tbuckley/cabot-search huggingface dataset:
Interpretation of treatment changes in 6-minute walk distance in patients with COPD
Authors: M. A. Puhan, M. J. Mador, U. Held, R. Goldstein, G. H. Guyatt, H. J. Schünemann
Journal: European Respiratory Journal (2008)

There is uncertainty about the interpretation of changes in the 6-min walk distance (6MWD) in chronic obstructive pulmonary disease (COPD) patients and whether the minimal important difference (MID) for this useful outcome measure exists. Data were used from nine trials enrolling a wide spectrum of COPD patients with 6MWD at baseline and follow-up and used to determine threshold values for important changes in 6MWD using three distribution-based methods. Anchor-based methods to determine a MID were also evaluated. Data were included of 460 COPD patients with a mean± sd forced expiratory volume in one second (FEV 1 ) of 39.2±14.1% predicted and 6MWD of 361±112 m at baseline. Threshold values for important effects in 6MWD were between 29 and 42 m, respectively, using the empirical rule effect size and the standardised response mean. The threshold value was 35 m (95% confidence interval 30–42 m) based on the standard error of measurement. Correlations of 6MWD with patient-reported anchors were too low to provide meaningful MID estimates. 6-min walk distance should change by ∼35 m for patients with moderate to severe chronic obstructive pulmonary disease in order to represent an important effect. This corresponds to a 10% change of baseline 6-min walk distance. The low correlations of 6-min walk distance with patient-reported anchors question whether a minimal important difference exists for the 6-min walk distance.
Treatment of Parkinson Disease
Authors: Daniel Tarsy
Journal: JAMA (2012)

In early stages, Parkinson disease typically begins with asymmetric or unilateral motor symptoms due to combinations of mild bradykinesia, rigidity, and tremor. In most cases, with progression, signs of more generalized bradykinesia appear, which include facial masking, reduced voice volume, and slowing of activities of daily living. In more advanced Parkinson disease, other disabling manifestations may follow, such as impaired balance, gait freezing, falls, speech disturbance, and cognitive impairment. Levodopa is the most effective medical treatment for Parkinson disease. However, motor complications uniquely related to levodopa treatment may emerge that may be difficult to manage. These include fluctuating levodopa responses and involuntary movements and postures known as dyskinesia and dystonia. Medication adjustments are usually effective, but in some cases surgical intervention with deep brain stimulation becomes necessary to alleviate motor complications. The case of Mr L, a man with an 11-year history of Parkinson disease, illustrates these emerging motor complications and the manner in which they may be managed both medically and surgically.
Abstract 1999: Aberrant expression of HOX transcript in ovarian carcinoma
Authors: Kevin J. Thompson, G. Kirk Southern, Zahra Bahrani-Mostafavi, M. Taghi Mostafavi, David L. Tait
Journal: Cancer Research (2010)

Abstract Ovarian cancer is a complex disease phenotype that is challenging to diagnose, primarily because patients tend to remain non-symptomatic until after metastasis has initiated. For those individuals identified early in the disease progression the survival rate is promising, but for the majority, diagnosed late, the 5-year survival rate is dismal. Our eventual goal is to identify a panel of circulating markers that distinguish early onset of the disease. In particular, we have examined the homeobox (HOX) transcript family of genes, known to be involved in cancer progression. These genes are intrinsic cellular factors regulating positional development during embryogenesis and bone formation, and are documented upstream regulators of 16 signaling pathways. Methods: The tissue-specific gene expression from 35 human ovarian tissue samples, using Affymetrix GeneFocusTM microarrays was examined. The microarray analysis was performed on tissues from 8 normal ovaries, 12 benign and 15 malignant epithelial tumors. Microarray output was processed with a stringent data cleansing pipeline to ensure the investigated genes can be unambiguously interpreted. Results: ANOVA analysis reveals a significant alteration in the HOX expression profiles between ovarian tumorous and non-tumorous tissues. While several members of the homeobox gene family are reported to be differentially expressed, we observed a significant shift from healthy HOXC6 expression to an aberrant HOXB2 expression. Whereas non-tumorous tissue demonstrated elevated levels of HOXC6 mRNA transcript, the malignant tissues demonstrated elevated levels of HOXB2 transcript. A possible consequence of the aberrant HOX expression levels is to increase the production and hence the paracrine signaling of osteopontin (SPP1), which is reported to be negatively regulated by a SMAD-HOX interaction. Osteopontin has been correlated to cancer progression, metastasis, and patient survival. We observed a significant correlation between elevated SPP1 expression and the observed HOX disregulation. Conclusion: We demonstrated a correlation between malignant associated SPP1 upregulation and aberrant HOX transcript regulation. These alterations in transcript and protein levels are significant to the epithelial microenvironment. These results have been validated by qRT-PCR and IHC and confirmed with additional patient specimens. The correlation between these two events needs to be further investigated as to their significance in the progression of the disease and as potential candidate biomarkers for ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1999.
Comparison of occlusion pressure and ventilatory responses.
Authors: D H Lederer, M D Altose, S G Kelsen, N S Cherniack
Journal: Thorax (1977)

