tbuckley/cabot-search huggingface dataset:
Lateral Instability of the Knee following Polyarthritis: An Experimental Study
Authors: E. N. Coomes
Journal: Annals of the Rheumatic Diseases (1962)

Although joint instability frequently follows certain types of polyarthritis it has seldom been investigated in the past; the end results vary from the nuisance of the unstable wrist to the catastrophe of atlanto-axial dislocation. It is upon the ligaments that stability so often depends, yet few studies have been performed to assess their functional state and physical characteristics either in health or disease. The aim of this investigation has been to provide some data to clarify the situation. Apart from the condition included in this study, joint instability is a feature of several diverse states. There are certain hereditary disorders of connective tissue in which there have been consistent reports of excessive joint mobility. Carter and Sweetnam (1958) described a family with very mobile joints complicated by recurrent dislocation of the patella -a condition recognized as familial joint laxity quite distinct from seemingly related conditions. McKusick (1960) and many others have reported similar mobile joints in osteogenesis imperfecta, Marfan's syndrome, and Ehlers-Danlos syndrome, in addition to the other manifestations. In all of these conditions there is some primary abnormality of the connective tissue. There are other conditions that produce instability because of their effect upon previously normal ligaments. Trauma is an important cause of this, and there have been numerous clinical reports, a good example of which is that of Ritchey (1960) who studied 28 cases of unstable knees following injury. Infection can produce an unstable jointapart from gross destructive change-in some unknown way. After a naso-pharyngeal infection, the transverse ligament of the atlas can give way leading to atlanto-axial dislocation. This complication has been recorded by Bell (1830), Grisel (1930), and Watson-Jones (1932), but the ligaments were not examined histologically, nor were any attempts made to measure strength or elasticity, so that the mechanism of the dislocation remains obscure. Similar dislocations have been reported
Collapsin Response Mediator Protein-1 and the Invasion and Metastasis of Cancer Cells
Authors: J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, P.-C. Yang
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Numerous genetic changes are associated with metastasis and invasion of cancer cells. To identify differentially expressed invasion-associated genes, we screened a panel of lung cancer cell lines (CL1–0, CL1–1, CL1–5, and CL1–5-F4 in order of increasing invasive activity) for such genes and selected one gene, collapsin response mediator protein-1 (CRMP-1), to characterize. Methods: We used a microarray containing 9600 gene sequences to assess gene expression in the cell panel and selected the differentially expressed CRMP-1 gene for further study. We confirmed the differential expression of CRMP-1 with northern and western blot analyses. After transfecting and overexpressing CRMP-1 in highly invasive CL1–5 cells, the cells were assessed morphologically and with an in vitro invasion assay. We used enhanced green fluorescent protein-tagged CRMP-1 and fluorescence microscopy to localize CRMP-1 intracellularly. CRMP-1 expression in 80 lung cancer specimens was determined by real-time quantitative reverse transcription–polymerase chain reaction (RT–PCR). All statistical tests were two-sided. Results: Expression of CRMP-1 was inversely associated with invasive activity in the cell panel, an observation confirmed by northern and western blot analyses. CRMP-1-transfected CL1–5 cells became rounded and had fewer filopodia and statistically significantly lower in vitro invasive activity than untransfected cells (all P<.001). During interphase, CRMP-1 protein was present uniformly throughout the cytoplasm and sometimes in the nucleus; during mitosis, CRMP-1 was associated with mitotic spindles, centrosomes, and the midbody (in late telophase). Real-time RT-PCR of lung cancer specimens showed that reduced expression of CRMP-1 was statistically significantly associated with advanced disease (stage III or IV; P = .010), lymph node metastasis (N1, N2, and N3; P = .043), early postoperative relapse (P = .030), and shorter survival (P = .016). Conclusions: CRMP-1 appears to be involved in cancer invasion and metastasis and may be an invasion-suppressor gene.
Elevated BP after AKI
Authors: Chi-yuan Hsu, Raymond K. Hsu, Jingrong Yang, Juan D. Ordonez, Sijie Zheng, Alan S. Go
Journal: Journal of the American Society of Nephrology (2015)

The connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP--defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit--during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization.
Repression of IFN Regulatory Factor 8 by DNA Methylation Is a Molecular Determinant of Apoptotic Resistance and Metastatic Phenotype in Metastatic Tumor Cells
Authors: Dafeng Yang, Muthusamy Thangaraju, Kristy Greeneltch, Darren D. Browning, Patricia V. Schoenlein, Tomohiko Tamura, Keiko Ozato, Vadivel Ganapathy, Scott I. Abrams, Kebin Liu
Journal: Cancer Research (2007)

Abstract Apoptotic resistance is often associated with metastatic phenotype in tumor cells and is considered a hallmark of tumor progression. In this study, IFN regulatory factor 8 (IRF8) expression was found to be inversely correlated with an apoptotic-resistant and metastatic phenotype in human colon carcinoma cell lines in vitro. This inverse correlation was further extended to spontaneously arising primary mammary carcinoma and lung metastases in a mouse tumor model in vivo. Exogenous expression of IRF8 in the metastatic tumor cell line restored, at least partially, the sensitivity of the tumor cells to Fas-mediated apoptosis, and disruption of IRF8 function conferred the poorly metastatic tumors with enhanced apoptotic resistance and metastatic capability. DNA demethylation restored IRF8 expression and sensitized the metastatic tumor cells to Fas-mediated apoptosis. Analysis of genomic DNA isolated from both primary and metastatic tumor cells with methylation-sensitive PCR revealed hypermethylation of the IRF8 promoter in metastatic tumor cells but not in primary tumor cells. Taken together, our data suggest that IRF8 is both an essential regulator in Fas-mediated apoptosis pathway and a metastasis suppressor in solid tumors and that metastatic tumor cells use DNA hypermethylation to repress IRF8 expression to evade apoptotic cell death and to acquire a metastatic phenotype. [Cancer Res 2007;67(7):3301–9]
Possible Association of Heart Failure Status With Synthetic Balance Between Aldosterone and Dehydroepiandrosterone in Human Heart
Authors: Shota Nakamura, Michihiro Yoshimura, Masafumi Nakayama, Teruhiko Ito, Yuji Mizuno, Eisaku Harada, Tomohiro Sakamoto, Yoshihiko Saito, Kazuwa Nakao, Hirofumi Yasue, Hisao Ogawa
Journal: Circulation (2004)

