tbuckley/cabot-search huggingface dataset:
THE MOST ANCIENT SPLINTS
Authors: G. E. Smith
Journal: BMJ (1908)

THE MOST.ANCIENT SPLINTS.29.gelatine 2 ft.from us -sho4l check those dieouselons which we foolishly carry on over the wounds we inflict.All my hospital transplantatibns are treated as out- patients, and return to their homes on the day of operation, and no difficulties of any kind arlse therefrom.With the limited time at my disposal, I have thought it best not to discuss Individual operations nor to dwell upon statistice.I have preferred,.to lay before you certain prin- ciples which I hope may prove useful.Both arthrodesis and tendon transplantation are, if properly appreciated and applled, valued surgical, assets.'they give us an interest and encouragement in our treatment of paralytics which we sorely needed.Failures, and we are bound to experience many, should prove our welcome counsellors, and we should be unsparing of our efforts to learn from them all we can.
Optimal Blood Glucose Control During 18 Years Preserves Peripheral Nerve Function in Patients With 30 Years’ Duration of Type 1 Diabetes
Authors: Jakob R. Larsen, Hans Sjoholm, Kristian F. Hanssen, Leiv Sandvik, Tore J. Berg, Knut Dahl-Jorgensen
Journal: Diabetes Care (2003)

OBJECTIVE—To assess the association between 18 years of mean HbA1c and nerve conduction parameters of the lower limb in patients with type 1 diabetes of 30 years’ duration. RESEARCH DESIGN AND METHODS—HbA1c has been examined prospectively since 1982 in a group of 39 patients with type 1 diabetes. Mean age at baseline was 25 years (range 18–40) with 12 years’ disease duration. The mean age at diagnosis of diabetes was 12.5 years. Nerve function of lower limbs was assessed at baseline, after 8 years, and after 18 years. RESULTS—A total of 23 men and 16 women were studied. Mean age was 43 years. Mean HbA1c was 8.2% (range 6.6–11.3) during 18-year follow-up. Nerve conduction velocity (NCV) and nerve action potential amplitude (NAPA) at the last examination were significantly associated with mean HbA1c (P &amp;lt; 0. 05). From 1982 to 1999, there was a significant reduction in nerve function in patients with mean HbA1c ≥8.4% (highest tertile). For example, the mean NCV in the tibial nerve was reduced from 47 to 31 m/s (P &amp;lt; 0.01). The number of nerves with NCV (P &amp;lt; 0.01) and NAPA (P = 0.01) reduced to below the reference level in each patient was also significantly associated to mean HbA1c. No significant associations were found between nerve function parameters, sex, disease duration, blood pressure, serum cholesterol, microalbuminuria, or smoking. CONCLUSIONS—The present study shows that mean HbA1c is a strong predictor of nerve function. Mean HbA1c &amp;lt;8.4% over 18 years was associated with near-normal nerve function.
Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma
Authors: A Palumbo, S V Rajkumar, M A Dimopoulos, P G Richardson, J San Miguel, B Barlogie, J Harousseau, J A Zonder, M Cavo, M Zangari, M Attal, A Belch, S Knop, D Joshua, O Sezer, H Ludwig, D Vesole, J Bladé, R Kyle, J Westin, D Weber, S Bringhen, R Niesvizky, A Waage, M von Lilienfeld-Toal, S Lonial, G J Morgan, R Z Orlowski, K Shimizu, K C Anderson, M Boccadoro, B G Durie, P Sonneveld, M A Hussein
Journal: Leukemia (2007)
MicroRNAs as Potential Agents to Alter Resistance to Cytotoxic Anticancer Therapy
Authors: Joanne B. Weidhaas, Imran Babar, Sunitha M. Nallur, Phong Trang, Sarah Roush, Michelle Boehm, Erin Gillespie, Frank J. Slack
Journal: Cancer Research (2007)

