tbuckley/cabot-search huggingface dataset:
Selective Blockade of Matrix Metalloprotease-14 with a Monoclonal Antibody Abrogates Invasion, Angiogenesis, and Tumor Growth in Ovarian Cancer
Authors: Rajani Kaimal, Raid Aljumaily, Sarah L. Tressel, Rutika V. Pradhan, Lidija Covic, Athan Kuliopulos, Corrine Zarwan, Young B. Kim, Sheida Sharifi, Anika Agarwal
Journal: Cancer Research (2013)

Most patients with ovarian cancer are diagnosed late in progression and often experience tumor recurrence and relapses due to drug resistance. Surface expression of matrix metalloprotease (MMP)-14 on ovarian cancer cells stimulates a tumor-stromal signaling pathway that promotes angiogenesis and tumor growth. In a cohort of 92 patients, we found that MMP-14 was increased in the serum of women with malignant ovarian tumors. Therefore, we investigated the preclinical efficacy of a MMP-14 monoclonal antibody that could inhibit the migratory and invasive properties of aggressive ovarian cancer cells in vitro. MMP-14 antibody disrupted ovarian tumor-stromal communication and was equivalent to Avastin in suppressing blood vessel growth in mice harboring Matrigel plugs. These effects on angiogenesis correlated with downregulation of several important angiogenic factors. Furthermore, mice with ovarian cancer tumors treated with anti-MMP-14 monotherapy showed a marked and sustained regression in tumor growth with decreased angiogenesis compared with immunoglobulin G (IgG)-treated controls. In a model of advanced peritoneal ovarian cancer, MMP-14-dependent invasion and metastasis was effectively inhibited by intraperitoneal administration of monoclonal MMP-14 antibody. Together, these studies provide a preclinical proof-of-concept for MMP-14 targeting as an adjuvant treatment strategy for advanced ovarian cancer.
Assessment of progression of COPD: report of a workshop held in Leuven, 11-12 March 2004
Authors: M Decramer
Journal: Thorax (2005)

Recently performed long term trials have enhanced the insight into the assessment of progression of COPD. The present review focuses on the initial assessment of COPD in general practice and the assessment of disease progression. Several variables may be used to assess this progression, all of which are associated with significant methodological problems. Finding the appropriate mix of outcome measures to capture all aspects of disease progression is a significant challenge.
Thalidomide in the treatment of neuro-Behcet's syndrome
Authors: C.G. RAMSELAAR, R.M. BOONE, H.C. KLUIN-NELEMANS
Journal: British Journal of Dermatology (1986)

Journal Article Thalidomide in the treatment of neuro‐Behçet's syndrome Get access C.G. RAMSELAAR, C.G. RAMSELAAR Departments of Dermatology, St Antonius Hospital, Nieuwegein, The Netherlands Dr C.G.Ramselaar, Department of Dermatology, St Antonius Hospital, Koekoekslaan 1,3435 CM Nieuwegein, The Netherlands. Search for other works by this author on: Oxford Academic Google Scholar R.M. BOONE, R.M. BOONE Departments of Neurology, St Antonius Hospital, Nieuwegein, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar H.C. KLUIN‐NELEMANS H.C. KLUIN‐NELEMANS Departments of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue 3, 1 September 1986, Pages 367–370, https://doi.org/10.1111/j.1365-2133.1986.tb05753.x Published: 01 September 1986 Article history Accepted: 26 February 1986 Published: 01 September 1986
High-dose chemotherapy and autologous hematopoietic progenitor cell transplantation for non-Hodgkin's lymphoma in patients &gt;65 years of age
Authors: C. Hosing, R.M. Saliba, G.-J. Okoroji, U. Popat, D. Couriel, T. Ali, L. De Padua Silva, P. Kebriaei, A. Alousi, M. De Lima, M. Qazilbash, P. Anderlini, S. Giralt, R.E. Champlin, I. Khouri
Journal: Annals of Oncology (2008)
Perennial allergic rhinitis and keratoconjunctivitis
Authors: J P Rihoux
Journal: Thorax (2000)

There are many studies dedicated to the allergic nose, but most of them deal with seasonal allergic rhinitis and particularly with acute experimental situations. Perennial allergic rhinitis is less well documented.

