tbuckley/cabot-search huggingface dataset:
Dopamine decreases expression of type-1 angiotensin II receptors in renal proximal tubule.
Authors: H F Cheng, B N Becker, R C Harris
Journal: Journal of Clinical Investigation (1996)

Systemic and/or locally produced angiotensin II stimulates salt and water reabsorption in the renal proximal tubule. In vivo, dopamine (DA) may serve as a counterregulatory hormone to angiotensin II's acute actions on the proximal tubule. We examined whether dopamine modulates AT1 receptor expression in cultured proximal tubule cells (RPTC) expressing DA1 receptors. Dopamine decreased basal RPTC AT1 receptor mRNA levels by 67 +/- 7% (n = 10; P < 0.005) and decreased 125I-angiotensin II binding by 41 +/- 7% (n = 4; P < 0.05). The DA1-specific agonist, SKF38393 decreased basal AT1 receptor mRNA levels (65 +/- 5% inhibition; n = 5; P < 0.025), and the DA1-specific antagonist, SCH23390 reversed dopamine's inhibition of AT1 receptor mRNA expression (24 +/- 10% inhibition; n = 8; NS) and angiotensin II binding (5 +/- 15%; n = 4; NS). DA2-specific antagonists were ineffective. In rats given L-DOPA in the drinking water for 5 d, there were decreases in both proximal tubule AT1 receptor mRNA expression (80 +/- 5%; n = 6; P < 0.005) and specific [125I] Ang II binding (control: 0.74 +/- 0.13 fmol/mg pro vs. 0.40 +/- 0.63 fmol/mg pro; n = 5; P < 0.05). In summary, dopamine, acting through DA1 receptors, decreased AT1 receptor expression in proximal tubule, an effect likely mediated by increased intracellular cAMP levels. Local dopamine production also led to decreased AT1 receptor expression, suggesting dopamine may reset sensitivity of the proximal tubule to angiotensin II.
How much of orthodox medicine is evidence based?
Authors: John S Garrow
Journal: BMJ (2007)

Scientific heavyweights deplore the NHS money wasted on unproved and disproved treatments used by practitioners of complementary and alternative medicine (CAM),1 2 but Lewith, a CAM proponent [see previous letter], is cited elsewhere as saying that the BMJ reckons that 50% of the treatments used in general practice aren't proved, and 5% are pretty harmful but still being used.3

His data were taken from the BMJ Clinical Evidence website (http://clinicalevidence.com/ceweb/about/knowledge/jsp, viewed 6 May 2007). A pie chart indicates that, of about 2500 treatments supported by good evidence, only 15% of treatments were rated as beneficial, 22% as likely to be beneficial, 7% part …
Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells.
Authors: J A Nadel, D J Conrad, I F Ueki, A Schuster, E Sigal
Journal: Journal of Clinical Investigation (1991)

In reticulocytes, the enzyme 15-lipoxygenase (15-LO) is believed to contribute to cellular differentiation, and in leukocytes and airway cells 15-LO generates inflammatory mediators. The recent availability of antibodies to 15-LO now allows us to determine which specific cells contain the enzyme, to characterize its subcellular localization, and to determine its expression at the translational level. A polyclonal antibody to recombinant human reticulocyte 15-LO was used with a standard immunofluorescent technique. In rabbit red blood cells, fluorescence appeared during the course of anemia. Early reticulocytes did not fluoresce, but more mature reticulocytes showed increased fluorescent intensity. Late reticulocytes contained little fluorescence. Among human leukocytes, only eosinophils fluoresced. In human trachea, 15-LO immunofluorescence was localized to epithelial cells, and both basal and ciliated cells fluoresced. In all cells studied, fluorescence was localized to the cytoplasm and was variable in degree among cells in each preparation. We conclude that the 15-LO of airway cells and eosinophils is immunologically related to the reticulocyte 15-LO. Furthermore, the variable fluorescence among cells (e.g., in epithelium) and during development (e.g., reticulocytes) suggests a role of 15-LO in cell growth and development.
A Medical Reminder
Authors: William Gordon
Journal: JAMA (1966)

