tbuckley/cabot-search huggingface dataset:
In vivo blockade of pemphigus vulgaris acantholysis by inhibition of intracellular signal transduction cascades
Authors: I. Sanchez-Carpintero, A. Espana, B. Pelacho, N. Lopez Moratalla, D.S. Rubenstein, L.A. Diaz, M.J. Lopez-Zabalza
Journal: British Journal of Dermatology (2004)

Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. The mechanism of blister formation in pemphigus has not been defined; however, in vitro data suggest a role for activation of intracellular signalling cascades.To investigate the contribution of these signalling pathways to the mechanism of PV IgG-induced acantholysis in vivo.We used the passive transfer mouse model. Mice were injected with IgG fractions of sera from a patient with PV, with or without pretreatment with inhibitors of proteins that mediate intracellular signalling cascades.Inhibitors of tyrosine kinases, phospholipase C, calmodulin and the serine/threonine kinase protein kinase C prevented PV IgG-induced acantholysis in vivo.These observations strongly support the role of intracellular signalling cascades in the molecular mechanism of PV IgG-induced acantholysis.
Ionizing Radiation Induces Prostate Cancer Neuroendocrine Differentiation through Interplay of CREB and ATF2: Implications for Disease Progression
Authors: Xuehong Deng, Han Liu, Jiaoti Huang, Liang Cheng, Evan T. Keller, Sarah J. Parsons, Chang-Deng Hu
Journal: Cancer Research (2008)

Abstract Radiation therapy is a first-line treatment for prostate cancer patients with localized tumors. Although some patients respond well to the treatment, ∼10% of low-risk and up to 60% of high-risk prostate cancer patients experience recurrent tumors. However, the molecular mechanisms underlying tumor recurrence remain largely unknown. Here we show that fractionated ionizing radiation (IR) induces differentiation of LNCaP prostate cancer cells into neuroendocrine (NE)-like cells, which are known to be implicated in prostate cancer progression, androgen-independent growth, and poor prognosis. Further analyses revealed that two cyclic AMP–responsive element binding transcription factors, cyclic AMP–response element binding protein (CREB) and activating transcription factor 2 (ATF2), function as a transcriptional activator and a repressor, respectively, of NE-like differentiation and that IR induces NE-like differentiation by increasing the nuclear content of phospho-CREB and cytoplasmic accumulation of ATF2. Consistent with this notion, stable expression of a nonphosphorylatable CREB or a constitutively nuclear-localized ATF2 in LNCaP cells inhibits IR-induced NE-like differentiation. IR-induced NE-like morphologies are reversible, and three IR-resistant clones isolated from dedifferentiated cells have acquired the ability to proliferate and lost the NE-like cell properties. In addition, these three IR-resistant clones exhibit differential responses to IR- and androgen depletion–induced NE-like differentiation. However, they are all resistant to cell death induced by IR and the chemotherapeutic agent docetaxel and to androgen depletion–induced growth inhibition. These results suggest that radiation therapy–induced NE-like differentiation may represent a novel pathway by which prostate cancer cells survive the treatment and contribute to tumor recurrence. [Cancer Res 2008;68(23):9663–70]
Can gynaecology teaching associates provide high quality effective training for medical students in the United Kingdom? Comparative study
Authors: S. Pickard
Journal: BMJ (2003)

