tbuckley/cabot-search huggingface dataset:
Effects of sho-saiko-to, a japanese herbal medicine, on hepatic fibrosis in rats
Authors: Ichiro Shimizu, Yue-Rong Ma, Yoko Mizobuchi, Fei Liu, Tetsuo Miura, Yoichiro Nakai, Mitugi Yasuda, Masako Shiba, Takahiro Horie, Sakae Amagaya, Norifumi Kawada, Hitoshi Hori, Susumu Ito
Journal: Hepatology (1999)

It has been shown that lipid peroxidation is associated with hepatic fibrosis and stellate cell activation. Sho–saiko–to (TJ–9) is an herbal medicine, which is commonly used to treat chronic hepatitis in Japan, although the mechanism by which TJ–9 protects against hepatic fibrosis is not known. As a result, we assayed the preventive and therapeutic effects of TJ–9 on experimental hepatic fibrosis, induced in rats by dimethylnitrosamine (DMN) or pig serum (PS), and on rat stellate cells and hepatocytes in primary culture, and assessed the antioxidative activities and the active components of TJ–9. Male Wistar rats were given a single intraperitoneal injection of 40 mg/kg DMN or 0.5 mL PS twice weekly for 10 weeks. In each model, rats were fed a basal diet throughout, or the same diet, which also contained 1.5% TJ–9, for 2 weeks before treatment or for the last 2 weeks of treatment. TJ–9 suppressed the induction of hepatic fibrosis, increased hepatic retinoids, and reduced the hepatic levels of collagen and malondialdehyde (MDA), a production of lipid peroxidation. Immunohistochemical examination showed that TJ–9 reduced the deposition of type I collagen and the number of α–smooth muscle actin (α–SMA) positive–stellate cells in the liver and inhibited, not only lipid peroxidation in cultured rat hepatocytes that were undergoing oxidative stress, but also the production of type I collagen, α–SMA expression, cell proliferation, and oxidative burst in cultured rat stellate cells. In addition, TJ–9 inhibited Fe 2+ /adenosine 5′–diphosphate–induced lipid peroxidation in rat liver mitochondria in a dose–dependent manner and showed radical scavenging activity. Among the active components of TJ–9, baicalin and baicalein were found to be mainly responsible for the antioxidative activity. These findings suggest that Sho–saiko–to (TJ–9) functions as a potent antifibrosuppressant by inhibition of lipid peroxidation in hepatocytes and stellate cells in vivo .
Role of<scp>l</scp>-Selectin in Leukocyte Sequestration in Lung Capillaries in a Rabbit Model of Endotoxemia
Authors: WOLFGANG M. KUEBLER, JOERG BORGES, AXEL SCKELL, GERHARD E. H. KUHNLE, KARE BERGH, KONRAD MESSMER, ALWIN E. GOETZ
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

After a variety of pathophysiologic stimuli, neutrophils accumulate in lung capillaries and contribute to the pathogenesis of acute lung injury. Lung neutrophil sequestration has previously been attributed to mechanical retention of stiffened neutrophils, but l-selectin-mediated leukocyte/endothelial interaction may be an essential step. We investigated the effect of the anti-l-selectin antibody HuDreg 200 on leukocyte sequestration and microhemodynamics in alveolar capillaries in a model of acute endotoxemia. We used in vivo fluorescence microscopy to analyze kinetics of fluorescently labeled red and white blood cells in alveolar capillary networks of the rabbit lung. Investigations were performed over 2 h after an intravenous infusion of 0.2 ml/kg body weight (bw) NaCl, 2 mg/kg bw HuDreg 200, 20 μ g/kg bw lipopolysaccharide (LPS) of Escherichia coli 0111:B4, or the combination of HuDreg 200 and LPS, respectively. Infusion of LPS induced leukocyte sequestration in alveolar capillaries, which was accompanied by a reduction of alveolar capillary perfusion and functional capillary density. These effects could be completely blocked by pretreatment of animals with HuDreg 200. We conclude that l-selectin-mediated leukocyte/endothelial interaction is a necessary prerequisite for leukocyte sequestration in alveolar capillaries in this model. Impaired alveolar capillary perfusion appeared to result directly from capillary leukocyte sequestration. Kuebler WM, Borges J, Sckell A, Kuhnle GEH, Bergh K, Messmer K, Goetz AE. Role of l-selectin in leukocyte sequestration in lung capillaries in a rabbit model of endotoxemia.
Enforced adenoviral vector-mediated expression of HOXB4 in human umbilical cord blood cd34+ cells promotes myeloid differentiation but not proliferation
Authors: Ann C.M Brun, Xiaolong Fan, Jon Mar Björnsson, R.Keith Humphries, Stefan Karlsson
Journal: Molecular Therapy (2003)

