tbuckley/cabot-search huggingface dataset:
586. Anti-HIV-1 Neutralizing Antibody Gene Delivery to Rhesus Macaques and Rodents: A Novel Vaccination Approach
Authors: K. Reed Clark, Jianchao Zhang, David C. Montefiori, Philip R. Johnson
Journal: Molecular Therapy (2006)

We are continuing to develop a novel vaccination approach that is predicated on providing protective anti-HIV-1 humoral immune responses through antibody gene transfer. Our strategy is to utilize rAAV mediated antibody gene transfer to skeletal muscle to supply the host with a renewable source of anti-HIV-1 antibodies in their systemic circulation. The genes encode several rare, but broadly neutralizing scFv HIV-1 antibodies (X5, 3B3, and 3B3-hCC). One potential challenge to this approach is whether therapeutic levels of NAbs are achievable. Data from previous passive immunization protection studies in primates indicate that protective levels may be achieved with serum concentrations of potent NAbs in the range of 50 -100 ug/ml. To address this issue, we have optimized several variables for efficient antibody gene delivery and expression; these include rAAV serotype, antibody genetic fusions for increased half- life, and inclusion of cis sequences for maximal expression. This has resulted in increased antibody levels by greater than 100-fold over our initial efforts. Significantly, optimization of delivery and expression parameters has yielded NAb levels exceeding 500 ug/ml in mice and up to 43 ug/ml in primates - levels which approach or exceed the predicted therapeutic range. Consistent with their broad neutralization activity, animal sera containing X5 and 3B3-hCC from rAAV vaccinated mice and primates possess potent in vitro neutralization activity against TCLA and primary HIV-1 single- cycle HIV-1 pseudoviruses as measured by reduction of luciferase reporter gene activity in TZM-BL cells. These data now set the stage for future challenge experiments to determine whether the in vivo levels observed to date provide protection (reduction in viral load) upon a virulent SHIV challenge.
A "prime-pull" immunotherapy approach using a lentiviral vector and intratumoral TLR4 agonist redirects cytotoxic T cells
Authors: Tina C Albershardt, Andrea J Parsons, Patrick Flynn, Peter Berglund, Jan ter Meulen
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts The clinical efficacy of tumor specific effector T cells is limited by their proper trafficking to the site of the tumor and the locally immunosuppressive environment. Strategies to improve homing and activity of immune effector cells to tumors are needed to unlock the potential
Cell Therapy for Parkinson's Disease
Authors: Gerald D. Fischbach, Guy M. McKhann
Journal: New England Journal of Medicine (2001)

Parkinson's disease is characterized by the progressive loss of dopamine neurons in the substantia nigra of the midbrain. These neurons project widely throughout the cerebral hemispheres, but the motor symptoms of Parkinson's disease — bradykinesia, muscle rigidity, and resting tremor — are almost certainly due to the loss of dopamine nerve terminals in the caudate and putamen nuclei (the striatum) of the basal ganglia and the unbalancing of circuits required for coordinated movement. One of the therapeutic successes of clinical neurology has been the use of levodopa, the precursor of dopamine, in patients with Parkinson's disease. In nearly all patients, . . .
[513] EFFICACY OF TELBIVUDINE VS LAMIVUDINE AT 2 YEARS IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B WHO ARE ELIGIBLE FOR TREATMENT BASED ON GUIDELINES
Authors: J. Rasenack, T. Poynard, C.-L. Lai, E. Gane, N.A. Brown, J. Heathcote
Journal: Journal of Hepatology (2007)
TETANUS IN TWO BROTHERS: SUBDURAL AND SUBCUTANEOUS INJECTIONS OF SERUM: RECOVERY
Authors: J. Adam
Journal: BMJ (1906)

As the value of the serum treatment of tetanus seems demonstrated by one, if not by both, of these cases, they may be worth publislling; that others may judge I give the notes in some detail.In narrating the cases the days are numbered from the date of injury and unless otherwise stated the injections were made into the abdominal wall.CASE I (X.).
URETERAL COMPRESSION DUE TO METASTASIS FROM CARCINOMA OF SIGMOID
Authors: George R. Krause
Journal: JAMA (1952)

