tbuckley/cabot-search huggingface dataset:
Evidence for glomerular actions of epidermal growth factor in the rat.
Authors: R C Harris, R L Hoover, H R Jacobson, K F Badr
Journal: Journal of Clinical Investigation (1988)

Epidermal growth factor (EGF), an endogenous mitogenic peptide, has recently been shown to be a potent vasoconstrictor of vascular smooth muscle. In view of its potential role in proliferative and inflammatory renal glomerular diseases, we examined the effects of EGF both on cultured rat mesangial cells and on in vivo glomerular hemodynamics. Mesangial cells possess specific, saturable EGF receptors of differing affinities, with Kd's of 0.1 and 1.7 nM, respectively. EGF produced a rapid increase in intracellular pH of 0.12 +/- 0.01 pH U, which was sodium dependent and amiloride inhibitable. The addition of EGF to mesangial cells cultured on either glass or dimethylpolysiloxane substratum induced reproducible cell contraction. Intrarenal EGF infusion did not affect systemic blood pressure or hematocrit but reversibly decreased GFR and renal blood flow from 4.19 +/- 0.33 to 3.33 +/- 0.26 and from 1.17 +/- 0.09 to 0.69 +/- 0.07 ml/min, respectively. Glomerular micropuncture confirmed decreases in single nephron plasma flow and in single nephron GFR (from 142 +/- 9 to 98 +/- 8 and from 51.6 +/- 11.7 to 28.5 +/- 3.5 nl/min, respectively) which were due to significant increases in both pre- and postglomerular arteriolar resistances (from 1.97 +/- 0.31 to 2.65 +/- 0.36 and from 1.19 +/- 0.11 to 2.00 +/- 0.15 10(10) dyn.s.cm-5 respectively) and to a significant decrease in the ultrafiltration coefficient, Kf, which fell from 0.100 +/- 0.019 to 0.031 +/- 0.007 nl/(s.mmHg). These studies demonstrate that mesangial cells possess specific receptors for EGF, and exposure of these cells to physiologic concentrations of EGF results in an in vitro functional response characterized by activation of Na+/H+ exchange and by resultant intracellular alkalinization, as well as by cell contraction. EGF administration in vivo significantly reduces the glomerular capillary ultrafiltration coefficient, Kf, which, in combination with EGF-induced constriction of both preglomerular and postglomerular arterioles, results in acute major reductions in the rates of glomerular filtration and perfusion.
An Instructive Role for Patterned Spontaneous Retinal Activity in Mouse Visual Map Development
Authors: Hong-ping Xu, Moran Furman, Yann S. Mineur, Hui Chen, Sarah L. King, David Zenisek, Z. Jimmy Zhou, Daniel A. Butts, Ning Tian, Marina R. Picciotto, Michael C. Crair
Journal: Neuron (2011)
COMPULSORY HEALTH INSURANCE
Authors: Morris H. Kahn
Journal: JAMA (1926)

<h3>To the Editor:</h3> —Compulsory health insurance concerns itself with the great economic problem of the wage earner. It has for its basis insufficient wages, or wages out of which no surplus is left to cover the needs during a period of illness. One of the needs being medical care, health insurance proposes to stand sponsor for that item. But medical attention is only one of the needs of a sick wage earner. He needs rent, clothing, bread, nursing and several other necessaries, even though he is ill. Therefore, if health insurance is contemplated at present, the next logical step to ameliorate conditions is compulsory bread or food insurance and compulsory rent insurance. That is, the movement is in the direction of an industrial state in which the wage earner will have his domestic needs supplied. That is one corrective for low wages. It appears that the desired social benefit can
The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney. Inhibition by a soluble P-selectin ligand.
Authors: M Takada, K C Nadeau, G D Shaw, K A Marquette, N L Tilney
Journal: Journal of Clinical Investigation (1997)