Aldosterone is produced not only in the adrenal gland but also in the extra-adrenal tissues, including failing human heart. This study examined the production of dehydroepiandrosterone (DHEA) in human heart and elucidated the possible physiological significance. Method and Results- Using left ventricular tissues obtained at autopsy, reverse transcription-polymerase chain reaction followed by Southern blot analysis revealed the gene expressions of CYP17. By measuring plasma aldosterone and DHEA levels at the coronary sinuses and aortic roots during cardiac catheterization, we found that DHEA but not aldosterone was secreted from control subjects (P<0.0001 and P=0.74, respectively), whereas aldosterone but not DHEA was secreted from patients with heart failure (P=0.0017 and P=0.67, respectively). To examine the significance of DHEA, we measured myocyte cell sizes and the gene expression of B-type natriuretic peptide (BNP), using a neonatal rat cardiocyte culture system. We found that DHEA (10(-8) mol/L) significantly inhibited the increase in myocyte cell sizes and BNP mRNA levels upregulated by endothelin-1 (P=0.031 and P<0.0001, respectively).CYP17 gene expression and production of DHEA were demonstrated in human control heart. Also, we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects.
Inhibition of Jun NH2-Terminal Kinases Suppresses the Growth of Experimental Head and Neck Squamous Cell Carcinoma
Authors: Neil D. Gross, Jay O. Boyle, Baoheng Du, Vikram D. Kekatpure, Agnieszka Lantowski, Howard T. Thaler, Babette B. Weksler, Kotha Subbaramaiah, Andrew J. Dannenberg
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This study was carried out to investigate whether c-Jun NH2-terminal kinases (JNK) are potential targets for treating head and neck squamous cell carcinoma (HNSCC). Experimental Design: JNK activity was first evaluated in 20 paired samples of human HNSCC. The antitumor activity of SP600125, a reversible nonselective ATP-competitive inhibitor of JNKs, was then investigated both in an HNSCC xenograft model and in vitro using immunohistochemistry, immunoblotting, enzyme immunoassay, flow cytometry, and a Matrigel assay of capillary tube formation. Complementary studies were carried out using small interfering RNA to JNK1/2. Results: JNK activity was increased in human HNSCC compared with normal-appearing epithelium. Treatment of mice bearing HNSCC xenografts with SP600125 resulted in &amp;gt;60% inhibition of tumor growth relative to vehicle-treated animals. Inhibition of tumor growth was associated with significant reductions in both cell proliferation and microvessel density. SP600125 inhibited tumor cell proliferation by causing delays in both the S and G2-M phases of the cell cycle. Inhibition of angiogenesis seemed to reflect effects on both tumor and endothelial cells. The JNK inhibitor suppressed the production of vascular endothelial growth factor and interleukin-8 by tumor cells and also inhibited endothelial cell proliferation and capillary tube formation. Reduced amounts and phosphorylation of epidermal growth factor receptor were found in tumor cells after treatment with SP600125. Small interfering RNA–mediated suppression of JNK1/2 led to reduced tumor cell proliferation and decreased levels of epidermal growth factor receptor, vascular endothelial growth factor, and interleukin-8. Conclusions: JNK activity is commonly increased in HNSCC. Our preclinical results provide a rationale for evaluating JNK inhibition as an approach to treating HNSCC.
High adiponectin in chronic liver disease and cholestasis suggests biliary route of adiponectin excretion in vivo
Authors: Frank Tacke, Torsten Wüstefeld, Rüdiger Horn, Tom Luedde, Annavarapu Srinivas Rao, Michael P. Manns, Christian Trautwein, Georg Brabant
Journal: Journal of Hepatology (2005)
Climate and aeroallergen levels in asthma: a 12 month prospective study
Authors: M. J. Epton, I. R. Martin, P. Graham, P. E. Healy, H. Smith, R. Balasubramaniam, I. C. Harvey, D. W. Fountain, J. Hedley, G. I. Town
Journal: Thorax (1997)

BACKGROUND: There is evidence to suggest that changes in weather and airborne fungal spore and pollen counts may affect asthma symptoms. METHODS: The relationship between climate, airborne fungal spore, and pollen counts and peak expiratory flow rate (PEFR) and asthma symptoms was prospectively investigated in a population of mild to moderate asthmatic subjects in Blenheim, New Zealand. Subjects recorded twice daily PEFR measurements and asthma symptom scores for up to one year. Spore and pollen counts were measured two hourly and meteorological data were measured hourly. Individual, within person, multiple linear regression analyses were conducted, adjusting for auto-correlation. A random effects model was assumed for the individual regression co-efficients and weighted estimates of the mean of these coefficients were obtained by the method of maximum likelihood. RESULTS: One hundred and thirty nine asthmatic patients (60% atopic) aged 17-80 years completed the study. Of the weather variables, only temperature showed a small but consistent association with PEFR. The mean rise in PEFR for an 8.8 degrees C (2 SD) change in temperature was 0.78% (95% CI 0.44% to 1.11%), approximately 3.0 l/min. There was a weak association between days of high basidiospore counts and increased nocturnal wakening and reliever medication use. Pollen counts showed no consistent association with either PEFR or asthma symptoms. CONCLUSIONS: The results of this study suggest that the effects of weather and aeroallergens on PEFR and asthma symptoms in this population are small, and that other causes need to be sought to account for variations in asthma severity and exacerbations.
The Fc receptor on thymus-derived lymphocytes. I. Detection of a subpopulation of murine T lymphocytes bearing the Fc receptor.
Authors: R D Stout, L A Herzenberg
Journal: The Journal of Experimental Medicine (1975)