When studying the allergic nose, several aspects must be taken into consideration: the genetic background of the patient, various environmental factors (antigens, air pollution, climate), and the peculiar characteristics of the nose itself including its anatomy—total surface area: 150 cm2, volume: 15 ml—and histology—epithelium (ciliated, non ciliated, pseudostratified, columnar, goblet cells), mucus, immunocompetent cells, lamina propria, basement membrane, blood supply, and nerves and neurotransmitters.1 

It is well recognised that the symptoms of perennial allergic rhinitis are caused by overproduction of different families of chemical mediators. These mediators are produced by migrating or resident inflammatory cells, by resident cells, or by inflammatory cells produced locally from progenitors—for example, T cells, mast cells, eosinophils, neutrophils, epithelial cells, endothelial cells, and antigen presenting cells (APCs). This review focuses on some recent aspects of perennial allergic rhinitis which cast new light on the pathophysiology of this common disease.

Since the description by Mosmann2 of the dichotomy of the murine T cell, a Th2/Th1 imbalance has been described in allergic conditions in humans. The nasal mucosa in perennial allergic rhinitis is characterised by the presence of a high percentage of activated Th2 cells accompanied by high levels of Th2 …
Use of inhaled corticosteroids during the first trimester of pregnancy and the risk of congenital malformations among women with asthma
Authors: L. Blais, M.-F. Beauchesne, E. Rey, J.-L. Malo, A. Forget
Journal: Thorax (2006)

<b>Aim:</b> To investigate whether the maternal use of different doses of inhaled corticosteroids (ICSs) during the first trimester of pregnancy for the treatment of asthma increases the risk of congenital malformations in the offspring. <b>Methods:</b> From the linkage of three administrative Canadian databases, a cohort of 4561 pregnancies from women with asthma who delivered between 1990 and 2000 was reconstructed. A two-stage sampling cohort design was used to acquire additional data from the woman's medical chart. Cases of congenital malformation were identified from the medical services database or the hospital database. Using refill patterns of medications, the average daily dose of ICSs used during the first trimester was calculated and categorised as follows: 0, 1–500, 500–1000 and &gt;1000 μg/day in beclomethasone–chlorofluorocarbon equivalent. A Generalized Estimation Equation model was used to estimate the adjusted odds ratio of congenital malformation as a function of ICS daily dose. All analyses were performed for all malformations and major malformations separately. <b>Results:</b> Within the cohort 418 babies were identified with a congenital malformation (9.2%), 278 of which had a major malformation. About 40% of women used ICSs during the first trimester, but only 5.3% of women used &gt;500 μg/day. The adjusted odds ratio (95% CI) for all malformations associated with the use of ICSs during the first trimester was: 0.77 (0.53 to 1.13) for 1–500, 0.41 (0.19 to 0.92) for 501–1000 and 1.00 (0.42 to 2.36) for &gt;1000 μg/day. The corresponding figures for major malformations were 0.90 (0.64 to 1.24), 0.56 (0.22 to 1.43) and 1.67 (0.56 to 5.03). <b>Conclusion:</b> This study adds evidence to the safety of ICSs for the treatment of asthma during pregnancy, with regard to the likelihood of congenital malformation.
HDM2 promotes WIP1-mediated medulloblastoma growth
Authors: M. C. Buss, T.-A. Read, M. J. Schniederjan, K. Gandhi, R. C. Castellino
Journal: Neuro-Oncology (2012)

Medulloblastoma is the most common malignant childhood brain tumor. The protein phosphatase and oncogene WIP1 is over-expressed or amplified in a significant number of primary human medulloblastomas and cell lines. In the present study, we examine an important mechanism by which WIP1 promotes medulloblastoma growth using in vitro and in vivo models. Human cell lines and intracerebellar xenografted animal models were used to study the role of WIP1 and the major TP53 regulator, HDM2, in medulloblastoma growth. Stable expression of WIP1 enhances growth of TP53 wild-type medulloblastoma cells, compared with cells with stable expression of an empty-vector or mutant WIP1. In an animal model, WIP1 enhances proliferation and reduces the survival of immunodeficient mice bearing intracerebellar xenografted human medulloblastoma cells. Cells with increased WIP1 expression also exhibit increased expression of HDM2. HDM2 knockdown or treatment with the HDM2 inhibitor Nutlin-3a, the active enantomer of Nutlin-3, specifically inhibits the growth of medulloblastoma cells with increased WIP1 expression. Nutlin-3a does not affect growth of medulloblastoma cells with stable expression of an empty vector or of mutant WIP1. Knockdown of WIP1 or treatment with the WIP1 inhibitor CCT007093 results in increased phosphorylation of known WIP1 targets, reduced HDM2 expression, and reduced growth specifically in WIP1 wild-type and high-expressing medulloblastoma cells. Combined WIP1 and HDM2 inhibition is more effective than WIP1 inhibition alone in blocking growth of WIP1 high-expressing medulloblastoma cells. Our preclinical study supports a role for therapies that target WIP1 and HDM2 in the treatment of medulloblastoma.
End-of-Life Cancer Care in Ontario and the United States: Quality by Accident or Quality by Design?
Authors: David Goodman
Journal: JNCI Journal of the National Cancer Institute (2011)