The airway pressure 100 msec after the onset of an inspiratory effort against a closed airway (P100, occlusion pressure) is theoretically a more accurate index of respiratory neuron motor output than ventilation. Occlusion pressure and ventilation responses to hypercapnia were compared in repeated trials in 10 normal subjects while in the seated and supine positions. During progressive hypercapnia changes in P100 were also compared to changes in tidal volume and inspiratory airflow. These studies show that occlusion pressure increases linearly with hypercapnia in both sitting and supine subjects. Changing from the seated to the supine position, or vice versa, had no significant effect on either ventilation or occlusion pressure responses to CO2. Correlations between P100 and ventilation or airflow rate were significantly higher than correlations between P100 and tidal volume or breathing frequency. Intermittent random airway occlusion had no effect on either ventilation or pattern of breathing during hypercapnia. Occlusion pressure responses were no less variable than ventilation responses in groups of subjects whether studied seated or supine. However, maintenance of a constant moderate breathing frequency (20 breaths per minute) reduced the interindividual variability in ventilation and occlusion pressure responses to hypercapnia.
Activation of Barium-Sensitive Inward Rectifier Potassium Channels Mediates Remote Dilation of Coronary Arterioles
Authors: Richard J. Rivers, Travis W. Hein, Cuihua Zhang, Lih Kuo
Journal: Circulation (2001)

Background Conducted vasodilation seems to be critical for the functional distribution of blood flow in the skeletal muscle microcirculation. However, this vasoregulatory phenomenon has not been documented in the coronary microcirculation, and its underlying mechanism remains elusive. Because potassium ions are potent metabolic vasodilators in the heart, by activating vascular inward rectifier K + (K ir ) channels, we tested the hypothesis that coronary arterioles exhibit remote vasodilation through activation of this type of channel. Methods and Results Porcine coronary arterioles were isolated, cannulated, and pressurized for in vitro study. Vessels dilated concentration-dependently to extraluminal KCl (5 to 20 mmol/L), bradykinin, adenosine, pinacidil, and sodium nitroprusside. A K ir channel blocker, BaCl 2 (30 μmol/L), inhibited vasodilatory responses to KCl and bradykinin but not to adenosine, pinacidil, or nitroprusside. In a flow chamber, localized administration of bradykinin, adenosine, and KCl to the downstream end of the arterioles caused ≈80% dilation at the site of drug application (local site) and also produced 30% to 60% dilation at the upstream end of arterioles (remote site). Nitroprusside produced a similar dilation at the local site but failed to initiate remote vasodilation. In the presence of Ba 2+ , adenosine still dilated the local site, but the local dilations to bradykinin and KCl and the remote dilations to adenosine, bradykinin, and KCl were inhibited. Conclusions We demonstrated that some modes of local vasodilation can be conducted to remote sites in coronary arterioles and that local and remote dilations can occur through different vasodilatory mechanisms. Activation of K ir channels seems critical for some agonist-induced local vasodilations and also for the initiation and/or transmission of signals causing remote vasodilation.
Inspiratory Muscle Training Improves Blood Flow to Resting and Exercising Limbs in Patients With Chronic Heart Failure
Authors: Gaspar R. Chiappa, Bruno T. Roseguini, Paulo J.C. Vieira, Cristiano N. Alves, Angela Tavares, Eliane R. Winkelmann, Elton L. Ferlin, Ricardo Stein, Jorge P. Ribeiro
Journal: Journal of the American College of Cardiology (2008)
Market penetration of new drugs. Compare Britain with other national markets.
Authors: J P Griffin
Journal: BMJ (1993)