Ischemia/reperfusion (I/R) injury associated with renal transplantation may influence both early graft function and late changes. The initial (</= 7 d) events of warm and in situ perfused cold ischemia of native kidneys in uninephrectomized rats were examined. mRNA expression of the early adhesion molecule, E-selectin, peaked within 6 h; PMNs infiltrated in parallel. T cells and macrophages entered the injured kidney by 2-5 d; the associated upregulation of MHC class II antigen expression suggested increased immunogenicity of the organ. Th1 products (IL-2, TNFalpha, IFNgamma) and macrophage-associated products (IL-1, IL-6, TGFbeta) remained highly expressed after 2 d. To examine directly the effects of selectins in I/R injury, a soluble P-selectin glycoprotein ligand (sPSGL) was used. Ischemic kidneys were perfused in situ with 5 microg of sPSGL in UW solution; 50 microg was administered intravenously 3 h after reperfusion. E-selectin mRNA remained at baseline, leukocytes did not infiltrate the injured organs throughout the 7-d period, and their associated products were markedly inhibited. Class II expression did not increase. No renal dysfunction secondary to I/R occurred. The early changes of I/R injury may be prevented by treatment with soluble P- and E-selectin ligand. This may reduce subsequent host inflammatory responses after transplantation.
Alcohol Consumption and Risk of Atrial Fibrillation in Men and Women
Authors: Kenneth J. Mukamal, Janne S. Tolstrup, Jens Friberg, Gorm Jensen, Morten Grønbæk
Journal: Circulation (2005)

The relationship of the full range of alcohol consumption with risk of incident atrial fibrillation has been inconsistent in previous, mainly case-control studies.In a prospective cohort study, we studied the association between self-reported alcohol use and incident atrial fibrillation among 16,415 women and men enrolled in the Copenhagen City Heart Study. We ascertained use of beer, wine, and spirits individually at up to 3 study visits with a structured questionnaire. We identified cases of atrial fibrillation by routine study ECGs and a validated nationwide registry of all hospitalizations. A total of 1071 cases occurred during follow-up. Among both women and men, alcohol consumption throughout the moderate range was not associated with risk of atrial fibrillation. However, consumption of 35 or more drinks per week among men was associated with a hazard ratio of 1.45 (95% CI 1.02 to 2.04); few women consumed this amount of alcohol. Approximately 5% of cases of atrial fibrillation among men were attributable to heavy alcohol use. Further adjustment for blood pressure and incident coronary heart disease and congestive heart failure did not attenuate the association (hazard ratio 1.63; 95% CI 1.15 to 2.31).Heavy alcohol consumption is associated with a higher risk of atrial fibrillation, at least among men. This relationship does not appear to be related to the adverse effects of heavy drinking on coronary heart disease or blood pressure.
Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis
Authors: Takumi Kawaguchi, Shotaro Sakisaka, Michio Sata, Michio Mori, Kyuichi Tanikawa
Journal: Hepatology (1999)

Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.
My Dearest Julia: The Love Letters of Dr. Benjamin Rush to Julia Stockton
Authors: Hilda Slive
Journal: JAMA (1980)

Julia Stockton was 16 years old when Benjamin Rush fell in love and became determined to marry her. She was, he said, everything he wanted in a wife—intelligent, moral, religious, and wise beyond her years. Rush was 30 years old, a supremely confident man, already a respected physician in Philadelphia and well known for his passionate involvement in the colonies' struggle for independence from England. This small volume containing several of the love letters that Rush wrote to Julia just before their marriage discloses a different facet to the character of the famous physician and medical educator. The letters were inherited and preserved by their great-great granddaughter, Julia Rush Biddle Henry. Others were destroyed by Julia after his death as not "fit for scarcely any eyes but those to whom they are addressed." They are a mixture of practicality, tender expressions of love, and philosophic, often pompous, views on marriage.
Immunohistochemical demonstration of ?-naphthoflavone-inducible cytochrome P450 1A1/1A2 in rat intrahepatic biliary epithelial cells
Authors: Jinshan Shen, Jadine A. Moy, Mitchell D. Green, Peter F. Guengerich, Jeffrey Baron
Journal: Hepatology (1998)

