tbuckley/cabot-search huggingface dataset:
C-Reactive Protein Inhibits Insulin Activation of Endothelial Nitric Oxide Synthase via the Immunoreceptor Tyrosine-Based Inhibition Motif of FcγRIIB and SHIP-1
Authors: Keiji Tanigaki, Chieko Mineo, Ivan S. Yuhanna, Ken L. Chambliss, Michael J. Quon, Ezio Bonvini, Philip W. Shaul
Journal: Circulation Research (2009)

Insulin promotes the cardiovascular protective functions of the endothelium including NO production by endothelial NO synthase (eNOS), which it stimulates via Akt kinase which phosphorylates eNOS Ser1179. C-reactive protein (CRP) is an acute-phase reactant that is positively correlated with cardiovascular disease risk in patients with type 2 diabetes. We previously showed that CRP inhibits eNOS activation by insulin by blunting Ser1179 phosphorylation. We now elucidate the underlying molecular mechanisms. We first show in mice that CRP inhibits insulin-induced eNOS phosphorylation, indicating that these processes are operative in vivo. In endothelial cells we find that CRP attenuates insulin-induced Akt phosphorylation, and CRP antagonism of eNOS is negated by expression of constitutively active Akt; the inhibitory effect of CRP on Akt is also observed in vivo. A requirement for the IgG receptor FcgammaRIIB was demonstrated in vitro using blocking antibody, and reconstitution experiments with wild-type and mutant FcgammaRIIB in NIH3T3IR cells revealed that these processes require the ITIM (immunoreceptor tyrosine-based inhibition motif) of the receptor. Furthermore, we find that endothelium express SHIP-1 (Src homology 2 domain-containing inositol 5'-phosphatase 1), that CRP induces SHIP-1 stimulatory phosphorylation in endothelium in culture and in vivo, and that SHIP-1 knockdown by small interfering RNA prevents CRP antagonism of insulin-induced eNOS activation. Thus, CRP inhibits eNOS stimulation by insulin via FcgammaRIIB and its ITIM, SHIP-1 activation, and resulting blunted activation of Akt. These findings provide mechanistic linkage among CRP, impaired insulin signaling in endothelium, and greater cardiovascular disease risk in type 2 diabetes.
Renal Insufficiency and Heart Failure Therapy
Authors: Michael G. Shlipak
Journal: Annals of Internal Medicine (2004)

Letters6 April 2004Renal Insufficiency and Heart Failure TherapyMichael G. Shlipak, MD, MPHMichael G. Shlipak, MD, MPHFrom Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, CA 94121.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-7-200404060-00036 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:I greatly appreciate Dr. Spital's thoughtful comments on my review and regarding the choice of ACE inhibitor in patients with renal dysfunction. He is correct that fosinopril may be the ideal ACE inhibitor in this setting because it has the greatest hepatobiliary elimination (1, 2). Therefore, if discontinuation is required in response to an adverse event, fosinopril should have a more rapid elimination than other ACE inhibitors. However, because studies have not compared clinical outcomes among the ACE inhibitors, and fosinopril has not been evaluated in a heart failure survival trial, I cannot strongly endorse fosinopril as the ...References1. Hoyer J, Schulte KL, Lenz T. Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal failure. Clin Pharmacokinet. 1993;24:230-54. [PMID: 8462229] CrossrefMedlineGoogle Scholar2. White CM. Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors. Pharmacotherapy. 1998;18:588-99. [PMID: 9620109] MedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, CA 94121. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPharmacotherapy for Heart Failure in Patients with Renal Insufficiency Michael G. Shlipak Renal Insufficiency and Heart Failure Therapy Aaron Spital Metrics 6 April 2004Volume 140, Issue 7Page: 584KeywordsACE inhibitorsAdverse eventsClinical trialsForecastingHeart failureLongitudinal studiesRenal failure ePublished: 6 April 2004 Issue Published: 6 April 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
1074 EVALUATION OF EFFICACY OF ANTIANGIOGENIC TREATMENT IN A MURINE MODEL OF HEPATOCELLULAR CARCINOMA UNDER DIFFERENT TREATMENT SCHEDULES
Authors: V. Salvatore, S. Marinelli, M. Baron Toaldo, M. Milazzo, L. Croci, L. Venerandi, C. Palamà, M. Cipone, L. Bolondi, F. Piscaglia
Journal: Journal of Hepatology (2013)
Dysregulation of Met receptor tyrosine kinase activity in invasive tumors
Authors: Alla Danilkovitch-Miagkova, Berton Zbar
Journal: Journal of Clinical Investigation (2002)

