tbuckley/cabot-search huggingface dataset:
Tissue Inhibitor of Matrix Metalloproteinase-1 Is Prognostic in Head and Neck Squamous Cell Carcinoma: Comparison of the Circulating and Tissue Immunoreactive Protein
Authors: Henni Ruokolainen, Paavo Pääkkö, Taina Turpeenniemi-Hujanen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Tissue inhibitors of metalloproteinases (TIMP) are capable of inhibiting the matrix metalloproteinases, but they also possess other biological functions. Little is known about the role of TIMP-1 in the progression and spreading of cancer cells among patients with head and neck squamous cell carcinoma (HNSCC). In this study, the pretreatment serum levels of TIMP-1 or the overexpression of TIMP-1 immunoreactive protein in the primary tumor was correlated to the clinical course in patients with HNSCC. Experimental Design: The TIMP-1 immunoreactive protein was studied in 74 cases representing HNSCC. The tissue immunoreactive protein was evaluated from paraffin-embedded tumor sections in 68 cases using immunohistologic staining with a specific antibody, and in 68 cases the pretreatment serum levels of TIMP-1 were quantitatively measured by ELISA assay. The results were compared with the clinicopathologic factors of the disease and the patients' outcome. Results: A positive correlation was found between the size of the primary tumor (T) and the circulating TIMP-1 level (P = 0.021) or the positive immunoreaction of TIMP-1 in tumor (P = 0.039). The 5-year cause-specific survival was significantly lower in patients presenting with a high serum TIMP-1 level than in those with a low level of TIMP-1 (38% versus 64%, P = 0.034). They also had an unfavorable 5-year relapse-free survival rate (37% versus 56%, respectively). Similarly, the expression of TIMP-1 in tumor was prognostic for shortened survival, the 5-year cumulative relapse-free survival being 42% in patients with a TIMP-1–positive tumor versus 75% in cases with a negative tumor (P = 0.035). Tissue TIMP-1 positivity also seemed associated to the cause-specific survival (P = 0.075) and to be connected with later lymph node or hematogenic relapses. Conclusions: This study shows for the first time that both circulating and tissue TIMP-1 immunoreactive protein predicts the clinical course and dissemination in HNSCC, suggesting that TIMP-1 might be related to both tumor growth and metastasis in HNSCC.
An aberrant prostate antigen–specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans
Authors: Yafei Hou, Jason DeVoss, Vinh Dao, Serena Kwek, Jeffrey P. Simko, Douglas G. McNeel, Mark S. Anderson, Lawrence Fong
Journal: Journal of Clinical Investigation (2009)

Chronic prostatitis is a common disease of unclear etiology and has no specific treatment. Mice deficient in the expression of the autoimmune regulator (Aire) gene, which are defective in thymic expression of self antigens and central tolerance, develop spontaneous prostatitis. In this study, we found that Aire-deficient mice developed spontaneous B and T cell immune responses to a prostate autoantigen, seminal vesicle secretory protein 2 (SVS2), which we believe to be novel. We show that thymic expression of this self antigen was Aire dependent. Moreover, prostatitis was induced in WT mice through immunization with SVS2, demonstrating that immunity to SVS2 was sufficient to induce prostatitis. The clinical relevance of this antigen was highlighted by our observation that patients with chronic prostatitis possessed specific autoantibodies against the human SVS2-like seminal vesicle protein semenogelin. These results provide direct evidence that spontaneous chronic prostatitis is an autoimmune disease and is regulated by both central and peripheral tolerance. Moreover, SVS2 and semenogelin are among the relevant autoantigens in mice and humans, respectively.
β-Cell Function in Relation to Islet Cell Antibodies During the First 3 Yr After Clinical Diagnosis of Diabetes in Type II Diabetic Patients
Authors: Anders Gottsäter, Mona Landin-Olsson, Per Fernlund, Åke Lernmark, Göran Sundkvist
Journal: Diabetes Care (1993)

