tbuckley/cabot-search huggingface dataset:
The growth factor midkine regulates the renin-angiotensin system in mice
Authors: Akinori Hobo, Yukio Yuzawa, Tomoki Kosugi, Noritoshi Kato, Naoto Asai, Waichi Sato, Shoichi Maruyama, Yasuhiko Ito, Hiroyuki Kobori, Shinya Ikematsu, Akira Nishiyama, Seiichi Matsuo, Kenji Kadomatsu
Journal: Journal of Clinical Investigation (2009)

The renin-angiotensin system plays a pivotal role in regulating blood pressure and is involved in the pathogenesis of kidney disorders and other diseases. Here, we report that the growth factor midkine is what we believe to be a novel regulator of the renin-angiotensin system. The hypertension induced in mice by 5/6 nephrectomy was accompanied by renal damage and elevated plasma angiotensin II levels and was ameliorated by an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blocker. Notably, ACE activity in the lung, midkine expression in the lung, and midkine levels in the plasma were all increased after 5/6 nephrectomy. Exposure to midkine protein enhanced ACE expression in primary cultured human lung microvascular endothelial cells. Furthermore, hypertension was not induced and renal damage was less severe in midkine-deficient mice. Supplemental administration of midkine protein to midkine-deficient mice restored ACE expression in the lung and hypertension after 5/6 nephrectomy. Oxidative stress might be involved in midkine expression, since expression of NADH/NADPH oxidase-1, -2, and -4 was induced in the lung after 5/6 nephrectomy. Indeed, the antioxidative reagent tempol reduced midkine expression and plasma angiotensin II levels and consequently ameliorated hypertension. These results suggest that midkine regulates the renin-angiotensin system and mediates the kidney-lung interaction after 5/6 nephrectomy.
Abstract 2020: Next-generation sequencing for mutation discovery in Ewing sarcoma.
Authors: Andrew S. Brohl, Young Song, Laura Hurd, Hongling Liao, Li Chen, Rajesh Patidar, John F. Shern, Jun S. Wei, Javed Khan
Journal: Cancer Research (2013)

Abstract Background: Ewing sarcoma (EWS) is the second most common type of primary bone tumor to affect children and adolescent and accounts for 2.9% of all childhood cancers. Despite advances in multidisciplinary treatment leading to improved outcomes over time, long term survival still remains less than 50% for patients older than 15 years of age and only 65% in younger patients. In an effort to identify novel prognostic and therapeutic targets, we utilized next generation sequencing techniques to evaluate EWS samples for somatic mutation. Methods: Whole genome paired-end sequencing using the Complete Genomics method was performed on the DNA from 6 EWS matched tumor-normal samples. Somatic mutations were identified and classified using standard bioinformatics techniques and mutations of interest were verified using capillary sequencing. To extend discoveries and evaluate for mutational recurrence, targeted sequencing was performed on a validation cohort of 61 EWS tumors and 22 EWS cell lines using a custom multiplex PCR design followed by high-coverage sequencing on the Ion Torrent system. Results: In the discovery cohort, we detected an average of 361 somatic mutations per tumor in non-repetitive regions and an average of 6 somatic mutations per tumor in protein coding regions (=0.15 mutations/Mb of coding sequence). The well-established FLI1-EWSR1 gene fusion was detected by the whole genome sequencing in all 6 samples. Additional previously reported genetic events were also seen including frequent chromosomal trisomy and deletion of the CDKN2A containing locus on chromosomal region 9p21 in 2 of 6 samples. In the validation cohort of tumors, known recurrent mutations such as in TP53 (3/61 = 4.9%) were seen at rates similar to that previously reported in EWS. Continued efforts are underway to verify novel recurrent mutations. Conclusion: Next-generation sequencing provides a powerful tool to characterize the genetic landscape and evaluate for recurrent mutations in cancer. We utilize this tool in Ewing sarcoma in a project that provides both a comprehensive genomic evaluation from whole genome sequencing data and as well evaluates for recurrent mutations using a targeted sequencing approach. Citation Format: Andrew S. Brohl, Young Song, Laura Hurd, Hongling Liao, Li Chen, Rajesh Patidar, John F. Shern, Jun S. Wei, Javed Khan. Next-generation sequencing for mutation discovery in Ewing sarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2020. doi:10.1158/1538-7445.AM2013-2020
Musculoskeletal injuries in the ultramarathon: the 1990 Westfield Sydney to Melbourne run.
Authors: K E Fallon
Journal: British Journal of Sports Medicine (1996)