To the Editor:—  E. G. Dimond's plea for the medical continuum in which the physician remains a student all his life brings to mind two teachings from earlier days.  One of these was the remark of J. Chalmers Da Costa who once told a graduating class of the Jefferson Medical College where he taught surgery, Each of us, however old, is still an undergraduate in the school of experience. When a man thinks he has graduated he becomes a public menace.  The other is the excerpt from Tennyson's Ulysses, which Arthur A. Stevens, a teacher of my student days, used for the title page of his A Manual of the Practice of Medicine:   Yet all experience is an arch where-through  Gleams that untravelled world, whose margin fades  Forever and forever when I move.
Abstract P5-10-04: Amplification of Topoisomerase 2 Alpha <i>(TOP2A)</i> in HER2/neu Negative Breast Cancer
Authors: RW Glynn, S Mahon, N Miller, G Callagy, MJ. Kerin
Journal: Cancer Research (2010)

Abstract Background: TOP2A is of particular interest in breast cancer because of its association with response to anthracycline-based chemotherapies. Much of the work which has examined levels of TOP2A has concluded that amplification is restricted to those who are also HER2/neu amplified, leading some commentators to conclude that HER2/neu negative patients should not receive anthracyclines as part of their treatment. A couple of studies have identified TOP2A alterations in the absence of that of HER2/neu however, and the relationship between these targets needs to be better defined. We aimed to investigate the relationship between HER2/neu and TOP2A, whilst elucidating their association with clinicopathological variables thereby providing further insight into which patients are most amenable to anthracycline-based regimens. Materials and Methods: Hierarchical clustering was performed on a 20 patient cDNA microarray to identify gene clusters of clinicopathological interest. RQ-PCR was then performed (n=96) to further assess gene amplification, and levels were determined using the comparative Ct approach &amp; Taqman assays. An IHC microarray (n=76) was then employed to check for correlation between gene amplification and protein expression levels. Results: Amplification levels of TOP2A did not differ significantly according to HER2/neu status by either cDNA microarray (p=0.623), RQ-PCR (p=0.475) or IHC microarray (p=0.736). By RQ-PCR, 14/48 (29.1%) of the HER2/neu negative patients demonstrated levels of TOP2A above the third quartile. Similarly, 11/48 (22.9%) of the HER2/neu positive patients returned values in the first quartile, thereby indicating low-level amplification. Of 60 patients characterised as HER2/neu negative using IHC and FISH, 14 (22.9%) were classified as TOP2A positive on the IHC microarray. Of the 14 patients deemed HER2/neu positive using IHC and FISH, meanwhile, the majority (n=10) were classified as TOP2A positive. Discussion: Our results indicate that amplification of TOP2A in breast cancer is not confined to those who are concomitantly HER2/neu positive, and suggest that a significant proportion of HER2/neu negative patients exhibit high levels of TOP2A. These findings were not expected, are contrary to popular opinion, and have significant implications in the rationalisation of anthracycline-based therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-04.
Preoperative and Postoperative 18FDG PET/CT and Bone Scintigraphy Images in a Patient With Parathyroid Adenoma
Authors: Lebriz Uslu, Arzu Çalşkan, Sait Sağer, Serkan Teksöz, Metin Halaç
Journal: Clinical Nuclear Medicine (2013)

A 35-year-old male patient with generalized body pain had multiple hyperactive lesions on bone scan, suggestive of metastatic disease. FDG PET/CT scan performed 2 weeks later showed multiple hypermetabolic lesions on skeletal system; also a hypermetabolic and hypodense lesion was present adjacent to the left thyroid lobe, suggestive of primary parathyroid adenoma and multiple brown tumors. Serum parathyroid hormone level was elevated, and parathyroid scintigraphy confirmed parathyroid adenoma. The patient underwent parathyroidectomy operation, and histopathology result revealed parathyroid adenoma. Five months after the operation, complete metabolic regression was observed on PET/CT, whereas bone scan did not show any significant difference.
STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION
Authors: Oswald H. Robertson, Richard H. P. Sia, Shutai T. Woo
Journal: The Journal of Experimental Medicine (1924)

