tbuckley/cabot-search huggingface dataset:
Abstract 5070: Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) reduces colon cancer cell migration and metastasis
Authors: Ryo Yuge, Yasuhiko Kitadai, Kei Shinagawa, Mieko Onoyama, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama
Journal: Cancer Research (2015)

Abstract Accumulating evidence suggests that a unique set of receptor tyrosine kinases, known as discoidin domain receptors (DDRs), plays a role in cancer progression by regulating the interactions of tumor cells with their surrounding collagen matrix. We investigated the role of DDR1 in the tumor progression of colorectal cancer. We examined the DDR1 mRNA and protein expression levels in a series of human colorectal cancer cell lines by RT-PCR and Western blotting. We also analyzed the DDR1 protein expression in 27 surgical specimens of colorectal cancer by immunohistochemistry. Migration, invasion, and proliferation assays were conducted with a high-content time-lapse assay system in a series of colon cancer cell lines. Nilotinib, a well-known DDR1 inhibitor, and DDR1-silenced colon cancer cells were used for inhibition of DDR1 tyrosine kinase activity. In an in vivo study, we orthotopically implanted KM12SM human colon cancer cells into the cecum of nude mice and administered nilotinib (100 mg/kg/day) by daily oral gavage. After 4 weeks of treatment, primary tumors and metastatic lesions were resected, and specimens were analyzed histologically. DDR1 mRNA and protein expression was observed in the human colon cancer cell lines and in cancer cells of most of the surgical specimens. Colon cancer cell lines KM12SM, KM12c, LoVo, and HT29 exposed to nilotinib (20 μM) showed reduced migration. When incubated with type I collagen, however, these cells showed increased migratory activity. Nilotinib treatment significantly inhibited this effect. The migratory activity of DDR1-silenced cells was not affected by nilotinib treatment. The orthotopic xenografts grew invasively as aggressive tumors with a stromal reaction, but under nilotinib treatment, the stromal reaction was reduced, and tumors grew expansively. In addition, the numbers of lymph node metastases were significantly reduced. Disruption of DDR1 attenuated colon cancer cell migration and led to altered primary tumor morphology and to impaired lymph node metastasis. DDR1 may be a promising therapeutic target in patients with colon cancer. Citation Format: Ryo Yuge, Yasuhiko Kitadai, Kei Shinagawa, Mieko Onoyama, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama. Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) reduces colon cancer cell migration and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5070. doi:10.1158/1538-7445.AM2015-5070
Group of private eye surgeons fined £0.5m for breaching competition law
Authors: Nigel Hawkes
Journal: BMJ (2015)

The United Kingdom’s largest group of eye surgeons has been fined £500 000 (€720 000; $780 000) for breaches of competition law in the first such case brought against UK medical professionals.

Consultant Eye Surgeons Partnership, which represents 37 consultant partnerships and more than 200 consultants, admitted a series of offences between September 2008 and May 2015. These included recommending members not to accept lower fees offered by an insurer, recommending that they charge higher fees to insured patients than to patients who pay themselves, circulating price lists for procedures such as cataract surgery, and …
Pulmonary rehabilitation - an underutilized treatment
Authors: Deepu Cheriamane, Vinod Joshi, Kailash Agarwal, Gopal Purohit, Chainaram Choudhary
Journal: European Respiratory Journal (2014)

