tbuckley/cabot-search huggingface dataset:
Sir Ian William James McAdam John Randall Archibald Joan ("Judy") Britton (nee Kelly) Margaret Yvonne ("Peggy") Currie Donald Andrew Ewing William Ian Leslie Fraser Ian Goodhall Meiklejohn Maurice James Dewar Noble George Ronald Crompton Peatfield Robert Pollock Ruth Margaret Taylor (nee Howitt)
Authors: D. Carter, N. Lye, F. Maggy, T. Bates, J. I Currie, J Hefferman, P. W Thornton, D. Mitchell, J M Stuart, J. Valentine, R. Peatfield, E. M Pollock, S. Taylor
Journal: BMJ (1999)

# Sir Ian William James McAdam {#article-title-2}

Former professor of surgery Makerere University, Kampala, Uganda ( b 1917; q Edinburgh 1940; FRCSE, FRCS; OBE), d 4 March 1999. His appointment enabled him to play a leading part in the growing international reputation of the medical school, then the only one in east Africa. The first generation of east African surgeons were trained in his department, and the quality of their training was such that the MMed in surgery was recognised by the surgical royal colleges in Britain. Although he laid no claim to be a basic scientist, he made major contributions to clinical research. He was a prime mover in establishing the Uganda Blood Transfusion Service, and was instrumental in establishing the Polio Treatment Centre and the Cancer Institute. A founder member of the East African Association of Surgeons, he later became its president.

There can be few surgeons who have had to deal with a major head wound sustained by their country's president (Obote) after a failed coup and operate in a theatre full of excited soldiers with automatic weapons. McAdam's contribution to the development of a multiracial society and his leadership qualities made it inevitable that he would come into contact with the brutal regime imposed by Obote's successor, Idi Amin. In 1972 he and two professorial colleagues were expelled, and he devoted his considerable energies in exile to the plight of colleagues, many of them of Asian descent, who had been forced to leave. After a year at the National Cancer Institute in Washington he returned to Africa, to Plettenburg Bay in South Africa where he undertook all the surgery in Knysna Hospital until he was 72.

An outstanding sportsman, McAdam gained a blue for tennis at Edinburgh and represented Uganda at many sports, winning national titles at golf, tennis, and motor rallying. His other …
Association Between Quantity of Liver Fat and Cardiovascular Risk in Patients With Nonalcoholic Fatty Liver Disease Independent of Nonalcoholic Steatohepatitis
Authors: Ahilan Arulanandan, Brandon Ang, Ricki Bettencourt, Jonathan Hooker, Cynthia Behling, Grace Y. Lin, Mark A. Valasek, Joachim H. Ix, Bernd Schnabl, Claude B. Sirlin, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2015)
Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest
Authors: Michael B Ujiki, Xian-Zhong Ding, M Reza Salabat, David J Bentrem, Laleh Golkar, Ben Milam, Mark S Talamonti, Richard H Bell, Takeshi Iwamura, Thomas E Adrian
Journal: Molecular Cancer (2006)

Many chemotherapeutic agents have been used to treat pancreatic cancer without success. Apigenin, a naturally occurring flavonoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer cell growth in vitro.Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation in four pancreatic cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25, which are all proteins required for G2/M transition.Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest, and may be a valuable drug for the treatment or prevention of pancreatic cancer.
Noninvasive optical inhibition with a red-shifted microbial rhodopsin
Authors: Amy S Chuong, Mitra L Miri, Volker Busskamp, Gillian A C Matthews, Leah C Acker, Andreas T Sørensen, Andrew Young, Nathan C Klapoetke, Mike A Henninger, Suhasa B Kodandaramaiah, Masaaki Ogawa, Shreshtha B Ramanlal, Rachel C Bandler, Brian D Allen, Craig R Forest, Brian Y Chow, Xue Han, Yingxi Lin, Kay M Tye, Botond Roska, Jessica A Cardin, Edward S Boyden
Journal: Nature Neuroscience (2014)
Itraconazole therapy in pityriasis versicolor
Authors: A.DEL PALACIO HERNANZ, J. FRIAS-INIESTA, O. GONZALEZ-VALLE, M. BORGERS, J. CUTSEM, G. CAUWENBERGH
Journal: British Journal of Dermatology (1986)

