tbuckley/cabot-search huggingface dataset:
Inactivation of the Mitogen-Activated Protein Kinase Pathway as a Potential Target-Based Therapy in Ovarian Serous Tumors with KRAS or BRAF Mutations
Authors: Gudrun Pohl, Chung-Liang Ho, Robert J. Kurman, Robert Bristow, Tian-Li Wang, Ie-Ming Shih
Journal: Cancer Research (2005)

Activation of mitogen-activated protein kinase (MAPK) occurs in response to various growth stimulating signals and as a result of activating mutations of the upstream regulators, KRAS and BRAF, which can be found in many types of human cancer. To investigate the roles of MAPK activation in tumors harboring KRAS or BRAF mutations, we inactivated MAPK in ovarian tumor cells using CI-1040, a compound that selectively inhibits MAPK kinase, an upstream regulator of MAPK and thus prevents MAPK activation. Profound growth inhibition and apoptosis were observed in CI-1040-treated tumor cells with mutations in either KRAS or BRAF in comparison with the ovarian cancer cells containing wild-type sequences. Long serial analysis of gene expression identified several differentially expressed genes in CI-1040-treated MPSC1 cells harboring an activating mutation in BRAF (V599L). The most striking changes were down-regulation of cyclin D1, COBRA1, and transglutaminase-2 and up-regulation of tumor necrosis factor-related apoptosis-induced ligand, thrombospondin-1, optineurin, and palladin. These patterns of gene expression were validated in other CI-1040-treated tumor cells based on quantitative PCR. Constitutive expression of cyclin D1 partially reversed the growth inhibitory effect of CI-1040 in MPSC1 cells. Our findings indicate that an activated MAPK pathway is critical in tumor growth and survival of ovarian tumors with KRAS or BRAF mutations and suggest that the CI-1040 induced phenotypes depend on the mutational status of KRAS and BRAF in ovarian tumors.
SUPERIOR METHOD OF STAINING TUBERCLE BACILLI
Authors: Peter Mjedloff
Journal: JAMA (1923)

<h3>To the Editor:</h3> —At the Kula Sanitarium, for some time, we have been using, as a routine, a method of staining tubercle bacilli which is eminently satisfactory and is superior to the usual Ziehl-Neelsen stain. A smear of sputum is prepared and fixed in the usual manner. It is steamed for two full minutes with anilin gentian violet prepared according to the method of Weigert, as described by Stitt, boiling being avoided. The slide is rinsed with running water and covered with gram-iodin solution (Lugol) for two minutes. It is decolorized with acid alcohol (usual solution), washed in running water, and counterstained with 0.1 per cent, solution of pyronin for several seconds. Though we have found pyronin to be the best counterstain, any other may be used. In the medical literature accessible to me I have not been able to find this method described and would appreciate greatly if you
The lack of significant changes in scalp hair follicle density with advancing age
Authors: R. Sinclair, A. Chapman, J. Magee
Journal: British Journal of Dermatology (2005)

Age-related reduction in hair is seen in the axillary and pubic regions as well as the scalp; however, it has not been investigated qualitatively on the scalp. Horizontally sectioned scalp biopsy is an ideal tool to investigate the impact of advancing age on scalp hair follicle density and morphology.To examine the effect of age and follicle miniaturization on total hair count in 1666 horizontally sectioned mid-scalp biopsies from 928 women aged between 13 and 84 years with hair loss.Specialist hair loss referral clinic in a teaching hospital.Analysis of data set. Methods: All scalp biopsies were 4 mm in diameter and taken from the crown. Miniaturization was assessed by calculating the ratio of terminal to vellus-like hairs (T/V) at the mid-isthmus level and considered significant if the ratio was < or = 4 : 1. Fibrosis was documented when present. Linear regression was used to examine the association between total hair count, age and miniaturization.The average number of hair follicles per biopsy was 39.6 (SD +/- 10.8). A highly significant negative association (P < 0.0001) was found between age and total follicle number, although the predictive value of age in total hair count was found to be small [root error mean square (R2) < 2%]. Controlling for T/V < or = 4 : 1, the association was weakened, but remained significant. The relationship unconfounded by T/V < or = 4 : 1 shows that for every additional year of ageing, 0.077 total hair follicles (0.22%) are lost per biopsy.Age and follicular miniaturization were found to be extremely weak predictors of total hair count in women with hair loss.
ACCESSORY PLASMA FACTORS INVOLVED IN THE BACTERICIDAL TEST FOR TYPE-SPECIFIC ANTIBODY TO GROUP A STREPTOCOCCI
Authors: Gene H. Stollerman, Michael Rytel, Jesse Ortiz
Journal: The Journal of Experimental Medicine (1963)