PURPOSE:To evaluate a 6 week outpatient pulmonary rehabilitation program in COPD patients.  METHODS:This was a prospective, parallel-group randomized control study of an outpatient pulmonary rehabilitation program in 100 patients with COPD.The active group(n=50) took part in 6 week rehabilitation, with 2 visits/wk to the center [3 h/wk, 1 h education and 2 h exercise] and 2 days/wk exercise schedule at home. The control group(n=50) was reviewed routinely as outpatients and given standard medical treatment. The following evaluations were carried out at study entry and at the end of 6 weeks in both the groups:1)spirometry 2) 6-minutes walking test 6MWT 3) quality of life using SGRQ and 4)BORG dyspnea scale .  RESULTS:89 patients completed the study, 45 patients from the active group (mean age, 59.17±8.65 years; mean FEV1, 1.19±0.37 liter; (51.93±14.09 % ); and 44 patients from the control group( age, 60.11±9.56 years) FEV1 1.12±0.40 liter (49.27±13.34%). No changes in pulmonary function parameters were observed in the active group and the control group at the end of six weeks. Whereas, there were significant changes in the SGRQ score and its components (13.71 improvement) for the patients in active group but not for the patients in control group ( 1.32 improvement ), a significant increase in the mean six minute walk distance was seen in the active group (66.38±9.05m) but not for the patients of the control group ( 6.9±4.60 m), we found a reduction of 3.25 points in the active group BORG Dyspnea scale and no change in the control group .  CONCLUSIONS:A 6 week pulmonary rehabilitation program improves QOL, dyspnea and exercise capacity in COPD patients and should be offered to all COPD patients along with standard medical treatment.
Patients' Views on how to Run Hospital Outpatient Clinics
Authors: F Bishop, F J Matthews, C S J Probert, J Billett, T Battcock, S D Frisby, J F Mayberry
Journal: Journal of the Royal Society of Medicine (1991)

To investigate patients' views and expectations when attending outpatient clinics a questionnaire-based study was performed. The questionnaires asked about appointment systems, continuity of care, staff appearance, chaperons and medical students. Patients wanted fixed appointment times, to see the same doctor on successive visits, for the staff to be formally dressed and to have chaperons during examination. The number of medical students should be restricted especially for women patients. Staff should be sensitive to patients' needs.
Awareness campaign at World COPD Day
Authors: Cecília Pacheco, João Filipe Cruz, Catarina Lacerda, Lurdes Ferreira, João Cunha
Journal: European Respiratory Journal (2013)

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity, affecting 14% of the Portuguese population. The World COPD Day was on November 14th, 2012. At Hospital de Braga was held an awareness campaign.  Objective: To characterize epidemiological, clinical and functional participants in the campaign of World COPD Day.  Methods: Cross-sectional study with a questionnaire and spirometry to all individuals participating in the campaign.  Results: 160 subjects were included, 51% male, mean age 56 years. A significant part of the population (44.3%) attended 4 years of school and had a history of smoking habits (44,3%). The body mass index was 26.9 kg/m2. A quarter of the participants had a history of respiratory disease (asthma and chronic bronchitis were the main entities). When asked about if they know COPD and its methods of diagnosis, 62.5% of the population claimed to have no knowledge of this disease and only 29.4% knew what a spirometry was. Twenty-five subjects had previously performed a spirometry. We found that 3 spirometry were not likely to be reported because they did not meet acceptability and reproducibility criteria. Sixteen individuals (10.2%) presented with obstructive ventilatory changes, ten of which with respiratory history. In this group the average FEV1 was 77%, FVC 98% and FEV1/FVC ratio of 64. Two participants in this group had an obstruction considered severe.  Conclusion: The aim of these campaigns is to raise awareness and inform the population about diseases often ignored despite their prevalence. It’s also important to diagnose, treat and possible monitor some individuals who didn’t kow they had a problem.  In our population there was a prevalence of obstructive respiratory disease of 10.2%.
Japan's vision for health care in 2035
Authors: Hiroaki Miyata, Satoshi Ezoe, Manami Hori, Machiko Inoue, Kazumasa Oguro, Toshihisa Okamoto, Kensuke Onishi, Kohei Onozaki, Takeshi Sakakibara, Kazuhisa Takeuchi, Yasuharu Tokuda, Yuji Yamamoto, Mayuka Yamazaki, Kenji Shibuya
Journal: The Lancet (2015)
The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias.
Authors: P M Sharp, W H Li
Journal: Molecular Biology and Evolution (1987)

Genes sequences from Escherichia coli, Salmonella typhimurium, and other members of the Enterobacteriaceae show a negative correlation between the degree of synonymous-codon usage bias and the rate of nucleotide substitution at synonymous sites. In particular, very highly expressed genes have very biased codon usage and accumulate synonymous substitutions very slowly. In contrast, there is little correlation between the degree of codon bias and the rate of protein evolution. It is concluded that both the rate of synonymous substitution and the degree of codon usage bias largely reflect the intensity of selection at the translational level. Because of the high variability among genes in rates of synonymous substitution, separate molecular clocks of synonymous substitution might be required for different genes.
Smoking worsens effect of early menopause on mortality, study finds:
Authors: Susan Mayor
Journal: BMJ (2015)

Smoking seems to exacerbate the effect of early menopause on early mortality, a Swedish study has found.