The efficacy of itraconazole was assessed in an open trial in 30 patients with disseminated lesions of pityriasis versicolor confirmed by direct microscopy. The patients were allocated randomly to one of two treatment regimens, 200 mg once daily for 5 days or 100 mg once daily for 10 days. On assessment 3 weeks after the end of the treatment, 25 patients were healed, two patients had mild residual lesions, two had considerable residual lesions and one patient had relapsed. One patient reported dyspepsia and one patient reported stomach ache. One patient had asymptomatic elevation of serum transaminase (GOT and GPT) but this had returned to normal 3 weeks after the end of therapy.
Targeting Methylguanine-DNA Methyltransferase in the Treatment of Neuroblastoma
Authors: Lars M. Wagner, Roger E. McLendon, K. Jin Yoon, Brian D. Weiss, Catherine A. Billups, Mary K. Danks
Journal: Clinical Cancer Research (2007)

The combination of temozolomide and irinotecan has preclinical schedule-dependent synergy against neuroblastoma but is not curative for relapsed high-risk patients. We hypothesized that the DNA repair protein methylguanine-DNA methyltransferase (MGMT) is an important resistance factor, and that inactivation of MGMT would sensitize neuroblastoma cells to these agents.MGMT protein expression was assessed in 74 primary neuroblastoma tumors. Growth inhibition assays were done to determine the IC(50) and the extent of synergy observed with various concentrations of temozolomide, irinotecan, and the MGMT-inactivating agent O(6)-benzylguanine, using cultured syngeneic neuroblastoma cells with either low or high levels of MGMT expression. We then assessed efficacy in a mouse xenograft model of metastatic neuroblastoma.MGMT was expressed by all 74 tumors evaluated. Pretreatment of neuroblastoma cells with O(6)-benzylguanine reduced the IC(50) of temozolomide by 10-fold regardless of level of MGMT expression, and pretreatment with BG followed by temozolomide + irinotecan further reduced the IC(50) in cells with high MGMT expression another 10-fold, to well below clinically achievable concentrations. The combination index was 0.27 to 0.30 for all three drugs in both cell lines, indicating strong synergy. Survival at 100 days for mice with metastatic neuroblastoma was 56% with three-drug treatment, compared with untreated controls (0%, P < 0.001) or temozolomide + irinotecan (10%, P = 0.081).MGMT is widely expressed in primary neuroblastoma tumors, and is a relevant therapeutic target. Both in vitro and in vivo studies suggest inactivation of MGMT with O(6)-benzylguanine may increase the activity of temozolomide and irinotecan against neuroblastoma.
Cannabis intoxication and fatal road crashes in France: population based case-control study
Authors: Bernard Laumon, Blandine Gadegbeku, Jean-Louis Martin, Marie-Berthe Biecheler
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To evaluate the relative risk of being responsible for a fatal crash while driving under the influence of cannabis, the prevalence of such drivers within the driving population, and the corresponding share of fatal crashes. <b>Design</b> Population based case-control study. <b>Participants</b> 10 748 drivers, with known drug and alcohol concentrations, who were involved in fatal crashes in France from October 2001 to September 2003. <b>Main outcome measures</b> The cases were the 6766 drivers considered at fault in their crash; the controls were 3006 drivers selected from the 3982 other drivers. Positive detection of cannabis was defined as a blood concentration of Δ<sup>9</sup>tetrahydrocannabinol of over 1 ng/ml. The prevalence of positive drivers in the driving population was estimated by standardising controls on drivers not at fault who were involved in crashes resulting in slight injuries. <b>Results</b> 681 drivers were positive for cannabis (cases 8.8%, controls 2.8%), including 285 with an illegal blood alcohol concentration (0.5 g/l). Positive cannabis detection was associated with increased risk of responsibility (odds ratio 3.32, 95% confidence interval 2.63 to 4.18). A significant dose effect was identified; the odds ratio increased from 2.18 (1.22 to 3.89) if 0 &lt; Δ<sup>9</sup>tetrahydrocannabinol &lt; 1 ng/ml to 4.72 (3.04 to 7.33) if Δ<sup>9</sup>tetrahydrocannabinol 5 ng/ml. The effect of cannabis remains significant after adjustment for different cofactors, including alcohol, with which no statistical interaction was observed. The prevalence of cannabis (2.9%) estimated for the driving population is similar to that for alcohol (2.7%). At least 2.5% (1.5% to 3.5%) of fatal crashes were estimated as being attributable to cannabis, compared with 28.6% for alcohol (26.8% to 30.5%). <b>Conclusions</b> Driving under the influence of cannabis increases the risk of involvement in a crash. However, in France its share in fatal crashes is significantly lower than that associated with positive blood alcohol concentration.
Ventilatory pattern during bronchial histamine challenge in asthmatics
Authors: NO Stromberg, PM Gustafsson
Journal: European Respiratory Journal (1993)