The MET protooncogene was discovered because of the ability of oncogenic Met to mediate chemically induced transformation of a human osteogenic sarcoma cell line (1). The normal product of this gene, Met, is an unusual receptor tyrosine kinase that can be distinguished from most other such proteins on the basis of its biosynthesis and its structural features. This transmembrane protein is synthesized as a single-chain precursor, which undergoes intracellular proteolytic cleavage at a basic amino acid site, yielding a disulfide-linked heterodimer. Its C-terminal, intracellular region contains a multifunctional docking site that binds to various signaling molecules. These features define a Met receptor tyrosine kinase family consisting of three related proteins, Met, Ron, and c-Sea, the last of which may be the chicken ortholog of Ron.
Brucellosis still spreading
Authors: J. Reynolds
Journal: BMJ (1969)

MEDICALJOTRNALwas isolated from one of these and this animal was therefore also sold on the open market.Further samples at this stage were negative, and over the following months a series of doubt- ful positive M.R.T.s culminating in a single positive guinea-pig were the only results of much hard work.The positive test obtained through the guinea-pig was of course useless owing to the time interval, for the law requires action within 42 days.The discovery of more strongly positive M.R.T.s, together with the history of the herd, determined the medical officer of health to take action.Accordingly a pasteurization order was imposed and fortunately Br. abortus was cultured a day or two later, confirming the justice of the order.At the end of 12 months the balance-sheet read as follows: On the debit side the labora- tory had, in the course of the year, examined some 500 specimens from the farm.This
Use of Prostaglandin E2 in the Management of Missed Abortion, Missed Labour, and Hydatidiform Mole
Authors: S. M. M. Karim
Journal: BMJ (1970)

Treatment of six cases of missed abortion and one case of hydatidiform mole with intravenous infusion of prostaglandin E(2) resulted in complete abortion in all cases. Of 15 patients with missed labour, 14 were delivered successfully with similar treatment. The technique appears to be a safe, reliable, and rapid method of managing missed abortion, missed labour, and hydatidiform mole.
Two cases of aggressive nontumoral folliculotropic mycosis fungoides with visceral involvement
Authors: C. Brugière, M. Karanian‐Philippe, F. Comoz, A. Dompmartin, F. Galateau‐Sallé, L. Verneuil
Journal: British Journal of Dermatology (2014)

Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma (CTCL), and folliculotropic MF (FMF) is one clinical variant of classic MF. MF generally has a good prognosis with an indolent clinical course, but for FMF greater therapeutic resistance is suggested. Visceral involvement is very rare in these two clinical forms. We report two exceptional cases of FMF with pulmonary and hepatic involvement. Five years after their initial diagnoses, patient 1 presented with a pulmonary localization of his FMF, and patient 2 with liver involvement, without lymph node or T-cell clones in the blood. These two patients had FMF corresponding to stage T2N0M1B0. These two cases highlight the aggressiveness of this rare variant of MF. They suggest that the T lymphocytes found in the folliculotropic form of CTCL could be characterized by greater visceral tropism. They raise the question of the molecular and functional characteristics of these T lymphocytes, and the possibility of a common target in the hair follicles and certain organs. Studies have shown that chemokine receptors are likely to be involved in the skin tropism that characterizes CTCL. These two cases show the aggressiveness of FMF and point to the interest in comparing the molecular characteristics of T lymphocytes in the folliculotropic and nonfolliculotropic forms of CTCL.
Reversion from precore/core promoter mutants to wild-type hepatitis B virus during the course of lamivudine therapy
Authors: Hikmet Akkiz, Yilmaz Ergun, Salih Colakoglu, Macit Sandikci, Mehmet Serin, Aynur Bekar, Murat Oksuz, Fatih Isiksal, Fatin Kocak, Bahri Abayli
Journal: Journal of Hepatology (2002)
Efficacy of interferon alfa therapy in chronic hepatitis C patients depends primarily on hepatitis C virus RNA level
Authors: Gotaro Yamada, Masahiro Takatani, Fumitoshi Kishi, Michiko Takahashi, Toshihiko Doi, Takao Tsuji, Sadahito Shin, Masashi Tanno, Mickey S. Urdea, Janice A. Kolberg
Journal: Hepatology (1995)