Coupled with the editorial by Tony Noble arguing against the routine postnatal examination at six weeks,5 this concern about initiating contra- ception before the earliest likely ovulation suggests that the optimum time for a routine postnatal appointment is at or just before four weeks.This should be seen as a safety net for contraception, since the subject is much better raised during the third trimester, at around 30 weeks' gestation, and discussed again with the woman during the post- partum home visit at around 10 days.I have suggested to both the Royal College of Obstetri- cians and Gynaecologists and the Royal College of General Practitioners that these recommendations should be discussed with a view to becoming the colleges' official policy.
Topical Therapy for Acne
Authors: John W. Melski, Kenneth A. Arndt
Journal: New England Journal of Medicine (1980)

There have been major advances in the understanding and treatment of acne in recent years.1 , 2 Since most patients can be successfully managed with topical agents alone, thus avoiding systemic exposure to potentially toxic agents, review of the current approach to topical treatment is warranted. In this brief review, agents are categorized according to their presumed mechanisms of action: sebostatics, comedolytics, exfoliants, bacteriostatics, anhydrotics, and antiinflammatory agents.SebostaticsSebum is a mixture of the products of follicular keratinization and the secretions of the sebaceous gland.3 It has been called the "fuel" of acne because in the anaerobic depths of the sebaceous . . .
EXPERIMENTS ON THE RELATIONSHIP BETWEEN THE NERVOUS SYSTEM AND HAIR GROWTH*
Authors: L. BALUS
Journal: British Journal of Dermatology (1961)

Journal Article EXPERIMENTS ON THE RELATIONSHIP BETWEEN THE NERVOUS SYSTEM AND HAIR GROWTH Get access L. BALUS L. BALUS Institute of Therapeutics, Sos. Stefan Cel Mare 89, Bucharest, Rumania Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 2, 1 February 1961, Pages 69–77, https://doi.org/10.1111/j.1365-2133.1961.tb14410.x Published: 01 February 1961
Rat renal epinephrine synthesis.
Authors: M G Ziegler, B Kennedy, H Elayan
Journal: Journal of Clinical Investigation (1989)

Rats that underwent adrenal demedullation had a 93% decrease in plasma epinephrine (E) levels, but did not decrease their renal E. Even further treatment with 6-hydroxydopamine and reserpine failed to lower renal E levels. Similarly, urine E levels failed to decrease after adrenal demedullation and renal denervation. There is a renal E-synthesizing enzyme that differs from adrenal phenylethanolamine-N-methyltransferase (PNMT) in that it is only weakly inhibited by SKF 29661 and can synthesize epinine from dopamine, while adrenal PNMT does so poorly. When an adrenalectomized rat received intravenous [3H]methionine, its urine contained radioactivity that appeared to be [3H]E, with small amounts of [3H]epinine. However, after [3H]methionine was infused in the renal artery, the major product in urine appeared to be [3H]epinine, with a small amount of [3H]E. Adrenal demedullation induced renal E synthesis, but denervation returned the rate of renal E synthesis to control values. The combination of adrenal demedullation, 6-hydroxydopamine, and reserpine treatments increased renal E-forming activity to 350% of control. We conclude that appreciable portions of renal and urinary E are synthesized in the kidney by an enzyme distinct from PNMT. The enzyme is induced by some treatments that lower E and NE levels.
Abstract 424: Amplification of <i>OCT4</i>-pseudogene <i>POU5F1B</i> is a poor prognostic factor in gastric cancer
Authors: Hidetoshi Hayashi, Tokuzo Arao, Kazuko Matsumoto, Tomoyuki Nagai, Hideharu Kimura, Marco A. De Velasco, Yoshihiko Fujita, Yasuhide Yamada, Isamu Okamoto, Kazuhiko Nakagawa, Kazuto Nishio
Journal: Cancer Research (2012)

