tbuckley/cabot-search huggingface dataset:
Luminal secretion of ammonia in the mouse proximal tubule perfused in vitro.
Authors: G T Nagami
Journal: Journal of Clinical Investigation (1988)

A major portion of the total ammonia (tNH3 = NH3 + NH+4) produced by the isolated perfused mouse proximal tubule is secreted into the luminal fluid. To assess the role of Na+-H+ exchange in net tNH3 secretion, rates of net tNH3 secretion and tNH3 production were measured in proximal tubule segments perfused with control pH 7.4 Krebs-Ringer bicarbonate (KRB) buffer or with modified KRB buffers containing 10 mM sodium and 0.1 mM amiloride. Net tNH3 secretion was inhibited by 90% in proximal tubule segments perfused with the pH 7.4 modified KRB buffer while tNH3 production remained unaffected. The inhibition of net tNH3 secretion by perfusion with the modified KRB buffer was only partially reversed by acidifying the modified KRB luminal perfusate from 7.4 to as low as 6.2. These data indicate that the Na+-H+ exchanger facilitates a major portion of net tNH3 secretion by the proximal tubule and that luminal acidification may play only a partial role in the mechanism by which the Na+-H+ exchanger mediates net tNH3 secretion.
Anesthesia by acupuncture.
Authors: S G Hamilton
Journal: BMJ (1972)

<h3>Summary</h3> Progressive striatal gene expression changes and epigenetic alterations are a prominent feature of Huntington’s disease (HD), but direct relationships between the huntingtin (HTT) protein and chromatin remain poorly described. Here, using chromatin immunoprecipitation and sequencing (ChIP-seq), we show that HTT reproducibly occupies specific locations in the mouse genome, including thousands of genomic loci that are differentially occupied in striatal tissue from a knock-in mouse model of HD (B6.<i>Htt<sup>Q111/+</sup></i>) versus wildtype controls. ChIP-seq of histone modifications, generated in parallel, revealed genotype-specific colocalization of HTT with trimethylation of histone 3 lysine 27 (H3K27me3), a repressive chromatin mark. Near genes that are differentially regulated in HD, greater HTT occupancy in <i>Htt<sup>Q111/+</sup></i> vs. wildtype mice predicted increased H3K27me3, reduced histone 3 lysine 4 (H3K4me3), a marker of poised and active promoters, and down-regulated gene expression. Altered huntingtin-chromatin interactions may therefore play a direct role in driving transcriptional dysregulation in HD.
Rosiglitazone: a cautionary tale
Authors: F. Godlee
Journal: BMJ (2010)

This week a BMJ investigation suggests that the diabetes drug rosiglitazone should never have been licensed and should now be withdrawn (doi:10.1136/bmj.c4848).

The tale of rosiglitazone is a cautionary one from which we must hope the main parties will learn for the future. Hailed as a much needed new approach for patients with type 2 diabetes, the drug was licensed 10 years ago with only limited evidence of its effectiveness and concerns over its safety. While allowing the drug onto the market, the regulators asked the manufacturer GlaxoSmithKline to do additional trials. This the company did while marketing the drug around the …
979-33 Ischemia-Reperfusion Injury Impairs Endothelium-Dependent Relaxations Acutely, but not Chronically, and does not Affect Endothelial Pertussis Toxin-Sensitive G Protein Function in Canine Coronary Arteries
Authors: John J. Lee, Leopoldo Olmos, Paul M. Vanhoutte
Journal: Journal of the American College of Cardiology (1995)
pH <sub>i</sub> Regulation in Myocardium of the Spontaneously Hypertensive Rat
Authors: Néstor G. Pérez, Bernardo V. Alvarez, María C. Camilión de Hurtado, Horacio E. Cingolani
Journal: Circulation Research (1995)

