esposti, Elena Fanelli, Céline Boursier, Céline Henry, Joel Chopineau, Giuseppe Calamita, Guido Kroemer, Antoinette Lemoine, Catherine Brenner
Journal: Hepatology (2012)

Abstract Nonalcoholic steatosis is a liver pathology characterized by fat accumulation and severe metabolic alterations involving early mitochondrial impairment and late hepatocyte cell death. However, mitochondrial dysfunction mechanisms remain elusive. Using four models of nonalcoholic steatosis, i.e., livers from patients with fatty liver disease, ob/ob mice, mice fed a high-fat diet, and in vitro models of lipotoxicity, we show that outer mitochondrial membrane permeability is altered and identified a posttranslational modification of voltage-dependent anion channel (VDAC), a membrane channel and NADH oxidase, as a cause of early mitochondrial dysfunction. Thus, in nonalcoholic steatosis VDAC exhibits reduced threonine phosphorylation, which increases the influx of water and calcium into mitochondria, sensitizes the organelle to matrix swelling, depolarization, and cytochrome c release without inducing cell death. This also amplifies VDAC enzymatic and channel activities regulation by calcium and modifies its interaction with proteic partners. Moreover, lipid accumulation triggers a rapid lack of VDAC phosphorylation by glycogen synthase kinase 3 (GSK3). Pharmacological and genetic manipulations proved GSK3 to be responsible for VDAC phosphorylation in normal cells. Notably, VDAC phosphorylation level correlated with steatosis severity in patients. Conclusion : VDAC acts as an early sensor of lipid toxicity and its GSK3-mediated phosphorylation status controls outer mitochondrial membrane permeabilization in hepatosteatosis. (Hepatology 2013)
Low Rates of Silent Substitution in Nuclear Genes of Two Distantly Related Scrophulariaceae (Antirrhinum and Verbascum)
Authors: Cristina P. Vieira, Deborah Charlesworth
Journal: Molecular Biology and Evolution (2001)

Low levels of genetic diversity and divergence at nuclear loci have previously been observed for cycloidea and fil1-like genes within and between several Antirrhinum species, and divergence at these loci is also low between species in genera at different levels of relatedness in the former family Scrophulariaceae (Digitalis and Verbascum). The low divergence values are surprising, because (based on the sequences of chloroplast loci) the Scrophulariaceae are thought to be polyphyletic, with two anciently diverged clades, and the species we compared belonged to the two different clades. Here, we extend our studies of sequence divergence to more nuclear genes: fil2, far, globosa, and Adh. Detailed studies revealed that in Antirrhinum these genes belong to gene families. Low levels of divergence between Antirrhinum and Verbascum were observed for four of the loci studied, fil2-1, fil2-2, far-L, and globosa, similar to our previous observations. We discuss hypotheses to explain these low synonymous divergence values. For Adh, no cases of very similar sequences were found, but, rather, our sequences from the three different genera (Antirrhinum, Digitalis, and Verbascum) were all very diverged. Repeated gene duplication and loss of elements in the Adh gene family is likely in these lineages, making it impossible to determine orthology of the Adh genes.
Correlation Between Albuminuria and Spontaneous Platelet Microaggregate Formation in Type 2 Diabetic Patients
Authors: Shin-ichi Araki, Hiroyuki Matsuno, Masakazu Haneda, Daisuke Koya, Yosuke Kanno, Junko Itho, Akio Kishi, Keiji Isshiki, Toshiro Sugimoto, Hiroshi Maegawa, Atsunori Kashiwagi, Takashi Uzu
Journal: Diabetes Care (2009)