Retroviral overexpression of the transcription factor HOXB4 results in a rapid increase in proliferation of murine hematopoietic stem cells both in vivo and in vitro. Therefore, we asked whether transient overexpression of HOXB4 would increase proliferation of human primitive hematopoietic progenitors. Transient overexpression of HOXB4 was generated in umbilical cord blood (CB) CD34(+) cells by a recombinant adenovirus (AdHOXB4) expressing HOXB4 together with the enhanced green fluorescent protein (GFP). Transduced, GFP(+) cells were cultured in serum-free medium containing cytokines that primarily support the growth of primitive hematopoietic progenitors. In contrast to previous findings using retroviral overexpression of HOXB4, we did not observe any increase in proliferation of primitive progenitors or increased colony formation of clonogenic progenitors, including progenitor progeny from long-term culture-initiating cells following adenoviral vector overexpression of HOXB4 in CB CD34(+) cells. However, enforced expression of HOXB4 by the adenoviral vector significantly increased myeloid differentiation of primitive hematopoietic progenitors. Since retroviral vectors generate low and continuous levels of transgene expression in contrast to the high, transient levels generated by the adenoviral vector, our findings suggest that the high levels of HOXB4 expression generated by AdHOXB4 in human CB CD34(+) cells direct the cells toward a myeloid differentiation program rather than increased proliferation.
Superficial collections of fluid tophaceous material as clinical presentation of anorexia nervosa
Authors: C Garcia-Porrua
Journal: Annals of the Rheumatic Diseases (2005)

hydrocephalus (fig 1).Because of the hydrocephalus, it was neurologically advisable not to perform a cerebrospinal fluid puncture.There was no indication of tuberculosis (chest x ray examination, tuberculin test, sputum culture) or any other infection.The neoplasia investigation was also negative.An anamnestic investigation showed that there was no need to use ibuprofen or sulindac.When the situation became life threatening we initiated immunosuppressive treatment with cyclophosphamide (100 mg/day), as well as intravenous steroids (100 mg) initially.The initial intravenous cortisone treatment relieved the headache symptoms.Follow up examinations for up to 1 year (every 3 months) showed remission of clinical and MRI findings with this treatment (fig 2).Stable partial remission occurred after 8 months, and oral administration of cyclophosphamide was stopped.Treatment to preserve remission was changed to azathioprine (100 mg).The prednisone dose was finally reduced to 5 mg.
Human Cd4+ T Lymphocytes Consistently Respond to the Latent Epstein-Barr Virus Nuclear Antigen Ebna1
Authors: Christian Münz, Kara L. Bickham, Marion Subklewe, Ming L. Tsang, Ann Chahroudi, Michael G. Kurilla, Dan Zhang, Michael O'Donnell, Ralph M. Steinman
Journal: The Journal of Experimental Medicine (2000)

The Epstein-Barr virus (EBV)-encoded nuclear antigen EBNA1 is critical for the persistence of the viral episome in replicating EBV-transformed human B cells. Therefore, all EBV-induced tumors express this foreign antigen. However, EBNA1 is invisible to CD8(+) cytotoxic T lymphocytes because its Gly/Ala repeat domain prevents proteasome-dependent processing for presentation on major histocompatibility complex (MHC) class I. We now describe that CD4(+) T cells from healthy adults are primed to EBNA1. In fact, among latent EBV antigens that stimulate CD4(+) T cells, EBNA1 is preferentially recognized. We present evidence that the CD4(+) response may provide a protective role, including interferon gamma secretion and direct cytolysis after encounter of transformed B lymphocyte cell lines (B-LCLs). Dendritic cells (DCs) process EBNA1 from purified protein and from MHC class II-mismatched, EBNA1-expressing cells including B-LCLs. In contrast, B-LCLs and Burkitt's lymphoma lines likely present EBNA1 after endogenous processing, as their capacity to cross-present from exogenous sources is weak or undetectable. By limiting dilution, there is a tight correlation between the capacity of CD4(+) T cell lines to recognize autologous B-LCL-expressing EBNA1 and DCs that have captured EBNA1. Therefore, CD4(+) T cells can respond to the EBNA1 protein that is crucial for EBV persistence. We suggest that this immune response is initiated in vivo by DCs that present EBV-infected B cells, and that EBNA1-specific CD4(+) T cell immunity be enhanced to prevent and treat EBV-associated malignancies.
Tai Chi and Postural Stability in Patients with Parkinson's Disease
Authors: Fuzhong Li, Peter Harmer, Kathleen Fitzgerald, Elizabeth Eckstrom, Ronald Stock, Johnny Galver, Gianni Maddalozzo, Sara S. Batya
Journal: New England Journal of Medicine (2012)