In this month’s issue of the Journal, Warren et al. (1) report the results of their carefully conducted analysis of patients who died with non–small cell lung cancer in the United States and Ontario. The study design selected a group of patients with well-documented advanced cancer at diagnosis. Given the cancer type and stage, the clinical teams caring for these patients would have known the generally poor survival prognosis. The article reports two major findings : care patterns differed between the United States and Ontario and the overall use of community palliative care appears to have fallen short of the average patient preferences in both countries—most patients prefer supportive measures that avoid a hospital death (2,3). The US patients received more chemotherapy, whereas Ontario patients had more inpatient days, greater emergency room use, and were much more likely to die in the hospital. Despite relatively high use of community supportive care, the rates of inpatient death are too high in the United States and much too high in Ontario.
Nicotine-Induced Limbic Cortical Activation in the Human Brain: A Functional MRI Study
Authors: Elliot A. Stein, John Pankiewicz, Harold H. Harsch, Jung-Ki Cho, Scott A. Fuller, Raymond G. Hoffmann, Marjorie Hawkins, Stephen M. Rao, Peter A. Bandettini, Alan S. Bloom
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. Little is known about the neuropharmacology and sites of action of nicotine in the human brain. Such knowledge might help in the development of new behavioral and pharmacological therapies to aid in treating nicotine dependence and to improve smoking cessation success rates. METHOD: Functional magnetic resonance imaging, a real-time imaging technique, was used to determine the acute CNS effects of intravenous nicotine in 16 active cigarette smokers. An injection of saline followed by injections of three doses of nicotine (0.75, 1.50, and 2.25 mg/70 kg of weight) were each administered intravenously over 1-minute periods in an ascending, cumulative-dosing paradigm while whole brain gradient-echo, echo-planar images were acquired every 6 seconds during consecutive 20-minute trials. RESULTS: Nicotine induced a dose-dependent increase in several behavioral parameters, including feelings of “rush” and “high” and drug liking. Nicotine also induced a dose-dependent increase in neuronal activity in a distributed system of brain regions, including the nucleus accumbens, amygdala, cingulate, and frontal lobes. Activation in these structures is consistent with nicotine's behavior-arousing and behavior-reinforcing properties in humans. CONCLUSIONS: The identified brain regions have been previously shown to participate in the reinforcing, mood-elevating, and cognitive properties of other abused drugs such as cocaine, amphetamine, and opiates, suggesting that nicotine acts similarly in the human brain to produce its reinforcing and dependence properties. (Am J Psychiatry 1998; 155:1009–1015)
Treatment of Type 2 Diabetes in Childhood Using a Very-Low-Calorie Diet
Authors: Steven M. Willi, Kelley Martin, Farrah M. Datko, Bethany P. Brant
Journal: Diabetes Care (2004)

OBJECTIVE—Pharmacologic agents currently approved for use in children with type 2 diabetes (metformin and insulin) are less than optimal for some patients. We evaluated the use of a ketogenic, very-low-calorie diet (VLCD) in the treatment of type 2 diabetes. RESEARCH DESIGN AND METHODS—We conducted a chart review of 20 children (mean age 14.5 ± 0.4 years) who consumed a ketogenic VLCD in the treatment of type 2 diabetes. Several response variables (BMI, blood pressure, HbA1c, blood glucose, and treatment regimens) were examined before, during, and up to 2 years after the diet and compared with a matched diabetic control group. RESULTS—Before starting the diet, 11 of 20 patients were treated with insulin and 6 with metformin. Mean daily blood glucose values fell from 8.9 ± 1.1 to 5.5 ± 0.38 mmol/l (P &amp;lt; 0.0001) in the first 3 days of the VLCD, allowing insulin and oral agents to be discontinued in all but one subject. BMI fell from 43.5 ± 1.8 to 39.3 ± 1.8 kg/m2 (P &amp;lt; 0.0001) and HbA1c dropped from 8.8 ± 0.6 to 7.4 ± 0.6% (P &amp;lt; 0.005) as the diet was continued for a mean of 60 ± 8 days (range 4–130 days), and none required resumption of antidiabetic medications. Sustained decreases in BMI and insulin requirements were observed in patients remaining on the VLCD for at least 6 weeks when compared with those of the control group. CONCLUSIONS—The ketogenic VLCD is an effective short-term, and possibly long-term, therapy for pediatric patients with type 2 diabetes. Blood glucose control and BMI improve, allowing the discontinuation of exogenous insulin and other antidiabetic agents. This diet, although strict, has potential as an alternative to pharmacologic therapies for this emerging subset of diabetic individuals.
The Tprk Protein of <i>Treponema pallidum</i> Is Periplasmic and Is Not a Target of Opsonic Antibody or Protective Immunity
Authors: Karsten R.O. Hazlett, Timothy J. Sellati, Tung T. Nguyen, David L. Cox, Michael L. Clawson, Melissa J. Caimano, Justin D. Radolf
Journal: The Journal of Experimental Medicine (2001)

