tbuckley/cabot-search huggingface dataset:
The Systemic-Onset Variant of Juvenile Idiopathic Arthritis Needs to Be Recorded as an Autoinflammatory Syndrome: Comment on the Review by Nigrovic
Authors: Donato Rigante, Luca Cantarini
Journal: Arthritis & Rheumatology (2014)

We read with interest the recent review article by Nigrovic (1) describing the uniqueness of systemic juvenile idiopathic arthritis (JIA) among the different subtypes of JIA, because it is characterized by systemic features during the initial phase and severe articular signs during the later phase of disease. As discussed by Nigrovic, there is increasing evidence that initiating cytokine blockade early during the systemic phase might alter disease pathophysiology to avoid chronic inflammation and even the arthritic manifestations of systemic JIA. The umbrella-term "JIA" still identifies a heterogeneous group of inflammatory joint diseases. In particular, according to the International League of Associations for Rheumatology classification (2), JIA refers to all forms of arthritides of unknown etiology beginning before age 16 years and persisting for at least 6 weeks, supposing that all other known causes of arthritis have been ruled out. The results of previous studies have indicated that systemic JIA is associated with abnormalities of the innate immune system rather than the classic autoimmune system, because neither autoantibodies nor strong HLA genetic associations can be demonstrated (3). Indeed, systemic JIA does not behave as an articular disease, and many investigators have shown how its manifestations closely mimic those of autoinflammatory syndromes, with an exaggerated innate immune response leading to recurrent sterile inflammation, phagocyte activation, and oversecretion of proinflammatory cytokines such as interleukin-1β (IL-1β), in synergy with endogenous Toll-like receptor ligands, resulting in significant long-term morbidity (4). Although many investigators agree that the systemic inflammation in systemic JIA is driven mostly by up-regulated innate immune pathways, including IL-1, it remains unestablished whether this is attributable to intrinsic abnormalities in caspase 1 activation or environmental triggers. Pascual et al (5) showed that different innate immunity genes were overworking in patients with active systemic JIA. Moreover, different studies have also revealed the dramatic impact of IL-1 blockade, in the form of either the IL-1 receptor antagonist anakinra or the anti–IL-1β blocker canakinumab, in the induction of clinical remission in a substantial subset of patients with systemic JIA. Although we believe that reconsidering the nomenclature of JIA should be approached with caution and global consensus, the newer insights into the pathogenesis and treatment of systemic JIA suggest that this disorder should be drawn away from the group of juvenile arthritides and definitely included in the group of acquired autoinflammatory syndromes, which day after day continues to enlarge and includes nonhereditary periodic fever syndromes, vascular diseases, and metabolic diseases.
Anemia ameliorates progressive renal injury in experimental DOCA-salt hypertension.
Authors: H M Lafferty, D L Garcia, H G Rennke, J L Troy, S Anderson, B M Brenner
Journal: Journal of the American Society of Nephrology (1991)

To explore the role of systemic hematocrit in the vascular adaptations which characterize desoxycorticosterone-salt hypertension, studies were performed in three groups of rats with uninephrectomy, desoxycorticosterone administration, and 1% saline in the drinking water. One group received recombinant human erythropoietin to increase hematocrit, and another group was subjected to phlebotomy and fed a low-iron diet to induce anemia. Control rats exhibited systemic and glomerular capillary hypertension, proteinuria, and substantial glomerular sclerosis at 8 wk. Erythropoietin modestly increased hematocrit and blood pressure and substantially aggravated glomerular capillary pressure, proteinuria, and glomerular sclerosis. In contrast, reduction of hematocrit with a low-iron diet significantly attenuated systemic and glomerular hypertension, proteinuria, and sclerosis. It was concluded that the pace of progression of glomerular injury can be limited by chronic reduction in hematocrit, which effectively ameliorates both systemic and glomerular hypertension in this model of salt-sensitive hypertensive renal disease.
Molecular characterization and antimicrobial susceptibility profiles in Streptococcus agalactiae colonizing strains: association of erythromycin resistance with subtype III-1 genetic clone family
Authors: C. Florindo, S. Viegas, A. Paulino, E. Rodrigues, J.P. Gomes, M.J. Borrego
Journal: Clinical Microbiology and Infection (2010)
Delayed Hypersensitivity to Simian Virus 40 Tumor Cells in BALB/c Mice Demonstrated by a Radioisotopic Foot-Pad Assay
Authors: Meera S. Paranjpe, Charles W. Boone
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Delayed Hypersensitivity to Simian Virus 40 Tumor Cells in BALB/c Mice Demonstrated by a Radioisotopic Foot-Pad Assay Get access Meera S. Paranjpe, Meera S. Paranjpe Cell Biology Section, National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles W. Boone Charles W. Boone Cell Biology Section, National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 2, February 1972, Pages 563–566, https://doi.org/10.1093/jnci/48.2.563 Published: 01 February 1972 Article history Received: 03 January 1972 Published: 01 February 1972
Randomized, Double-Blind, Phase 3 Trial of Triple Therapy With Dapagliflozin Add-on to Saxagliptin Plus Metformin in Type 2 Diabetes
Authors: Chantal Mathieu, Aurelian Emil Ranetti, Danshi Li, Ella Ekholm, William Cook, Boaz Hirshberg, Hungta Chen, Lars Hansen, Nayyar Iqbal
Journal: Diabetes Care (2015)