OBJECTIVE Albuminuria in type 2 diabetic patients is a risk factor for cardiovascular disease. We investigated the correlation between albuminuria and spontaneous microaggregation of platelets (SMAP) formed under shear stress. RESEARCH DESIGN AND METHODS The study subjects were 401 type 2 diabetic individuals (252 with normoalbuminuria and 149 with albuminuria) who were examined for SMAP under conditions of shear stress only (no agonist stimulation) and the reversibility of platelet microaggregation after stimulation with 1 μmol/l ADP, measured by a laser light-cattering method. Active glycoprotein IIb/IIIa (GPIIb/IIIa) and P-selectin expression levels on platelets as an index of platelet activation were measured by whole-blood flow cytometry. RESULTS SMAP formation was noted in 53% of diabetic patients. All patients with SMAP showed an irreversible pattern of platelet microaggregates by a low dose of ADP. SMAP was observed in 75% of diabetic subjects with albuminuria and in 39% of those with normoalbuminuria. Multivariate logistic regression analysis identified urinary albumin excretion rate and brachial-ankle pulse-wave velocity as independent factors associated with SMAP. The degree of SMAP correlated with active GPIIb/IIIa (γ = 0.59, P &amp;lt; 0.001) and P-selectin (γ = 0.55, P &amp;lt; 0.001) expression levels. These early-activated platelet profiles were significantly inhibited in albuminuric patients with aspirin intake, although the effect was incomplete. CONCLUSIONS Our study demonstrated an independent association between albuminuria and early changes in activated platelet profiles of type 2 diabetic patients. Further follow-up and intervention studies are needed to establish whether the inhibition of SMAP affects the course of cardiovascular disease in type 2 diabetic patients.
Increased insulin binding by hepatic plasma membranes from diabetic rats: normalization by insulin therapy.
Authors: M B Davidson, S A Kaplan
Journal: Journal of Clinical Investigation (1977)

Hepatic plasma membranes prepared from rats rendered diabetic by streptozotocin bound approximately twice as much insulin per 50 mug protein as control membranes. Glucagon binding of diabetic and control membranes was virtually identical. This increased insulin binding was not due to a nonspecific effect of streptozotocin, decreased degradation of insulin slower dissociation from its receptor, or a selective higher yield of membranes prepared from the diabetic livers. Diabetic and control membranes both showed negative cooperativity. Scatchard analysis suggested that the difference in binding was due to an enhanced binding capacity of the diabetic membranes rather than increased affinity of the binding sites. Increased insulin binding of diabetic membranes was returned to normal by insulin treatment. These data are consistent with the postulate that there is an inverse relationship between circulating insulin levels and insulin binding and that insulin may modulate its own receptor. However, since it has been reported that fat, muscle, and hepatic tissue from rats made diabetic by alloxan administration are insensitive to insulin, the capacity for binding can not be the sole factor determining the response to insulin in diabetes mellitus. Therefore, sensitivity of the diabetic liver to insulin is determined, at least in part, by events subsequent to the binding of insulin to its receptor.
Technetium-99m Sestamibi Marrow Uptake in a Patient With Myelodysplastic Syndrome
Authors: PAUL A. THOMAS, RAYMOND J. GIBBONS
Journal: Clinical Nuclear Medicine (1994)

Technetium-99m sestamibi has been reported to localize in a variety of benign and malignant tumors. Scintigraphic results of a patient having refractory anemia with ringed sideroblasts are presented.
THE TREATMENT OF HEMOPHILIA WITH CHLORID OF CALCIUM, WITH REPORT OF A CASE.
Authors: J. CLIFFORD PERRY
Journal: JAMA (1897)

The treatment of hemophilia with the usual agents recommended for this disease, has been so ineffective that much difficulty has been experienced in arresting the hemorrhage from the slightest wounds, and many patients have died from the excessive loss of blood after the most trivial injuries. The only advance in the therapy of this disease, has been made by Dr. E. A. Wright,<sup>1</sup>who taking as a basis for his investigations the physiologic fact that a certain per cent. of calcium salts is necessary for the coagulation of the blood, made a series of experiments with calcium chlorid, and demonstrated its efficacy in increasing the coagulability of the blood. In a later article the author reports the results of his examination of the blood of a case of hemophilia, and the coagulability of the blood before and after the administration of chlorid of calcium. He found that the blood
Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat
Authors: Thorsten P. Degenhardt, Nathan L. Alderson, David D. Arrington, Robert J. Beattie, John M. Basgen, Michael W. Steffes, Suzanne R. Thorpe, John W. Baynes
Journal: Kidney International (2002)
Differential Binding of Plasminogen, Plasmin, and Angiostatin4.5 to Cell Surface β-Actin: Implications for Cancer-Mediated Angiogenesis
Authors: Hao Wang, Jennifer A. Doll, Keyi Jiang, Deborah L. Cundiff, Jarema S. Czarnecki, Mindy Wilson, Karen M. Ridge, Gerald A. Soff
Journal: Cancer Research (2006)