Utilizing the fluorescence-activated cell sorter (FACS) and washed murine antibody-antigen complexes formed in antibody excess, we have demonstrated the presence of the Fc receptor on the surface of a distinct subpopulation of murine T lymphocytes. No differences in intensity of labeling with the complexes was observed when the Fc+ T lymphocytes were compared with Fc+ B lymphocytes. The majority of Fc+ T lymphocytes are small lymphocytes determined by light-scattering characteristics on the FACS. Separating Fc+ from Fc- T lymphocytes from spleens of mice primed 1 wk or 1 mo previously with keyhole limpet hemocyanin (KLH) revealed that the T cells capable of cooperating with DNP-KLH primed B cells to give an adoptive anti-DNP PFC response do not bear the Fc receptor.
An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection.
Authors: J L Flynn, J Chan, K J Triebold, D K Dalton, T A Stewart, B R Bloom
Journal: The Journal of Experimental Medicine (1993)

Tuberculosis, a major health problem in developing countries, has reemerged in recent years in many industrialized countries. The increased susceptibility of immunocompromised individuals to tuberculosis, and many experimental studies indicate that T cell-mediated immunity plays an important role in resistance. The lymphokine interferon gamma (IFN-gamma) is thought to be a principal mediator of macrophage activation and resistance to intracellular pathogens. Mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculosis, although they develop granulomas, gko mice fail to produce reactive nitrogen intermediates and are unable to restrict the growth of the bacilli. In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma.
Contamination Rates of Blood Cultures Obtained by Dedicated Phlebotomy vs Intravenous Catheter
Authors: Alonna Norberg, Norman C. Christopher, Maria L. Ramundo, John R. Bower, Shirley A. Berman
Journal: JAMA (2003)

Blood culture is the criterion standard for identifying children with bacteremia. However, elevated false-positive rates are common and are associated with substantial health care costs.To compare contamination rates in blood culture specimens obtained from separate sites vs through newly inserted intravenous catheters.Observational study conducted January 1998 through December 1999 among patients aged 18 years or younger who were seen at a US children's hospital emergency department and had a blood culture obtained as part of their care. Medical records were reviewed in all cases with a positive blood culture. Patients with indwelling vascular catheters were excluded.All phlebotomy was performed by emergency department registered nurses. During the baseline phase, blood specimens for culture were obtained simultaneously with intravenous catheter insertion. During the postintervention phase, specimens were obtained by a separate, dedicated procedure.Contamination rate in the postintervention period compared with the baseline period.A total of 4108 blood cultures were evaluated, including 2108 during the baseline phase and 2000 in the postintervention phase. The false-positive blood culture rate decreased from 9.1% to 2.8% (P<.001). A statistical process control chart demonstrated a steady-state process in the baseline phase and the establishment of a significantly improved steady state in the postintervention phase. Young age was associated with increased contamination rate in both the baseline and postintervention periods.Blood culture contamination rates were lower when specimens were drawn from a separate site compared with when they were drawn through a newly inserted intravenous catheter.
Tumour necrosis factor-α enhances intraepithelial lymphocyte proliferation and migration
Authors: E C Ebert
Journal: Gut (1998)

Background —Tumour necrosis factor α (TNF-α) is a proinflammatory cytokine found in abundance in diseased intestine. Aims —The T cell production of TNF-α and the impact of this cytokine on intestinal T cell proliferation, migration, and cytotoxicity were studied. Methods —Intestinal lymphocytes from normal jejunum were used. TNF-α production in culture supernates was measured by enzyme linked immunosorbent assay (ELISA). Lymphocyte proliferation was measured using 3 H thymidine uptake; migration, using transwell chambers; and cytotoxicity of HT-29 colon cancer cells, using the chromium-51 release assay. Results —TNF-α was produced mainly by the CD8+ T cells in the intraepithelial lymphocytes (IEL) and the CD4+ T cells in the lamina propria lymphocytes in response to CD2 stimulation: 478 (94) and 782 (136) pg/ml, respectively. TNF-α (1 ng/ml or greater) augmented proliferation of IEL in response to interleukin 2 (IL-2), IL-7, or antibody to CD3 due to increased activation that did not involve IL-2 production or receptor generation. Conversely, antibody to TNF-α reduced IEL proliferation in response to IL-2 or IL-7. TNF-α also induced calcium mobilisation and chemokinesis (by 2.8 (0.5) fold over spontaneous migration). TNF-α had no effect on lymphokine activated killer cell activity. Conclusions —TNF-α increases the proliferation and migration of IEL, which may expand their number in the epithelium.
Toremifene Improves Lipid Profiles in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer: Interim Analysis of a Multicenter Phase III Study
Authors: Matthew R. Smith, S. Bruce Malkowicz, Franklin Chu, John Forrest, Paul Sieber, K. Gary Barnette, Domingo Rodriquez, Mitchell S. Steiner
Journal: Journal of Clinical Oncology (2008)