Experiments were undertaken with the purpose of determining the type of non-nutrient fluid most suitable for the suspension of pneumococci with a minimum amount of injury. For comparative studies, dilutions in the various fluids tested were made from a standard suspension containing approximately 1,000 million pneumococci per cc. The protective properties of each solution were judged by the length of time viable organisms could be recovered (in culture) from a suspension containing 0.0000001 cc. of the standard suspension. The hydrogen ion concentration of the solutions, the temperature at which the suspensions were kept, and the culture media were carefully controlled. Furthermore, plates were made at the beginning of the experiment to determine the number of organisms present in a unit of suspension. It was found that pneumococci suspended in Locke's solution, 0.5 and 0.9 per cent NaCl solutions, and water, remained alive for only a few hours at most. Salt solution was shown to be the least suitable of these three; not infrequently by the time the 0.000001 cc. dilution in this fluid had been reached, the suspension was sterile. The addition, however, of 0.1 per cent gelatin to the above fluids transformed all, except 0.9 per cent NaCl, into highly favorable solutions. Pneumococci suspended in gelatin-water and gelatin-Locke's solution remained alive at room temperature for 6 to 7 days; in gelatin-salt 0.5 per cent solution, for at least 2 days. It was possible to vary the H ion concentration of the suspension fluids from pH 7.0 to 8.2 without any marked effect on the results. However, a pH of 7.4 to 8.0 appeared to be the most suitable. The nature of the protective action of gelatin was investigated. Series of plates made at frequent intervals failed to reveal any growth in suspensions of pneumococci containing this small concentration of gelatin. The beneficial effect of gelatin in the above solutions was found to lie largely in its protection of the pneumococci against the mechanical injury which occurs during the process of dilution in crystalloid solutions or water. Gelatin shows in addition a well marked preservative action, that is to say, it protected organisms against early dissolution. The nature of this preservation is uncertain. The presence of 0.1 per cent gelatin in 0.9 per cent NaCl failed to protect pneumococci against the toxic action of Na. But it was found possible to neutralize to a considerable degree this toxic effect of sodium by the addition of a small quantity (2 per cent) of a M/15 balanced phosphate mixture or sodium phosphate. In a gelatin-salt 0.9 per cent solution buffered with phosphate, pneumococci survived for 24 to 48 hours. Even in gelatin-salt, 0.5 per cent the presence of phosphate had a definite beneficial effect.
NUCLEIC ACIDS AND THE PRODUCTION OF ANTIBODY BY PLASMA CELLS
Authors: William E. Ehrich, David L. Drabkin, Carolyn Forman
Journal: The Journal of Experimental Medicine (1949)

A study has been made of the relationship of antibody formation and the changes in amount of the nucleic acids in rabbit lymph nodes draining areas injected with typhoid vaccine. The increase in DNA was found to parallel the increase in weight of the nodes, as might be expected from the active multiplication of cells. The peak of PNA increase occurred between the 4th and 6th days after vaccine injection when antibody formation was at its maximum. A histologic study of methyl green- and pyronine-stained sections of the nodes revealed that during the first 6 days of the experiment the cellular reaction was chiefly one of plasma cells. During the first 3 days plasmoblasts predominated; on the 5th and 6th days mature plasma cells were the prevailing cells. Most of the PNA was contained in the plasma cells. The lymphocytes began to proliferate in significant numbers on the 3rd and 4th days, and germinal centers began to appear on the 4th and 5th days. They showed their greatest activity only on the 9th day when PNA and antibody formation had passed their peaks. These results are interpreted as indicating that the plasma cell and not the lymphocyte is responsible for antibody formation.
Psychosis during Methylphenidate Abuse
Authors: James Spensley, Don A. Rockwell
Journal: New England Journal of Medicine (1972)

METHYLPHENIDATE (Ritalin), discovered in 1954 by Meier1 and others, has been recommended for a variety of maladies.2 , 3 Little attention has been paid to its abuse potential in this country although as early as 1960, Rioux4 raised the question of its "addiction potential" in a report on a patient who was taking 125 tablets of methylphenidate daily. The Scandinavian literature contains several reports of abuse.5 6 7 8 Use of oral methylphenidate in the United States is widespread. Its prescription for children with behavior problems and the "hyperkinetic syndrome" has reached large proportions. Earlier reports on the use of oral methylphenidate indicated little potential . . .
John Alan Kennedy
Authors: A. Innes
Journal: BMJ (2004)

General practitioner Dumfries (b Inverness 1954; q Aberdeen 1979; MRCGP), d 10 August 2003.​2003.