The finding that Treponema pallidum, the syphilis spirochete, contains 12 orthologs of the Treponema denticola outer membrane major sheath protein has engendered speculation that members of this T. pallidum repeat (Tpr) family may be similarly surface exposed. In this regard, the TprK protein was reported to be a target of opsonic antibody and protective immunity and subject to immunologically driven sequence variation. Despite these findings, results from our previous analyses of treponemal outer membranes in concert with computer-based predictions for TprK prompted us to examine the cellular location of this protein. TprK-alkaline phosphatase fusions expressed in Escherichia coli demonstrate that TprK contains a signal peptide. However, opsonophagocytosis assays failed to indicate surface exposure of TprK. Moreover, results from three independent methodologies, i.e., (a) indirect immunofluorescence analysis of agarose-encapsulated organisms, (b) proteinase K treatment of intact spirochetes, and (c) Triton X-114 phase partitioning of T. pallidum conclusively demonstrated that native TprK is entirely periplasmic. Consistent with this location, immunization with the recombinant protein failed to induce either protective immunity or select for TprK variants in the rabbit model of experimental syphilis. These findings challenge the notion that TprK will be a component of an efficacious syphilis vaccine.
Transglutaminase 1-deficient recessive lamellar ichthyosis associated with a LINE-1 insertion in Jack Russell terrier dogs
Authors: K.M. Credille, J.S. Minor, K.F. Barnhart, E. Lee, M.L. Cox, K.A. Tucker, K.L. Diegel, P.J. Venta, D. Hohl, M. Huber, R.W. Dunstan
Journal: British Journal of Dermatology (2009)

Congenital, nonepidermolytic cornification disorders phenotypically resembling human autosomal recessive ichthyosis have been described in purebred dog breeds, including Jack Russell terrier (JRT) dogs. One cause of gene mutation important to humans and dogs is transposon insertions.To describe an autosomal recessive, severe nonepidermolytic ichthyosis resembling lamellar ichthyosis (LI) in JRT dogs due to insertion of a long interspersed nucleotide element (LINE-1) in the transglutaminase 1 (TGM1) gene.Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Phenotypic information and genotyping with a canine microsatellite marker suggested TGM1 to be a candidate gene. Genomic DNA samples and cDNA generated from epidermal RNA were examined. Consequences of the mutation were evaluated by Western blotting, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme activity from cultured keratinocytes.Affected dogs had generalized severe hyperkeratosis. Histological examination defined laminated to compact hyperkeratosis without epidermolysis; ultrastructurally, cornified envelopes were thin. Affected dogs were homozygous for a 1980-bp insertion within intron 9 of TGM1. The sequence of the insertion was that of a canine LINE-1 element. Quantitative RT-PCR indicated a significant decrease in TGM1 mRNA in affected dogs compared with wild-type. TGM1 protein was markedly decreased on immunoblotting, and membrane-associated enzyme activity was diminished in affected dogs.Based on morphological and molecular features, this disease is homologous with TGM1-deficient LI in humans, clinically models LI better than the genetically modified mouse and represents its first spontaneous animal model. This is the first reported form of LI due to transposon insertion.
Prognostic value of TDI assessment of right ventricular function in patients with acute pulmonary embolism
Authors: Rosen Petkov, Yordanka Yamakova, Emilia Petkova
Journal: European Respiratory Journal (2014)