OBJECTIVE To compare the efficacy and safety of treatment with dapagliflozin versus that with placebo add-on to saxagliptin plus metformin in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin treatment. RESEARCH DESIGN AND METHODS Patients receiving treatment with stable metformin (stratum A) (screening HbA1c level 8.0–11.5% [64–102 mmol/mol]) or stable metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor (stratum B) (HbA1c 7.5–10.5% [58–91 mmol/mol]) for ≥8 weeks received open-label saxagliptin 5 mg/day and metformin for 16 weeks (stratum A) or 8 weeks (stratum B) (saxagliptin replaced any DPP-4 inhibitor). Patients with inadequate glycemic control (HbA1c 7–10.5% [53–91 mmol/mol]) were randomized to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin. The primary end point was the change in HbA1c from baseline to week 24. Secondary end points included fasting plasma glucose (FPG) level, 2-h postprandial glucose (PPG) level, body weight, and proportion of patients achieving an HbA1c level of &amp;lt;7% (53 mmol/mol). RESULTS Treatment with dapagliflozin add-on to saxagliptin plus metformin resulted in a greater mean HbA1c reduction than placebo (−0.82 vs. −0.10% [−9 vs. −1.1 mmol/mol], P &amp;lt; 0.0001). Significantly greater reductions in FPG level, 2-h PPG level, and body weight were observed, and more patients achieved an HbA1c level of &amp;lt;7% (53 mmol/mol) with treatment with dapagliflozin versus placebo. Adverse events were similar across treatment groups, with a low overall risk of hypoglycemia (∼1%). Genital infections developed in more patients with dapagliflozin treatment (5%) than with placebo (0.6%). CONCLUSIONS Triple therapy with dapagliflozin add-on to saxagliptin plus metformin improves glycemic control and is well tolerated in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin therapy.
Proliferation and Behavior of Phagocytic Cells in Mouse Lymphoma Tissue&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D. Metcalf, M. Ishidate, M. Brumby
Journal: JNCI Journal of the National Cancer Institute (1967)

Large phagocytic cells were found to be a constant component of lymphoma tissue in AKR mice with lymphoid leukemia. Determination of mitotic indexes and labeling patterns after the administration of tritiated thymidine suggested that the phagocytic cells divided every 200–300 hours, much more slowly than the doubling time of 24–48 hours of the lymphoma cell population. This required a continuous recruitment of new cells into the phagocytic cell population as the lymphoma mass expanded. Parabiotic studies indicated that such cells did not enter lymphoma tissue from the blood; the most likely source of new cells transforming to phagocytic cells was the surviving population of normal reticuloendothelial cells in the organs infiltrated by lymphoma tissue. Phagocytosed cells were rapidly broken down by the phagocytic cells, but their nuclear material did not accumulate in the cytoplasm of the phagocytic cells. Lymphoma cells in contact with phagocytic cells had higher mitotic activity than lymphoma cells elsewhere in the tumor mass.
Increased toll-like receptor 4 expression in mice lung tissue under intermittent hypoxia
Authors: Hyeon Hui Kang, Kihoon Park, Ju Sang Kim, Sang Haak Lee, Hwa Sik Moon
Journal: European Respiratory Journal (2012)

Objective : Obstructive sleep apnea (OSA) is highly prevalent and is associated with increased risk of cardiovascular disease. OSA is characterized by episodic cycles of hypoxia and normoxia during sleep. While OSA is considered as a proinflammatory condition, there is little data on cellular inflammation in OSA. The aim of this study was to examine the expression of lung tissue TLR4 mRNA and protein in mice under intermittent hypoxia condition.   Methods : Eight-week old male C57BL/6J mice were exposed to intermittent hypoxia (30 s exposure to 5 % oxygen, followed by 30 s exposure to 21% oxygen) for 8 h/day during daytime or maintained under normoxic conditions for 2, 3, or 4 weeks. The mRNA expression levels of anti-TLR4, anti-nuclear factor-kappa B (NF-κB), anti-inhibitory I kappa B protein (I-κB), anti-transforming growth factor (TGF-β) and anti-β-actin antibody in lung tissue were measured by real time reverse-transcription PCR, and protein levels were assayed by Western blot.   Results : Under intermittent hypoxia, the mRNA expression of TLR4 was increased more than that of the control group. There was a positive correlation between the mRNA and protein level of TLR4 in a time-dependent manner, although it was not statistically significant. The expressions of I-κB and TGF-β were increased with the period of intermittent hypoxia.   Conclusions : These results show that TLR4 expression is increased in lung tissue under intermittent hypoxia condition. These data suggest that intermittent hypoxia in OSA can influence TLR4 expression and TLR4-associated pathway may be related with systemic inflammatory response in OSA.
Secondary Cytotoxic Response In Vitro Against Moloney Lymphoma Cells Antigenically Altered by Drug Treatment In Vivo
Authors: Angela Santoni, Yvonne Kinney, Abraham Goldin
Journal: JNCI Journal of the National Cancer Institute (1978)

