tbuckley/cabot-search huggingface dataset:
An electrogenic sodium pump and baroreceptor function in normotensive and spontaneously hypertensive rats.
Authors: W R Saum, A M Brown, F H Tuley
Journal: Circulation Research (1976)

Postexcitatory depression (PED) and adaptation were examined in slowly adapting aortic baroreceptors of normotensive rats (NTR) and spontaneously hypertensive rats (SHR); an aortic arch-aortic nerve preparation in vitro was used. PED was elicited either mechanically by employing single or double pressure steps, or electrically by antidromic stimulation of the aortic nerve. During PED the axon of the receptor was capable of conducting action potentials and the receptor itself could respond to increased pressures. The relationship between duration of PED and number of impulses preceding it was hyperbolic. In NTR's and SHR's PED was abolished by ouabain or solutions containing no potassium, neither of which affected the steady state pressure-volume relationship of the aorta. These interventions, which are known to block electrogenic pumps, also lowered the pressure threshold and increased the curvature of the steady state pressure-frequency curve. Furthermore, lithium, another agent that blocks electrogenic pumps, also abolished PED. Thus, PED is attributed mainly to an electrogenic sodium pump which operates normally in baroreceptors. We found that adaptation from peak transient to steady state frequency did not appear to be altered significantly when the pump was blocked. Blockage of the pump by ouabain is responsible for the baroreceptor reflex effects elicited by this drug. We conclude that resetting and reduced sensitivity in SHR baroreceptors are not attributed to significant differences in electrogenic pump activity.
William Logan Jack
Authors: F L Jack
Journal: BMJ (2002)

Former general practitioner and surgeon Herefordshire (b Kalgoorlie, Western Australia, 1907; q Adelaide 1929), d 20 November 2001.

Bill Jack came to England in 1932. He worked as resident medical officer at St Mary Abbotts Hospital before becoming a general practitioner, going into partnership in Kington, Herefordshire, and staying in practice for more than 40 years, maintaining his surgical skills at the same time. A founder member of the Royal College of General Practitioners, he was active in medical politics and voluntary organisations such as the St John Ambulance, as well as being closely involved in local community affairs. His many interests included gardening, shooting, fly fishing, and beekeeping. He leaves a wife, Dorothy; five children; and six grandchildren.
Vitamin A deficiency and small intestinal secretory function in the rat.
Authors: H Nzegwu, R J Levin
Journal: Gut (1991)

The influence of vitamin A on the functions of the small intestine was examined in rats made vitamin A deficient for 40 days by feeding a special diet after weaning and in pair fed vitamin A deficient rats that were given supplementary vitamin A (240 IU/day) in their drinking water. The basal and stimulated electrogenic secretory and absorptive functions of the jejunum and proximal and distal ileum removed from these rats were examined in vitro using the short circuit current as the index of transport activity. The basal short circuit current in the jejunum and proximal ileum was not significantly different but that of the distal ileum was lower. Electrogenic glucose transfer was not significantly affected by the vitamin deficiency. Cholinergic stimulation using the M1/M2 agonist bethanechol showed a greatly enhanced electrogenic secretion in the jejunum of the deficient rats while secretion stimulated by dibutyryl cyclic adenosine monophosphate was significantly greater in their distal ilea compared with the supplemented group. The vitamin deficiency also disrupted the normal higher/lower hierarchical pattern of transport activity between the proximal and distal ileum. The enhanced secretory activity of the vitamin A deficient small intestine offers a putative explanation for the well known relation between vitamin A deficiency and diarrhoea found in humans.
GMC to consult on radical structural changes
Authors: L. Beecham
Journal: BMJ (2000)

The United Kingdom's General Medical Council is asking doctors and the public for their views on several options for changing its size and structure and increasing the number of lay members who participate in its work.

Last July the GMC set up a working group after months of complaints from doctors and the public about, for example, the slowness of the council's procedures and the small number of lay members. These complaints culminated in a vote of no confidence in the council “as presently constituted and functioning” at the BMA's annual meeting (8 July, p 69).