Tumor cells use preexisting prosurvival signaling pathways to evade the damaging and cytotoxic effects of anticancer agents. Radiation therapy is a primary form of cytotoxic anticancer treatment, but agents that successfully modify the radiation response in vivo are lacking. MicroRNAs (miRNA) are global gene regulators that play critical roles in oncogenesis and have been found to regulate prosurvival pathways. However, there is little understanding of how cellular miRNA expression affects the response of a cancer to cytotoxic therapy and ultimately outcome. The let-7 family of miRNAs regulates expression of oncogenes, such as RAS, and is specifically down-regulated in many cancer subtypes. In fact, low levels of let-7 predict a poor outcome in lung cancer. Here, we report that the let-7 family of miRNAs is overrepresented in a class of miRNAs exhibiting altered expression in response to radiation. More strikingly, we also can create a radiosensitive state when the select let-7 family of miRNAs is overexpressed in vitro in lung cancer cells and in vivo in a Caenorhabditis elegans model of radiation-induced cell death, whereas decreasing their levels causes radioresistance. In C. elegans, we show that this is partly through control of the proto-oncogene homologue let-60/RAS and genes in the DNA damage response pathway. These findings are the first direct evidence that miRNAs can suppress resistance to anticancer cytotoxic therapy, a common feature of cancer cells, and suggest that miRNAs may be a viable tool to augment current cancer therapies.
681 The influence of loratadine (LO) on bronchial histamine challenge, early (EAR) and late (LAR) asthmatic reactions and the development of bronchial reactivity after single allergen challenge
Authors: G CIESLEWICZ, I GRZELEWSKARZYMOWSKA, L DUBUSKE, K GONDOROWICZ, B WOJCIECHOWSKA, J ROZNIECKI, M KROL, G JUSZCZYK
Journal: Journal of Allergy and Clinical Immunology (1996)
HIV and CXCR4 in a kiss of autophagic death
Authors: B. Levine
Journal: Journal of Clinical Investigation (2006)

AIDS is characterized by CD4+ T lymphocyte depletion, yet the mechanisms underlying this central aspect of HIV pathogenesis are still poorly understood. In this issue of the JCI, Espert et al. identify a mechanism by which the HIV envelope glycoprotein can induce death in uninfected CD4+ T cells (see the related article beginning on page 2161). The HIV envelope glycoprotein interacts with CXC chemokine receptor 4 to activate the lysosomal degradation pathway of autophagy, which is necessary for both apoptotic and nonapoptotic cell death.
Central Processing of Gut Pain in Diabetic Patients With Gastrointestinal Symptoms
Authors: Jens Brøndum Frøkjær, Eirik Søfteland, Carina Graversen, Georg Dimcevski, Line Lindhardt Egsgaard, Lars Arendt-Nielsen, Asbjørn Mohr Drewes
Journal: Diabetes Care (2009)

To evaluate the brain's responses to painful visceral and somatic stimuli in diabetic patients with gastrointestinal symptoms.The sensitivity to electrical esophageal and median nerve stimulations was assessed in 15 healthy volunteers and 14 type 1 diabetic patients with autonomic neuropathy and gastrointestinal symptoms using a euglycemic-hyperinsulinemic clamp. Evoked brain potentials were recorded.Patients had reduced sensitivity to esophageal (48%; P < 0.001) and median nerve (80%; P < 0.001) stimulations. They also had increased (8.8%; P = 0.007) and nonreproducible (P = 0.006) latencies of evoked potentials in response to esophageal stimulations, with 26% reduction in amplitude (P = 0.011). No potential differences were seen to median nerve stimulations. In diabetic patients, the topographic location of the first peak in potentials was more central (P < 0.001) and gastrointestinal symptoms correlated with characteristics of brain potentials (P = 0.049).This study supports that diabetes induces changes in peripheral visceral nerves as well as in the central nervous system.
PMO-176 Induction maintenance treatment in chronic hepatitis B; step-down from tenofovir and lamivudine to lamivudine monotherapy is effective
Authors: U S Gill, L Payaniandy, D Payaniandy, J Schulz, V Ross, Y Kallis, P Kooner, R Marley, P T F Kennedy, G R Foster
Journal: Gut (2012)