Abstract POU5F1B is a processed pseudogene and highly homologous to OCT4, which is crucial in the regulation of pluripotency during embryonic development of embryonic stem cell. Since recent reports have demonstrated that POU5F1B mRNA is expressed in several types of cancer tissue, their oncogenic role remains unclear. Here we further investigated that the biological function of POU5F1B. We found that POU5F1B, which is located side by side with MYC gene on 8q24, was frequently involved in MYC amplicons in gastric cancer. Gene copy number analysis revealed that POU5F1B and MYC genes were highly amplified in several gastric cancer cell lines. In addition, the POU5F1B mRNA expression levels were certainly upregulated using PCR and sequencing analysis. Then, we hypothesized that gene amplification of POU5F1B mediates some biological roles in cancer cells. We introduced POU5F1B gene into SNU-16 or TU-KATO III gastric cancer cell lines and established stable cell lines SNU-16/GFP, /POU5F1B, TU-KATOIII/GFP and /POU5F1B. Overexpression of POU5F1B clearly decreased cellular proliferation and inhibited colony forming ability. Interestingly, we found that the increased gene copy number of POU5F1B is a significant poor prognostic factor in 180 cases of gastric cancer. We are now under investigation for its oncogenic properties, gene expression changes by microarray analysis and chemoresistance using these stable POU5F1B transfectants. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 424. doi:1538-7445.AM2012-424
Attenuation of Flightless I, an actin-remodelling protein, improves burn injury repair via modulation of transforming growth factor (TGF)-β1 and TGF-β3
Authors: D.H. Adams, N. Ruzehaji, X.L. Strudwick, J.E. Greenwood, H.D. Campbell, R. Arkell, A.J. Cowin
Journal: British Journal of Dermatology (2009)

The pathophysiological mechanisms involved in burn injury repair are still not fully understood but include processes involving cellular proliferation, migration and adhesion. The actin cytoskeleton is intricately involved in these key wound repair processes. Flightless I (Flii), an actin-remodelling protein and transcriptional regulator, is an important regulator of wound healing.To investigate the function of Flii gene expression in burn injury repair.Partial-thickness scald wounds were created on Flii heterozygous (Flii(+/-)), wild-type (WT) and Flii transgenic (Flii(Tg/+)) mice. Burns were assessed using histology and immunohistochemistry, real-time quantitative polymerase chain reaction and biochemical analysis.Flii expression, while upregulated in burn injuries, was significantly lower in the wounds of Flii(+/-) vs. WT vs. Flii(Tg/+) mice and healing was improved in Flii(+/-) mice with their burns healing faster than WT and Flii(Tg/+). Pro-scarring transforming growth factor (TGF)-beta1 protein and gene expression were reduced in Flii(+/-) burns while antiscarring TGF-beta3 was significantly elevated. Anti-alpha-smooth muscle actin (alpha-SMA) was decreased in Flii(+/-) burns suggesting a decrease in contractile myofibroblasts in the developing scars. Although Flii is primarily a nuclear and cytoplasmic protein it is also released by wounded cells. Intradermal injection of Flii-neutralizing antibodies (FliAbs) to WT burn wounds significantly improved their healing, indicating a potential novel approach for treating burns. Decreased TGF-beta1 and elevated TGF-beta3 expression were observed in FliAb-treated burns, which may contribute to their observed improvement in healing.Strategies aimed at reducing Flii expression, for example using neutralizing antibodies, may lead to improved burn outcomes.
What are the complications of influenza and can they be prevented? Experience from the 1989 epidemic of H3N2 influenza A in general practice.
Authors: A M Connolly, R L Salmon, B Lervy, D H Williams
Journal: BMJ (1993)