A study was made of the nature of the thermolabile plasma factors in human blood which promote the phagocytosis of Group A streptococci in vitro in the presence of optimal amounts of type-specific M antibody. The plasmas of individuals with strong opsonic activity (normal) were compared with those of some individuals whose opsonic activity was consistently weak (deficient). A general relationship was established between encapsulation of streptococci and the opsonic requirement for thermolabile plasma factor(s). Marked differences in phagocytosis of Group A organisms by human bloods were demonstrated with encapsulated strains only. Human bloods deficient in the cofactor required for opsonization of encapsulated streptococci (coopsonin) showed a normal rate of phagocytosis against all other organisms and particles studied. Furthermore, coopsonin-deficient bloods contained normal levels of four components of complement, of properdin, of lysozyme, and of direct bactericidal activity against several species of Gram-negative organisms and of E. coli bacteriophage. The independence of the streptococcal coopsonin from complement was also demonstrated by absorption of plasma with bentonite and with zymosan. Under appropriate conditions, the coopsonin was reduced without significant loss of complement. The data support the concept that the capsule of the streptococcus imposes an opsonic requirement for a plasma factor(s) which is present in varying amounts in human bloods and which appears to be independent of the complement system. The possibility that it is accessory to the latter components has not been excluded.
Staphylococcus aureus Endocarditis
Authors: Ralph J. Faville, Darwin E. Zaske, Edward L. Kaplan, Kent Crossley, L. D. Sabath, Paul G. Quie
Journal: JAMA (1978)

Two children with persistent bacteremia and endocarditis due to<i>Staphylococcus aureus</i>failed to respond to vancomycin therapy, even though serum levels greatly exceeded the inhibitory concentrations. The<i>Staphylococcus</i>from one patient was resistant to methicillin; the other patient had a penicillin hypersensitivity. There was a wide disparity between the minimum inhibitory and the minimum bactericidal concentrations of vancomycin. Striking clinical and laboratory evidence of improvement was demonstrated with the addition of rifampin therapy. (<i>JAMA</i>240:1963-1965, 1978)
Scientists Probe Brain’s Role in Obesity
Authors: Huan J. Chang
Journal: JAMA (2010)

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
Foreign Body in Nasal Cavity: Removal and Subsequent Rhinoplasty
Authors: J. H. Bartlet
Journal: BMJ (1870)

the sixth day of the outbreak, the fluid in the vesicles was-evidently drying up, and the whole eruption just beginning to subside.CASE XVII.Ifydroa in associationt with Erl'thema Nodosumn in a Child: Erugption cuiefly onz Lower Extrernzities.-PatrickHaffenie, aged
Modulation of carotid sinus afferent input to nucleus tractus solitarius by parabrachial nucleus stimulation.
Authors: R B Felder, S W Mifflin
Journal: Circulation Research (1988)

There is increasing evidence that the parabrachial nucleus (PBN) may be integrally involved in cardiovascular reflex regulation. In cats in which anesthesia was induced with pentobarbital and maintained with alpha-chloralose, we studied the effects of PBN stimulation on cardiovascular afferent inputs to nucleus tractus solitarius (NTS), the site of first central termination for cardiovascular afferent fibers. Electrical stimulation of PBN resulted in an initial excitation followed by prolonged inhibition of the spontaneous activity of NTS neurons activated by ipsilateral carotid sinus nerve (CSN) stimulation. In 53 units recorded extracellularly in and around NTS, the number of action potential responses to ipsilateral CSN stimulation was reduced 73 +/- 3% by a prior conditioning stimulus to PBN at an interval of 30-60 msec. CSN input to 10 units excited by selective baroreceptor stimulation was inhibited by the PBN conditioning stimulus, as were convergent inputs from contralateral CSN, vagus, and renal nerves. The inhibitory influence of the PBN stimulus lasted as long as 450 msec. We examined the mechanism for these phenomena in additional intracellular recording experiments. In 57 units, PBN stimulation evoked a long lasting (65-359 msec) membrane potential hyperpolarization. In 42 cells, the PBN evoked inhibitory postsynaptic potential (IPSP) was preceded by an excitatory postsynaptic potential (EPSP). CSN and convergent inputs were inhibited when timed to occur during the PBN induced IPSP. Conversely, CSN and convergent afferent nerves inhibited PBN input to NTS neurons with no associated change in membrane potential (n = 9 of 14). These data demonstrate for the first time a potent modulatory influence of PBN on NTS neurons processing cardiovascular afferent input.
Echocardiographic Evaluation of Pulmonary Hypertension
Authors: NAVIN C. NANDA, RAYMOND GRAMIAK, TREVOR I. ROBINSON, PRAVIN M. SHAH
Journal: Circulation (1974)