We wanted to investigate whether asthmatic subjects change their ventilatory pattern consistently when forced expiratory volume in one second (FEV1) has declined by at least 20% during bronchial histamine challenge, in order to assess whether respiratory pattern analysis can be used to monitor bronchial obstruction continuously. Histamine challenge was performed twice within a four week period, in eight asthmatic teenagers. Respiratory inductive plethysmography (RIP) was used for respiratory pattern evaluation, whilst the patients breathed on a mouthpiece attached to a pneumo-tachometer (PTM) whilst wearing a noseclip (first histamine challenge), and during natural breathing (second HiCh). End-tidal carbon dioxide tension (PETCO2) was measured on both occasions. During the second histamine challenge, four of the eight patients responded with a 72% (mean) increase in minute ventilation (VE), an 80% increase in mean inspiratory flow (VI), and a 20% decrease in PETCO2. VE and VI were unchanged, or tended to decrease, among the other four patients (ventilatory nonresponders). Neither provocative dose producing a 20% fall in FEV1 (PD20) to histamine nor the magnitude of the fall in FEV1 differed between ventilatory responders and nonresponders. The ventilatory response to inhaled histamine was abolished when breathing through a PTM. Histamine induced bronchospasm is not uniformly reflected in the breathing pattern. Hyperventilation during histamine challenge might be the consequence of vagal airway receptor activation. Respiratory pattern analysis is not a feasible way to monitor bronchial obstruction during histamine challenge.
Discontinuation of empirical antibiotic therapy in neutropenic leukaemia patients with fever of unknown origin is ethical
Authors: C. Orasch, D. Averbuch, M. Mikulska, C. Cordonnier, D.M. Livermore, I.C. Gyssens, G. Klyasova, D. Engelhard, W. Kern, C. Viscoli, M. Akova, O. Marchetti
Journal: Clinical Microbiology and Infection (2014)
Determinants of ventricular septal motion. Influence of relative right and left ventricular size.
Authors: A S Pearlman, C E Clark, W L Henry, J Morganroth, S B Itscoitz, S E Epstein
Journal: Circulation (1976)

To test the hypothesis that the ventricular septum moves during systole toward the center of the ventricular mass (so that the end-diastolic position of the septum within the heart should determine both the direction and the magnitude of septal motion during systole), echocardiograms from patients with several different hemodynamic burdens were analyzed. A linear relation was noted between the end-diastolic intracardiac position of the ventricular septum and the direction and magnitude of systolic septal motion in 1) forty three patients with an atrial septal defect )regression coefficient r = 0.80), 2) fourteen patients with other causes of right ventricular volume overload (r = 0.82), 3) nineteen patients with left ventricular volume overload (r = 0.74), 4) ten patients with right ventricular pressure overload (r = 0.93), 5) ten patients with left ventricular pressure overload (r = 0.80), 6) twenty-eight normal subjects (r = 0.82). We conclude that, in the presence of normal ventricular activation and contraction, the direction and magnitude of sepatal motion during systole is determined by the intracardiac position of the septum at enddiastole.
Grip strength and forearm straps in tennis elbow.
Authors: A K Burton
Journal: British Journal of Sports Medicine (1985)