To elucidate the mechanisms controlling pHi in myocardium of the spontaneously hypertensive rat (SHR), experiments were performed in papillary muscles (isometrically contracting at 0.2 Hz) from SHR and age-matched normotensive Wistar-Kyoto (WKY) rats loaded with the pH-sensitive fluorescent probe BCECF-AM. An enhanced activity of the Na(+)-H+ exchanger was detected in the hypertrophic myocardium of SHR. This conclusion was based on the following: (1) The myocardial pHi was more alkaline in SHR (7.23 +/- 0.03) than in WKY rats (7.10 +/- 0.03) (P < .05) in HEPES buffer. (2) SITS (0.1 mmol/L in HEPES buffer) did not alter pHi in the SHR (pHi 7.26 +/- 0.03 and 7.28 +/- 0.03 before and after SITS, respectively). (3) The fall in pHi observed after 20 minutes of Na(+)-H+ exchanger inhibition [5 mumol/L 5-(N-ethyl-N-isopropyl)amiloride (EIPA)] was greater in SHR (-0.16 +/- 0.01) than in WKY rats (-0.09 +/- 0.02, P < 0.05). (4) The velocity of pHi recovery from an intracellular acid load was faster in SHR than in WKY rats (0.068 +/- 0.02 versus 0.014 +/- 0.002 pH units/min at pHi 6.99, P < .05). (5) After EIPA inhibition, the rate of pHi recovery from the same acid load decreased to a similar value in both rat strains (0.0032 +/- 0.002 pH units/min in SHR and 0.0032 +/- 0.002 pH units/min in WKY rats). Under the more physiological HCO3(-)-CO2 buffer, no significant difference in steady state myocardial pHi was detected between rat strains (7.15 +/- 0.03 in SHR and 7.11 +/- 0.05 in WKY rats).(ABSTRACT TRUNCATED AT 250 WORDS)
Melanocyte Expression of Survivin Promotes Development and Metastasis of UV-Induced Melanoma in HGF-Transgenic Mice
Authors: Joshua Thomas, Tong Liu, Murray A. Cotter, Scott R. Florell, Kyle Robinette, Adrianne N. Hanks, Douglas Grossman
Journal: Cancer Research (2007)

Abstract We previously found the apoptosis inhibitor Survivin to be expressed in melanocytic nevi and melanoma but not in normal melanocytes. To investigate the role of Survivin in melanoma development and progression, we examined the consequences of forced Survivin expression in melanocytes in vivo. Transgenic (Tg) mouse lines (Dct-Survivin) were generated with melanocyte-specific expression of Survivin, and melanocytes grown from Dct-Survivin mice expressed Survivin. Dct-Survivin melanocytes exhibited decreased susceptibility to UV-induced apoptosis but no difference in proliferative capacity compared with melanocytes derived from non-Tg littermates. Induction of nevi in Dct-Survivin and non-Tg mice by topical application of 7,12-dimethylbenz(a)anthracene did not reveal significant differences in lesion onset (median, 10 weeks) or density (4 lesions per mouse after 15 weeks). Dct-Survivin mice were bred with melanoma-prone MH19/HGF-B6 Tg mice, and all progeny expressing either individual, neither, or both (Survivin/HGF) transgenes were UV-treated as neonates and then monitored for 43 weeks. Melanocytes in neonatal Survivin+/HGF+ mouse skin were less susceptible to UV-induced apoptosis than those from Survivin−/HGF+ mice. Onset of melanocytic tumors was earlier (median, 18 versus 24 weeks; P = 0.01, log-rank test), and overall tumor density was greater (7.7 versus 5.2 tumors per mouse; P = 0.04) in Survivin+/HGF+ compared with Survivin−/HGF+ mice. Strikingly, melanomas arising in Survivin+/HGF+ mice showed a greater tendency for lymph node (35% versus 0%; P = 0.04) and lung (53% versus 22%) metastasis and lower rates of spontaneous apoptosis than those in Survivin−/HGF+ mice. These studies show a role for Survivin in promoting both early and late events of UV-induced melanoma development in vivo. [Cancer Res 2007;67(11):5172–8]
The effects of partial hepatectomy on serum sex steroids in humans
Authors: Christopher Liddle, Michael Hollands, Miles J. Little, Geoffrey C. Farrell
Journal: Hepatology (1992)