To train laywomen to become professional patients in order to teach medical students speculum and bimanual examination, to assess their effectiveness in this role, and to incorporate this method of teaching into the undergraduate curriculum of a medical school in the United Kingdom.Comparative study.Guy's, King's, and St Thomas's School of Medicine, London.44 medical students trained by gynaecology teaching associates; 48 control students.Skills in pelvic examination.Six laywomen were recruited and all successfully graduated to become gynaecology teaching associates. At assessment 1, in the third week of the reproductive and sexual health block, the mean score achieved by students trained by gynaecology teaching associates was 155, compared with 104 for control group students (difference in mean scores 51 (95% confidence interval 41 to 61), P < 0.001). Similar results were obtained at assessment 2, at the end of the attachment-the mean score for trained students was 148, compared with a mean score of 114 for control group students (difference in mean scores 34 (21 to 46), P < 0.001).Laywomen can be trained to teach pelvic examination to medical students in the United Kingdom. Students who receive this training have better skills than students who receive the traditional training alone.
Standard skin prick testing and sensitization to inhalant allergens across Europe – a survey from the GA<sup>2</sup>LEN network*
Authors: L. Heinzerling, A. J. Frew, C. Bindslev‐Jensen, S. Bonini, J. Bousquet, M. Bresciani, K.‐H. Carlsen, P. van Cauwenberge, U. Darsow, W. J. Fokkens, T. Haahtela, H. van Hoecke, B. Jessberger, M. L. Kowalski, T. Kopp, C. N. Lahoz, K. C. Lodrup Carlsen, N. G. Papadopoulos, J. Ring, P. Schmid‐Grendelmeier, A. M. Vignola, S. Wöhrl, T. Zuberbier
Journal: Allergy (2005)

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA 2 LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20 min exposure with positive results defined as a wheal &gt;3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus : 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA 2 LEN Pan‐European core SPT panel.
Prospective comparison of double-contrast barium meal examination and fibreoptic endoscopy in acute upper gastrointestinal haemorrhage.
Authors: G W Stevenson, R R Cox, C J Roberts
Journal: BMJ (1976)

Fibre-optic endoscopy was compared prospectively with double-contrast radiology in 53 consecutive patients admitted with acute gastrointestinal haemorrhage. The bleeding site was correctly identified by endoscopy in 94% of patients and the final diagnosis was correctly given in 89%. The corresponding figures with radiology were 83% and 74%. Among the 50 patients with a final diagnosis of a bleeding site in the upper gastrointestinal tract endoscopy indicated the site of bleeding in all and radiology indicated it in 88%. Both investigations were well tolerated by patients. Endoscopy is the investigation of choice, but when it is not available double-contrast radiology will show the site of bleeding in 80-90% of patients.
EU will fund research on stem cells only from embryos created before June 2002
Authors: R. Watson
Journal: BMJ (2003)

The European Commission has proposed a set of ethical guidelines to cover human embryonic stem cell research funded by the European Union. The initiative is designed to enable the union to give financial support to projects investigating cures for major diseases in the overall framework of the sixth research programme.

The programme specifically allows for research in this area. Announcing the draft guidelines, Philippe Busquin, the research commissioner, said: “By setting strict ethical rules for such funding, the EU contributes in a responsible way …
The scandal of medical device regulation
Authors: F. Godlee
Journal: BMJ (2012)

Try describing Europe’s system for regulating medical devices and, as Peter McCulloch says in his editorial this week, the response from your audience will be incredulous (doi:10.1136/bmj.e7126). Read his description and see if you too find yourself asking, “How could this have come about?” It’s a question that now demands urgent remedy. If this was not already clear from recent BMJ investigations ( BMJ 2011;342:d2748, BMJ 2012;344:e1410), a new investigation makes it uncontrovertibly so. Working with undercover reporters from the Telegraph newspaper, the BMJ ’s Deborah Cohen has exposed a fragmented, poorly regulated, market driven system, with financial incentives to prioritise manufacturers’ interests over …
Handbook of Nautical Medicine
Authors: William R. Barclay
Journal: JAMA (1985)