To clarify the viral factors that may predict the therapeutic effect of interferon (IFN) in chronic hepatitis C (CHC) patients, we investigated the quantitative serum hepatitis C virus (HCV) RNA level, genotype, and liver biopsy histological features in 60 patients who were treated with 360 x 10(6) U of natural IFN-alpha for 36 to 48 weeks and for more than 12 months after therapy. A branched DNA (bDNA) assay was used to measure HCV RNA levels. All responders, defined as those individuals with normal alanine transaminase (ALT) levels at 48 weeks after therapy, had less than 2 x 10(6) HCV RNA Eq/mL before administration of IFN. Of 39 patients with RNA levels (less than 2 x 10(6) Eq/L) 23 (59.0%) were responders. The genotype was determined for each patient using type-specific polymerase chain reaction (PCR) primers. There was a significant difference in rate of response between subtype 1b and subtypes 2a and 2b (P < .0002); however, all responders had less than 2 x 10(6) Eq/L independent of genotype. In a multivariate analysis, RNA level was the most statistically significant factor affecting response to IFN. Although disease severity, as defined by histological features, was not statistically correlated with nonresponse, patients that responded to IFN tended to have less severe disease.
A Case of Amputation in Middle Age for Albuminuria, Following Tuberculous Knee: Recovery
Authors: J. J. H. Holt
Journal: BMJ (1897)

T Mz BRmAL 457 castration in the operative treatment of enlarged prostate, but I am by no means converted.The condition of some of my patients years after prostatectomy is such as to make me feel that in the operation suggested by my lamented colleague McGill and by Belfield, independently, but almost simul- taneously some years ago, we have to chronicle a real ad- vance in the treatment of enlarged prostate which has failed to be relieved by catheterism and other milder measures.The details I gave in a paper at the International Medical Congress at Rome still holds good in my practice, both with regard to the preliminary preparation of the patient, the steps of the operation, and the subsequent treatment during convalescence.
HIGH AMPUTATION OF THE CERVIX VERSUS HYSTERECTOMY FOR CARCINOMA OF THE CERVIX.
Authors: C. C. FREDERICK
Journal: JAMA (1902)

The results of hysterectomy for carcinoma of the cervix have been so unsatisfactory in the experience of most operators that the question naturally arises whether there is any necessity of subjecting the woman so suffering to one operation more serious than another, if the lesser one will do as much to ameliorate her suffering, or give her as long a respite from the ravages of the disease as the more serious one.  CERVICAL CANCER TO BE STUDIED ALONE.  Hysterectomy for carcinoma of the body of the uterus, when the malignant process has not invaded the peritoneal covering of the organ or the perimetrium, gives results so satisfactory that no one can question its advisability in every case. The roseate and misleading reports of from 30 to 40 per cent, of non-recurrences after hysterectomy done for carcinoma of the uterus must have included all forms of the disease, those of the
BILATERAL GONORRHEAL SALPINGITIS IN A CHILD THREE DAYS AFTER INITIAL INFECTION
Authors: Minas Joannides
Journal: JAMA (1926)

This case is reported because it presents the following important features: A girl, aged 6½ years, was infected innocently by a careless mother; the disease spread into the tubes and the pelvic peritoneum within three days after the initial infection, and the child recovered after double salpingectomy and appendectomy with drainage. The child was living at home when the mother was infected with gonorrheal vaginitis and endocervitis. Although the mother was warned against careless handling of her three girls and two boys, ranging between the ages of 3 and 10 years, this child did not escape. She had a strong desire to urinate when at school, but the teacher did not allow her to go out of the room, with the consequent result that she soiled herself. Ever since babyhood, she had had poor control of her bladder sphincter. On going home she was cleaned by the mother, who had
Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island
Authors: Jérôme Viala, Catherine Chaput, Ivo G Boneca, Ana Cardona, Stephen E Girardin, Anthony P Moran, Rafika Athman, Sylvie Mémet, Michel R Huerre, Anthony J Coyle, Peter S DiStefano, Philippe J Sansonetti, Agnès Labigne, John Bertin, Dana J Philpott, Richard L Ferrero
Journal: Nature Immunology (2004)
Late Contralateral Pneumothorax After Pneumonectomy for Carcinoma
Authors: Frank Turner Kurzweg
Journal: JAMA (1963)