Although intrahepatic biliary epithelial cells are targets for certain hepatotoxic chemicals, including some procarcinogens, their ability to monooxygenate, and thereby bioactivate and inactivate xenobiotics, remains to be established. Thus, the present study was undertaken to immunohistochemically determine if cytochrome P450 (CYP) 1A1/1A2 is present and can be induced within these nonparenchymal liver cells. Immunoperoxidase and immunofluorescent staining for CYP1A1/1A2 was detected within intrahepatic biliary epithelial cells as well as hepatocytes of control rats and was markedly enhanced in both cell types by beta-naphthoflavone (BNF). Color confocal laser microscopic analyses of dual immunofluorescent staining for CYP1A1/1A2 and cytokeratins 6 and 9 (56 and 64 kd, respectively) provided unequivocal evidence for the presence and induction of CYP1A1/1A2 within intrahepatic bile duct epithelia. Moreover, microdensitometric analyses of immunoperoxidase staining intensities for CYP1A1/1A2 revealed that intrahepatic biliary epithelial cells of control rats contain 44%, 56%, and 58% as much CYP1A1/1A2 as do centrilobular, midzonal, and periportal hepatocytes, respectively. These analyses further revealed that BNF increased the content of CYP1A1/1A2 in biliary epithelial cells by approximately 120%, while CYP1A1/1A2 levels in centrilobular, midzonal, and periportal hepatocytes were increased by 82%, 159%, and 160%, respectively. The results of this study represent the first in situ demonstration that mammalian intrahepatic biliary epithelial cells contain a CYP isoform, and further that CYP1A1/1A2 can be induced in these cells by BNF. These findings therefore indicate that intrahepatic biliary epithelial cells can oxidatively metabolize xenobiotics in situ and that their ability to bioactivate and inactivate xenobiotics can be significantly enhanced by CYP1A1/1A2 induction.
THE TRANSPLANTATION OF BONE
Authors: W. E. GALLIE
Journal: JAMA (1918)

During recent years the science of bone transplantation has been occupying the attention of orthopedic surgeons to a steadily increasing degree. While the earlier operations were pure experiments attended by success or failure, depending on whether the surgeon chanced to employ the principles that are essential to success, the mass of evidence now at hand as the result of experimentation on animals has clearly outlined these principles and placed the clinical employment of the procedure on a sound scientific basis. This is most fortunate at the present moment when thousands of soldiers are returning to our hospitals with injuries to the bones that urgently call for radical operative treatment before the men can be fitted to return to useful civilian life. <h3>CHANGES IN TRANSPLANTED BONE</h3> The experiments on which we have based the principles that have guided our operative work have been Fig. 2.—High power photomicrograph of one of the
How the UK drug regulator became the herbalists' marketeer
Authors: M. McCartney
Journal: BMJ (2014)

Devil’s claw, arnica flower, palmetto fruit, and feverfew are among herbs recently endorsed as meeting standards of “safety, quality, and efficacy” by the Medicines and Healthcare Products Regulatory Agency (MHRA).1 Yes: the supposedly serious governmental regulator of drugs and devices in the United Kingdom has approved the use of a bunch of non-evidence based interventions.2