The<i>Handbook of Nautical Medicine</i>is written for two groups of physicians: those who specialize in occupational health and those who serve as physicians aboard ships. Thirty-six contributors have provided information on a wide variety of subjects, including the history of nautical medicine, the role of a ship's physician aboard many different kinds of vessels, health examinations for seamen, environmental hazards aboard ships, diseases and accidents to which seamen are prone, nutritional needs at sea, psychological problems in seafaring, the construction of different kinds of ships, the design of the ship's medical center, and the content of the ship's medicine chest. Nautical medicine is a highly specialized subject that holds little interest for most physicians, so this book will not appeal to a large audience. Nevertheless, those physicians to whom it is specifically directed will find it to be a valuable reference. It describes in great detail the environments in
Preliminary toxicity results of a phase II trial of adjuvant docetaxel/cyclophosphamide plus trastuzumab in HER2+ early stage breast cancer patients.
Authors: SE Jones, RP Collea, R Oratz, D Paul, SM Sedlacek, FA Holmes, RM Portillo, MW Crockett, L Asmar, JA O'Shaughnessy, NJ Robert
Journal: Cancer Research (2009)

Abstract Abstract #2111 Background: Docetaxel/cyclophosphamide (TC) has demonstrated superior activity to doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of patients (pts) with early breast cancer and is devoid of known cardiac toxicity (Jones et al, SABCS 2007, abstract 12). Although the addition of trastuzumab (H) to anthracycline-based adjuvant regimens has proven effective, it has also been associated with increased cardiac toxicity. Therefore, a short course of the nonanthracycline TC regimen coupled with H appeared to be a logical combination for women with lower risk HER2+ breast cancer. We report safety and tolerability of the TC+H regimen.&amp;#x2028; Patients and Methods: 256 of a planned 260 patients (pts) were registered to the study and stratified by positive or negative nodes. On Day 1 of each 21-day cycle for a total of 4 cycles, pts received (in order): (T) 75 mg/m2 IV, followed by (C) 600 mg/m2 IV. Weekly (H) was also given at 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (Days 1, 8, 15) thereafter throughout chemotherapy. After completion of chemotherapy, H was administered at a dose of 6 mg/kg IV every 3 weeks to complete 12 months of therapy with H. Pts must have had LVEF &amp;gt;50% at the time of registration and had regular cardiac evaluation throughout the study (MUGA or ECHO).&amp;#x2028; Results: To date, 231 pts were treated and comprise the safety population; this first report focused on toxicity occurring during the first 4 months of co-administration of chemotherapy and H. The median age was 55 years; 84% of pts were ECOG 0; 61% were ER+. Selected treatment-related toxicities in ≥3% of pts are listed in Table 1. Of the 231 pts, 10 pts came off treatment due to adverse events: hypersensitivity (3), gastrointestinal (2), hematologic (2), pulmonary (1), skin (1), and cardiac (1). To date, only 1 patient has had a significant drop in LVEF to 40%, and was taken off treatment.&amp;#x2028; &amp;#x2028; Conclusion: 4 cycles of TC combined with H is a well-tolerated adjuvant treatment with an acceptable toxicity profile for lower risk patients with HER2+ breast cancer.&amp;#x2028; This research was supported, in part, by a research grant from sanofi-aventis, Bridgewater, NJ. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2111.
Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice
Authors: W. Joost Lesterhuis, Cornelis J.A. Punt, Stanleyson V. Hato, Dagmar Eleveld-Trancikova, Bastiaan J.H. Jansen, Stefan Nierkens, Gerty Schreibelt, Annemiek de Boer, Carla M.L. Van Herpen, Johannes H. Kaanders, Johan H.J.M. van Krieken, Gosse J. Adema, Carl G. Figdor, I. Jolanda M. de Vries
Journal: Journal of Clinical Investigation (2011)