Twenty-seven patients who presented with tennis elbow had their grip strengths measured without a forearm strap, with an elastic strap and with an inelastic strap. Of these 85% displayed an increased pain-free grip strength with one or both straps. The increase in pain-free grip strength was statistically significant for both types of strap (p less than 0.001) and the results showed no consistent difference between them. The possible mode of action is discussed.
Regulatory T Cells Are Expanded in Blood and Disease Sites in Patients with Tuberculosis
Authors: Valerie Guyot-Revol, John A. Innes, Sarah Hackforth, Tim Hinks, Ajit Lalvani
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: T-cell responses during tuberculosis (TB) help contain Mycobacterium tuberculosis in vivo but also cause collateral damage to host tissues. Immune regulatory mechanisms may limit this immunopathology, and suppressed cellular immune responses in patients with TB suggest the presence of regulatory activity. CD4+CD25high regulatory T cells mediate suppressed cellular immunity in several chronic infections but have not been described in TB.Objective: To determine whether regulatory T cells are increased in patients with TB and whether they suppress cellular immune responses.Methods: We compared the frequency of circulating regulatory T cells in 27 untreated patients with TB and 23 healthy control subjects using two specific markers: cell-surface CD25 expression and FoxP3 mRNA expression in peripheral blood mononuclear cells.Measurements and Main Results: We detected a threefold increase in the frequency of CD4+CD25high T cells (p < 0.001) and a 2.2-fold increase in FoxP3 expression (p = 0.006) in patients with TB, and there was a positive correlation between these markers (r = 0.58, p < 0.001). Increased expression of interleukin-10 and transforming growth factor-β1 mRNA was also detected in patients with TB but did not correlate with regulatory T-cell markers. Ex vivo depletion of CD4+CD25high cells from peripheral blood mononuclear cells resulted in increased numbers of M. tuberculosis antigen–specific IFN-γ–producing T cells in seven of eight patients with TB (p = 0.005). Finally, FoxP3 expression was increased 2.3-fold in patients with extrapulmonary TB compared with patients with purely pulmonary TB (p = 0.01) and was amplified 2.6-fold at disease sites relative to blood (p = 0.043).Conclusions: Regulatory T cells are expanded in patients with TB and may contribute to suppression of Th1-type immune responses.
Does interferon- improve pulmonary function in idiopathic pulmonary fibrosis?
Authors: A. Prasse, K-M. Müller, C. Kurz, H. Hamm, J.C. Virchow
Journal: European Respiratory Journal (2003)

Idiopathic pulmonary fibrosis (IPF) is a disease with progressive and devastating deterioration of lung function and a fatal prognosis, despite aggressive therapeutic attempts, which, in the majority of cases are futile. Recently, a preliminary study of long-term treatment with interferon (IFN)-gamma1b and low-dose prednisolone in patients with IPF suggested that IFN-gamma1b treatment may improve lung function parameters of patients with IPF. Ever since, specialists in respiratory medicine who treat patients with IPF, are called by patients demanding treatment with IFN-gamma1b. Therefore, the authors here present another prospective investigation of IFN-gamma1b in five patients with IPF. According to the previously published design, patients received 200 microg IFN-gamma1b subcutaneously three-times per week and 10 mg prednisolone orally for 12 months. Two patients stopped IFN-gamma1b treatment after 4 months due to side-effects and further lung function deterioration and one patient died 3 months after commencement of therapy. In total, pulmonary function improved in only one patient during IFN-gamma1b treatment, while four patients deteriorated. To conclude, this small series of idiopathic pulmonary fibrosis cases treated with interferon-gamma1b and corticosteroids does not support previous data that this treatment improves pulmonary function or alters the natural course of idiopathic pulmonary fibrosis. Furthermore, in the authors' experience, side-effects of interferon-gamma1b treatment can significantly reduce patients' quality of life.
Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line.
Authors: K Matsushima, C G Larsen, G C DuBois, J J Oppenheim
Journal: The Journal of Experimental Medicine (1989)

A novel basic heparin-binding monocyte chemotactic factor (MCF) was purified to homogeneity from the conditioned media of human myelomonocytic cell line THP-1 based on its in vitro monocyte chemotactic activity. The purified MCF was homogenous and estimated to be 15 kD on SDS-PAGE. Purified MCF stimulated normal human monocytes to be growth inhibitory in vitro at 2-3 d for several human tumor cell lines. This represents the first report of the identification and purification of a chemoattractant cytokine that also activates monocytes but is distinct from interferons and other known cytokines.
A TANDEM FOREARM PLETHYSMOGRAPH FOR STUDY OF ACUTE RESPONSES OF THE PERIPHERAL VEINS OF MAN: THE EFFECT OF ENVIRONMENTAL AND LOCAL TEMPERATURE CHANGE, AND THE EFFECT OF POOLING BLOOD IN THE EXTREMITIES1
Authors: J. Edwin Wood, John W. Eckstein
Journal: Journal of Clinical Investigation (1958)