Metastasis to retroperitoneal lymph nodes from carcinoma of the sigmoid colon or rectum may compress and obstruct the ureters, especially the left one. Two recent articles 1 mentioned this, but, unfortunately, there was not enough emphasis in either. One of the reports included cases with other sites of primary neoplasm; the other laid greatest stress on changes in position of the ureters that follow reperitonealization of the pelvic floor during an abdominoperineal resection of the rectum. Recent experiences have led us to believe that ureteral compression by metastasis from carcinoma of the sigmoid colon or rectum is of sufficient importance to deserve undivided attention.  During the past five years we have seen five patients who have had at least one ureter compressed by lymph nodes containing tumor that was metastatic from a carcinoma of the distal colon. The primary tumor had been removed from four of these patients, but they
Variation IN Microsporum Canis AND Microsporum Audouini
Authors: Jacqueline Walker
Journal: British Journal of Dermatology (1950)

Journal Article Variation IN Microsporum Canis AND Microsporum Audouini Get access Jacqueline Walker Jacqueline Walker Mycological Reference Laboratory, Public Health Laboratory Service, London School of Hygiene and Tropical Medicine Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 62, Issue 10, 1 October 1950, Pages 395–401, https://doi.org/10.1111/j.1365-2133.1950.tb14344.x Published: 01 October 1950
Abstract 4869: β-caryophyllene inhibits solid tumor growth and metastasis of B16F10 melanoma cells in C57BL/6 mice fed on a high-fat diet.
Authors: Jae In Jung, Eun Ji Kim, Yoo Jin Jung, Hyang Sook Chun, Jung Han Yoon Park
Journal: Cancer Research (2013)

Abstract We previously observed that chronic consumption of a high-fat diet (HFD) increased the melanoma progression and lymph node metastasis in C57BL/6N mice injected with B16F10 melanoma cells. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils especially clove and oregano oils. In the present study, we examined whether BCP inhibits HFD-induced melanoma growth and metastasis in the B16F10 allograft model. Four-week old, male C57BL/6 mice were fed on a HFD (60 kcal% fat) or control diet (CD, 10 kcal% fat) with or without BCP (0.15, 0.3% in diet) for a period of 21 weeks. Following 16 weeks of either CD or HFD in the absence or presence of BCP, B16F10 melanoma cells were subcutaneously injected into mice and all mice were continuously fed identical diets. Three weeks post-injection, tumors were resected and mice were sacrificed three weeks post-resection. The body weights and the growth of solid tumors were markedly increased in the HFD group as compared to the CD group, and these increases were suppressed by BCP treatment. The expression of proteins related to cell proliferation (Ki67, CDK4, cyclin A, and cyclin D1), angiogenesis (VEGF-A, VEGFR-2, and CD31) and lymphangiogenesis (VEGF-C, VEGF-D, VEGFR-3, and LYVE-1) was markedly increased in tumor tissues of the HFD group as compared to the CD group, and these increases were blocked by BCP treatment. HFD feeding increased the infiltration of CD45+ leukocytes and F4/80+ macrophages into tumor tissues. The administration of BCP significantly suppressed HFD-induced the infiltration of the immune cells into tumor tissues. HFD feeding reduced TUNEL-positive apoptotic cells in the tumor tissues, which was prevented by BCP treatment. Two weeks after tumor resection, the mice evidenced lung and lymph node metastasis. Lung and lymph node metastasis were increased in the mice fed on HFD, and these increases were markedly suppressed by BCP treatment. The present results demonstrate that BCP suppressed HFD-stimulated melanoma progression and metastasis, which may have been mediated via the suppression of cell cycle progression, angiogenesis and lymph angiogenesis, and induction of apoptosis in tumor tissues. These results suggest that BCP has potential as an anti-cancer agent for the prevention of obesity-stimulated melanoma progression. Citation Format: Jae In Jung, Eun Ji Kim, Yoo Jin Jung, Hyang Sook Chun, Jung Han Yoon Park. β-caryophyllene inhibits solid tumor growth and metastasis of B16F10 melanoma cells in C57BL/6 mice fed on a high-fat diet. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4869. doi:10.1158/1538-7445.AM2013-4869
Multiple factors in leukaemogenesis.
Authors: P G Smith, M C Pike, L D Hamilton
Journal: BMJ (1973)

miRnsH MEDICAL JouRNAL 26 MAY 1973 to intervene inmiediately in crisis situations, and worked out a shorter and more practical technique of interviewing than social workers are traditionally taught.I suspect that many more social workers would do the same if given the chance.At present most of them can only be contacted during office hours and then only if the clerk in the social services department office chooses to tell them that you phoned.The ideal would be local-authority attachment to particular prac- tices, but the next best thing would be re- imbursement of the social workeres salary.
Morphological evidence for the antiatherogenic effect of scoparone in hyperlipidaemic diabetic rabbits
Authors: Y.-L. Chen, H.-C. Huang, Y.-I Weng, Y.-J. Yu, Y.-T. Lee
Journal: Cardiovascular Research (1994)