Tumor microenvironments feature immune inhibitory mechanisms that prevent T cells from generating effective antitumor immune responses. Therapeutic interventions aimed at disrupting these inhibitory mechanisms have been shown to enhance antitumor immunity, but they lack direct cytotoxic effects. Here, we investigated the effect of cytotoxic cancer chemotherapeutics on immune inhibitory pathways. We observed that exposure to platinum-based chemotherapeutics markedly reduced expression of the T cell inhibitory molecule programmed death receptor-ligand 2 (PD-L2) on both human DCs and human tumor cells. Downregulation of PD-L2 resulted in enhanced antigen-specific proliferation and Th1 cytokine secretion as well as enhanced recognition of tumor cells by T cells. Further analysis revealed that STAT6 controlled downregulation of PD-L2. Consistent with these data, patients with STAT6-expressing head and neck cancer displayed enhanced recurrence-free survival upon treatment with cisplatin-based chemoradiation compared with patients with STAT6-negative tumors, demonstrating the clinical relevance of platinum-induced STAT6 modulation. We therefore conclude that platinum-based anticancer drugs can enhance the immunostimulatory potential of DCs and decrease the immunosuppressive capability of tumor cells. This dual action of platinum compounds may extend their therapeutic application in cancer patients and provides a rationale for their use in combination with immunostimulatory compounds.
Carbenicillin Concentrations in Normal and Diseased Kidneys
Authors: ANDREW WHELTON
Journal: Annals of Internal Medicine (1973)

Renal tissue concentrations of carbenicillin and its intrarenal distribution are markedly influenced by alterations in the physiologic activity of the normal kidney or by the presence of severe disease in the renal parenchyma. In the hydropenic state, cortical, papillary, and urinary levels may be as much as 3, 17½, or 535 times greater, respectively, than the concomitant serum level. Hydration abolishes this increased cortico-papillary-urinary gradient pattern. Severe disease in human kidneys markedly decreases the renal parenchymal penetration of carbenicillin and significantly reduces the urine concentrations. This decreased renal tissue concentration averages 4 to 14 times less than the concentration in normal renal tissue. These changes in the renal and urinary pharmacokinetics of carbenicillin, in health and disease, have not been previously defined; they must be taken into account in the therapy of pyelonephritis and urinary tract infections.
Oncogenic BRAF Regulates Oxidative Metabolism via PGC1α and MITF
Authors: Rizwan Haq, Jonathan Shoag, Pedro Andreu-Perez, Satoru Yokoyama, Hannah Edelman, Glenn C. Rowe, Dennie T. Frederick, Aeron D. Hurley, Abhinav Nellore, Andrew L. Kung, Jennifer A. Wargo, Jun S. Song, David E. Fisher, Zolt Arany, Hans R. Widlund
Journal: Cancer Cell (2013)
Design of a temporally and spatially controlled drug delivery system for the treatment of liver diseases in mice
Authors: Isao Shibuya, Toshihiro Akaike, Yoshifumi Watanabe
Journal: Hepatology (2000)

Strict regulation of the distribution and degradation kinetics is the ultimate aim of drug delivery system. Regulation of drug delivery would increase the therapeutic efficacy and decrease the potential side effects. We encapsulated and used Z-Asp, a caspase inhibitor in poly-N-p-vinylbenzyl-D-lactonamide (PVLA) coated-poly (L-lactic acid) (PLA)-nanospheres in a mouse model of acute hepatitis. These nanospheres were internalized and accumulated in hepatocytes both in vitro and in vivo. Encapsulation significantly extended the intracellular retention time of the content in hepatocytes, which increased the bioavailability of the caspase inhibitor. In addition, the therapeutic effect was temporally controllable in vivo by modifying the component of the nanospheres. A cocktail of nanospheres with diverse degradation kinetics showed persistent therapeutic effects in acute hepatitis, and only nanospheres that targeted hepatocytes and controlled degradation rescued mice from lethal hepatic injury. This temporally and spatially controlled drug delivery system could be used in various liver diseases.
Smooth Muscle Antibody in Malignant Disease
Authors: J. M. A. Whitehouse, E. J. Holborow
Journal: BMJ (1971)

Smooth muscle antibody at titres of 1/10 or more was found in 54 (67.5%) out of 80 patients with malignant disease and in 9 (20%) out of 46 controls. The incidence of S.M. antibody ranged from 18/30 (60%) in malignant melanoma to 7/8 (83%) in carcinoma of the ovary. The presence of this antibody is possibly related to changes in the malignant cell membrane.A new antibody directed at an antigen presumed to be located in bile canaliculi among other sites is described.
Role of ethanol-inducible cytochrome P-450 IIE1 in carbon tetrachloride—induced damage to centrilobular hepatocytes from ethanol-treated rats
Authors: Kai O. Lindros, Yuan Cai, Kai E. Penttilä
Journal: Hepatology (1990)