But devil’s claw (harpagoside) has not been shown to be effective or safe for long term use.3 Evidence is insufficient to back the use of arnica,4 and if it does work it is likely to have more side effects than topical ibuprofen.5 Palmetto does not improve the urinary symptoms for which the agency allows it to …
Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen–specific CD8+ T-cell function in Hodgkin lymphoma patients
Authors: Maher K. Gandhi, Eleanore Lambley, Jaikumar Duraiswamy, Ujjwal Dua, Corey Smith, Suzanne Elliott, Devinder Gill, Paula Marlton, John Seymour, Rajiv Khanna
Journal: Blood (2006)
Most NHS Direct callers are offered self care advice, study shows
Authors: R. Dobson
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives</b>: To determine whether rate of development of AIDS is affected by category of exposure to HIV and whether the more rapid development found in older subjects persists for each exposure category. <b>Design</b>: Longitudinal study of people with known date of seroconversion to HIV. <b>Setting</b>: 16 HIV treatment centres throughout Italy. <b>Subjects</b>: 1199 people infected with HIV through use of injected drugs, homosexual sex, or heterosexual sex. <b>Main outcome measures</b>: AIDS as defined by 1987 definition of Centers for Disease Control (including and excluding neoplasms) and by 1993 European definition. <b>Results</b>: 225 subjects (18.8%) progressed to AIDS (Centers for Disease Control 1987 definition) during median follow up of 5.8 years. Univariate analyses showed more rapid progression to AIDS for older subjects compared with younger subjects and for homosexual men compared with other exposure categories. The age effect was of similar size in each exposure category and in men and women. In a bivariate model with age and exposure categories simultaneously included as covariates, differences by exposure category disappeared for use of injected drugs and heterosexual sex compared with homosexual sex (relative hazards 1.02 (95% confidence interval 0.71 to 1.45) and 1.07 (0.70 to 1.64) respectively), while the age effect remained (relative hazard 1.55 (1.32 to 1.83) for 10 year increase in age). Analyses using the other definitions for AIDS did not appreciably change these results. <b>Conclusions</b>: There was no evidence of differences in rate of development of AIDS by exposure category, while there was a strong tendency for more rapid development in older subjects for all three groups. This supports the view that external cofactors do not play major role in AIDS pathogenesis but that age is of fundamental importance. <h3>Key messages</h3> Many studies have found an age effect on progression to AIDS, but it is not clear if this is due to specific AIDS defining diseases such as neoplasms and if it differs by exposure groups or by sex Our study of 1199 subjects with known date of seroconversion to HIV showed that older subjects progressed to AIDS more rapidly in all exposure groups considered, for both men and women, and for different definitions of AIDS After adjustment for age at seroconversion, there was no evidence of different rates of progression among subjects belonging to different exposure categories Behavioural cofactors do not seem to play a major role in AIDS pathogenesis but age is of fundamental importance in disease progression
STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS
Authors: Lester S. King
Journal: The Journal of Experimental Medicine (1939)

After inoculation with equine encephalomyelitis virus by various routes, guinea pigs were sacrificed at early stages, before symptoms were apparent. The brains were studied histologically, with serial sections; all lesions were noted, and subjected to topographical analysis. Nine cases are presented in detail. With any given mode of inoculation the distribution of lesions varied very widely from one instance to another. In some cases, affected regions bore a striking and definite anatomical relationship to each other. These distributions can be explained only by the assumption that the anatomical pathways played some rôle in the spread of the virus. In other instances lesions were present in areas, the anatomical connections of which were entirely normal. Attention is called to the frequency of lesions in the neocortex, with intact subcortical centers. Such distribution is held to render nerve spread extremely improbable. The only satisfactory explanation of such random distributions is by direct passage of virus from the blood stream into the brain tissue. There is no histological difference between lesions which result from blood spread and those resulting from nerve spread.
Does autistic enterocolitis exist?
Authors: N. Wright
Journal: BMJ (2010)

Despite the retracted Wakefield study, questions remain

In the linked feature (doi: 10.1136/bmj.c1127),1 Brian Deer tries to unravel the journey of the histopathological reports on the biopsies that formed the basis of the recently retracted study by Andrew Wakefield and colleagues in the Lancet ,2 which introduced the entity “autistic enterocolitis.” Apparently, the biopsies were first reported on by Susan Davies, a consultant histopathologist and coauthor on the study, but they were also seen and interpreted by three other coauthors before final publication. One of them was Professor Amar Dhillon, also a consultant histopathologist, although his role was apparently only to grade the biopsy inflammation on a grading sheet.1 However, there has been some dispute about this grading sheet, or proforma. In a letter published in 2007,3 Wakefield stated that it was designed by Dhillon and published by Wakefield’s group in 2000,4 although Dhillon was not a coauthor of the latter paper. This proforma published in 2000 referred to some unusual histopathological changes, such as “disruption of the epithelial basal lamina” and “condensation of the lamina propria”—terms with which few gastrointestinal pathologists would be familiar—and also referred to hyperplasia of mucosal lymphoid follicles, the importance of which is disputed.5 However, in a response to Wakefield’s 2007 letter, Dhillon denied that he had designed the proforma, stating that he provided one that he did design, which was based on British Society of Gastroenterology guidelines, and from which most of these terms are missing.6 