Echocardiographic studies of the pulmonary valve were obtained in 63 adults. Patients with normal pulmonary artery pressure (22 cases) showed an oblique position of the valve images in diastole, slow valve opening slopes (≤ 300 mm/sec), sizable (&gt; 2 mm) posterior displacement of the cusp echoes with atrial systole (`a' dip), and a relatively short right ventricular pre-ejection period. In contrast, pulmonary valves in pulmonary hypertension (mean pressure &gt; 20 mm Hg, 41 cases) appeared straight in diastole with rapid opening slopes (&gt; 350 mm/sec) and prolonged pre-ejection periods ( P &lt; 0.001). In patients maintaining sinus rhythm (25 cases), mild to moderate pulmonary hypertension (mean pressure ≤ 40 mm Hg) was indicated by small `a' dips (≤ 2 mm), while absence of `a' dips denoted more severe pulmonary hypertension (mean pressure &gt; 40 mm Hg) when uncomplicated by severe right heart failure. In the latter instance rapid valve opening slopes were associated with large `a' dips. Echocardiography appears to be of value in the assessment of pulmonary hypertension.
Questions You Don't Ask Your Doctor
Authors: Charles G. Roland
Journal: JAMA (1968)

For a variety of reasons patients and their families fail to get appropriate medical information. The questions in this book represent three broad groups of questioners: those who have a problem, usually minor, which they have not taken to a physician; those who wish a second opinion (usually about proposed therapy); and those separated by a real information gap from their physician. In the last group, perhaps the patient never asked his physician the question he sent to Dr. Bolton, or the physician didn't answer the question, or his answer was not understood. Bolton's replies are much more satisfactory for the first two groups of questioners than for the last kind. He displays a kind of good-humored common sense that is most appealing; for example, after passing on much good advice to a lady worried about drugs she had taken early in pregnancy, Bolton concludes, "Fortunately, just worrying about it
Angiotensin AT <sub>1</sub> and AT <sub>2</sub> Receptors Differentially Regulate Angiopoietin-2 and Vascular Endothelial Growth Factor Expression and Angiogenesis by Modulating Heparin Binding–Epidermal Growth Factor (EGF)–Mediated EGF Receptor Transactivation
Authors: Soichiro Fujiyama, Hiroaki Matsubara, Yoshihisa Nozawa, Katsuya Maruyama, Yasukiyo Mori, Yoshiaki Tsutsumi, Hiroya Masaki, Yoko Uchiyama, Yoko Koyama, Atsuko Nose, Osamu Iba, Eriko Tateishi, Nahoko Ogata, Nobuo Jyo, Shigeki Higashiyama, Toshiji Iwasaka
Journal: Circulation Research (2001)