In both rats and humans, partial hepatectomy results in a substantial increase in serum estradiol concentrations. Because mammalian liver of both sexes contains estrogen receptor, it has been suggested that this surge in serum estrogen concentration may initiate or facilitate liver regeneration. We have reexamined the potential role of sex steroids in human liver regeneration by measuring serum estradiol and testosterone concentrations in men and postmenopausal women before and after hepatic resection. The results were compared with those obtained in patients subjected to other forms of major surgery. In both men and postmenopausal women, serum estradiol levels increased after partial hepatectomy. However, the magnitude of increase was not related to the amount of liver removed. Moreover, similar increases occurred in patients undergoing other major surgical procedures not involving the liver. Serum testosterone concentrations decreased in men and increased in postmenopausal women undergoing all forms of surgery. It is concluded that effects of partial hepatectomy on serum sex steroid levels are nonspecific and probably related to stress. These observations diminish the likelihood that such changes are an important factor in the control of liver regeneration in humans. (Hepatology 1992;15:623-628).
Analysis of Ha-ras 1 allele frequencies in hereditary non-polyposis colorectal cancer.
Authors: P Jeevaratnam, P J Browett, N S Van de Water, J R Jass
Journal: Gut (1995)

Restriction enzyme digests of genomic DNA show multiple alleles of common, intermediate, and rare frequencies at the minisatellite locus of Ha-ras. It has been suggested that a higher frequency of rare alleles is associated with the presence of colorectal and other types of cancer. This study investigated the distribution of Ha-ras alleles in 40 members of hereditary non-polyposis colorectal carcinoma (HNPCC) families and in 34 cancer free subjects (spouses). There was no difference in rare allele frequency between the cancer group and cancer free group (chi2 = 0.25, not significant).
Chinese Lessons to Western Medicine: A Contribution to Geographical Medicine from the Clinics of Peiping Union Medical College
Authors: Samuel Vaisrub
Journal: JAMA (1965)

The first edition of<i>Chinese Lessons</i>, published in 1941, was intended to acquaint the Western clinician with diseases as encountered in China, and with medicine as practiced there, and "to bear testimony to the excellent reputation that the Peiking Union Medical College, better known as the PUMC, enjoyed as a medical center of teaching and research." The second edition, appearing after a lapse of 24 years, has the avowed purpose "to try and keep alive the memory of the PUMC." The main interest lies in the panoramic view of diseases in China, presented against the background of poverty, malnutrition, and established traditions of its people. A newly added chapter provides a historical perspective of two decades of medical progress, and indicates the shifting emphasis from clinical to physiological aspects of medicine.
Ampicillin-associated Colitis
Authors: A. Russo, E. Cirino, G. Sanfilippo, G. Grasso, G. Giannone
Journal: Endoscopy (1980)

A case of ampicillin-associated colitis is described. The authors stress the importance of emergency colonoscopy for the correct diagnosis and treatment of severe diarrhea and hemorrhage occurring during treatment with antibiotics.
Histone Modifications are Associated with the Persistence or Silencing of Vector-mediated Transgene Expression In Vivo
Authors: Efren Riu, Zhi-Ying Chen, Hui Xu, Chen-Yi He, Mark A Kay
Journal: Molecular Therapy (2007)