Scoparone (6,7-dimethoxycoumarin), a coumarin isolated from a hypolipidaemic Chinese herb Artemisia scoparia, has vasodilator and antiproliferative activities and possesses free radical scavenging properties in vitro. The aim of the study was to investigate the morphological effects of scoparone in the antiatherogenic process in vivo by using hyperlipidaemic diabetic rabbits as an animal model.Male New Zealand White rabbits were divided into three groups: control (normal), hyperlipidaemic diabetic, and scoparone treated hyperlipidaemic diabetic. The plasma concentration of total cholesterol and triglycerides were determined. The thickness of the tunica intima was measured on paraffin sections of the aortas stained with Movat's pentachrome. The aortic samples were also processed for scanning and transmission electron microscopy.Neither the lipid profile in the plasma nor the structures of the aortic wall from the control group showed abnormalities. In contrast, the aortas from the hyperlipidaemic diabetic group showed prominent atherosclerotic plaques. Large numbers of monocytes were found adherent to the luminal surface and a markedly thickened intima filled with many lipid laden foam cells was clearly observed. By comparison, the scoparone treated group showed less advanced atherosclerosis with a lower plasma cholesterol. In the scoparone treated rabbits, the proportion of the aortic surface area covered with macroscopic plaques was 30%, and the thickness of the tunica intima 17%, of that of the non-scoparone treated hyperlipidaemic diabetic rabbits.Scoparone has an antiatherogenic action in hyperlipidaemic diabetic rabbits.
Redesigning health care
Authors: J. Smith
Journal: BMJ (2001)

Dysregulation of dopamine neurotransmission has been linked to the development of HIV-1 associated neurocognitive disorders (HAND). To investigate the mechanisms underlying this phenomenon, this study utilized an inducible HIV-1 transactivator of transcription (Tat) transgenic (iTat-tg) mouse model, which demonstrates brain-specific Tat expression induced by administration of doxycycline. We found that induction of Tat expression in the iTat-tg mice for either 7 or 14 days resulted in a decrease (~30%) in the Vmax of [3H]DA uptake via both the dopamine transporter (DAT) and norepinephrine transporter (NET) in the prefrontal cortex (PFC), which was comparable to the magnitude (~35%) of the decrease in Bmax for [3H]WIN 35,428 and [3H]Nisoxetine binding to DAT and NET, respectively. The decreased Vmax was not accompanied by a reduction of total or plasma membrane expression of DAT and NET. Consistent with the decreased Vmax for DAT and NET in the PFC, the current study also found an increase in the tissue content of DA and dihydroxyphenylacetic acid (DOPAC) in the PFC of iTat-tg mice following 7-day administration of doxycycline. Electrophysiological recordings in layer V pyramidal neurons of the prelimbic cortex from iTat-tg mice found a significant reduction in action potential firing, which was not sensitive to selective inhibitors for DAT and NET, respectively. These findings provide a molecular basis for using the iTat-tg mouse model in the studies of NeuroHIV. Determining the mechanistic basis underlying the interaction between Tat and DAT/NET may reveal novel therapeutic possibilities for preventing the increase in comorbid conditions as well as HAND. <h3>SIGNIFICANCE STATEMENT</h3> HIV-1 infection disrupts dopaminergic neurotransmission, leading to HIV-1 associated neurocognitive disorders. Based on our in vitro and in vivo studies, dopamine uptake via both dopamine and norepinephrine transporters is decreased in the prefrontal cortex of HIV-1 Tat transgenic mice, which is consistent with the increased dopamine and DOPAC contents in this brain region. Thus, these plasma membrane transporters are an important potential target for therapeutic intervention for patients with HAND.
Study of information submitted by drug companies to licensing authorities.
Authors: E Hemminki
Journal: BMJ (1980)