In its document The Structure, Constitution and …
The best laid plans?
Authors: T. Groves
Journal: BMJ (2010)

The Icelandic island volcano pushed the UK parliamentary elections from most front pages this week, but not from the BMJ ’s cover. “How I long for a politician brave enough to say the NHS is unsafe in our hands…it begs for a Martin Luther to nail his 95 theses to the door.” So says Nigel Hawkes in our round up of views on the election’s health issues (doi:10.1136/bmj.c2095). Among many contributors, Ann McPherson wants government to stop the endless NHS reorganisations, to build on valuable experience, and to cherish general practice; Angela Coulter has her vote ready for whichever party produces a …
What do patients want of performance information?
Authors: I. Passarani
Journal: BMJ (2010)

Marshall and McLoughlin remind us that, especially in healthcare, there is no such thing as a rational consumer. Hence we are likely to take more time looking for information to get the best deal for a laptop or a plane ticket than searching for the best healthcare setting for our heart surgery. Information asymmetry and behavioural theories support the evidence quoted in the article suggesting that, so far, in those few countries where performance data are made publicly available, patients’ choices are not really influenced by them. More simply this can also be explained by the fact that in most cases patients are too sick, too old, or too vulnerable to seek this particular kind of “technical” information. Many are not literate enough to do it. Those who are in the position …
RECK Negatively Regulates Matrix Metalloproteinase-9 Transcription
Authors: Satoshi Takagi, Siro Simizu, Hiroyuki Osada
Journal: Cancer Research (2009)

RECK, a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of some matrix metalloproteinases (MMP), thereby suppressing tumor cell metastasis; however, the detailed mechanism is still obscure. In this study, we compared the gene expression profiles between mock- and RECK-transfected HT1080 cells and showed that RECK decreases MMP-9 mRNA levels but not other MMP mRNA levels. Moreover, treatment with RECK-specific siRNA increased MMP-9 mRNA in RECK-expressing cells. The promoter assay showed that MMP-9 promoter activity was suppressed by RECK and that RECK-mediated suppression of MMP-9 promoter activity requires 12-O-tetradecanoylphorbol-13-acetate-responsive element (TRE) and kappaB sites. Moreover, the binding ability of Fra-1 and c-Jun to TRE within the MMP-9 promoter region was suppressed by RECK. Thus, these results show that RECK is a negative regulator of MMP-9 transcription.
Influence of chronic renal failure on protein synthesis and albumin metabolism in rat liver.
Authors: S B Grossman, S H Yap, D A Shafritz
Journal: Journal of Clinical Investigation (1977)

Chronic renal failure in rats leads to changes in hepatic protein synthesis and albumin metabolism at both the cellular and molecular level. In rats with chronic uremia (blood urea nitrogen greater than 45 mg/100 ml 1 mo after surgical reduction in renal mass), cell-free protein synthesis is reduced 30--40% in liver membrane-bound polyribosomes. Albumin synthesis by membrane-bound polysomes in uremia is reduced even more than the reduction in total protein synthesis. Activity of free polysomes remains norma. There is also intracellular accumulation of albumin in liver of uremic rats and a concomitant decrease in serum albumin. In normal liver, most intracellular albumin is located in the microsomal fraction, whereas in liver from uremic animals the excess albumin is found in the free cytosol fraction. These results can be explained either by a defect in synthesis of albumin by membrane-bound polysomes with release of newly synthesized albumin into the cytosol or by a reduced ability of polysomes synthesizing albumin to associate with the membrane fraction in rats with chronic renal failure.
Genotypes and phenotypes of Shiga toxin producing-Escherichia coli isolated from healthy cattle in Thailand
Authors: N Panutdaporn, M Chongsa-nguan, G.B Nair, T Ramamurthy, S Yamasaki, U Chaisri, P Tongtawe, B Eampokalarp, P Tapchaisri, Y Sakolvaree, H Kurazono, W.B Thein, H Hayashi, Y Takeda, W Chaicumpa
Journal: Journal of Infection (2003)
Maharishi Ayur-Veda
Authors: Wallace Sampson
Journal: JAMA (1991)