PNEUMOTHORAX occurring a year or longer after pneumonectomy may be considered late. This division of time allows for the development of some of the compensatory changes in the remaining lung. Late contralateral pneumothorax following pneumonectomy for carcinoma is rare. Blalock,<sup>1</sup>reviewing 340 pneumonectomies, reported four cases and collected an additional nine from the literature in which it occurred immediately postoperatively. A ruptured bleb or bulla was probably the cause of the pneumothorax in most of these patients. The mortality from this complication was high. Two of the four patients reported by him and all nine of the cases previously reported died. Late pneumothorax was not noted. Melick and Gutekunst,<sup>2</sup>observed pneumothorax occurring 60 days postoperatively in a 42-yr-old male following a left pneumonectomy for tuberculosis complicated by bronchiectasis. Borrie,<sup>3</sup>described this complication occurring 3 mo post left pneumonectomy for bronchiectasis in a 10-yr-old male. Both patients survived
Abstract 4750: Real-time imaging of 3-dimensional cancer cell movement in tissues
Authors: Michelle Digman, Jose A. Aguilar, Enrico Gratton, Atsushi Suetsugu, Robert M. Hoffman
Journal: Cancer Research (2011)

Abstract Our knowledge of how cells move in 3D in tissues is limited due to the lack of imaging methods that can produce 3D images fast enough and with sufficient resolution. Cancer cells migrate in 3D by forming adhesion points at the end of very long cellular protrusions. These protrusions are very thin and it is difficult to visualize adhesions along the protrusion surface. Conventional 3D stack reconstruction has relatively low resolution unless it is done using many frames. This results in a very slow acquisition in 3D confocal microscopy. Faster methods of 3D data acquisition (spinning disk microscopy) cannot be easily implemented since there is significant amount of scatter in tissues. A major obstacle in imaging adhesions is to find and track them so that they will not go out of focus. We are developing a new method which is based on orbiting imaging around cellular protrusions to visualize protein dynamics during extravasation. A feedback mechanism controls the center of the orbit to be at the center of the fluorescence distribution. A program reconstructs the shape of the protrusions in 3D. The fluorescence intensity in one or more channels is also simultaneously measured. The fluorescence intensity of one channel is used to paint the protrusion shape, which results in the 3D reconstruction of the protrusion. During the orbit, the second channel of the microscope measures the second harmonic generation (SHG) signal. We then correlated the appearance of bright fluorescence spots on the protrusion surface with the points of contact of the protrusion. This method will enable imaging of cancer cell invasion in 3-dimentions in live mice in real time. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4750. doi:10.1158/1538-7445.AM2011-4750
COMPARISON OF FLUBENDAZOLE AND DIETHYLCARBAMAZINE IN TREATMENT OF ONCHOCERCIASIS
Authors: Alfredo Dominguez-Vazquez, HughR. Taylor, A.M. Ruvalcaba-Macias, RobertP. Murphy, BruceM. Greene, A.R. Rivas-Alcala, F. Beltran-Hernandez
Journal: The Lancet (1983)
Dwale: an anaesthetic from old England
Authors: A. J Carter
Journal: BMJ (1999)

> I'll imitate the pities of old surgeons
> 
> To this lost limb, who ere they show their art
> 
> Cast one asleep, then cut the diseased part.
> 
> Thomas Middleton (1570-1627), Women beware Women 

Before the advent of general anaesthesia, it is generally believed, a patient undergoing an operation could have expected little in the way of support other than from the bottle or from an ability to “bite the bullet.” But there is compelling evidence of an earlier age of anaesthesia. Descriptions of anaesthetics based on mixtures of medicinal herbs have been found in manuscripts dating from before Roman times until well into the Middle Ages. Most originated in regions of southern Europe where the relevant herbs grew naturally. A typical one, dated 800 AD, from the Benedictine monastery at Monte Cassino in southern Italy, used a mixture of opium, henbane, mulberry juice, lettuce, hemlock, mandragora, and ivy.1

There is no evidence to suggest that similar recipes existed in the British Isles at that time.2 However, in 1992, an extensive study succeeded in identifying a large number of similar recipes in late medieval (12th-15th century) English manuscripts.3 All identified the anaesthetic, a drink, by the name dwale. A typical manuscript (fig 1), translated into modern English, reads:

#### Summary points

Although general anaesthesia is little more than 150 years old, the use of medicinal herbs to render patients unconscious before surgery goes back to Roman times