Reports of clinical trials included in applications submitted by drug companies to licensing authorities in Finland and Sweden in four different years were studied. Many reports were submitted, but most of the trials were uncontrolled and of poor quality. Many of the reports were unpublished, and thus, as the submissions are secret, were not available to doctors. These unpublished reports were in most respects as valuable as the published reports. Most of the reports included some information about adverse effects; the information was often deficient, but skilled analysis might increase its value. This study provides support for those who want to see public disclosure of the reports of trials submitted in licensing applications.
The Influence of Osier on His Students
Authors: Earl F. Nation
Journal: JAMA (1969)

Dr. Charles N. B. Camac, a former Osler resident, wrote Lady Osler, May 9, 1913, as follows:  My dear Mrs. Chief,  In 1905 when I was in Oxford the Chief and I planted some seeds which have yielded fruit; just how much this has been is hard to estimate. That many hungry souls have been fed by this fruit is attested to by the letters & expressions I get every year. Besides this soul feeding success the planting has yielded practical returns. I have waited till these took on some proportions & while these are yet modest I want you & The Chief to have them. If you know of some book he wants and something you would like to get for yourself with this little figure will you please be the Middleman and turn the trick.  Affectionately yours,  C.N.B. Camac  Accompanying this letter was a memorandum of exchange from
Small airway closure and positive end-expiratory pressure in mechanically ventilated patients with chronic obstructive pulmonary disease.
Authors: C Guerin, S LeMasson, R de Varax, J Milic-Emili, G Fournier
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The effects of positive end-expiratory pressure (PEEP) on alveolar recruitment and closing volume were studied in ten supine, sedated, and paralyzed patients with chronic obstructive respiratory disease and acute respiratory failure. We applied PEEP (0, 5, 10, and 15 cm H2O) and constructed inflation static volume-pressure (V-P) curves. In all patients, the static V-P curves obtained at different PEEP levels were superimposed on each other, indicating that with PEEP there was no recruitment of previously atelectatic lung units. However, the static V-P curves exhibited an inflection point, which should reflect the critical pressure (Po) required to reopen all closed airways, whilst the corresponding lung volume (Vo) reflects the opening volume. On average, Vo was 0.71 L above the relaxation volume of the respiratory system (Vr). All patients, however, exhibited dynamic hyperinflation, i.e., with zero PEEP (ZEEP) the end-expiratory lung volume (EELV) was 0.54 L above Vr. Nevertheless, in seven patients the EELV on ZEEP was below Vo, resulting in cyclic reopening and closure of small airways with each breathing cycle, with concomitant mechanical stresses on the peripheral airways that may lead to low-volume barotrauma. Such barotrauma may be prevented by increasing with PEEP the EELV to Vo.
Toxaemia of Pregnancy Treated with Progesterone During the Symptomatic Stage
Authors: K. Dalton
Journal: BMJ (1957)

BRITIsHThere have been no accidents as a result of the test, and the patients are not distressed by it.Indeed, when a patient is given a good prognosis concerning her baby, considerable peace of mind is derived from such news.Summary A report is given of liquor amnii tests on 101 sensitized rhesus-negative women.It has been found that: (1) the liquor must be tested fresh before the 35th week; and (2) an accurate prediction can be obtained in at least 94.9% of cases.This work has been made possible by the willing co-operation of all members of the medical and nursing staffs of St. Mary's Hospitals, Manchester.I wish to thank
High 18F-FDG Uptake For Uterine Smooth Muscle Tumor of Uncertain Malignant Potential
Authors: Ruiguo Zhang, Xun Tian, Lan Qin, Dongyan Lu, Jie Shen
Journal: Clinical Nuclear Medicine (2015)

Uterine smooth muscle tumor of uncertain malignant potential is rare. It can have recurrence metastasis but is much less aggressive than leiomyosarcoma. We report a case of a 42-year-old woman who underwent PET/CT scan, which showed intense 18F-FDG uptake in the uterus. Results of pathological examination after hysterectomy combined with bilateral oophorectomy were consistent with uterine smooth muscle tumor of uncertain malignant potential.
SYPHILITIC MACULAR ATROPHY
Authors: G. B. DOWLING
Journal: British Journal of Dermatology (1927)