OBJECTIVE— To determine the effects of islet cell antibodies on β-cell function during the first 3 yr after diagnosis in type II diabetic patients. RESEARCH DESIGN AND METHODS— β-cell function in type II diabetic patients with (n = 11, 50 ± 5 yr of age) and without (n = 10, 52 ± 4 yr of age) ICA was followed prospectively and compared with β-cell function in type I adult diabetic patients (n = 17, 37 ± 5 yr of age) and in healthy control subjects (n = 34, age 45 ± 3 yr). β-cell function was evaluated as fasting C-peptide, 1 + 3 min C-peptide after intravenous glucose, and ∆ C-peptide after glucagon. RESULTS— Fasting C-peptide was equal in type II diabetic patients with ICA (0.30 ± 0.03 nM) and type I diabetic patients (0.24 ± 0.03 nM) at diagnosis, and decreased (P &amp;lt; 0.05) during 3 yr in these groups but not in type II diabetic patients without ICA. At diagnosis, type II diabetic patients with ICA showed a 1 + 3 min C-peptide (0.92 ± 0.17 nM) lower (P &amp;lt; 0.001) than control subjects but higher (P &amp;lt; 0.05) than type I diabetic patients (0.53 ± 0.11 nM). After 1 yr, 1 + 3 min C-peptide in type II diabetic patients with ICA had decreased (P &amp;lt; 0.05) to 0.18 ± 0.11 nM and was equal to type I diabetic patients (0.38 ± 0.10 nM). ∆ C-peptide after glucagon was equally impaired in type II diabetic patients with ICA (0.38 ± 0.06 nM) and type I diabetic patients (0.35 ± 0.11 nM) at diagnosis. After 3 yr, type II diabetic patients with ICA had fasting C-peptide of 0.09 ± 0.04 nM, 1 + 3 min C-peptide of 0.18 ± 0.10 nM, and ∆ C-peptide after glucagon of 0.20 ± 0.09 nM, values equal to type I diabetic patients but lower (P &amp;lt; 0.01) than in type II diabetic patients without ICA, whose values remained unchanged; fasting C-peptide of 0.97 ± 0.17 nM, 1 + 3 min C-peptide of 2.31 ± 0.50 nM, and ∆ C-peptide after glucagon of 1.76 ± 0.28 nM. CONCLUSIONS— In patients considered type II diabetic with ICA, β-cell function progressively decreased after diagnosis, and after 3 yr was similar to type I diabetic patients, whereas β-cell function in type II diabetic patients without ICA was unchanged.
Phase III Trial Evaluating the Addition of Paclitaxel to Doxorubicin Followed by Cyclophosphamide, Methotrexate, and Fluorouracil, As Adjuvant or Primary Systemic Therapy: European Cooperative Trial in Operable Breast Cancer
Authors: Luca Gianni, José Baselga, Wolfgang Eiermann, Vincente Guillem Porta, Vladimir Semiglazov, Aňa Lluch, Milvia Zambetti, Dolores Sabadell, Günther Raab, Antonio Llombart Cussac, Alla Bozhok, Angel Martinez-Agulló, Marco Greco, Mikhail Byakhov, Juan Josè Lopez Lopez, Mauro Mansutti, Pinuccia Valagussa, Gianni Bonadonna
Journal: Journal of Clinical Oncology (2009)

To evaluate the addition of paclitaxel to an anthracycline-based adjuvant regimen and to compare this combination with the same regimen given as primary systemic (neoadjuvant) therapy.A total of 1,355 women with operable breast cancer were randomly assigned to one of three treatments: surgery followed by adjuvant doxorubicin (75 mg/m(2)) followed by cyclophosphamide, methotrexate, and fluorouracil (CMF; arm A); surgery followed by adjuvant paclitaxel (200 mg/m(2)) plus doxorubicin (60 mg/m(2)), followed by CMF (arm B); or paclitaxel (200 mg/m(2)) plus doxorubicin (60 mg/m(2)) followed by CMF followed by surgery (arm C). The two coprimary objectives were to assess the effects on relapse-free survival (RFS) of the addition of paclitaxel to postoperative chemotherapy (arm B v arm A) and primary chemotherapy versus adjuvant chemotherapy (arm B v arm C).Doxorubicin plus paclitaxel followed by CMF was well-tolerated as adjuvant or as primary chemotherapy. The addition of paclitaxel to adjuvant doxorubicin followed by CMF significantly improved RFS compared with adjuvant doxorubicin alone followed by CMF (hazard ratio [HR], 0.73; P = .03). Distant RFS was similarly improved (HR, 0.70; P = .027). There was no significant difference in RFS when the paclitaxel/doxorubicin/CMF chemotherapy was given before surgery compared with the same regimen given after surgery (HR, 1.21; P = .18). However, the rate of breast-conserving surgery was significantly higher with preoperative chemotherapy (63% v 34%; P < .001).Incorporating paclitaxel into anthracycline-based adjuvant therapy resulted in a significant improvement in RFS and distant RFS. When given as primary systemic therapy, the paclitaxel-containing regimen allowed breast-sparing surgery in a significant percentage of patients.
Dextran sulphate induced arthritis in rabbits.
Authors: J Steinberg, C B Sledge, J Noble, H G Gillies
Journal: Annals of the Rheumatic Diseases (1980)