<h3>Introduction</h3> Tenofovir Disoproxil Fumarate (TDF) is a potent and effective oral antiviral used to treat Chronic Hepatitis B (CHB), but concerns remain about possible long-term toxicity and the costs of indefinite use. An induction-maintenance treatment strategy may allow the use of combination Lamivudine (LAM) and TDF, to avert the development of resistance, followed by maintenance of viral suppression with LAM. To date, there are no data on such a step-down strategy in HBeAg negative CHB. Here we report on patients in whom we safely discontinued TDF, while maintaining viral suppression and normal liver biochemistry. <h3>Methods</h3> We selected patients who were had received combination therapy for a minimum of 18 months. Selection criteria included HBeAg negative disease, fibrosis score of &lt;4/6 on biopsy, undetectable HBV DNA and normal serum ALT for a minimum of 12 consecutive months. Patients meeting these criteria were invited to stop TDF and step-down to maintenance LAM monotherapy. Patients were followed at monthly intervals to determine whether viral suppression and ALT normalisation was maintained in the absence of TDF. <h3>Results</h3> 21 patients (13 male), median age 47, (range 39–62) discontinued TDF. Median follow-up was 3 months (range 1–10 months). During monthly follow-up biochemical and serological data have been measured. All patients had undetectable HBV DNA prior to step-down therapy to LAM and this remained undetectable during follow-up. Pre-discontinuation of TDF the median ALT was 27 (range 15–38) and during follow-up, on LAM monotherapy, was 22 (range 15–45), (p=NS). Median HBsAg level pre-discontinuation of TDF was log 3.48 (range 1.55–4.49) and 3.49 (range 1.55–4.55), (p=NS) on LAM monotherapy. <h3>Conclusion</h3> We demonstrate no viral breakthroughs or biochemical flares on discontinuing TDF. These data suggest that an induction-maintenance strategy may be pursued in selected CHB patients to avoid long-term exposure to TDF and reduce the burden on healthcare budgets in the context of lifelong oral antiviral therapy. <h3>Competing interests</h3> None declared.
Talampanel With Standard Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma: A Multicenter Phase II Trial
Authors: Stuart A. Grossman, Xiaobu Ye, Marc Chamberlain, Tom Mikkelsen, Tracy Batchelor, Serena Desideri, Steven Piantadosi, Joy Fisher, Howard A. Fine
Journal: Journal of Clinical Oncology (2009)

Purpose Recent data suggest that the glutamatergic system is important in the proliferation and migration of glioblastoma. Talampanel is a well-tolerated, oral α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker that could be beneficial in this disease. Patients and Methods This trial was designed to estimate overall survival in adults with newly diagnosed glioblastoma treated with talampanel in addition to standard radiation (RT) and temozolomide (TMZ). A secondary purpose was to evaluate talampanel toxicity in this setting. Talampanel was initiated with RT + TMZ and discontinued for toxicity or disease progression. Survival was compared with historical controls. Results Seventy-two patients were enrolled from December 2005 to July 2006. Their median age was 60 years (range, 37 to 85 years, with 17% &gt; 70 years), median Karnofsky performance score was 90 (range, 70 to 100), and 77% had a debulking procedure. With a median follow-up time of 18 months, 55 patients (76%) have died, yielding a median survival time of 18.3 months (95% CI, 14.6 to 22.5 months). When the 60 patients who were 18 to 70 years old were compared with the European Organisation for Research and Treatment of Cancer (EORTC) RT + TMZ data, the median survival (20.3 v 14.6 months, respectively) and percentage of patients surviving at 24 months (41.7% v 26.5%, respectively; P = .02) seemed superior. The percentage of patients methylated at O 6 -methylguanine–DNA methyltransferase was lower than on the EORTC study (29% v 43%, respectively). Talampanel was well tolerated and did not increase the known hematologic or nonhematologic toxicities of TMZ. Conclusion Talampanel can be added to RT + TMZ without significant additional toxicity. The encouraging survival results in methylated and unmethylated patients suggest that blocking AMPA receptors may be a useful strategy in newly diagnosed glioblastoma.
Airflow Limitation in Smokers Is Associated with Subclinical Atherosclerosis
Authors: Hiroshi Iwamoto, Akihito Yokoyama, Yoshihiro Kitahara, Nobuhisa Ishikawa, Yoshinori Haruta, Kiminori Yamane, Noboru Hattori, Hitoshi Hara, Nobuoki Kohno
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality from cardiovascular disease. Although a close association between COPD and atherosclerosis has been speculated, such scientific information is limited.Objectives: To evaluate subclinical atherosclerosis in smokers with airflow limitation.Methods: The subjects of this study were healthy middle-aged men. Smokers with airflow limitation (n = 61) and age-matched control smokers (n = 122) and control never-smokers (n = 122) without airflow limitation were included in the present study. Subjects with diabetes, acute infection, and respiratory disease other than COPD were excluded beforehand. All subjects underwent chest radiogram, spirometry, blood sampling, and carotid ultrasonography. We determined carotid intima-media thickness and focal atheromatous plaque as indicators of subclinical atherosclerosis.Measurements and Main Results: Mean carotid intima-media thickness was greater in smokers with airflow limitation than in control smokers (P < 0.01) and control never-smokers (P < 0.005). Focal carotid plaque was significantly more prevalent in smokers with airflow limitation than in control never-smokers (P < 0.005). Multivariate analyses showed significant associations between thickened intima-media thickness and decreased percent predicted FEV1 (P = 0.001) and between plaque and log10 C-reactive protein (P = 0.013) independent of age, pack-years of smoking, body mass index, peripheral mean arterial pressure, heart rate, glucose, and low-density lipoprotein cholesterol.Conclusions: Smokers with airflow limitation had exaggerated subclinical atherosclerosis. This study suggests that middle-aged men who are susceptible to COPD may also be susceptible to vascular atherosclerosis by smoking, and atherosclerotic change starts early in the disease process of COPD.
In Vivo Antitumor Activity of Sindbis Viral Vectors
Authors: J.-C. Tseng
Journal: JNCI Journal of the National Cancer Institute (2002)