The study, published in Menopause ,1 asked a population based cohort of 25 474 postmenopausal women aged 48-83 questions about their age at menopause (based on the last menstrual period) and smoking, in a self administered questionnaire. The women were all members of the Swedish Mammography Cohort, which was established from 1987 to 1990.

A total of 5942 of women in the cohort died during 16 …
Avian Oncovirus Mill Hill No. 2: Pathogenicity in Chickens&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: R W Alexander, C Moscovici, P K Vogt
Journal: JNCI Journal of the National Cancer Institute (1979)

Mill Hill No. 2 (MH2), an avian tumor virus, was studied for its transforming and oncogenic effects. In tissue culture it induced transformation of chicken fibroblasts and yolk sac macrophages. When injected into the chicken, the main feature of this virus was its ability to cause liver and kidney carcinoma, in addition to sarcoma. MH2-associated viruses did not transform cell cultures but were able to cause only lymphoma in the birds. Light and electron microscopy were used in a detailed histologic study of the tumors induced by MH2 virus. An unclassified round cell sarcoma was produced in soft tissues at sites of injection; there was no evidence of origin from endothelium. In the kidney, carcinomas mixed with a malignant stroma were found. Hepatocarcinomas were the dominant tumors found in the liver. The lymphomas produced by the associated virus were poorly differentiated and highly malignant. The study illustrated the highly oncogenic potential of this virus and offered a model for the analysis of the carcinogenic events in a more specific way.
Successful pregnancy after allogeneic bone marrow transplant with embryos isolated before transplant.
Authors: J H Lipton, M Virro, H Solow
Journal: Journal of Clinical Oncology (1997)

METHODS AND RESULTS: Autologous embryos from in vitro-fertilized ova were successfully implanted in a 29-year-old woman, 2 years after successful allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML). A second pregnancy, similarly initiated, is in progress at 4 years posttransplant. CONCLUSION: Our experience offers a fertility-salvaging technique to some women after cytotoxic therapy, where time permits ovarian hyperstimulation before the need for definitive myeloblative therapy of their malignancy, and where the risk of subsequent infertility is high.
Zoledronic Acid Is Superior to Pamidronate in the Treatment of Hypercalcemia of Malignancy: A Pooled Analysis of Two Randomized, Controlled Clinical Trials
Authors: P. Major, A. Lortholary, J. Hon, E. Abdi, G. Mills, H. D. Menssen, F. Yunus, R. Bell, J. Body, E. Quebe-Fehling, J. Seaman
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Patients with moderate to severe HCM (corrected serum calcium [CSC] ≥ 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2-hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. RESULTS: Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, respectively. Normalization of CSC occurred by day 4 in approximately 50% of patients treated with zoledronic acid and in only 33.3% of the pamidronate-treated patients. The median duration of complete response favored zoledronic acid 4 and 8 mg over pamidronate 90 mg with response durations of 32, 43, and 18 days, respectively. CONCLUSION: Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia.
The European network of Biosafety-Level-4 laboratories: enhancing European preparedness for new health threats
Authors: C. Nisii, C. Castilletti, A. Di Caro, M.R. Capobianchi, D. Brown, G. Lloyd, S. Gunther, A. Lundkvist, M. Pletschette, G. Ippolito
Journal: Clinical Microbiology and Infection (2009)
Occupational Risks for Intracranial Gliomas in Sweden
Authors: Joseph K. McLaughlin, Hans S. R. Malker, William J. Blot, Birgitta K. Malker, B. J. Stone, Jan A. Weiner, Jan L. E. Ericsson, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1987)

With the use of the Cancer-Environment Registry, which links cancer incidence for the years 1961-79 with 1960 census information on occupation for all employed individuals in Sweden, a systematic population-based assessment according to employment classifications was made of the occurrence of intracranial gliomas. Statistically significant (P less than .05) increases in the incidence of intracranial gliomas were observed among several professional and white-collar occupations, possibly due in part to higher levels of diagnosis and reporting of this particular neoplasm. Significantly elevated rates were noted among male dentists, agricultural research workers, and public prosecutors and among female physicians and employees in the health care industry. For blue-collar workers, significant excesses were found among welders and metal cutters; glass, porcelain, or ceramic workers; cellulose plant employees; brick and tile workers; and women employed in the wool industry. Several findings of this survey may represent new clues to the etiology of intracranial gliomas, while other findings support observations reported in previous studies.
Tympanic Epithelium: An Ultrastructural, Experimental and Clinical Study
Authors: Gerard M O'Donoghue
Journal: Journal of the Royal Society of Medicine (1984)