The biopsy sections were also examined by Andrew Anthony, then a junior pathologist, and by Wakefield, who as Deer points out is not a professional pathologist but a surgeon. It might be assumed that such a plethora of opinions would have produced consensus about the nature of the histopathological changes. …
Modifiable risk factors in periodontitis: at the intersection of aging and disease
Authors: Mark A. Reynolds
Journal: Periodontology 2000 (2013)

Abstract Chronic inflammation is a prominent feature of aging and of common age‐related diseases, including atherosclerosis, cancer and periodontitis. This volume examines modifiable risk factors for periodontitis and other chronic inflammatory diseases. Oral bacterial communities and viral infections, particularly with cytomegalovirus and other herpesviruses, elicit distinct immune responses and are central in the initiation of periodontal diseases. Risk of disease is dynamic and changes in response to complex interactions of genetic, environmental and stochastic factors over the lifespan. Many modifiable risk factors, such as smoking and excess caloric intake, contribute to increases in systemic markers of inflammation and can modify gene regulation through a variety of biologic mechanisms (e.g. epigenetic modifications). Periodontitis and other common chronic inflammatory diseases share multiple modifiable risk factors, such as tobacco smoking, psychological stress and depression, alcohol consumption, obesity, diabetes, metabolic syndrome and osteoporosis. Interventions that target modifiable risk factors have the potential to improve risk profiles for periodontitis as well as for other common chronic diseases.
Thalidomide and Neurological Damage Revisited
Authors: John Archer
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Lessons are still being learned from thalidomide. On May 11 and Sept 7 of 1961, as a member of the Food and Drug Administration in conferences with representatives of the US applicant to market the drug, I questioned its safety in pregnancy. My reasons were theoretical. Our attention had been drawn to published information that thalidomide could cause peripheral neuropathy. The reaction was unpredictable for a given individual and might regress at least to degree if the drug were discontinued, but it could reasonably be expected to progress with continued administration of the drug. It seemed possible that with repeated use, a mother who was escaping the reaction might thus give no warning that a developing fetus was experiencing it to increasing and perhaps devastating degree. With the shocking information that developed soon afterward of the teratogenic effects of thalidomide, my speculation seemed just a pale coincidence:
Human T-Cell Lymphotropic Virus Type I (HTLV-I)-Associated Adult T-Cell Leukemia-Lymphoma in a Patient Infected with Human Immunodeficiency Virus Type 1 (HIV-1)
Authors: Darryl Shibata
Journal: Annals of Internal Medicine (1989)

A patient had adult T-cell leukemia-lymphoma in the unusual setting of coinfection with human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-1). The leukemic cells were CD4 positive and showed clonal genetic rearrangement of the T-cell receptor complex. Cytogenetic analysis showed three clonal karyotypic abnormalities: trisomy 3 and two translocations [t(1;15), (X;1)]. The patient was seropositive for HIV and HTLV-I; HTLV-I and HIV-1 DNA sequences were detected in peripheral blood leukocytes by the polymerase chain reaction. The HTLV-I sequences were detected in a relatively high proportion of mononuclear cells (at least 1 in 30 cells), whereas HIV-1 sequences were detected in a smaller proportion of cells (at least 1 in 3000 cells). Clinical remission was achieved after chemotherapy. There was a decrease in the proportion of HTLV-I positive mononuclear cells (at least 1 in 1000 cells), whereas the proportion of HIV-1 positive cells was relatively unchanged (at least 1 in 1000 cells). Adult T-cell leukemia-lymphoma in the setting of HIV coinfection may become increasingly common because asymptomatic retroviral coinfections are frequent.