OBJECTIVE: To document the injuries sustained by participants in a 1005 km ultramarathon. METHODS: Clinical notes were reviewed on entrants in the 1005 km Sydney to Melbourne ultramarathon. An injury was recorded following self referral by a participant or if the history obtained from the runner or his support crew indicated the likelihood of a significant injury which could have an impact upon performance. RESULTS: 64 injuries were found in 32 runners. The knee (31.3%) and ankle (28.1%) regions were most commonly injured. The most common single diagnosis was retropatellar pain syndrome, and Achilles tendinitis and medial tibial stress syndrome were the next most common injuries. Peritendinitis/tendinitis of the tendons passing under the extensor retinaculum at the ankle, an injury infrequently reported in other sports, was common (19% of all injuries). CONCLUSIONS: The injuries were typically associated with running but 12 (19% of the total) involved the tendons of the muscles of the anterior compartment of the lower leg, and in almost every case the major site of inflammation was at the extensor retinaculum at the anterior aspect of the ankle. This injury appears to be relatively specific to the ultramarathon-"ultramarathoner's ankle".
Development of Investigational Radiation Modifiers
Authors: A. Dimitrios Colevas, J. Martin Brown, Stephen Hahn, James Mitchell, Kevin Camphausen, C. Norman Coleman, Barbara Conley, Richard Cumberlin, Helen B. Stone, Rosemary Wong, Boris Freidlin, Ken Kobayashi, Anthony J. Murgo, Robert Shoemaker, Philip J. Tofilon, Hak Choy, Adam Dicker, James H. Doroshow, Silvia C. Formenti, Adam Garden, Stephen Gately, Richard Hill, Timothy J. Kinsella, Malcolm Moore, Jann Sarkaria, Dietmar Siemann, Gerald Sokol, Beverly A. Teicher, Andy Trotti, Andrew T. Turrisi, Raul Urtasun, Everett E. Vokes
Journal: JNCI Journal of the National Cancer Institute (2003)
Colonic explosion during endoscopic polypectomy: avoidable complication or bad luck?
Authors: D. Josemanders, E. Spillenaar Bilgen, A. van Sorge, P. Wahab, R. de Vries
Journal: Endoscopy (2006)

We were confronted recently by an intraluminal colonic explosion during a colonic polypectomy procedure using snare loop electrocautery, probably caused by the presence of hydrogen and/or methane in combustible concentrations. Our patient needed immediate surgery, when several lacerations were found in the colon: a right hemicolectomy and a partial sigmoid resection with primary anastomoses were performed. Colonic bacteria, rests of fecal fluids, certain cleansing solutions, and oxygen insufflation are the main factors involved in cases of colonic explosion. We describe this dramatic event in our patient and discuss whether this complication might be avoidable in the future.
Hypothermia, abdominal pain, and lactic acidosis in phenformin-treated diabetic.
Authors: G G Shirriffs, P D Bewsher
Journal: BMJ (1970)

A case of lactic acidosis in a phenformnin-treated diabetic is described. CASE REPORTA 73-year-old man had had a laparotomy in 1962, and sub- sequently developed an incisional hernia.Primary diabetic symp- toms developed in 1964, and he was eventually controlled by diet and phenformin.In February 1967 he was admitted to a surgical ward complaining of abdominal pain, the cause of which was not determined.The rectal temperature on admission was 89' F. (31-70 C.) and the blood pressure 105/60 mm.Hg.The blood sugar was 80 mg./100 ml. and the plasma CO2 8.5 mEq/l.His abdominal pain subsided and he was discharged home four days later.In December 1967 the dose of phenformin was increased from 75 to 125 mg.daily, in divided doses.
Chronic Hypoxia Activates Lung 15-Lipoxygenase, Which Catalyzes Production of 15-HETE and Enhances Constriction in Neonatal Rabbit Pulmonary Arteries
Authors: Daling Zhu, Meetha Medhora, William B. Campbell, Nancy Spitzbarth, John E. Baker, Elizabeth R. Jacobs
Journal: Circulation Research (2003)