Journal Article SYPHILITIC MACULAR ATROPHY Get access G. B. DOWLING, M.D., M.R.C.P. G. B. DOWLING, M.D., M.R.C.P. Dermatologist to the West London Hospital; Assistant Physician, St. John's Hospital for Diseases of the Skin Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 39, Issue 2, 1 February 1927, Pages 55–61, https://doi.org/10.1111/j.1365-2133.1927.tb10047.x Published: 01 February 1927
12 HCV KINETICS AND QUASISPECIES EVOLUTION WITHIN THE FIRST HOURS OF TELAPREVIR-BASED TRIPLE THERAPY IN PREVIOUSLY TREATED HCV-PATIENTS
Authors: V. Cento, F. De Luca, F. Valenti, M. Tontodonati, V.C. Di Maio, M.C. Bellocchi, D. Armenia, L. Carioti, F. Trave, P. Cacciatore, G. Madeddu, A. Bertoli, M. Angelico, S. Babudieri, G. Parruti, F. Ceccherini-Silberstein, C.F. Perno
Journal: Journal of Hepatology (2013)
Hydrated Magnesium Trisilicate in Peptic Ulceration
Authors: N. Mutch
Journal: BMJ (1936)

Synthetic magnesium trisilicate (Mg2Si3O8 nH1O) is a tasteless white insoluble powder, possessing adsorbent and antacid properties of particular value in the treatment of gastric hyperacidity and chronic peptic ulceration of the stomach, duodenum, and jejunum.As an adsorbent it far transcends bismuth salts, magnesia, aluminium hydroxide, prepared chalk, and other medicaments in common use in these conditions.In Table I are givenTABLE I.-Adsorption Poweys of Common Antacid Substances Potency (Weight of Methylene-blue Adsorbent Removed per gram of Substance Tested the Saturation Poi Magnesium trisilicate (synthetic sepiolite Type 11) 176 Ditto (allowing for loss on ignition) ... ...244 Aluminium hydroxide (B.P.C.) ... ... ... ... Less than 1 ("alocol") 2 Bismuth oxycarbonate (B.P.) ... ... ... ... Less than 1 Calcium phosphate (tribasic, 1B.P.) ... ... 0 Chalk (prepared, B.P.) ... ... ... ...
Inhibition of Nitric Oxide Synthesis Reduces Infarct Size by an Adenosine-Dependent Mechanism
Authors: Robin G. Woolfson, Vanlata C. Patel, Guy H. Neild, Derek M. Yellon
Journal: Circulation (1995)

Background Nitric oxide (NO) is both a potent endogenous vasodilator with potential to attenuate ischemia-reperfusion injury and a mediator of tissue injury. The aim of the present study was to investigate the mechanism by which prior inhibition of NO synthesis can lessen ischemia-reperfusion injury in the isolated rabbit heart. Methods and Results We examined the effects of inhibition of NO synthesis on infarct size using a model of coronary artery ligation in isolated rabbit hearts perfused at a constant flow rate of 35 mL/min. Infarct size averaged 65% of the zone at risk after 45 minutes of ischemia and 180 minutes of reperfusion. The addition of 30 μmol/L N G -nitro- l -arginine methyl ester (L-NAME), an inhibitor of NO synthesis, to the perfusate reduced the infarct-to-risk (I/R) ratio to an average of 41% ( P &lt;.05 versus control). This effect was abolished by pretreatment with 75.5 μmol/L 8- p -sulfophenyl theophylline (SPT), an adenosine receptor antagonist (I/R ratio, 63%). Ischemic preconditioning (5 minutes of ischemia and 10 minutes of reperfusion) before 45 minutes of ischemia and 3 hours of reperfusion reduced the I/R ratio to an average of 21%, and this was not augmented by pretreatment with L-NAME (I/R ratio, 20%). However, all protection due to preconditioning and L-NAME was lost in hearts pretreated with SPT (I/R ratio, 59%). In a separate set of experiments, adenosine concentration in the coronary perfusate and myocardial lactate concentrations were measured. Treatment with L-NAME increased the average adenosine concentration in the perfusate from 5.7 μmol/L per 100 g of heart (control) to a peak of 24.0 μmol/L per 100 g of heart; however, there was no effect on average myocardial lactate concentration (control, 4.6 μmol/g dry wt; L-NAME, 5.5 μmol/g dry wt). In contrast, after 5 minutes of global ischemia, the average adenosine concentration peaked at 139.0 μmol/L per 100 g of heart, and the average myocardial lactate concentration increased to 27.1 μmol/g dry wt. Conclusions Infarct size limitation after inhibition of NO synthesis shares a common mechanism with that of ischemic preconditioning and is dependent on the release of adenosine. However, in this model, adenosine release after inhibition of NO synthesis is not secondary to myocardial ischemia. The protection of the heart against ischemic injury by adenosine appears to be concentration dependent.