Abstract Angiostatin4.5 (AS4.5) is the product of plasmin autoproteolysis and consists of kringles 1 to 4 and ∼85% of kringle 5. In culture, cancer cell surface globular β-actin mediates plasmin autoproteolysis to AS4.5. We now show that plasminogen binds to prostate cancer cells and that the binding colocalizes with surface β-actin, but AS4.5 does not bind to the cell surface. Plasminogen and plasmin bind to immobilized β-actin similarly, with a Kd of ∼140 nmol/L. The binding is inhibited by ε-aminocaproic acid (εACA), indicating the requirement for a lysine-kringle domain interaction. Using a series of peptides derived from β-actin in competitive binding studies, we show that the domain necessary for plasminogen binding is within amino acids 55 to 69 (GDEAQSKRGILTLKY). Substitution of Lys61 or Lys68 with arginine results in the loss of the ability of the peptide to block plasminogen binding, indicating that Lys61 and Lys68 are essential for plasminogen binding. Other actin peptides, including peptides with lysine, did not inhibit the plasminogen-actin interaction. AS4.5 did not bind actin at concentrations up to 40 μmol/L. Plasminogen, plasmin, and AS4.5 all contain kringles 1 to 4; however, kringle 5 is truncated in AS4.5. Isolated kringle 5 binds to actin, suggesting intact kringle 5 is necessary for plasminogen and plasmin to bind to cell surface β-actin, and the truncated kringle 5 in AS4.5 results in its release from β-actin. These data may explain the mechanism by which AS4.5 is formed locally on cancer cell surfaces and yet acts on distant sites. (Cancer Res 2006; 66(14): 7211-5)
Internationally agreed strategy is needed on vaginal birth after caesarean
Authors: Rajesh Varma, Janesh K Gupta
Journal: BMJ (2004)

EDITOR—The review by Guise et al concurs with other studies in showing that vaginal birth after caesarean section is harmful for fetus and mother, and repeated elective caesarean is not completely protective.1 Systematically interrogating the 160 cases of uterine rupture reported may have not only identified important predictive factors for uterine …
Acid suppressants and postoperative pneumonia
Authors: N. Vakil
Journal: BMJ (2010)

The risk is uncertain, so prescription remains appropriate in selected patients 

Postoperative pneumonia is an important cause of morbidity and mortality in patients who have undergone surgery. A systematic review found that age over 60 years, mild or severe systemic disease (such as congestive heart failure and chronic obstructive pulmonary disease), reduced functional capacity, low serum albumin, and the type of surgery (patients having aortic aneurysm repair, thoracic surgery, and abdominal procedures have the highest risk) were associated with an increased risk.1 Gram negative organisms are the most commonly isolated.2 In the linked study (doi:10.1136/bmj.c2608), Redelmeier and colleagues assess whether gastric acid suppressants are associated with an increased risk of postoperative pneumonia in patients undergoing elective surgery.3 

After surgery, mechanically ventilated patients often develop colonisation of the oropharynx, oesophagus, and stomach with Gram negative organisms, and aspiration may occur despite the presence of an endotracheal tube. The source of the organisms causing the pneumonia is controversial. In one study, most of the organisms came from the stomach.4 Another found that oropharyngeal organisms were more important, and that selective decontamination of the oropharynx using topical antibiotics prevented postoperative …
Differential expression of thymus- and activation-regulated chemokine (CCL17) and macrophage-derived chemokine (CCL22) by human fibroblasts from cornea, skin, and lung
Authors: Ken Fukuda, Youichiro Fujitsu, Keisuke Seki, Naoki Kumagai, Teruo Nishida
Journal: Journal of Allergy and Clinical Immunology (2003)