Persistent effects of a short course of intra-articular dextran sulphate, dextrans, or chondroitin sulphate were examined in rabbit knees. Only dextran sulphate produced gross arthritis, associated with high synovial acid phosphatase and beta-glucuronidase activities. Synovial degradative capacity in synovium-cartilage cocultures was increased 2-fold by dextran sulphate and 1.5-fold by chondroitin sulphate treatments. Stimulation of cartilage breakdown in vitro paralleled the content of synovial marker enzyme at death of the animal, but the 2 responses could be dissociated.
Low Molecular Weight Heparin and Unfractionated Heparin Are Both Effective at Accelerating Pulmonary Vascular Maturation in Neonatal Rabbits
Authors: Stacy B. O’Blenes, Sandra L. Merklinger, Anusha Jegatheeswaran, Andrew Campbell, Marlene Rabinovitch, Ivan Rebeyka, Glen Van Arsdell
Journal: Circulation (2003)

Creation of a bi-directional cavopulmonary shunt after the Norwood procedure for hypoplastic left heart syndrome is delayed to allow pulmonary vascular resistance to fall with maturation of the pulmonary vascular bed. We hypothesized that unfractionated heparin (UFH) and low molecular weight heparin (LMWH), which promote angiogenesis and inhibit smooth muscle cell growth, could accelerate this process.Fifty-six newborn rabbits were randomly selected to receive UFH 225U/kg (n=12), LMWH 1 mg/kg (n=14), LMWH 10 mg/kg (n=16), or saline (n=14) by subcutaneous injection every 12 hours for 14 days. Treatment with heparin reduced mean pulmonary artery (PA) pressure by 12% to 16% relative to controls [9.0+/-0.2 (UFH), 9.4+/-0.1 (LMWH 1 mg/kg), 9.2+/-0.2 (LMWH 10 mg/kg) versus 10.7+/-0.2 mm Hg (saline), P=0.0001]. Lower PA pressures were associated with reduced alveolar:arterial ratio consistent with enhanced pulmonary angiogenesis in heparin treated animals [8+/-1 (UFH), 13+/-2 (LMWH 1 mg/kg), 12+/-2 (LMWH 10 mg/kg) versus 23+/-5 (saline), P<0.03]. Reduced PA medial wall thickness and muscularization, two additional features of pulmonary vascular maturation, were also more evident in heparin treated animals. Mean PA pressures in 14-day-old rabbits treated with heparin were lower than those measured in control rabbits less than 7 weeks of age suggesting that heparin shortens the pulmonary vascular maturation process by over 60%.These results indicate that both UFH and LMWH are effective at accelerating pulmonary vascular maturation in newborn rabbits. This raises the possibility that administration of heparin to children after the Norwood procedure might allow for earlier conversion to a bi-directional cavopulmonary shunt.
The Surgical Treatment of Supravalvular Aortic Stenosis Based on Two Cases
Authors: S. Nordstrom, T. Silander
Journal: Thorax (1962)

An increasing number of cases of supravalvular aortic stenosis have been reported in recent years.In those hitherto described, the stricture has consisted of either a fibrous membrane directly adjacent to the cusps or a true stenosis at the level of the upper border of the sinus of Valsalva where, as mentioned by Kreel, Reiss, Strauss, Blumenthal, and Baronofsky (1959), a slight, * In Case 1, operation consisted of local excision of the stenosis; and in Case 2, of splitting the aorta through the stenosis and insertion of a patch graft.
Gene Transfer of Calcitonin Gene–Related Peptide Prevents Vasoconstriction After Subarachnoid Hemorrhage
Authors: Kazunori Toyoda, Frank M. Faraci, Yoshimasa Watanabe, Toshihiro Ueda, Jon J. Andresen, Yi Chu, Shoichiro Otake, Donald D. Heistad
Journal: Circulation Research (2000)