Patients with Parkinson's disease have substantially impaired balance, leading to diminished functional ability and an increased risk of falling. Although exercise is routinely encouraged by health care providers, few programs have been proven effective.We conducted a randomized, controlled trial to determine whether a tailored tai chi program could improve postural control in patients with idiopathic Parkinson's disease. We randomly assigned 195 patients with stage 1 to 4 disease on the Hoehn and Yahr staging scale (which ranges from 1 to 5, with higher stages indicating more severe disease) to one of three groups: tai chi, resistance training, or stretching. The patients participated in 60-minute exercise sessions twice weekly for 24 weeks. The primary outcomes were changes from baseline in the limits-of-stability test (maximum excursion and directional control; range, 0 to 100%). Secondary outcomes included measures of gait and strength, scores on functional-reach and timed up-and-go tests, motor scores on the Unified Parkinson's Disease Rating Scale, and number of falls.The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion (between-group difference in the change from baseline, 5.55 percentage points; 95% confidence interval [CI], 1.12 to 9.97; and 11.98 percentage points; 95% CI, 7.21 to 16.74, respectively) and in directional control (10.45 percentage points; 95% CI, 3.89 to 17.00; and 11.38 percentage points; 95% CI, 5.50 to 17.27, respectively). The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach. Tai chi lowered the incidence of falls as compared with stretching but not as compared with resistance training. The effects of tai chi training were maintained at 3 months after the intervention. No serious adverse events were observed.Tai chi training appears to reduce balance impairments in patients with mild-to-moderate Parkinson's disease, with additional benefits of improved functional capacity and reduced falls. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00611481.).
Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial
Authors: Robert Pickard, Thomas Lam, Graeme MacLennan, Kath Starr, Mary Kilonzo, Gladys McPherson, Katie Gillies, Alison McDonald, Katherine Walton, Brian Buckley, Cathryn Glazener, Charles Boachie, Jennifer Burr, John Norrie, Luke Vale, Adrian Grant, James N'Dow
Journal: The Lancet (2012)
Clinical and prognostic heterogeneity of C and D GOLD groups
Authors: Alvar Agustí, Stephen Rennard, Lisa D. Edwards, William MacNee, Emiel Wouters, Bruce Miller, Ruth Tal-Singer, Hana Mullerova, Bartolomé Celli
Journal: European Respiratory Journal (2015)

"High risk" groups for exacerbations of chronic obstructive pulmonary disease (COPD) in the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposal ( i.e. groups C and D) [1] include: patients with a forced expiratory volume in 1 s FEV1 <50% reference and <2 exacerbations year-1 (subgroups C1 and D1); patients with ≥2 exacerbations·year-1 and an FEV1 ≥50% reference (subgroups C2 and D2); and patients with both FEV1 <50% ref. and ≥2 exacerbations·year-1 (subgroups C3 and D3) [2–5]. We hypothesised that these high-risk subgroups will differ in other clinical, functional and biological characteristics and will be associated with different long-term outcomes. We explored this hypothesis in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) cohort [6, 7]. The results of this study show that "high-risk" COPD patients (GOLD groups C and D) are highly heterogeneous <http://ow.ly/LTMOv> Authors thank all participants for their willingness to contribute to advance medical science in the field of COPD.
Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice
Authors: Tomonori Kaifu, Jin Nakahara, Masanori Inui, Kenichi Mishima, Toshihiko Momiyama, Mitsuji Kaji, Akiko Sugahara, Hisami Koito, Azusa Ujike-Asai, Akira Nakamura, Kiyoshi Kanazawa, Kyoko Tan-Takeuchi, Katsunori Iwasaki, Wayne M. Yokoyama, Akira Kudo, Michihiro Fujiwara, Hiroaki Asou, Toshiyuki Takai
Journal: Journal of Clinical Investigation (2003)