The ethanol-inducible form of cytochrome P-450 (IIE1) is expressed and induced by ethanol, predominantly in the centrilobular region. Because this isoenzyme has a particularly high capacity to convert carbon tetrachloride and several other hepatotoxins into reactive intermediates, its role in producing damage was studied by comparing the effect of carbon tetrachloride exposure on hepatocytes isolated from either the periportal or the perivenous region by digitonin-collagenase perfusion. After exposure for 18 hr of primary culture to 600 mumol/L of carbon tetrachloride, periportal cells were only slightly damaged, as estimated from dye exclusion and lactate dehydrogenase leakage. In marked contrast, perivenous cells, which contained a several-fold higher amount of immunoreactive P-450 IIE1 apoprotein, were partly damaged after exposure to 60 to 150 mumol/L of carbon tetrachloride and severely damaged after 600 mumol/L. Similarly, lipid peroxidation after carbon tetrachloride was much more prominent in perivenous cells. The differences between perivenous and periportal cells in carbon tetrachloride-induced injury were larger when cells were isolated from chronically ethanol-treated rats. Isoniazid, an efficient inhibitor of P-450 IIE1, protected against damage by carbon tetrachloride more efficiently than the general P-450 inhibitor cimetidine. Our results suggest that the greater susceptibility of the perivenous hepatocytes to carbon tetrachloride-induced damage is associated with the high expression of P-450 IIE1 in these cells. This enzyme may also be involved in damage elicited by several other typical centrilobular hepatotoxins.
Intestinal Neoplasm Mimicking a Meckel??s Diverticulum On Scintigraphic Imaging
Authors: CHRISTOPHER J. MEHALL, ROGER M. KLEIN, JAROSLAW MUZ, LAWRENCE P. DAVIS
Journal: Clinical Nuclear Medicine (1991)

A 33-year-old man presented with colicky, intermittent, midabdominal pain with nausea and vomiting. A Tc-99m pertechnetate abdominal scan was performed and revealed a focal area of increased uptake in the midabdomen associated with dilated proximal loops of small bowel. Surgery revealed a high-grade partial obstruction of the midportion of the jejunum secondary to an annular adenocarcinoma of the jejunum. This is the first known report of abnormal Tc-99m pertechnetate accumulation in an adenocarcinoma of the small bowel.
Mutations in Families at High Risk for Breast Cancer
Authors: Peter Cheung
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Noninvasive Detection of Atherosclerosis
Authors: David S. Celermajer
Journal: New England Journal of Medicine (1998)

Atherosclerosis has been a serious health epidemic in developed countries in the late 20th century, and its rising prevalence in developing nations suggests that it will become the chief cause of morbidity and mortality worldwide by early in the next century.1 Although the principal clinical complications of atherosclerosis, such as myocardial infarction and stroke, usually occur in middle-aged or older people, the atherogenic process actually begins in childhood and early adult life, with a preclinical phase lasting many decades.2 This pattern provides a window of opportunity for the presymptomatic detection of the disease, the identification of high-risk subjects, and the . . .
Estimation of Amount of Hemoglobin.
Authors: Burnside Foster
Journal: JAMA (1900)

St. Paul, Minn., Nov. 20, 1900. <h3>To the Editor:</h3> I was much interested in Dr. Allen Staples' letter in the last issue ofThe Journal, on "Medical Study in Helsingfors," and, particularly in his allusion to Tallquist's method of estimating the amount of hemoglobin by means of a color scale, because Tallquist's original article on this subject was published in the<i>St. Paul Medical Journal</i>for May, 1900, together with the color scale which was made for us in Helsingfors under his direction. Possibly some of your readers who are interested in this matter may be glad to know where this article can be found. The price of the<i>Journal</i>, with the color scale is fifty cents.