Abstract —We sought to determine whether adenovirus-mediated gene transfer in vivo of calcitonin gene–related peptide (CGRP), a potent vasodilator, ameliorates cerebral vasoconstriction after experimental subarachnoid hemorrhage (SAH). Arterial blood was injected into the cisterna magna of rabbits to mimic SAH 5 days after injection of AdRSVCGRP (8×10 8 pfu), AdRSVβgal (control virus), or vehicle. After injection of AdRSVCGRP, there was a 400-fold increase in CGRP in cerebrospinal fluid. Contraction of the basilar artery to serotonin in vitro was greater in rabbits after SAH than after injection of artificial cerebrospinal fluid ( P &lt;0.001). Contraction to serotonin was less in rabbits with SAH after AdRSVCGRP than after AdRSVβgal or vehicle ( P &lt;0.02). Basal diameter of the basilar artery before SAH (measured with digital subtraction angiogram) was 13% greater in rabbits treated with AdRSVCGRP than in rabbits treated with vehicle or AdRSVβgal ( P &lt;0.005). In rabbits treated with vehicle or AdRSVβgal, arterial diameter after SAH was 25±3% smaller than before SAH ( P &lt;0.0005). In rabbits treated with AdRSVCGRP, arterial diameter was similar before and after SAH and was reduced by 19±3% ( P &lt;0.01) after intracisternal injection of CGRP-(8-37) (0.5 nmol/kg), a CGRP 1 receptor antagonist. To determine whether gene transfer of CGRP after SAH may prevent cerebral vasoconstriction, we constructed a virus with a cytomegalovirus (CMV) promoter, which results in rapid expression of the transgene product. Treatment of rabbits with AdCMVCGRP after experimental SAH prevented constriction of the basilar artery 2 days after SAH. Thus, gene transfer of CGRP prevents cerebral vasoconstriction in vivo after experimental SAH.
Is there an injury epidemic in girls’ sports?
Authors: S B Knowles
Journal: British Journal of Sports Medicine (2009)

Injuries to prominent sportswomen have raised questions about whether there is an injury epidemic for female athletes. Our aim was to synthesise the data on overall injury incidence among female athletes and present the evidence for specific injuries for which female athletes appear to be at greater risk than male athletes. We also reviewed the severity of female injuries, the hypothesised risk factors and injury prevention studies. In general, women have a lower rate of injury than men. Women are at greater risk for specific injuries such as non-contact anterior cruciate ligament injuries, but these injuries are relatively rare. Further, women tend to have higher rates of surgery for the same injuries than men. Nevertheless, injury rates likely can be reduced by research efforts to identify modifiable risk factors using rigorous epidemiological methods and the investigation of effective prevention programmes.
A model for the development and implementation of a national plan for the optimal management of early spondyloarthritis: the Esperanza Program
Authors: Santiago Muñoz-Fernández, Loreto Carmona, Eduardo Collantes, Juan Mulero, M Jesús García-Yébenes, Eugenio de Miguel, Raquel Almodovar, Cristina Fernández-Carballido, José Francisco García Llorente, Milena Gobbo
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To evaluate the performance of a healthcare programme in early spondyloarthritis (SpA). <h3>Methods</h3> Based on previous analyses and expectations of a nominal group, the following were set: (1) minimum standards to create early SpA units; (2) standard operating procedures; and (3) eight performance indicators that can be measured in real time using a web-based platform. <h3>Results</h3> At the end of the evaluation of the programme the expected level of performance was achieved in three of the indicators: 'referral reliability' (standard (S) &gt;50%, real value (RV) 92%), 'accessibility' (S &gt;90%, RV=91%) and 'duration of first visit' (S &gt;50%, RV=53%). The performance in the remaining indicators was inferior: 'success of referral criteria' (S &gt;50%, RV=28%), 'clinical reports issued' (S &gt;90%, RV=25%), 'feedback guarantee' (S &gt;85%, RV=2%), 'missing data' (S &lt;10%, RV=24%) and 'frequency of review' (S &gt;90%, RV=84%). Explanations for the low performance are provided. <h3>Conclusions</h3> It is possible to implement a large-scale programme that is measurable.
A FIVE TO TEN YEAR FOLLOW-UP STUDY OF 641 SCHIZOPHRENIC CASES
Authors: CHARLES RUPP, ELIZABETH K. FLETCHER
Journal: American Journal of Psychiatry (1940)