Hypoxia causes localized pulmonary arterial (PA) constriction to divert blood flow to optimally ventilated regions of the lung. The biochemical mechanisms for this have remained elusive, especially during prolonged exposures to reduced P o 2 . We have evidence that subacute hypoxia activates 15-lipoxygenase (15-LO) in small PAs of neonatal rabbits maintained for 9 days in hypoxic environments (F io 2 =0.12) compared with siblings raised under normoxia. PA microsomal products of 15-LO, 15-hydroxyeicosatetraenoic acid (HETE), 11,14,15-trihydroxyeicosatrienoic acid (THETA), and 11,12,15-THETA were identified by gas chromatography/mass spectrometry. Increased amounts of these products are synthesized in vivo and in vitro by the lungs of animal raised in hypoxic versus normoxic environments. 15-HETE formation is attenuated by lipoxygenase, but not cytochrome P450 or cyclooxygenase inhibitors. Activation of 15-LO is associated with translocation of the enzyme from the cytosol to membrane as seen by Western immunoblotting. Immunohistochemical analysis demonstrates that 15-LO expression is clearly localized in vascular cells in lungs from normoxic and hypoxic kits. 15-HETE causes concentration-dependent constriction of PA rings from animals exposed to hypoxic but not normoxic environments. In addition, lipoxygenase inhibitors reduce phenylephrine-induced constriction of PA rings. Therefore, subacute hypoxia increases expression of and activates 15-LO, and enhances sensitivity of pulmonary arteries to its product, 15-HETE. Because 15-HETE is a constrictor in this vascular bed, it may play an important role in hypoxia-induced pulmonary vasoconstriction in rabbit kits. Although a clear causal relationship remains to be demonstrated, these data suggest a previously unrecognized role for 15-LO in hypoxic vasoconstriction in neonatal mammals.
A sensitive immunoradiometric assay for serum thyroid stimulating hormone: a replacement for the thyrotrophin releasing hormone test?
Authors: J Seth, H A Kellett, G Caldwell, V M Sweeting, G J Beckett, S M Gow, A D Toft
Journal: BMJ (1984)

The value as a thyroid function test of a new, rapid, and highly sensitive immunoradiometric assay for thyroid stimulating hormone (TSH) was assessed in 188 consecutive new patients with suspected hyperthyroidism. The diagnosis was made on clinical grounds and on the basis of serum total triiodothyronine and thyroxine concentrations and the response of TSH to thyrotrophin releasing hormone (TRH) as measured by radioimmunoassay. In all except one patient the basal TSH concentration by immunoradiometric assay predicted the response of TSH by radioimmunoassay to TRH, an undetectable value being recorded in patients with a subnormal response and a measurable value in those with a normal test result. This clear relation was not observed for basal TSH concentrations as measured by radioimmunoassay. In a series of 39 hospital inpatients with acute or chronic non-thyroidal illness, of whom 11 had low concentrations of total thyroxine or triiodothyronine, or both, basal TSH concentrations were detectable by both radioimmunoassay and immunoradiometric assay in all cases and were associated with normal responses to TRH. The immunoradiometric assay for TSH, which is commercially available, may therefore obviate the need for the more time consuming TRH test and simplify the approach to thyroid function testing in patients with suspected hyperthyroidism.
Abstract 3218: Bisphosphonates induce premature senescence and impair proliferation and migration of normal human oral keratinocytes
Authors: Reuben H. Kim, Rachel Lee, Jessica Woo, Qing-Hua Dong, Ki-Hyuk Shin, Mo Kang, No-Hee Park
Journal: Cancer Research (2010)