Deletions in the DAP12 gene in humans result in Nasu-Hakola disease, characterized by a combination of bone fractures and psychotic symptoms similar to schizophrenia, rapidly progressing to presenile dementia. However, it is not known why these disorders develop upon deficiency in DAP12, an immunoreceptor signal activator protein initially identified in the immune system. Here we show that DAP12-deficient (DAP12(-/-)) mice develop an increased bone mass (osteopetrosis) and a reduction of myelin (hypomyelinosis) accentuated in the thalamus. In vitro osteoclast induction from DAP12(-/-) bone marrow cells yielded immature cells with attenuated bone resorption activity. Moreover, immature oligodendrocytes were arrested in the vicinity of the thalamus, suggesting that the primary defects in DAP12(-/-) mice are the developmental arrest of osteoclasts and oligodendrocytes. In addition, the mutant mice also showed synaptic degeneration, impaired prepulse inhibition, which is commonly observed in several neuropsychiatric diseases in humans including schizophrenia, and aberrant electrophysiological profiles in the thalami. These results provide a molecular basis for a unique combination of skeletal and psychotic characteristics of Nasu-Hakola disease as well as for schizophrenia and presenile dementia.
Yellow nails, lymphoedema, and pleural effusions.
Authors: P A Emerson
Journal: Thorax (1966)

Schild regressions in isolated tissues are powerful tools for receptor classification only if they yield equillibrium dissociation constants of antagonists which can, in turn, occur only when measurements are made under equillbrium conditions. Regressions with slopes different from unity of nonlinear regressions indicate noncompliance to equillbrium. This paper describes a condition whereby Schild regressions apparently comply with criteria which signify equillbrium conditions but in fact are regressions obtained at nonequilibrium steady states yielding significant underestimations of the potency of the antagonist. Specifically, if agonist uptake processes in isolated tissues are inhibited by uptake inhibitors with receptor blocking properties, the experimental data and a theoretical model suggest that the resulting Schild regression will be linear, have a slope of unity and be shifted to the right of the true Schild regression, thereby significantly underestimating antagonist potency. Experiments with the effects of neuronal uptake inhibition (with desmethylimipramine and amitriptylene) on the phentolamine-inhibition of norepinephrine responses in rat anococcygeus muscle and the effects of metanephrine on the propranolol-inhibition of isoproterenol relaxation of guinea-pig trachea provided data to compare to a theoretical model. The data and the model help define the selectivity of the uptake inhibitor fo uptake over receptors needed to achieve steady states approaching true equilibrium, a condition required for satisfactory estimation of antagonist potency.
Biomarkers and Response to Bevacizumab—Response
Authors: Fiona Collinson, Michelle Hutchinson, Rachel A. Craven, David A. Cairns, Zougman Alexandre, Tobias C. Wind, Narinder Gahir, Michael P. Messenger, Sharon Jackson, Douglas Thompson, Cybil Adusei, Jonathan Ledermann, Geoffrey Hall, Gordon C. Jayson, Peter J. Selby, Rosamonde E. Banks
Journal: Clinical Cancer Research (2014)

We wish to thank Cremolini and colleagues for their interesting letter that highlights their previous finding that VEGFR-2 may be a predictive marker for benefit from bevacizumab therapy. Their data are derived from the setting of postprogression bevacizumab in advanced colorectal cancer, and there
Absence of Calsequestrin 2 Causes Severe Forms of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Alex V. Postma, Isabelle Denjoy, Theo M. Hoorntje, Jean-Marc Lupoglazoff, Antoine Da Costa, Pascale Sebillon, Marcel M.A.M. Mannens, Arthur A.M. Wilde, Pascale Guicheney
Journal: Circulation Research (2002)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmogenic disorder characterized by syncopal events and sudden cardiac death at a young age during physical stress or emotion, in the absence of structural heart disease. We report the first nonsense mutations in the cardiac calsequestrin gene, CASQ2, in three CPVT families. The three mutations, a nonsense R33X, a splicing 532+1 G>A, and a 1-bp deletion, 62delA, are thought to induce premature stop codons. Two patients who experienced syncopes before the age of 7 years were homozygous carriers, suggesting a complete absence of calsequestrin 2. One patient was heterozygous for the stop codon and experienced syncopes from the age of 11 years. Despite the different mutations, there is little phenotypic variation of CPVT for the CASQ2 mutations. Of the 16 heterozygous carriers of these various mutations, 14 were devoid of clinical symptoms or ECG anomalies, whereas 2 of them had ventricular arrhythmias at ECG on exercise tests. In line with this, the diagnosis of the probands was difficult because of the absence of a positive family history. In conclusion, these additional three CASQ2 CPVT families suggest that CASQ2 mutations are more common than previously thought and produce a severe form of CPVT. The full text of this article is available at http://www.circresaha.org.
Suppression of lipopolysaccharide-induced nitric oxide synthase expression by platelet-activating factor receptor antagonists in the rat liver and cultured rat kupffer cells
Authors: Shamimunisa B. Mustafa, Brent D. Flickinger, Merle S. Olson
Journal: Hepatology (1999)