One of the major obstacles to success in non-viral gene therapy is transcriptional silencing of the DNA vector. The mechanisms underlying gene silencing/repression in mammalian cells are complex and remain unclear. Because changes in chromatin structure and, in particular, histone modifications are involved in transcriptional regulation of endogenous genes, we hypothesized that changes in the pattern of histone modifications were related to the observed transcriptional silencing of exogenous DNA vectors. We used antibodies against specific modified histones to perform chromatin immunoprecipitation (ChIP) analyses on liver lysates from mice transfected with two types of plasmids: (i) DNA minicircles (MCs) devoid of bacterial plasmid backbone DNA, which showed marked persistence of transgene expression, and (ii) their parental plasmids, which were silenced over time. Silencing of the transgene from the parental vectors was accompanied by an increase in heterochromatin-associated histone modifications and a decrease in modifications typically associated with euchromatin. Conversely, the pattern of histone modifications on the MC DNA was consistent with euchromatin. Our data indicates that (i) episomal vectors undergo chromatinization in vivo, and (ii) both persistence and silencing of transgene expression are associated with specific histone modifications.
Activin Upregulation by NF-κB Is Required to Maintain Mesenchymal Features of Cancer Stem–like Cells in Non–Small Cell Lung Cancer
Authors: J. Jacob Wamsley, Manish Kumar, David F. Allison, Sheena H. Clift, Caitlyn M. Holzknecht, Szymon J. Szymura, Stephen A. Hoang, Xiaojiang Xu, Christopher A. Moskaluk, David R. Jones, Stefan Bekiranov, Marty W. Mayo
Journal: Cancer Research (2014)

Abstract Soluble growth factors and cytokines within the tumor microenvironment aid in the induction of the epithelial-to-mesenchymal transition (EMT). Although EMT promotes the development of cancer-initiating cells (CIC), cellular mechanisms by which cancer cells maintain mesenchymal phenotypes remain poorly understood. Work presented here indicates that induction of EMT stimulates non–small cell lung cancer (NSCLC) to secrete soluble factors that function in an autocrine fashion. Using gene expression profiling of all annotated and predicted secreted gene products, we find that NF-κB activity is required to upregulate INHBA/Activin, a morphogen in the TGFβ superfamily. INHBA is capable of inducing and maintaining mesenchymal phenotypes, including the expression of EMT master-switch regulators and self-renewal factors that sustain CIC phenotypes and promote lung metastasis. Our work demonstrates that INHBA mRNA and protein expression are commonly elevated in primary human NSCLC and provide evidence that INHBA is a critical autocrine factor that maintains mesenchymal properties of CICs to promote metastasis in NSCLC. Cancer Res; 75(2); 426–35. ©2014 AACR.
Predicting survival for diffuse large B‐cell lymphoma patients using baseline neutrophil/lymphocyte ratio
Authors: Luis F. Porrata, Kay Ristow, Thomas Habermann, David J. Inwards, Ivana N. Micallef, Svetomir N. Markovic
Journal: American Journal of Hematology (2010)

The neutrophil/lymphocyte (N/L) ratio at diagnosis has been shown to be a prognostic factor for survival in solid tumors. The N/L ratio at diagnosis as a prognostic factor for non-Hodgkin lymphoma (NHL) has not been studied. Thus, we studied N/L ratio at diagnosis as a prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL)treated with R-CHOP. From 2000 until 2007, 255 consecutive DLBCL patients, originally diagnosed, treated with R-CHOP, and followed at Mayo Clinic, Rochester, were included in this study. With a median follow-up of 4.0 years (range: 0.3-9.0 years), patients with an N/L ratio<3.5 at diagnosis experienced a superior overall survival (OS) and progression-free survival (PFS) compared with those patient with an N/L ratio ≥ 3.5 at diagnosis. The median OS was not reached versus 6.8 years, P < 0.0001; and the median PFS was not reached versus 3.3 years, P < 0.0001, respectively. Multivariate analysis showed N/L ratio to be an independent prognostic factor for OS and PFS. This study suggests that baseline N/L ratio at diagnosis is a simple, inexpensive,standardized prognostic factor to assess clinical outcomes in DLBCL patients treated with R-CHOP.
The Blood Groups in Relation to Peptic Ulceration and Carcinoma of Colon, Rectum, Breast, and Bronchus
Authors: I. Aird, H. H. Bentall, J. A. Mehigan, J. A. F. Roberts
Journal: BMJ (1954)