1. Of 641 clinically diagnosed cases of schizophrenia, admitted to the Rhode Island State Hospital for Mental Diseases, between 1929 and 1934, and followed for 5 to 10 years, 27.5 per cent were found to be at present in the community, 53.5 per cent were in mental hosiptals, 13.9 per cent were dead and for 5.1 per cent no adequate follow-up information could be obtained. 2. Adequate follow-up data were available for 608 patients; of these 6.6 per cent were much improved, 15.3 per cent improved, 63.5 per cent unimproved and 14.6 per cent dead. 3. Classification on the basis of diagnostic subtype showed that 35 per cent of the simple, 16.4 per cent of the hebephrenic, 30 per cent of the catatonic, 16 per cent of the paranoid and 36.4 per cent of the "other" group were much improved or improved. Many of the cases in the latter category were of the so-called schizoaffective type. 4. The age of onset of psychotic symptoms had little bearing on the outcome, except that those cases having an onset at the age of 45 or later tended to do less well than those having the onset at a younger age. 5. Of those cases with symptoms of less than 6 months duration prior to hospitalization 34.5 per cent were much improved or improved. For those with symptoms of 6 to 11 months, 29.4 were benefited; for those with symptoms of 12 to 23 months 27.8 per cent benefited; while for those with symptoms of 2 years or longer only 16 per cent were benefited. 6. 75.3 per cent of the patients requiring a hospital stay of 6 months or less were improved while only 4.2 per cent of those remaining in the hospital for 5 years or longer improved. Patients requiring hospital care for more than 2 years showed little tendency to improve. 7. Disregarding the dead and untraced cases, 259 or approximately 50 per cent of 519 patients left the hospital at some time or other for more than one month; of these 129 have continued to remain outside the hospital while 47 returned temporarily and 83 permanently. The much improved and improved groups show a higher percentage of cases remaining out of the hospital continuously and a smaller percentage of returns than the unimproved group. 8. Pulmonary tuberculosis was the most common cause of death, being responsible for 43 or 48.2 per cent of 89 deaths. 10 (11.2 per cent) cases committed suicide.
Structure and regulation of the anthranilate synthase genes in Pseudomonas aeruginosa: II. Cloning and expression in Escherichia coli.
Authors: I P Crawford, A Wilde, E M Yelverton, D Figurski, R W Hedges
Journal: Molecular Biology and Evolution (1986)

The genes for the large and small subunits of anthranilate synthase (trpE and trpG, respectively) have been cloned from Pseudomonas aeruginosa PAC174 into E. coli by R-prime formation with the broad-host-range plasmid R68.44. Sequential subcloning into plasmid vectors reduced the active Pseudomonas DNA fragment to a length of 3.1 kb. We obtained evidence that this region contains the promoter for its own expression and retains a vestigial regulatory response to tryptophan scarcity or excess.
Justifying Different Levels of Palliative Sedation
Authors: Victor Cellarius
Journal: Annals of Internal Medicine (2010)

Letters2 March 2010Justifying Different Levels of Palliative SedationVictor Cellarius, MD and Blair HenryVictor Cellarius, MDFrom Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada; and Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada. and Blair HenryFrom Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada; and Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-5-201003020-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with great interest the article by Quill and colleagues (1), which presented and discussed 3 categories of palliative sedation: ordinary sedation, proportionate palliative sedation (PPS), and palliative sedation to unconsciousness (PSU). One notion shared by these practices, and by all attempts to justify sedation, is that the degree of sedation should match the symptoms—proportionality.The prominence of proportionality in this and other discussions of palliative sedation suggests a simpler and ethically clearer classification. Instead of "ordinary," "proportionate," and "unconscious" sedation, we suggest that all palliative sedation be classified as PPS. This is not a confusion ...References1. Quill TE, Lo B, Brock DW, Meisel A. Last-resort options for palliative sedation. Ann Intern Med. 2009;151:421-4. [PMID: 19755367] LinkGoogle Scholar2. de Graeff A, Dean M. Palliative sedation therapy in the last weeks of life: a literature review and recommendations for standards. J Palliat Med. 2007;10:67-85. [PMID: 17298256] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada; and Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoLast-Resort Options for Palliative Sedation Timothy E. Quill , Bernard Lo , Dan W. Brock , and Alan Meisel Justifying Different Levels of Palliative Sedation Daniel P. Sulmasy , Farr Curlin , Gerard S. Brungardt , and Thomas Cavanaugh Justifying Different Levels of Palliative Sedation Timothy E. Quill , Daniel Brock , Bernard Lo , and Alan Meisel Metrics Cited ByPalliative Sedation: A Medical-Ethical ExplorationReflections on palliative sedationPalliative Sedation: A Medical-Ethical ExplorationPalliative sedation: Controversies and challengesPalliatieve sedatie: hoe diep? 2 March 2010Volume 152, Issue 5Page: 332KeywordsConflicts of interestSedation ePublished: 2 March 2010 Issue Published: 2 March 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...