Abstract —Angiotensin II (Ang II)–mediated signals are transmitted via heparin binding epidermal growth factor (EGF)–like growth factor (HB-EGF) release followed by transactivation of EGF receptor (EGFR). Although Ang II and HB-EGF induce angiogenesis, their link to the angiopoietin (Ang)–Tie2 system remains undefined. We tested the effects of Ang II on Ang1, Ang2, or Tie2 expression in cardiac microvascular endothelial cells expressing the Ang II receptors AT 1 and AT 2 . Ang II significantly induced Ang2 mRNA accumulations without affecting Ang1 or Tie2 expression, which was inhibited by protein kinase C inhibitors and by intracellular Ca 2+ chelating agents. Ang II transactivated EGFR via AT 1 , and inhibition of EGFR abolished the induction of Ang2. Ang II caused processing of pro–HB-EGF in a metalloproteinase-dependent manner to stimulate maturation and release of HB-EGF. Neutralizing anti–HB-EGF antibody blocked EGFR phosphorylation by Ang II. Ang II also upregulated vascular endothelial growth factor (VEGF) expression in an HB-EGF/EGFR–dependent manner. AT 2 inhibited AT 1 -mediated Ang2 expression and phosphorylation of EGFR. In an in vivo corneal assay, AT 1 induced angiogenesis in an HB-EGF–dependent manner and enhanced the angiogenic activity of VEGF. Although neither Ang2 nor Ang1 alone induced angiogenesis, soluble Tie2-Fc that binds to angiopoietins attenuated AT 1 -mediated angiogenesis. These findings suggested that (1) Ang II induces Ang2 and VEGF expression without affecting Ang1 or Tie2 and (2) AT 1 stimulates processing of pro–HB-EGF by metalloproteinases, and the released HB-EGF transactivates EGFR to induce angiogenesis via the combined effect of Ang2 and VEGF, whereas AT 2 attenuates them by blocking EGFR phosphorylation. Thus, Ang II is involved in the VEGF-Ang-Tie2 system via HB-EGF–mediated EGFR transactivation, and this link should be considerable in pathological conditions in which collateral blood flow is required.
Effects of cigarette smoke extract on human airway smooth muscle cells in COPD
Authors: Ling Chen, Qi Ge, Gavin Tjin, Hatem Alkhouri, Linghong Deng, Corry-Anke Brandsma, Ian Adcock, Wim Timens, Dirkje Postma, Janette K. Burgess, Judith L. Black, Brian G.G. Oliver
Journal: European Respiratory Journal (2014)

We hypothesised that the response to cigarette smoke in airway smooth muscle (ASM) cells from smokers with chronic obstructive pulmonary disease (COPD) would be intrinsically different from smokers without COPD, producing greater pro-inflammatory mediators and factors relating to airway remodelling. ASM cells were obtained from smokers with or without COPD, and then stimulated with cigarette smoke extract (CSE) or transforming growth factor-β1. The production of chemokines and matrix metalloproteinases (MMPs) were measured by ELISA, and the deposition of collagens by extracellular matrix ELISA. The effects of CSE on cell attachment and wound healing were measured by toluidine blue attachment and cell tracker green wound healing assays. CSE increased the release of CXCL8 and CXCL1 from human ASM cells, and cells from smokers with COPD produced more CSE-induced CXCL1. The production of MMP-1, -3 and -10, and the deposition of collagen VIII alpha 1 (COL8A1) were increased by CSE, especially in the COPD group which had higher production of MMP-1 and deposition of COL8A1. CSE decreased ASM cell attachment and wound healing in the COPD group only. ASM cells from smokers with COPD were more sensitive to CSE stimulation, which may explain, in part, why some smokers develop COPD.
CXCR2 ligands and G-CSF mediate PKC -induced intraepidermal inflammation
Authors: C. Cataisson, A. J. Pearson, M. Z. Tsien, F. Mascia, J.-L. Gao, S. Pastore, S. H. Yuspa
Journal: Journal of Clinical Investigation (2006)

Transgenic mice overexpressing PKCalpha in the epidermis (K5-PKCalpha mice) exhibit an inducible severe intraepidermal neutrophilic inflammation and systemic neutrophilia when PKCalpha is activated by topical 12-O-tetradecanoylphorbol-13-acetate (TPA). This inducible model of cutaneous inflammation was used to define mediators of skin inflammation that may have clinical relevance. Activation of cutaneous PKCalpha increased the production of the chemotactic factors cytokine-induced neutrophil chemoattractant (KC) and macrophage inflammatory protein 2 (MIP-2) in murine plasma. TPA treatment of cultured K5-PKCalpha keratinocytes also released KC and MIP-2 into culture supernatants through an NF-kappaB-dependent pathway. MIP-2 and KC mediated the infiltration of neutrophils into the epidermis, since this was prevented by ablating CXCR2 in K5-PKCalpha mice or administering neutralizing antibodies against KC or MIP-2. The neutrophilia resulted from PKCalpha-mediated upregulation of cutaneous G-CSF released into the plasma independent of CXCR2. These responses could be inhibited by topical treatment with a PKCalpha-selective inhibitor. Inhibiting PKCalpha also reduced the basal and TNF-alpha- or TPA-induced expression of CXCL8 in cultured psoriatic keratinocytes, suggesting that PKCalpha activity may contribute to psoriatic inflammation. Thus, skin can be the source of circulating factors that have both local and systemic consequences, and these factors, their receptors, and possibly PKCalpha could be therapeutic targets for inhibition of cutaneous inflammation.
Improving the Quality of Care — Can We Practice What We Preach?
Authors: Earl P. Steinberg
Journal: New England Journal of Medicine (2003)