We have previously shown an association between the ABO blood groups and cancer of the stomach, group A being significantly commoner in patients suffering from cancer of the stomach than in controls drawn from the same hospitals (Aird, Bentall, and Roberts, 1953).The further diseases for which fairly large numbers have so far been obtained are peptic ulceration and carcinoma of the colon, rectum, breast, and bronchus.The results are presented in this paper, which also includes some data on Rhesus grouping.In addition, further calculations have been made on the figures for cancer of the stomach already published.A detailed examination of our data follows.The results have proved remarkably clear-cut: blood group 0 is strikingly high and the other three groups correspondingly low in patients suffering from peptic ulcer.The three cancers now studied, unlike cancer of the stomach, showed no significant blood-group association. Collection of DataThe survey was carried out at 12 hospitals in England, and covers cases treated during the years 1948-53.At the first hospital visited, St. Mark's, London, cases from 1946 were included, but, as the blood groups were not often recorded in the earlier years, surveys in hospitals subsequently visited were restricted to 1948-53.It was also felt that during this period blood-grouping tech- niques were uniform and reliable.In such a study it was imperative to have rigid criteria of diagnosis in each disease.For the carcinomas, only cases proved by histological report on material obtained by biopsy, operation, or post-mortem examination were accepted.In peptic ulceration the criterion was a macroscopic report (operation or gastroscopy).The majority of these cases were perforated or bleeding ulcers or those submitted to elective surgery, for it is only in these cases that the blood group is often iecorded.Thus our series does not include many medically treated cases and therefore is not representa-
A5.19 In African Patients with Rheumatoid Arthritis ACPA Recognise Citrullinated Fibrinogen and the Immunodominant Epitopes Borne by the Fibrin Peptides α36–50 and β60–74, Like in Caucasians
Authors: L Nogueira, M Cornillet, M Singwe-Ngandeu, S Viatte, S Bas, C Gabay, G Serre
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Although most studies concerning the Rheumatoid Arthritis (RA)-specific antibodies to citrullinated proteins (ACPA) have been performed in populations of Caucasian ancestry, anti-CCP2 antibodies were demonstrated to be also good markers for RA in African patients. In one cohort from Cameroon, frequency of the HLA-DRB1 shared epitope (SE) alleles, although higher in RA patients than in controls, was lower than in Caucasian patients. Furthermore, known Caucasian non-HLA susceptibility genes did not confer the same risk in Africans. The purposes of the present study were, first, to analyse in African patients with RA the autoantibodies to citrullinated human fibrinogen (AhFibA), then, to investigate to what extent the two citrullinated fibrin peptides α36–50 and β60–74, which bear the immunodominant epitopes, were recognised by the sera of these patients. <h3>Methods</h3> AhFibA and autoantibodies to α36–50 and β60–74 were measured by ELISA in the serum of 56 consecutive RA patients with established disease from the Rheumatology unit of Yaoundé, Cameroon. 101 patients with other rheumatic diseases or healthy individuals were used as controls. <h3>Results</h3> Using the 95%-specificity thresholds previously defined with a French cohort, 73% of the RA sera from African patients were positive for AhFibA <i>ve</i>rsus 83% in French patients. The anti-β60–74 and anti-α36–50 autoantibodies were detected in 41/56 (73%) and 25/56 (45%) African RA sera <i>versus</i> 71% and 51% in French RA patients, respectively. Moreover, 38/41 (93%) of the AhFibA-positive sera recognised either α36–50 and/or β60–74, as previously observed in French patients. Finally, the mean AhFibA (OD = 1.28) and anti-β60–74 (OD = 1.32) titers were significantly higher in patients with at least one copy of the HLA-DRB1 SE (17/56, 30%) than in those without SE (OD = 0.64 and 0.60, respectively; p &lt; 0.005 and p &lt; 0.02), while the titer of anti-α36–50 autoantibodies did not differ. <h3>Conclusions</h3> AhFibA are markers for RA also in African patients. In these patients, autoantibodies to α36–50 and β60–74 peptides are present in proportions similar to those found in Caucasians. Like in Caucasians, they account for almost all the reactivity to fibrinogen. HLA-DRB1 SE alleles, although less common among African RA patients, are associated with higher titres of AhFibA and of auto antibodies to β60–74, suggesting that SE alleles partly control the AhFibA production, besides still unknown factors. This study shows that even in different genetic backgrounds the ACPA response is a hallmark of RA, and strongly suggests that its fine specificity to citrullinated fibrin is identical in Caucasians and Africans.
PAROXYSMAL TACHYCARDIA IN AN INFANT
Authors: Mildred Van Cleve
Journal: JAMA (1930)