Abstract Bisphosphonates (BPs) are potent anti-resorptive agents that are widely used to treat metastatic bone diseases in cancer patients. BPs target the mevalonate pathway and inhibit cholesterol synthesis and prenylation (e.g., geranylgernaylation and farnesylation) of small GTPases that are important for cell proliferation and survival. Long-term users of BPs are at the higher risk of developing osteonecrosis of the jaw (ONJ), which commonly occurs at the site of previous tooth extraction or other surgical interventions. Although bisphosphonate-related osteonecrosis of the jaw (BRONJ) is clinically defined as exposed necrotic bone with unhealed and open oral mucosa, the exact role of oral mucosa in the pathophysiology of BRONJ is not fully understood. The current study was undertaken to examine direct effects of BPs on the reepithelialization of oral mucosal cells. When normal human oral keratinocytes (NHOK) were treated with pamidronate (PAM), proliferation and migration were inhibited in dose-dependent manner as determined by MTT assay, proliferation assay, Western blotting against PCNA, and the scratch wound healing assay. Cell cycle analysis revealed increased S-phase content in PAM-treated NHOK, and this was associated with decreased mRNA and protein expressions of Cyclin A2 but not Cyclin D. PAM also induced premature senescence in NHOK as determined by increased β-galactosidase positivity, increased p16 expression, and phosphorylated p-38 MAP kinase pathway. PAM-induced premature senescence and proliferation inhibition were partially reversed by geranylgerniol (GGOH), but not farnesol (FOH), which reconstitute geranylgeranylation and farnesylation of the mevalonate pathway, respectively. Finally, using 3-dimensional (3D) raft culture system, we found that PAM-treated oral mucosal tissue constructs showed diminished immunohistochemical staining of PCNA and loss of reepithelialization in the wounded area, indicating that BPs impair proliferation and migration of oral epithelium constructs ex vivo. Our study demonstrates that BPs induce premature senescence and directly impair proliferation and migration of oral mucosal cells, which may explain the pathophysiology of BRONJ in cancer patients undergoing BP-treatment. This study was supported by NIDCR/NIH (DE017121). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3218.
OP0135 The New ACR/EULAR Criteria for Rheumatoid Arthritis is Able to Identify Patients with Same Disease Activity but Less Damage by Ultrasound
Authors: S. Z. Aydin, C. C. Gallego, J. Nam, J. Freeston, S. Horton, R. J. Wakefield, P. Emery
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The 1987 ACR classification criteria (OLD/RA) had the disadvantage of including features related to damage or prolonged disease, such as erosions/ rheumatoid nodules. The new ACR/EULAR criteria (NEW/RA) allows classification of patients with early disease prior to damage. This is important as earlier diagnosis and treatment has been shown to improve outcome. <h3>Objectives</h3> We aimed to compare the US findings of patients fulfilling each criterion to examine the impact of NEW/RA on disease characteristic particularly disease duration. <h3>Methods</h3> A total number of 2730 hand, wrist, elbow, shoulder, knee, ankle and feet joints of 105 consecutive patients registered in early arthritis register either fulfilling RA criteria (60 patients fulfilling the OLD/RA, 22 patients with the NEW/RA/not fulfilling the OLD/RA) or with undifferentiated arthritis (23 patients) were scanned by US. The sonographer was blinded to the diagnosis and clinical assessments. Synovitis, erosions and power Doppler (PD) findings were scored on a scale between 0-3; being 0: none, 1: mild, 2: moderate and 3 for severe US findings and those were added up to calculate a synovitis, PD and erosion scores for each patient. <h3>Results</h3> Patients with OLD/RA had similar SJC, TJC, CRP, acute phase response, patient global and DAS28 scores with NEW/RA patients (table1). Disease duration was longer in OLD/RA (39±38 months) compared to NEW/RA (17±13; p= 0.008) but statistically not different from patients with undifferentiated arthritis (25±17 months). Both OLD/RA and NEW/RA groups had similar synovitis scores and PD scores whereas erosion scores were higher in patients with OLD/RA (p=0.009). Patients with undifferentiated arthritis were older than RA patients. These patients had fewer swollen joints than NEW/RA patients (p=0.017). All the other disease activity parameters were similar compared with both NEW/RA and OLD/RA. Both the synovitis scores (p=0.006) and erosion scores (p=0.007) of patients with undifferentiated arthritis were lower than OLD/RA despite being similar to NEW/RA. <h3>Conclusions</h3> The new ACR/EULAR RA criteria allowed classification of patients with less damage but similar disease activity (as detected by clinical assessment and synovitis &amp; PD by US). The similar disease activity should ensure suitability for intervention whilst shorter duration and less damage should improve outcome with patient benefit. <h3>Disclosure of Interest</h3> None Declared
Birth Characteristics and Subsequent Risks of Maternal Cardiovascular Disease
Authors: Anna-Karin Edstedt Bonamy, Nisha I. Parikh, Sven Cnattingius, Jonas F. Ludvigsson, Erik Ingelsson
Journal: Circulation (2011)