Sindbis virus, a blood-borne virus transmitted by mosquitoes, has been used as a vector to efficiently express exogenous genes in vitro and in vivo and to induce apoptosis. Because Sindbis virus infects mammalian cells by interacting with the high-affinity laminin receptors, which are expressed at higher levels in several human cancers than in normal cells, we determined whether a Sindbis viral vector could be used to target cancers in vivo.C.B-17-SCID mice with established xenografts were given daily intraperitoneal injections of the Sindbis viral vector SinRep/LacZ containing the bacterial beta-galactosidase gene. Control mice were untreated or received injections with phosphate-buffered saline. Tumor size was measured daily. Expression of beta-galactosidase and Factor VIII (a marker for endothelial cells) was determined by immunohistochemical staining of tumor sections. Apoptosis was analyzed by TUNEL (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end labeling) staining. C.B-17-SCID beige mice, which lack natural killer (NK) cells, were used to assess the importance of NK cells in antitumor efficacy of Sindbis viral vectors.Tumors from mice treated with SinRep/LacZ were statistically significantly smaller than tumors from control mice. This effect was observed for tumor xenografts derived from BHK (kidney, hamster), LS174T (colon, human), HT29 (colon, human), and CFPAC (pancreas, human) cells. Expression of beta-galactosidase co-localized with that of Factor VIII in tumor sections. Tumors from SinRep/LacZ-treated mice contained more apoptotic cells than tumors from control mice. Complete tumor regression was observed in three of five C.B-17-SCID mice but in none of five C.B-17-SCID beige mice treated with SinRep/LacZ.Sindbis viral vectors efficiently targeted tumors in vivo, were apparently delivered through the circulation, and were more effective in the presence of NK cells.
Isolation of circulating immune complexes using Raji cells. Separation of antigens from immune complexes and production of antiserum.
Authors: A N Theofilopoulos, R A Eisenberg, F J Dixon
Journal: Journal of Clinical Investigation (1978)

Raji cells were used for the isolation of complement-fixing antigen-antibody complexes from serum. Immune complexes bound to these cells were radiolabeled at the cell surface with lactoperoxidase. The complexes were then eluted from the cells with isotonic citrate buffer pH 3.2 or recovered by immunoprecipitation of cell lysates. The antigen and antibody moieties of the complexes were isolated by dissociating sucrose density gradient centrifugation or by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A variety of preformed immune complexes were successfully isolated from serum with this approach. In addition, these techniques were used to isolate and identify the antigens in immune complexes in the serum of rabbits with chronic serum sickness and rats with Moloney virus-induced sarcomas. Methods were also developed for the production of antisera against the antigenic moiety of immune complexes isolated from serum. Repeated challenge of rabbits with whole Raji cells with bound complexes or eluates from such cells resulted in antibody production against the antigens of the immune complexes, although reactivity against cellular and serum components was also elicited. Monospecific antisera against the antigens in immune complexes were produced by immunizing rabbits with the alum-precipitated antigen isolated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These techniques may be useful in isolating antigens in immune complex-associated diseases of unknown etiology.
Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88
Authors: Cecile M. Fremond, Vladimir Yeremeev, Delphine M. Nicolle, Muazzam Jacobs, Valerie F. Quesniaux, Bernhard Ryffel
Journal: Journal of Clinical Investigation (2004)