Paroxysmal tachycardia is of rare occurrence in childhood, and especially so in early infancy. Willius and Amberg 1 recently collected and summarized the twenty-three cases previously reported, adding another case of their own of paroxysmal tachycardia with syncope in a child of 7 years. Only eight of these twenty-four cases occurred in infants less than 1 year of age.  The case here reported is one of paroxysmal tachycardia with syncope in an apparently healthy infant of 7 months, with no other evidence of cardiac disturbance.  REPORT OF CASE  M. M., a white girl, born after a full-term pregnancy terminated by a difficult labor with high forceps delivery, was apparently entirely normal at birth and weighed 8 pounds (3.6 Kg.). On discharge from the hospital at the age of 2 weeks she was in good condition and was on breast feedings supplemented by a cow's milk formula.  She was first seen
Treatment of Young Children with HIV Infection: Using Evidence to Inform Policymakers
Authors: Andrew J. Prendergast, Martina Penazzato, Mark Cotton, Philippa Musoke, Veronica Mulenga, Elaine J. Abrams, Diana M. Gibb
Journal: PLoS Medicine (2012)

CITATION: Prendergast, A. J. et al. 2012. Treatment of young children with HIV infection : using evidence to inform policymakers. PLoS Medicine, 9(7): e1001273, doi:10.1371/journal.pmed.1001273.
On Polypus Uteri
Authors: J. Ness
Journal: BMJ (1843)

MR. N1"g ON POLYPUS UTERI.as through it.The child was born alive; the mother, died six weeks after." On returning home from attending a case of labor, Dr. Merrimgan was infQrmed by his uncle, the late Dr. S. Merriman, that the patient had a scirrhus of the os uteri-that he thought she would never have anLother child, and would die from the disease, That, he said, was the result of his experience in other cases.She conceived again, however, and died soon after delivery.The child was born alive, and neither in this nor in the last case was any operation per- formed.
The angiotensin II pressor system of the rat forebrain.
Authors: D K Hartle, M J Brody
Journal: Circulation Research (1984)

An anterior hypothalamic knife cut that leaves intact two central sites of action of angiotension II produces the same deficits in the pressor responses to angiotensin II that have been attributed to destruction of two circumventricular organs (the subfornical organ and the organum vasculosum of the lamina terminalis). The central pressor actions of angiotensin II are necessary for the full expression of renin-dependent renal hypertension. The anterior hypothalamic knife cut attenuates renin-dependent aortic ligation hypertension. It has been shown that electrolytic destruction more anterior to this knife cut, in the anteroventral 3rd ventricle region, also attenuates two forms of renin-dependent hypertension, aortic ligation hypertension and two-kidney Goldblatt hypertension in the rat. Electrolytic lesions in the subfornical organ also reduce renin-dependent, two-kidney Goldblatt hypertension. These data are consistent with the hypothesis that a common efferent system from the organum vasculosum of the lamina terminalis and subfornical organ mediates the central pressor response to angiotensin II and is involved in the development of renin-dependent hypertension. A model is proposed for the circuitry in the rat forebrain that is involved in the pressor response to angiotensin II.