Prior studies showing an inverse relationship between low birth weight in offspring and maternal risks of cardiovascular diseases (CVD) are limited by lack of information on gestational age and/or insufficient adjustment for confounders.In a nationwide Swedish study, we included information on 923 686 women and their first singleton births between 1983 and 2005. Cox proportional hazards models were used to study associations between gestational length, fetal growth, and maternal incident hospitalization or death from CVD (coronary heart disease, cerebrovascular events, and heart failure). Multivariable adjusted models accounted for birth year, income, education, country of birth, smoking, diabetes mellitus, hypertension, and preeclampsia. The risk of maternal CVD increased with decreasing gestational age whereas the risk increase related to fetal growth appeared to be restricted to very small-for-gestational-age (SGA) infants. Compared with mothers of non-SGA infants born at term, the hazard ratio of CVD ranged from 1.39 (95% confidence interval 1.22-1.58) to 2.57 (95% confidence interval 1.97-3.34) among mothers to moderately and very preterm infants, respectively. There was a significant interaction between preterm birth and fetal growth with respect to mothers' risk of CVD (P<0.001). Among mothers to very SGA infants, the hazard ratio of CVD ranged from 1.38 (95% confidence interval 1.15-1.65) to 3.40 (95% confidence interval 2.26-5.11) in mothers to term and very preterm infants, respectively.Delivery of a preterm or SGA infant is associated with later life maternal hospitalization or death from CVD even after accounting for socioeconomic factors, smoking, and pregnancy-related complications.
Effect of Varying Doses of Reserpine on Gastric Secretion
Authors: Daniel Liebowitz, John V. Carbone, Valda Crevling
Journal: New England Journal of Medicine (1957)

RESERPINE has been shown to increase the production of hydrochloric acid in both man and animals.1 , 2 That reserpine is a potent stimulus to gastrointestinal secretions and motility has been clearly demonstrated by Haverback et al.,3 who observed this phenomenon after administering a dose of 1 to 3 mg. intravenously. The route of administration is not critical, since the same hypersecretory response has been observed repeatedly after the oral administration of 2 or 3 mg. daily.4 Reserpine in doses of 0.1 to 0.5 mg. daily has been found to have a tranquilizing effect and to act synergistically with hypotensive drugs.5 Because . . .
PSYCHIATRIC PROBLEMS IN A CLINIC FOR CONVULSIVE DISORDERS
Authors: THEODORE T. STONE, ALEX J. ARIEFF
Journal: American Journal of Psychiatry (1940)

Twenty-six cases of mental aberration occurring in a clinic for convulsive disorders are herewith presented. The causes of the psychiatric difficulties are as follows: idiosyncrasy to bromides; alcoholic intoxication; status epilepticus; psychic equivalents; encephalitis; trauma to the head; brain tumor; tuberous sclerosis; schizophrenia; mental depressions; emotional instability and an unclassified case of psychosis.
Zidovudine and the Natural History of the Acquired Immunodeficiency Syndrome
Authors: Richard D. Moore, Julia Hidalgo, Barbara W. Sugland, Richard E. Chaisson
Journal: New England Journal of Medicine (1991)

We sought to describe the trends in survival from 1983 to 1989 among persons with the acquired immunodeficiency syndrome (AIDS) and to examine the relative effects on the natural history of AIDS of zidovudine use and demographic and clinical characteristics. This longitudinal, observational, population-based study used data from the Maryland Human Immunodeficiency Virus Information System, a data base that links information from the Maryland AIDS Registry with data on public and private health care claims, vital statistics, and hospital, long-term care, and ambulatory care records.
Recent advances in investigations of toxicity of automotive exhaust
Authors: Maurice Stupfel
Journal: Environmental Health Perspectives (1976)

The influence of auto exhaust on man's health is difficult to gauge considering the intricacy of human environmental urban stresses and particularly of other air polluting (industrial, domestic) emissions. Epidemiological surveys made in road tunnel employees and in traffic officers have not demonstrated specific effects and have often been complicated by cigarette smoking as a factor. Long-term animal experiments run mostly on small rodents give evidence of little effect of the pathological actions of dilutions such as those encountered in high polluted cities. However the acute toxicity of gasoline exhaust emission is well known and mostly due to carbon monoxide. Considering the different types of cycles and operating conditions of vehicles (gasoline and diesel), auto exhaust gases constitute no more a chemical entity than they show, a definite toxicity. A great number of substances that they contain (nitrogen oxides, aldehydes, antiknock additives, heavy metals, possible catalysts are highly toxic as shown by in vivo and in vitro (mutagenic) tests. Interactions of the components are for the moment ignored or poorly understood. Besides, the evolution of the physicochemical properties and natures of the auto exhaust emission in the gaseous biotope of man under determined conditions of ultraviolet irradiation, temperature, and hygrometry provoke the formation of secondary products such as oxidants and ozone. Several experiments show clearly that irradiation increases the toxicity of auto exhaust significantly. For these reasons, geographical, meteorological, and chronological (circadian and seasonal) factors should be taken into consideration, especially with regard to emission standards.