OBJECTIVES--In an epidemic: to measure the incidence and risk of complications of influenza; to determine the effect of pre-existing disease on complications; to estimate vaccine uptake and efficacy. DESIGN--Case-control study. SETTING--Primary care: two group practices. SUBJECTS--342 of the 395 cases of clinically diagnosed influenza reported to the general practice surveillance of infectious diseases scheme of the Public Health Laboratory Service during the 1989 epidemic, and 342 age and sex matched controls. INTERVENTIONS--Examination of records. MAIN OUTCOME MEASURES--Documented recognised complications; hospital admission; previous vaccination. RESULTS--Of 15 recognised complications, bronchitis was the commonest (rate 190.1/1000 cases) and significantly commoner in cases (summary odds ratio 9.7) after adjusting for higher consultation rates (mean 6.1 per annum v 4.2 among controls; p &lt; 0.0001). No deaths were recorded. The risk of bronchitis complicating influenza was higher in patients with pre-existing illnesses regarded as an indication for vaccination (odds ratio 3.3; p &lt; 0.0001). Observed vaccination efficacy in those with pre-existing illnesses and in elderly subjects was high (63% and 77% respectively) but uptake was low (4.5% and 6.1% respectively). CONCLUSIONS--Bronchitis complicates about one fifth of all cases of influenza presenting to general practitioners. Patients with pre-existing illnesses regarded as an indication for vaccination are particularly at risk. Vaccine uptake is extremely low, precluding an unequivocal demonstration of a protective effect.
A Controlled Trial of Isoniazid in Persons with Anergy and Human Immunodeficiency Virus Infection Who Are at High Risk for Tuberculosis
Authors: Fred M. Gordin, John P. Matts, Carol Miller, Lawrence S. Brown, Richard Hafner, Stanley L. John, Mary Klein, Anita Vaughn, C. Lynn Besch, George Perez, Susan Szabo, Wafaa El-Sadr
Journal: New England Journal of Medicine (1997)

Patients with human immunodeficiency virus (HIV) infection and latent tuberculosis are at substantial risk for the development of active tuberculosis. As a public health measure, prophylactic treatment with isoniazid has been suggested for HIV-infected persons who have anergy and are in groups with a high prevalence of tuberculosis.
Environmental Hazards
Authors: Benjamin G. Ferris
Journal: New England Journal of Medicine (1966)

THE electromagnetic spectrum includes radiation over a wide range of energies and a variety of categories, many of which one senses or uses every day. These include microwaves, television and radio waves, heat, light and ultraviolet radiations from the sun. A part of this spectrum, when the energies are sufficiently high, can cause ionization. This includes some ultraviolet, x-rays and cosmic radiations. This presentation is limited mainly to the nonionizing forms of electromagnetic radiation. The characteristics of ionizing radiation have been covered in another article in this series by Dr. John B. Little, in the October 27 issue of the . . .
Highly Efficient Regulation of Gene Expression by Tetracycline in a Replication-Defective Herpes Simplex Viral Vector
Authors: Feng Yao, Christoph Theopold, Daniela Hoeller, Oliver Bleiziffer, Zheming Lu
Journal: Molecular Therapy (2006)

Employing the tetracycline repressor tetR and the wild-type hCMV major immediate-early promoter, we have developed a highly sensitive tetracycline-inducible transcription switch in mammalian cells (T-REx; Invitrogen, Carlsbad, CA, USA). In view of the previous difficulty in achieving regulatable gene expression in recombinant HSV vector systems, we constructed a T-REx-encoding replication-defective HSV-1 recombinant, QR9TO-lacZ, that encodes two copies of the tetR gene controlled by the HSV-1 immediate-early ICP0 promoter and a reporter, the LacZ gene, under the control of the tetO-bearing hCMV major immediate-early promoter. Infection of cells, such as Vero, PC12, and NGF-differentiated PC12 cells, with QR9TO-lacZ led to 300- to 1000-fold tetracycline-regulated gene expression. Moreover, the expression of the LacZ gene by QR9TO-lacZ can be finely controlled by tetracycline in a dose-dependent fashion. Efficiently regulated gene expression can also be achieved in vivo following intracerebral and footpad inoculations in mice. The demonstrated capability of T-REx for achieving high levels of sensitively regulated gene expression in the context of the HSV-1 genome will significantly expand the utility of HSV-based vector systems for studying gene function in the nervous system and delivering regulated gene expression in therapeutic applications, particularly in the treatment of CNS diseases.