Ultrastructural studies of the guinea pig tympanic membrane failed to reveal specific morphological features that could be associated with migration. A staining method was used to study epithelial migration on 68 normal guinea pig tympanic membranes. A very predictable migratory pattern emerged which was neither influenced by perforation or ventilating tube insertion. Clinical studies in children on 61 normal tympanic membranes revealed a rapid migration which was unchanged by middle ear effusion. A centrifugal pattern of migration was observed in relation to the 23 chronic perforations studied. The kinetics of epithelium in relation to 41 ventilating tubes and in 23 retraction pockets is described.
Mechanism of Resistance to Mammary Tumor Development in C57BL and I Strains of Mice. II. Inherent Differences Between the Two Strains2
Authors: S. Nandi
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Mechanism of Resistance to Mammary Tumor Development in C57BL and I Strains of Mice. II. Inherent Differences Between the Two Strains Get access S. Nandi S. Nandi Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 6, June 1974, Pages 1797–1804, https://doi.org/10.1093/jnci/52.6.1797 Published: 01 June 1974 Article history Received: 16 November 1973 Accepted: 01 March 1974 Published: 01 June 1974
Cardiopulmonary exercise testing in patients with common variable immunodeficiency and agammaglobulinemia
Authors: Maria Carrabba, Maria Cristina Pietrogrande, Aberto Pierini, Sergio Caravita, Marianna Giuditta, Rosa Maria Dellepiane, Giovanna Fabio
Journal: European Respiratory Journal (2013)

Cardiopulmonary exercise testing (CPET) is considered the gold standard to study a patient9s exercise intolerance and its causes. An heterogeneous group of chronic lung diseases occurs in CVID and X-LA and can affect the prognosis. The lung disease is usually assessed by spirometry, lung CT-scan, and 6-minute walking test (6-MWT). Aims: To characterize the pulmonary function and exercise capacity of adult patients with CVID and X-LA. Methods: CPET was performed by six CVID and two X-LA patients. Spirometry, CT-lung scan and 6-MWT data were acquired. Results: All the patients reached a maximal effort. Five patients had abnormalities in the aerobic exercise capacity at peak (VO2 peak) and the efficiency of ventilatory response to exercise at the anaerobic thresholds. On the contrary, 6-MWT was almost normal in seven patients. Conclusions: CPET can improve early detection of ventilatory disfunctions and help to set a highly individualized training intensity for exercise prescription to improve prognosis and quality of life.
Therapeutic hypercapnia prevents pulmonary hypertension in rats with bleomycin-induced chronic neonatal lung injury
Authors: Charlotte Sewing, Julijana Ivanovska, Crystal Kantores, Azhar Masood, Patrick J. McNamara, A. Keith Tanswell, Robert P. Jankov
Journal: European Respiratory Journal (2011)

Bleomycin (BLEO)-induced chronic neonatal lung injury (CNLI) is characterized by severe inflammation, arrest of lung development and pulmonary hypertension (PHT), in common with severe bronchopulmonary dysplasia. Chronic exposure to elevated concentrations of CO2 (hypercapnia) may limit lung inflammation.

Objectives: To examine the preventive effects of moderate (MH) or severe hypercapnia (SH) on BLEO-induced CNLI.

Methods: Rat pups received BLEO (1 mg/kg/d i.p.) or saline vehicle from postnatal days 1-14 while being exposed to FiCO2 0.05 (PaCO2 70 mmHg; MH), FiCO2 0.07 (PaCO2 90 mmHg; SH) or normocapnia (NC). Inflammation was assessed by tissue counts of immunoreactive macrophages (CD68) and neutrophils (MPO). PHT was assessed by echo-Doppler measurement of pulmonary vascular resistance (PVR), right ventricle (RV)/left ventricle+septum (LV+S) weight ratio and percentage medial wall thickness (%MWT) of pulmonary resistance arteries. Markers of lung development included weight, mean linear intercept, tissue fraction, secondary crest and peripheral vessel counts.