Excessive nitric oxide (NO) generated by hepatic cells in response to lipopolysaccharide (LPS) and inflammatory substances ( e.g. , platelet-activating factor [PAF]) is a key contributor to the pathophysiological outcomes observed in the liver during sepsis. In rats subjected to liver-focused endotoxemia, inducible nitric oxide synthase (iNOS) levels in the intact liver were elevated by 6 hours; cell-specific expression of iNOS messenger RNA (mRNA) was Kupffer cells (KCs), endothelial cells, and hepatocytes. Elevated serum alanine transaminase (ALT) levels at 6 hours confirmed hepatic damage. Pretreatment of endotoxemic rats with PAF receptor antagonists BN 50739 or WEB 2170 reduced serum ALT and iNOS mRNA levels in the intact liver. Pretreatment of cultured KCs with BN 50739 or WEB 2170 inhibited both LPS and PAF-induced iNOS mRNA formation. In addition, LPS-induced iNOS protein levels in KCs pretreated with BN 50739 or WEB 2170 were decreased. Exposure of KCs to either LPS or PAF caused the translocation of the p65 subunit of nuclear factor kappa B (NF-κB) into the nucleus and this process was attenuated by BN 50739 and WEB 2170. There was concomitant inhibition of LPS-dependent degradation of the inhibitory protein IκBα and increase in intracellular Ca 2+ in KC treated with BN 50739 or WEB 2170. Also, in KCs, LPS was able to induce iNOS mRNA expression independent of CD14. This response was inhibited by pretreatment of KCs with either BN 50739 or WEB 2170. Our findings indicate that PAF receptor antagonists convey protection against hepatocellular injury accompanied by a decrease in nitric oxide (NO) formation in the livers of endotoxemic rats.
Bupropion and other non-nicotine pharmacotherapies
Authors: Elin Roddy
Journal: BMJ (2004)

Although nicotine replacement has been the first line drug treatment for smoking cessation for many years, other drugs of proved efficacy are also now available. Foremost among these is bupropion (marketed as Zyban). Bupropion was developed and initially introduced in the United States as an antidepressant but was subsequently noted to reduce the desire to smoke cigarettes and shown in clinical trials to be effective in smoking cessation.

Bupropion is an atypical antidepressant structurally similar to diethylpropion, an appetite suppressant. The mechanism of the antidepressant effect of bupropion is not fully understood, but bupropion inhibits reuptake of dopamine, noradrenaline, and serotonin in the central nervous system, is a non-competitive nicotine receptor antagonist, and at high concentrations inhibits the firing of noradrenergic neurons in the locus caeruleus.

It is not clear which of these effects accounts for the antismoking activity of the drug, but inhibition of the reductions in levels of dopamine and noradrenaline levels in the central nervous system that occur in nicotine withdrawal is likely to be important. The antismoking effect of bupropion does not seem to be related to the antidepressant effect as bupropion is equally effective as a smoking cessation therapy in smokers with and without depression.



Effects of bupropion on the central nervous system



When given in association with intensive behavioural support, bupropion is as effective as nicotine replacement therapy (NRT), and like NRT, leads to a near doubling of the smoking cessation rate, achieving long term abstinence in 19% of smokers who use it to quit.

The effectiveness of bupropion in conjunction with less intensive levels of behavioural support has not been tested in …
Sledging related spinal injuries and fracture patterns: a report on five cases
Authors: S Basu, N K Makwana, R Khazim
Journal: British Journal of Sports Medicine (1999)

The cases are reported of five patients who presented to The Queens Medical Centre, Nottingham after a sledging accident. All five patients presented consecutively during the first weekend in 1997 having sustained the accident in the same public park. The mechanism and subsequent fracture type is described for each. These injuries are preventable, and increasing public awareness of the risk of sledging in public places may reduce the incidence.