<h3>To the Editor.</h3> —I hope that a lapse in attention caused the publication of "Letter From New Delhi"1 rather than fear of accusations of xenophobia. The TM movement makes false medical claims. Among them are longevity to infinity, levitation, the power of meditation to alter weather patterns, and correction of a number of medical conditions (a mild reduction in blood pressure may occur, but it is not permanent nor can one be removed from medication). The TM system also extracts extraordinary fees (over $200 for the privilege of a three-syllable mantra). These false claims did not appear in the article, but a collection of dubious results of "pulse diagnosis" and herbal and dietary treatments did. Although some of the results have been published, they have not been validated by independent observers. They are inconsistent with scientific knowledge and method. Having had an article or two (well-researched and valid) turned down
Induction of the early growth response gene-1, c-fos, and protein synthesis in adult cardiomyocytes by angiotensin II and endothelin
Authors: Ludwig Neyses, Janis Nouskas, Joachim Luyken, Stefan Fronhoffs, R.Sanders Williams, Vikas P. Sukhatme, Hans Vetter
Journal: Journal of the American College of Cardiology (1991)
Diagnostic Confusion from Lymphatic Lesions in Heroin Addicts
Authors: STEPHEN A. GELLER
Journal: Annals of Internal Medicine (1973)

Before biopsies, five patients who were heroin addicts had been diagnosed as having malignant disease. Two patients had generalized peripheral reactive lymphadenitis. The third patient was treated for malignant lymphoma on the basis of a lymph node biopsy, which was later interpreted as showing reactive lymphadenitis. Two patients had malignant lymphoma. Lymph node enlargement in patients addicted to heroin should not be interpreted as necessarily a manifestation of nonspecific responses to intravenous contamination, particularly when areas other than those draining local injection sites are involved.
Goodpasture's Dilemma
Authors: Joseph M. Merrill
Journal: JAMA (1985)

<h3>To the Editor.—</h3> On Jan 7, 1949, Ernst W. Goodpasture, dean of Vanderbilt University's School of Medicine, recommended to the University's chancellor that the program in undergraduate medical education be abandoned and that funds saved be used to expand medical research and graduate and postgraduate education, including "the most advanced medical training."<sup>1</sup> What led Goodpasture to articulate what many must have considered unthinkable? Goodpasture had noted the waning enthusiasm and spirit of the faculty following the decision by the university seven months earlier to stop subsidizing free hospital care for the poor, which it had supported for 21 years at an expenditure of $6 million of its endowment income. He concluded
PSYCHOSOMATIC DISORDERS AND THE NONPSYCHIATRIST
Authors: Bernard I. Lewis
Journal: JAMA (1952)

The current interest in so-called "psychosomatic medicine" has evoked many diverse responses from the general medical public. As with any new, or supposedly new, concept, there has been an initial wave of overenthusiasm opposed by a reef of rigid skepticism. The future may possibly reveal the truth to lie somewhere between these conflicting views. At present, however, there persists in many quarters much confusion regarding the incidence, mechanisms, diagnosis, and management of psychosomatic problems. In this presentation the prevailing opinion on these features will be briefly considered and various suggestions offered that may have practical value for the nonpsychiatrically trained physician. The actual incidence of ill health brought about wholly or in part by psychological factors is unknown. An approximation may be obtained, however, from the data presented in the following table. These analyses were made by several sets of observers on unselected medical patients of varying socioeconomic background. The
Ergasteric Hepatitis: Endemic Hepatitis Associated with Australia Antigen in a Research Laboratory
Authors: ALTON I. SUTNICK
Journal: Annals of Internal Medicine (1971)

Endemic hepatitis occurred among the personnel of a research laboratory working with human blood and tissues in the study of Australia antigen (Au(1)). All individuals were tested for serum glutamic-pyruvic transaminase (SGPT) levels and Au(1). Fifty-six were tested at monthly intervals on 5 to 32 occasions over 3½ years. Eighty-three others were tested less frequently. Twenty-seven changes were found in the serums of the 56 people tested frequently enough to have their course examined. There were four cases of typical acute hepatitis with Au(1) in the serum, fifteen staff members with rises in SGPT indicative of acute anicteric hepatitis, and eight staff members with small SGPT rises. We have termed this laboratory-acquired infection "ergasteric hepatitis" from the Greek word for laboratory. Seven patients were treated with bed rest as soon as the SGPT exceeded 50 units; in six the levels promptly returned to normal. We recommend strict infectious precautions and monthly monitoring of SGPT and Au(1) in personnel exposed to human (or nonhuman primate) blood or tissues.
NUTRITION OF THE HOST AND NATURAL RESISTANCE TO INFECTION
Authors: Howard A. Schneider
Journal: The Journal of Experimental Medicine (1946)