Figure 1




After house jobs in Glasgow and Inverness John trained in general practice in Dumfries, where he settled as a principal in 1983. His many outside interests including hill walking and, more recently, scuba diving with his younger son. He was always a generous host, and the Kennedy Christmas Eve party was regarded as the official opening of the festive season for his huge circle of friends and their families. He leaves a wife, Susan, and three children.
Effects of Three Therapies for Neck Pain
Authors: Oliver Kwan, Jon Friel
Journal: Annals of Internal Medicine (2003)

Letters15 April 2003Effects of Three Therapies for Neck PainOliver Kwan, PhD (Psy) and Jon Friel, PhD (Psy)Oliver Kwan, PhD (Psy)Edmonton, Alberta T5H 2L8, Canada (Kwan, Friel)Search for more papers by this author and Jon Friel, PhD (Psy)Edmonton, Alberta T5H 2L8, Canada (Kwan, Friel)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-138-8-200304150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their study of manual therapy, physical therapy, and general practitioner care for patients with neck pain, Hoving and colleagues concluded, In daily practice, manual therapy is a favorable treatment option for patients with neck pain compared with physical therapy or continued care by a general practitioner (1). We consider this an overstatement of the significance of their results. We note that although the manual therapy outcomes showed higher scores, scores were later referred to as not statistically different. We also see terms like trend, a way of saying that the results did not impress the statistician ...References1. Hoving JL, Koes BW, de Vet HC, van der Windt DA, Assendelft WJ, van Mameren H, . Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial. Ann Intern Med. 2002;136:713-22. [PMID: 12020139] LinkGoogle Scholar2. Bacchetti P. Peer review of statistics in medical research: the other problem. BMJ. 2002;324:1271-3. [PMID: 12028986] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Edmonton, Alberta T5H 2L8, Canada (Kwan, Friel) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoManual Therapy, Physical Therapy, or Continued Care by a General Practitioner for Patients with Neck Pain Jan Lucas Hoving , Bart W. Koes , Henrica C.W. de Vet , Danielle A.W.M. van der Windt , Willem J.J. Assendelft , Henk van Mameren , Walter L.J.M. Devillé , Jan J.M. Pool , Rob J.P.M Scholten , and Lex M. Bouter Effects of Three Therapies for Neck Pain Jan Lucas Hoving , Bart W. Koes , and Henrica C.W. de Vet Metrics 15 April 2003Volume 138, Issue 8Page: 685KeywordsPatients ePublished: 15 April 2003 Issue Published: 15 April 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Mrp4−/− mice have an impaired cytoprotective response in obstructive cholestasis
Authors: Albert Mennone, Carol J. Soroka, Shi-Ying Cai, Kathy Harry, Masashi Adachi, Lee Hagey, John D. Schuetz, James L. Boyer
Journal: Hepatology (2006)

Mrp4 is a member of the multidrug resistance–associated gene family that is expressed on the basolateral membrane of hepatocytes and undergoes adaptive upregulation in response to cholestatic injury or bile acid feeding. However, the relative importance of Mrp4 in a protective adaptive response to cholestatic injury is not known. To address this issue, common bile duct ligation (CBDL) was performed in wild-type and Mrp4−/− mice and animals followed for 7 days. Histological analysis and serum aminotransferase levels revealed more severe liver injury in the absence of Mrp4 expression. Western analyses revealed that Mrp4, but not Mrp3, was significantly increased after CBDL in wild-type mice. Serum bile acid levels were significantly lower in Mrp4−/− mice than in wild-type CBDL mice, whereas serum bilirubin levels were the same, suggesting that Mrp4 was required to effectively extrude bile acids from the cholestatic liver. Mrp3 and Ostα-Ostβ were upregulated in Mrp4−/− mice but were unable to compensate for the loss of Mrp4. High-performance liquid chromatography analysis on liver extracts revealed that taurine tetrahydroxy bile acid/beta-muricholic acid ratios were increased twofold in Mrp4−/− mice. In conclusion , hepatic Mrp4 plays a unique and essential protective role in the adaptive response to obstructive cholestatic liver injury. (Hepatology 2006;43:1013–1021.)
Doctors walk free after manslaughter conviction
Authors: C. Dyer
Journal: BMJ (2003)

Two junior doctors working in Britain were convicted of manslaughter last week but walked free after the judge imposed 18 month prison sentences suspended for two years.