Toll-like receptors (TLRs) such as TLR2 and TLR4 have been implicated in host response to mycobacterial infection. Here, mice deficient in the TLR adaptor molecule myeloid differentiation factor 88 (MyD88) were infected with Mycobacterium tuberculosis (MTB). While primary MyD88(-/-) macrophages and DCs are defective in TNF, IL-12, and NO production in response to mycobacterial stimulation, the upregulation of costimulatory molecules CD40 and CD86 is unaffected. Aerogenic infection of MyD88(-/-) mice with MTB is lethal within 4 weeks with 2 log(10) higher CFU in the lung; high pulmonary levels of cytokines and chemokines; and acute, necrotic pneumonia, despite a normal T cell response with IFN-gamma production to mycobacterial antigens upon ex vivo restimulation. Vaccination with Mycobacterium bovis bacillus Calmette-Guerin conferred a substantial protection in MyD88(-/-) mice from acute MTB infection. These data demonstrate that MyD88 signaling is dispensable to raise an acquired immune response to MTB. Nonetheless, this acquired immune response is not sufficient to compensate for the profound innate immune defect and the inability of MyD88(-/-) mice to control MTB infection.
Cyclic hematopoiesis: the mechanism of cyclic neutropenia in grey collie dogs
Authors: David C. Dale, David W. Alling, Sheldon M. Wolff
Journal: Journal of Clinical Investigation (1972)

Two grey collie dogs had regular cyclic fluctuations in the number of all formed elements of the blood. The period lengths for all elements for an individual dog were the same, but the pattern of fluctuation for each element was distinctive. Normal dogs lacked periodic fluctuations.The patterns of day-to-day variation in the normal dogs counts were consistent with a first-order autoregressive process of serial dependence (i.e., each observation of the series depends on the last preceding observation and no others). The grey collie counts showed the same pattern of serial dependence after the component of the over-all variability due to cyclic oscillation was removed. These data suggest that a defect of hematopoietic regulation at the stem cell level leads to periodic interruptions of production of all hematopoietic elements and accounts for the cycles seen in the peripheral blood counts.
Angiotensin II–Induced Reactive Oxygen Species and the Kidney
Authors: Anja Sachse, Gunter Wolf
Journal: Journal of the American Society of Nephrology (2007)

Angiotensin II (AngII) is an important mediator in renal injury. Accumulating evidence suggests that AngII stimulates intracellular formation of reactive oxygen species (ROS) such as the superoxide anion and hydrogen peroxide. AngII activates several subunits of the membrane-bound multicomponent NAD(P)H oxidase and also increases ROS formation in the mitochondria. Some of these effects may be induced by aldosterone and not directly by AngII. The superoxide anion and hydrogen peroxide influence other downstream signaling pathways, such as transcription factors, tyrosine kinases/phosphatases, ion channels, and mitogen-activated protein kinases. Through these signaling pathways, ROS have distinct functional effects on renal cells. They are transducers of cell growth, apoptosis, and cell migration and affect expression of inflammatory and extracellular matrix genes. For example, AngII-mediated expression of p27(Kip1), a cell-cycle regulatory protein, and induction of tubular hypertrophy depend on the generation of ROS. The effects of ROS generated within different renal cells ultimately depend on the locally generated concentrations and the balance of pro- and antioxidant pathways. Although the concept that AngII mediates oxidative stress in the kidney has been validated in experimental models, the exact role is still incompletely understood in human renal diseases.
Cancer Chemotherapy by Deoxynucleotide Depletion and E2F-1 Elevation
Authors: Ajin Wang, Chiang J. Li, Prem V. Reddy, Arthur B. Pardee
Journal: Cancer Research (2005)

Abstract We propose that the lethality of commonly used anticancer drugs, e.g., methotrexate and cis-platinum are due, at least in part, to an increase of the E2F-1–mediated apoptotic cascade. The drugs directly or indirectly decrease deoxynucleoside triphosphates. The E2F family acts to provide control of S phase by transcribing genes required for deoxynucleoside triphosphate and DNA synthesis. Thus, a mechanism for control of E2F-1 is essential, a signal safeguarding against aberrant or uncontrolled cell proliferation. We have proposed a feedback control by NTPs that down-regulates E2F-1. Here, we provide evidence in support of this hypothesis.