The property of a diet of whole wheat and whole dried milk to promote a higher survival rate among a stock of heterogenetic, outbred W-Swiss mice subjected to S. enteritidis infection, over that promoted by a "synthetic" diet, has been shown to be a function of the infecting bacterial population. Broth cultures so prepared as presumably to yield S. enteritidis organisms of uniform character have consistently failed to reveal an effect of diet on natural resistance, even though the parent bacterial populations revealed a dietary effect. The dietary difference effect on natural resistance could not be demonstrated with an avirulent culture of S. typhimurium, or with a freshly prepared virulent culture of S. typhimurium presumably uniform in character. The dietary effect on natural resistance was demonstrated by employing a 1:1 mixture of avirulent and virulent cultures of S. typhimurium.
Activation of adenylate cyclase by cholera toxin in rat liver homogenates.
Authors: J Flores, P Witkum, G W Sharp
Journal: Journal of Clinical Investigation (1976)

The effect of cholera toxin on adenylate cyclase from rat liver has been studied in a broken cell preparation. The activation of the enzyme in this in vitro preparation requires the addition of nicotinamide adenine dinucleotide (NAD) to the incubation medium and the presence of cell components other than the membrane-bound adenylate cyclase. Once the activation of the cyclase is produced, the effect persists despite repeated washing or solubilization of the enzyme. The effect can be obtained with concentrations of cholera toxin as low as 0.4 nM after 15 min of incubation at 22 degrees C, and stimulation can be detected after only 5 min of incubation at 37 degrees C. The activation of the enzyme is still apparent after at least 2 h at 0 degrees C. Preincubation with choleragenoid in vitro does not interfere with this effect of the toxin. Animals pretreated by an intravenous injection of cholera toxin do not respond to the in vitro addition of cholera toxin and NAD to the same extent as untreated animals; i.e., the effects overlap to suggest that the in vitro effect is the same as that in vivo. Responses to isoproterenol, glucagon, and NaF were also similar in the in vitro broken cell-activated system, as previously reported for the enzyme activated in vivo.
Two new modes of desmopressin (DDAVP) administration.
Authors: A Grossman, A Fabbri, P L Goldberg, G M Besser
Journal: BMJ (1980)

megaloblastic anaemia after taking metformin for eight years.True pernicious anaemia was excluded.There was no evidence of a lesion in the distal ileum and generalised malabsorption was excluded.We presumed that the vitamin B12 malabsorption was related to the effect of metformin on active absorption in the distal ileum but we could not prove that.The anaemia was cured, and treatment with chlorpropamide, metformin, and cyanocobalamin was continued.Although vitamin B12 malabsorption is relatively common with long-term metformin treatment, we think this is the first reported case of megaloblastic anaemia.The rarity of this complication might be expected since the malabsorption is not complete and the normal body stores contain more than a year's supply of vitamin B12.We advise annual screening for megaloblastic anaemia in patients on long-term metformin treatment, as it is an easily remediable compli- cation and does not necessitate withdrawal of the drug.
Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma
Authors: Jihun Kim, Cameron Fox, Shouyong Peng, Mark Pusung, Eirini Pectasides, Eric Matthee, Yong Sang Hong, In-Gu Do, Jiryeon Jang, Aaron R. Thorner, Paul Van Hummelen, Anil K. Rustgi, Kwok-Kin Wong, Zhongren Zhou, Ping Tang, Kyoung-Mee Kim, Jeeyun Lee, Adam J. Bass
Journal: Journal of Clinical Investigation (2014)

Patients with gastric and esophageal (GE) adenocarcinoma tumors in which the oncogene ERBB2 has been amplified are routinely treated with a combination of cytotoxic chemotherapy and the ERBB2-directed antibody trastuzumab; however, the addition of trastuzumab, even when tested in a selected biomarker-positive patient population, provides only modest survival gains. To investigate the potential reasons for the modest impact of ERBB2-directed therapies, we explored the hypothesis that secondary molecular features of ERBB2-amplified GE adenocarcinomas attenuate the impact of ERBB2 blockade. We analyzed genomic profiles of ERBB2-amplified GE adenocarcinomas and determined that the majority of ERBB2-amplified tumors harbor secondary oncogenic alterations that have the potential to be therapeutically targeted. These secondary events spanned genes involved in cell-cycle regulation as well as phosphatidylinositol-3 kinase and receptor tyrosine kinase signaling. Using ERBB2-amplified cell lines, we demonstrated that secondary oncogenic events could confer resistance to ERBB2-directed therapies. Moreover, this resistance could be overcome by targeting the secondary oncogene in conjunction with ERBB2-directed therapy. EGFR is commonly coamplified with ERBB2, and in the setting of ERBB2 amplification, higher EGFR expression appears to mark tumors with greater sensitivity to dual EGFR/ERBB2 kinase inhibitors. These data suggest that combination inhibitor strategies, guided by secondary events in ERBB2-amplified GE adenocarcinomas, should be evaluated in clinical trials.
970. Transcriptional Activat ion of krox-1 Induced by Sexual Hormones in Osteosarcoma Cells
Authors: Francisco Martinez-F, Fausto A. Jimenez-O, Catalina Machuca-R, Hilda Villegas-C, Kathleen Sakamoto
Journal: Molecular Therapy (2006)