The primary mechanism of action of the smooth muscle of the veins upon their contained blood is one of imparting pressure to the blood by a sur- rounding force.This mode of action is to be distinguished from that of the smooth muscle of the arterioles, which is one of maintenance of arterial pressure through resistance to the outflow of blood.The function of the arterioles as re- sistive elements in the circulation is evaluated by the relationship between the volume of the flow of blood through the arterioles per unit period of time and the change in pressure across the arterioles.The function of the veins as containers of the blood volume is best evaluated by the relationship between a change of the volume of the veins and the associated change of the pressure of the veins.It is the purpose of this paper to describe a new method for the simultaneous study of the functions of the arterioles and the veins of the ex- tremities of man.In addition, the effects of several stimuli upon veins and arterioles of the forearm are also described.The stimuli employed were the reduction of the temperature of the room, the reduction of the temperature surrounding the forearm under study, and the congestion of the veins of the three extremities not being studied. METHODSA water plethysmograph made of lucite which had two chambers was used in all of the experiments (Fig- ure 1).Each chamber was 8.5 cm.long and had sepa- rate sleeves which were thin, loose fitting rubber.The
Inhibition of cobalamin-dependent enzymes by cobalamin analogues in rats.
Authors: S P Stabler, E P Brass, P D Marcell, R H Allen
Journal: Journal of Clinical Investigation (1991)

To determine which parts of the cobalamin (cbl) molecule are required for enzyme activity and which parts, if altered, might inhibit cbl-dependent enzyme activity, we synthesized 16 cbl analogues and administered them to nutritionally normal rats. The cbl analogues, with either modifications of the propionamide side chains of the A-, B-, and C-rings, the acetamide side chain of the B-ring, or the nucleotide moiety, were administered to rats by continuous 14-d subcutaneous infusion. Infusion of cbl-stimulated, cbl-dependent activity. Changes in any part of the cbl molecule always abolished stimulation and, in some cases, caused potent inhibition of both cbl-dependent enzymes. The most inhibitory analogues, OH-cbl[c-lactam], a B-ring analogue, and OH-cbl[e-dimethylamide] and OH-cbl[e-methylamide], two C-ring analogues, decreased mean liver holo-L-methylmalonyl-coenzyme A mutase activity to 65% of control values and increased serum methylmalonic acid concentrations to as high as 3,200% of the control values. Liver methionine synthetase activity was decreased to approximately 20% of the control and mean serum total homocysteine concentrations were increased to 340% of control. A similar level of inhibition was demonstrated in rats who were exposed to 28 d of inhaled nitrous oxide or a prolonged period of dietary cbl deficiency. The inhibitory cbl analogues, nitrous oxide, and diet deficiency all depleted liver cbl. The naturally occurring cbl analogues with modifications of the nucleotide moiety had no effects. We conclude that all parts of the cbl molecule are necessary for in vivo cbl-dependent enzyme activity and that modifications of the side chains of the B and C rings are associated with potent in vivo inhibition of cbl-dependent enzyme activity.
Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants
Authors: Whitney E. Purtha, Thomas F. Tedder, Syd Johnson, Deepta Bhattacharya, Michael S. Diamond
Journal: The Journal of Experimental Medicine (2011)

Memory B cells (MBCs) and long-lived plasma cells (LLPCs) persist after clearance of infection, yet the specific and nonredundant role MBCs play in subsequent protection is unclear. After resolution of West Nile virus infection in mice, we demonstrate that LLPCs were specific for a single dominant neutralizing epitope, such that immune serum poorly inhibited a variant virus that encoded a mutation at this critical epitope. In contrast, a large fraction of MBC produced antibody that recognized both wild-type (WT) and mutant viral epitopes. Accordingly, antibody produced by the polyclonal pool of MBC neutralized WT and variant viruses equivalently. Remarkably, we also identified MBC clones that recognized the mutant epitope better than the WT protein, despite never having been exposed to the variant virus. The ability of MBCs to respond to variant viruses in vivo was confirmed by experiments in which MBCs were adoptively transferred or depleted before secondary challenge. Our data demonstrate that class-switched MBC can respond to variants of the original pathogen that escape neutralization of antibody produced by LLPC without a requirement for accumulating additional somatic mutations.