It has been 30 years since Wennberg and Gittelsohn published their landmark article demonstrating substantial variation among different geographic areas in the provision of medical services.1 Since then, investigators have found variation in the delivery of virtually every aspect of health care that has been examined. From the perspective of the quality of care, the variation that is the greatest cause for concern is that between actual practice and evidence-based “best practice.”Over the past 30 years, progress has been made in several areas that are vital to quality improvement. Practice guidelines have become more rigorously evidence-based and are now . . .
Series Introduction: Stimulation and inhibition of immune responses: an intricate balancing act
Authors: Gary Koretzky
Journal: Journal of Clinical Investigation (2002)

Development of the adaptive immune system and activation of mature effector lymphocytes require an intricate balance of stimulatory and inhibitory forces. Indeed, as the articles in this Perspective series make clear, the immune system’s balancing act must take place simultaneously and in a dynamic manner at multiple levels.
HTLV-I-seronegative, genome-positive adult T-cell leukemia: Report of a case
Authors: Tetsuya Kubota, Takayuki Ikezoe, Eiji Hakoda, Takashi Sawada, Hirokuni Taguchi, Isao Miyoshi
Journal: American Journal of Hematology (1996)

An HTLV-I-seronegative case of adult T-cell leukemia (ATL) carrying the HTLV-I genome is reported. Screening serological tests were negative and Western blot analysis revealed only a faint band for HTLV-I p24. Polymerase chain reaction (PCR) disclosed the presence of HTLV-I gag, pol, env, pX, and LTR sequences in the lymph node and peripheral blood. Southern blot analysis revealed a monoclonal integration of HTLV-I in the lymph node and peripheral blood. The tumor cells expressed viral antigens after short-term culture. The clinical course was consistent with ATL in that the patient exhibited hypercalcemia and abnormal lymphocytosis as well as hepatosplenomegaly and lymphadenopathy. We recommend that PCR analysis for HTLV-I be performed even in seronegative cases when ATL is clinically suspected.
Forrester laryngeal sprays as a source of pseudomonas respiratory tract infection.
Authors: M W Casewell, M T Dalton
Journal: BMJ (1977)

consultant, peripheral vascular unit Haemochromatosis presenting as angina and responding to venesection Congestive cardiac failure, pericarditis, arrhythmias, and conductive defects are well-recognised cardiac manifestations of idiopathic haemochromatosis.Angina pectoris may be the presenting symptom but is less well recognised.A case is described with the results of venesection and a seven-year follow-up period. Case reportA 38-year-old butcher presented in 1969 with a six-month history of angina on moderate exercise, palpitations, and dyspnoea on severe exercise.He did not smoke and drank two pints of beer per week.His family history on 14 July
Effects of Surgery on Angina (Pre- and Postinfarction) and Myocardial Function (Failure)
Authors: JACK C. MANLEY, W. DUDLEY JOHNSON
Journal: Circulation (1972)

With the advent of direct bypass surgery, the dramatic clinical responses in some patients has been followed by enormous enthusiasm in many centers. Surgical technics have advanced to such a point that nearly all patients with obstructive coronary disease could have the obstructions bypassed to one or many areas. Criteria for evaluating surgery include mortality, operative infarction rate, patency of grafts, clinical response, and stress testing. Many reports fail to correlate results with angiographic studies of vein function and with completeness of revascularization. When cine studies are performed, a good correlation exists between patent veins and relief of angina and improved stress response. Different patterns of response to stress, sometimes independent of relief of angina, are obtained depending on the completeness of revascularization. Predictable relief of angina is found if revascularization is complete. At times dramatic, but much less predictable, relief of failure (improved ventricular function) follows revascularization. Angina is a valuable aid in selecting some patients for surgery. Stress testing (bicycle ergometry) can now define general groups of patients who are likely, and who are not likely, to show improved myocardial response to stress after surgery. These studies also demonstrate the need for the surgeon to provide complete revascularization whenever possible. The criteria for selection for surgery of patients with symptoms of gross heart failure remain unclear. While revascularization technics could be technically applied to nearly all coronary patients, present methods are unable accurately to define who really needs the surgery and, equally important, which hearts will respond once revascularization is completed.