Top of pageAbstract
Transcriptional control of genes delivered by adenoviral vectors in target cells has recovered importance in gene therapy research. Several inductors have been reported to modulate transcriptional activity of krox-1 promoter (EGR-1). Androgens and estrogens activities are identified in muscle skeletal cell myoblast differentiation and hyperplasic stage. Based in this approach, we are exploring the consequence of steroid hormones on the growth and proliferation of osteosarcoma cells.

Objective: To evaluate the effect Steroid hormones in osteosarcoma cells transduced by adenoviral vector.

Material and Methods: Adenoviral vectors expressing the Luciferase gene under transcriptional control of |[minus]|600pb sequence of Krox-1 promoter and CMV (Ad-Krox-luc and Ad-CMV-luc, respectively.)

Constructs and viral vectors. |[minus]|600 pb of Krox 1 was cloned upstream of Luciferase gene, into pShutle vector of adEasy system. Resulting recombined plasmid was selected and analyzed by endonuclease restriction. After that, linearized plasmid was transfected into HEK-293 for large scale production by cesium chloride gradients.

Cell lines, (HEK-293, and HS1082, CG1, CgM3 ,C2C12) were cultured at 37|[deg]|C, 5% of CO2, and 21% of Oxygen and high humidity in Dmem/F12 (50:50) supplemented with 1 % of antibiotic, 1% of Glutamax, and 10% of heat inactivated FBS. Infection of myoblast was performed at MOI: 50 for both adenoviral vectors and different concentration of Testosterone, Estrogen, Progesterone and synthetic analogues of glucocorticoids.

Viability and Luciferase expression assay were performed using Glo cell titer viability and Luciferase assay system.

Results: Viability and proliferation assays, don't' show significative changes than the control at 24 hours. But, testosterone has very strong effect on the estrogen and progesterone effect at 36 hours on transcriptional effects. We are exploring the effect on proliferation for large time and cross over the expression pattern of Krox-1, on this cell lines and comparatively with myoblast cells.
High 10-Year Survival Rate in Patients With Early, Untreated Prostatic Cancer
Authors: Jan-Erik Johansson
Journal: JAMA (1992)

To learn about the natural history of untreated, early-stage prostatic cancer.Cohort study with a mean follow-up of 123 months (range, 81 to 165 months).Population-based, regionally well defined.A consecutive sample of 223 patients (98% of all eligible) with early-stage (T0-2, NX, M0), initially untreated prostatic cancer.Progression-free, disease-specific, and overall survival. Need for palliative and terminal care.Patients with tumor progression were hormonally treated (orchiectomy or estrogens) if they had symptoms.After complete follow-up, only 19 (8.5%) of the 223 patients had died of prostate cancer and 105 (85%) of a total of 124 deaths were from other causes. The 10-year, disease-specific survival rate was 86.8% (95% confidence interval, 80.7% to 92.9%) and was equally high (87.9%) in a subgroup of 58 patients who met current indications for radical prostatectomy. The progression-free, 10-year survival rate was 53.1% (95% confidence interval, 44.2% to 62.0%). In 50 of 76 patients, local growth provided the only evidence of progression, and endocrine treatment was generally successful in these cases. Following an initial increase, the rate of disease progression and death from prostate cancer decreased during the last years of follow-up.The low disease-specific mortality rate, especially in patients with highly and moderately differentiated tumors, means that any local or systemic therapy intended for patients with early prostatic cancer must be evaluated in clinical trials with untreated controls for comparison.