Amit Misra, aged 34, and Rajeev Srivastava, aged 38, were found guilty by majority verdicts of causing the death of 31 year old Sean Phillips by gross negligence. A jury at Winchester Crown Court took nine hours to deliver their verdict against the two doctors. The doctors qualified in India but were working as senior house officers in the NHS.

They were doing shifts …
[663] ELEVATED PLASMA NOCICEPTIN LEVEL IN EXPERIMENTALLY INDUCED CHOLESTASIS IN RATS
Authors: T. Csak, M. Hantos, A. Horvath, A. Folhoffer, I. Osztovits, Zs. Visnyei, A. Zalatnay, P. Nagy, K. Tekes, F. Szalay
Journal: Journal of Hepatology (2007)
Extracellular Calcium and Vascular Responses After Forearm Ischemia
Authors: Virginia A. Imadojemu, Kenneth Mooney, Cindy Hogeman, Mary E.J. Lott, Allen Kunselman, Lawrence I. Sinoway
Journal: Circulation (2004)

Background— The myogenic response is a phenomenon in which blood vessels respond to increases and decreases in transmural pressure with constriction and dilation, respectively. Despite intense investigation into the signaling mechanisms underlying this response, the precise mechanisms remain unclear. It has been suggested that the myogenic response occurs when pressure or stretch evokes increases in vessel wall tension that results in vessel smooth muscle cell depolarization. This causes Ca 2+ entry through voltage-gated Ca 2+ channels. Of note, in vitro studies demonstrate that the magnitude of the myogenic response is dependent on the extracellular Ca 2+ . We tested the hypothesis that in conscious humans, physiological changes in extracellular Ca 2+ concentrations would be an important determinant of the myogenic response. Methods and Results— Venous blood ionized calcium was used as an index of interstitial calcium and was measured 5, 15, and then every 15 seconds for 75 seconds, then every 30 seconds for 90 seconds, then finally at the 300-second mark. Forearm blood pressure and flow velocity were determined after 10 minutes of forearm ischemia. We found that the rate of change in serum calcium levels varied as a function of transmural pressure ( r =0.96). Moreover, the calcium concentration was inversely proportional to forearm blood velocity ( r =0.99). Conclusions— We hypothesize that muscle stretch caused by a rise in transmural pressure raises interstitial calcium by unknown mechanisms and this in turn acts to lower limb flow velocity.
Clinical and radiological damage in psoriatic arthritis
Authors: Fotios Siannis, Vernon T. Farewell, Richard J. Cook, Catherine T Schentag, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Psoriatic arthritis may progress to joint damage. Joint damage may be assessed clinically, by identifying deformed, fused, or flail joints, or radiologically, by recording erosions, joint space narrowing, ankylosis, lysis, or surgery. The relation between clinical and radiological damage is unclear. <b>Objective:</b> To study the ordering of clinical and radiological damage detection, and the clinical features associated with the type of damage detected first. <b>Methods:</b> The University of Toronto psoriatic arthritis database was used to relate clinical and radiological damage in the hand joints in 655 patients followed prospectively between 1978 and 2003. Generalised estimating equations were used to fit logistic regression models to identify factors that predict classification of damage by radiographic assessment first. <b>Results:</b> The majority of the joints were not informative, as they either had evidence of damage by both methods at entry, or remained undamaged. Of the remainder, 81% of the joints showed radiological damage first and 19% had clinical damage first. Development of radiological damage first was related to previous detection of swollen joints, and was inversely related to duration of arthritis. <b>Conclusions:</b> Radiological damage is often detected before clinical damage is observed. Clinical inflammation often precedes the detection of radiological damage.