Results: SH, but not MH, attenuated BLEO-induced macrophage influx and prevented PHT, as evidenced by normalized PVR and significantly (p<0.01 vs. BLEO+NC) decreased RV/LV+S and%MWT. Neither SH nor MH affected BLEO-induced neutrophil influx, inhibited lung growth, septal thinning, impaired alveolarization or pruning of peripheral blood vessels.

Conclusions: SH prevented PHT, which we speculate was the result, in major part, of inhibited macrophage influx. Neither influx of neutrophils nor pruning of peripheral arteries appeared to contribute significantly to PHT in BLEO-mediated CNLI. Funded by the CIHR.
Effects of exercise on ubiquitination and proteasome activity in skeletal muscle in COPD patients
Authors: Eivind Brønstad, Jose Bianco, Ulrik Wisløff, Sigurd Steinshamn
Journal: European Respiratory Journal (2012)

OBJECTIVE: COPD patients have reduced exercise capacity and skeletal muscle function. The aim of this study was to investigate exercise effects on proteasome actvity in skeletal muscle of COPD patients. We wanted to evaluate ventilatory limited and unlimited exercise by comparing whole body training against small isolated muscle training. The effects of oxidative stress and systemic inflammation were also evaluated.  METHODS: In total, 21 patients with moderate to severe COPD were studied. Spirometry, peak oxygen uptake (VO 2-peak ), ubiquitin activity, proteasome activity, protein carbonylation and systemic inflammation were measured before and after a 10 week aerobic exercise program (n=14) and a 6 week knee extensor exercise program (n=7). Five age- and sex-matched healthy individuals served as reference group.  RESULTS: At baseline all COPD groups had reduced proteasome activity compared to controls (p  CONCLUSION: COPD patients have altered skeletal muscle proteasome activity and whole body aerobic exercise training induces an increased proteasome activity compared to isolated muscle training. The increase exclusively in the whole body exercise groups could therefore suggest an inappropriate skeletal muscle response, and could imply that training small muscle groups is better for COPD patients.
Indatuximab Ravtansine (BT062) In Combination With Lenalidomide and Low-Dose Dexamethasone In Patients With Relapsed and/Or Refractory Multiple Myeloma: Clinical Activity In Len/Dex-Refractory Patients
Authors: Kevin R. Kelly, Asher Chanan-Khan, George Somlo, Leonard T Heffner, David S Siegel, Todd M Zimmerman, Sundar Jagannath, Nikhil C. Munshi, Sagar Lonial, Vivek Roy, Markus Ruehle, Shailesh Chavan, Pankaj Patel, Markus Rothenburger, Andrea Wartenberg-Demand, Thomas Haeder, Kenneth C. Anderson
Journal: Blood (2013)
Abnormal connexin expression in human chronic wounds
Authors: J.E.S. Sutcliffe, K.Y. Chin, C. Thrasivoulou, T.E. Serena, S. O'Neil, R. Hu, A.M. White, L. Madden, T. Richards, A.R.J. Phillips, D.L. Becker
Journal: British Journal of Dermatology (2015)

Regulated alteration of connexin expression has been shown to be integral to acute wound repair. Downregulation of the gap‐junction protein connexin 43 at the wound edge has been correlated with keratinocyte and fibroblast migration, while abnormal overexpression of connexin 43 significantly perturbs healing, as shown in the streptozotocin diabetic rodent impaired healing model. To examine the protein expression levels of connexin 43, in addition to connexins 26 and 30, in a variety of human chronic wounds. Wound‐edge punch biopsies and a matched control from the arm were taken from a cohort of patients with venous leg, diabetic foot or pressure ulcers. Wound connexin expression in each patient was compared with that in a matched, nonwounded arm punch. Tissue was sectioned, stained and imaged by confocal microscopy using identical parameters per patient to permit quantification. Epidermal connexin 43, connexin 26 and connexin 30, and dermal connexin 43 were discovered to be strikingly upregulated in every ulcer from all three wound types, pointing to connexin upregulation as a common feature between chronic wounds. This result supports efforts to target connexin 43 to promote cell migration and wound healing in chronic ulcers.