Recent studies have identified a large number of recipes for a herbal anaesthetic known as dwale, written in medieval English

These include two groups of ingredients, the harmless and ineffectual—bile, lettuce, vinegar, and bryony root—and the powerful and dangerous—hemlock, opium, and henbane

In spite of its dangers, dwale was widely known about, and would have been administered by ordinary housewives, caring for loved ones

“How to …
Cutaneous presentation of malignant fibrous histiocytoma
Authors: R.A.C. Graham-Brown, A. Fletcher
Journal: British Journal of Dermatology (1987)

Journal Article Cutaneous presentation of malignant fibrous histiocytoma Get access R.A.C. Graham‐Brown, R.A.C. Graham‐Brown Department of Dermatology, Leicester Royal Infirmary, Leicester Search for other works by this author on: Oxford Academic Google Scholar A. Fletcher A. Fletcher Department of Histopathology, Leicester Royal Infirmary, Leicester Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue s32, 1 June 1987, Page 17, https://doi.org/10.1111/j.1365-2133.1987.tb11998.x Published: 01 June 1987
Epidemic and Peace, 1918
Authors: Harry F. Dowling
Journal: JAMA (1976)

The average American, having witnessed the success of antibiotics against tuberculosis, syphilis, pneumonia, and meningitis and of vaccination in controlling polio and measles, still has a healthy respect for influenza. Although many articles and books have already been written about this disease, so much is continually being learned that an interpretation of the past in the light of new facts can both instruct and entertain the lay reader. Epidemic and Peace, 1918 manages to do this in part.  Crosby tells how the influenza epidemic of 1918-1919 came at a crucial time in World War I when the Germans were attempting to split the Allied forces while the Allies were desperately trying to hold them back until the Americans arrived. But Americans, in turn, were being held back by influenza. Crosby's accounts of the way two typical American cities attempted to combat the epidemic are thoroughly compiled and interestingly written, although
von Hippel-Lindau–Dependent Patterns of RNA Polymerase II Hydroxylation in Human Renal Clear Cell Carcinomas
Authors: Ying Yi, Olga Mikhaylova, Aygun Mamedova, Prabhat Bastola, Jacek Biesiada, Enas Alshaikh, Linda Levin, Rachel M. Sheridan, Jarek Meller, Maria F. Czyzyk-Krzeska
Journal: Clinical Cancer Research (2010)

Abstract Purpose: We have previously shown that von Hippel-Lindau (VHL) regulates ubiquitylation and proline 1465 hydroxylation of the large subunit of RNA polymerase II, Rpb1, in human renal clear cell carcinoma (RCC) cell lines. Here, our goal was to determine the effect of this VHL function and the status of P1465 hydroxylation in human RCC tumors. Experimental Design: Primary human tumors and matched normal kidney samples were probed for expression levels of the large subunit of RNA polymerase II (Rpb1), Rpb1 hydroxylated on P1465 [Rpb1(OH)], Rpb1 phosphorylated on Ser5 [Rpb1(S5P)], and proline hydroxylases PHD1, PHD2, and PHD3. Results from RCC tumors were categorized according to the status of VHL gene. Mechanistic analysis was performed in orthotopic xenograft model using 786-O RCC cells with wild-type (WT) VHL and knockdown of PHD2, characterized by high levels of Rpb1(OH) and PHD1. Results: Levels of Rpb1(OH), PHD1, and PHD2 were significantly higher in RCC tumors compared with normal kidneys. RCC tumors with WT VHL had higher levels of Rpb1(OH) and PHD1 and lower levels of PHD2 than tumors with VHL gene alterations. Levels of Rpb1(OH) significantly correlated with levels of PHD1 in tumors and normal kidneys. Knockdown of PHD2 in 786-O VHL(+) cells resulted in a more malignant phenotype in orthotopic xenografts and higher expression of specific cell cycle regulators (CDC25A, cyclin-dependent kinase 2, CCNA2) compared with VHL(−) RCC cells. Conclusions: Elevated PHD1 concomitant with decreased PHD2 are causatively related to Rpb1 hydroxylation and oncogenesis in human RCC tumors with WT VHL gene. Thus, P1465-hydroxylated Rpb1 and PHD1 represent attractive drug targets for new RCC treatments. Clin Cancer Res; 16(21); 5142–52. ©2010 AACR.