Purpose Androgen-deprivation therapy (ADT) is associated with greater risk of incident coronary heart disease and hospital admission for myocardial infarction; treatment-related increases in serum lipids may contribute to greater cardiovascular disease risk. We evaluated the effects of toremifene, a selective estrogen-receptor modulator, on fasting serum lipid levels in men receiving ADT for prostate cancer. Patients and Methods In an ongoing, multicenter, double-blind, placebo-controlled phase III fracture-prevention study, 1,389 men receiving ADT for prostate cancer were randomly assigned to receive toremifene (80 mg/d) or placebo. In this interim analysis of 188 patients, changes in fasting serum lipids from baseline to month 12 were compared between the placebo and toremifene groups. Results Changes in serum lipids differed significantly between the groups. Mean (± SE) total cholesterol decreased by 1.0% ± 1.7% from baseline to month 12 in the placebo group and decreased by 8.1% ± 1.4% in the toremifene group (P = .001 for between group comparison). Low-density lipoprotein (LDL) cholesterol increased by 0.8% ± 2.5% in the placebo group and decreased by 8.2% ± 2.5% in the toremifene group (P = .003). In contrast, high-density lipoprotein (HDL) cholesterol decreased by 4.9% ± 1.2% in the placebo group and increased by 0.5% ± 2.2% in the toremifene group (P = .018). Triglycerides increased by 6.9% ± 4.2% in the placebo group and decreased by 13.2% ± 3.6% in the toremifene group (P = .003). Conclusion Toremifene significantly decreased total cholesterol, LDL cholesterol, and triglycerides, and increased HDL cholesterol in men receiving ADT for prostate cancer.
On Some Cases of Idiopathic Neuritis
Authors: J. M'crea
Journal: BMJ (1873)

the adductors, and vastus externus muscles, in a partially disorgan- ised state.The integument showed no symptoms of thinning in any part.The anterior crural nerve was found deeply imbedded in the clot, and was the only recognisable structure in the tumour.An incision was made from the middle of Poupart's ligament to the um- bilicus, and thence to the sternum.The kidneys were in a healthy condition; the liver was enlarged, and showed appearances of waxy degeneration.On cutting across the aorta, and dissecting the external iliac artery downwards, it was found that an aneurism existed on the right superficial femoral artery.The femoral artery was then dissected upwards from the popliteal, as well as possible, to the tumour, and the mass removed for preservation.It consisted of a quantity of laminated fibrine, situated in Scarpa's triangle, where it appears to have burst, and this, I believe, took place before the patient applied for medical relief, at which time the tumour was localised, and about the size of two fists.The epigastric and circumflex ilii arteries were considerablv enlarged.The upper part of the femoral artery leading into the tumour was pervious; that immediately below it and leading from it was im- pervious.This case of diffused aneurism is, I think, worthy of record, on ac- count of the close resemblance of its symptoms to those of malignant disease.If the nature of the tumour had been discovered during its early stage, an effort to cure it might perhaps have been made.This case clearly shows that cachexia, rapid growth, and severe pain must not be accepted as sufficient evidences of cancer.In reviewing the history of this case, there are some points which should have suggested its non-malignant character; namely, the absence of lymphatic en- largements, or symptoms of secondary deposit, and of any tendency to ulceration of the skin over the tumour; the favourable family history; and the fact that the tumour was definitely bounded superiorly by Poupart's ligament.