The aim  was to determine whether the assessment of right ventricular function using tissue Doppler imaging (TDI) of the tricuspid annulus (TA) could be used as a prognostic marker in patients with pulmonary embolism (PE).   Materials and methods :Echocardiography (EchoCG) and pulsed TDI were performed in 167 patients with acute PE and normal left ventricular ejection fraction, and in 35 matched healthy volunteers (CG). The tricuspid annulus systolic (S tr_v) and diastolic velocities were acquired in apical four-chamber view using TDI.   Results  :  TDI EchoCG established: In patients with PE systolic and early diastolic TA velocities were significant lower that in CG (p  2.1 cm and inspiratory collapse  18cm 2 ). In PE patients with RV dysfunction S tr_v was significant lower 10.8 ± SD 1.5 cm/s that in patients with normal RV function 11.8 ± SD 1.8 cm/s (p 10.5 cm/swe observed 1 patient with recurrent PE and no deaths occurred. The major complications (recurrent PTE and death) had a significant higher rate in patients with RV dysfunction (p   Conclusion  : In clinical settings TDI EchoCG in PE patients was a valuable, noninvasive method for evaluation of RV function. The establishment ofRVdysfunction wasrelated with significantincrease inmajor complications, which should enhanceclinicalattention and careto thosepatients at risk.
Genetics and tuberculosis
Authors: G. H BOTHAMLEY
Journal: Thorax (1998)

Dr Richard Bellamy alludes to the important fact, frequently ignored by immunologists, geneticists and epidemiologists, that tuberculosis has several different clinical forms.1Physicians have emphasised the difference between primary tuberculosis, which is comparable to Lurie’s susceptible rabbits with disseminated disease, and post primary tuberculosis, best characterised by smear positive pulmonary tuberculosis and …
Risk of New Cancers After Radiotherapy in Long-Term Survivors of Retinoblastoma: An Extended Follow-Up
Authors: Ruth A. Kleinerman, Margaret A. Tucker, Robert E. Tarone, David H. Abramson, Johanna M. Seddon, Marilyn Stovall, Frederick P. Li, Joseph F. Fraumeni
Journal: Journal of Clinical Oncology (2005)

Many children diagnosed with retinoblastoma (Rb) survive into adulthood and are prone to subsequent cancers, particularly hereditary patients, who have germline Rb-1 mutations. We have extended the follow-up of a large cohort of Rb patients for 7 more years to provide new information on the risk of additional cancers after radiotherapy in long-term survivors.We analyzed the risk of new cancers through 2000 in 1,601 Rb survivors, diagnosed from 1914 to 1984, at two US medical centers. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cancers after hereditary and nonhereditary Rb to the expected number from the Connecticut Tumor Registry. The cumulative incidence of a new cancer after hereditary and nonhereditary Rb and radiotherapy was calculated with adjustment for competing risk of death.Subsequent cancer risk in 963 hereditary patients (SIR, 19; 95% CI, 16 to 21) exceeded the risk in 638 nonhereditary Rb patients (SIR, 1.2; 95% CI, 0.7 to 2.0). Radiation further increased the risk of another cancer in hereditary patients by 3.1-fold (95% CI, 2.0 to 5.3). Hereditary patients continued to be at significantly increased risk for sarcomas, melanoma, and cancers of the brain and nasal cavities. The cumulative incidence for developing a new cancer at 50 years after diagnosis of Rb was 36% (95% CI, 31% to 41%) for hereditary and 5.7% (95% CI, 2.4% to 11%) for nonhereditary patients.Hereditary Rb predisposes to a variety of new cancers over time, with radiotherapy further enhancing the risk of tumors arising in the radiation field.
The quality of health information on the internet
Authors: G. P Purcell
Journal: BMJ (2002)

This week's theme issue attempts to provide a framework for thinking about the quality of health information on the internet—a source of anxiety almost since its first appearance.

Five years ago Impicciatore and colleagues reviewed website advice on managing fever in children and concluded that it varied widely in terms of accuracy, completeness, and consistency.1 Pick any medical problem today, and the chances are you'll find the same. With at least 80 studies reporting similar findings (G Eysenbach, personal communication), we need no more convincing that the quality of information on the web varies as widely as it does in other media.

In 1997 Gagliardi and Jadad identified 47 instruments for measuring healthcare quality on the internet. Four years later, they found another 51—all of them unvalidated (p 569).2 Generating yet more unproved instruments looks like another activity that researchers could usefully stop. However, the proliferation of tools for assessing quality continues unabated, fuelled by anxieties about patient harm. As our international roundup shows (pp 566-7), countries now seem poised to get in on the act, although little beyond urban myths exists to justify the level of their concerns. …
A child with xeroderma pigmentosum and bone marrow failure
Authors: S.P. SALOB, D.K.H. WEBB, D.J. ATHERTON
Journal: British Journal of Dermatology (1992)

The case of a child with both xeroderma pigmentosum and bone marrow failure is reported. It is suggested that this is not a chance association, and that the bone marrow hypoplasia may reflect an increased susceptibility of this patient's haemopoietic stem cells to non‐UV mutagens.