Cell-mediated cytotoxic response in vitro to a Moloney strain of murine leukemia virus-induced tumor (LSTRA) altered by 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) was investigated with the use of mixed-leukocyte tumor cell cultures (MLTC). As assessed by means of a short-term 51Cr-release assay, minimal or no cytolytic activity was generated in primary MLTC. In contrast, high specific cytotoxic response against the altered tumor was obtained in secondary MLTC. Partial cross reactivity was found between the LSTRA and LSTRA/DTIC tumor lines.
Negative feedback–defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL
Authors: Benshang Li, Hui Li, Yun Bai, Renate Kirschner-Schwabe, Jun J Yang, Yao Chen, Gang Lu, Gannie Tzoneva, Xiaotu Ma, Tongmin Wu, Wenjing Li, Haisong Lu, Lixia Ding, Huanhuan Liang, Xiaohang Huang, Minjun Yang, Lei Jin, Hui Kang, Shuting Chen, Alicia Du, Shuhong Shen, Jianping Ding, Hongzhuan Chen, Jing Chen, Arend von Stackelberg, Longjun Gu, Jinghui Zhang, Adolfo Ferrando, Jingyan Tang, Shengyue Wang, Bin-Bing S Zhou
Journal: Nature Medicine (2015)
Cellular Cytotoxicity in Tumor-Bearing Mice After Transfer of Normal or Tumor-Sensitized Lymphoid Cells&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: B Fisher, N Wolmark, E A Saffer
Journal: JNCI Journal of the National Cancer Institute (1980)

The present investigations are a continuation of those indicating that the administration to normal inbred C3HeB/FeJ mice of syngeneic tumor-sensitized cells or cells from F344 Mai rats (xenogeneic) sensitized to mouse tumor imparted “information” that resulted in the production of tumor-specific cytotoxic cells by recipients. Current findings revealed that normal but not tumor-sensitized spleen cells when transferred to syngeneic tumor-bearing recipients enhanced the cytotoxicity of lymphoid cells in the reCipients. This enhanced cytotoxicity was specific for the immunizing tumor. Inoculation of normal or tumor-sensitized lymph node cells failed to prOduce such an effect. Our present and previous findings suggested that in the presence of a tumor. uncommitted cells that reside in the spleen and that are available for recruitment and “instruction” may become depleted. whereas no comparable deficit may exist in cells that are capable of information transfer.
Immune Response to L 2 C Guinea Pig Leukemia-Specific Antigens 2
Authors: Samuel G. Murphy, Harrington Laufman, Albert F. LoBuglio
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Immune Response to L2C Guinea Pig Leukemia-Specific Antigens Get access Samuel G. Murphy, Samuel G. Murphy Search for other works by this author on: Oxford Academic PubMed Google Scholar Harrington Laufman, Harrington Laufman Search for other works by this author on: Oxford Academic PubMed Google Scholar Albert F. LoBuglio Albert F. LoBuglio Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 6, June 1977, Pages 1815–1818, https://doi.org/10.1093/jnci/58.6.1815 Published: 01 June 1977 Article history Received: 16 September 1976 Accepted: 21 December 1976 Published: 01 June 1977
Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma.
Authors: M B Atkins, K R O'Boyle, J A Sosman, G R Weiss, K A Margolin, M L Ernest, K Kappler, J W Mier, J A Sparano, R I Fisher
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate the activity and toxicity of combined high-dose cisplatin, dacarbazine (DTIC), and tamoxifen chemotherapy and high-dose bolus interleukin-2 (IL-2) in patients with metastatic melanoma. PATIENTS AND METHODS Patients with metastatic melanoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and normal organ function were enrolled onto this multiinstitutional Cytokine Working Group trial. Patients received intensive chemoimmunotherapy consisting of cisplatin (50 mg/m2) and DTIC (350 mg/m2) intravenously (IV) on days 1 to 3 and 43 to 45, IL-2 600,000 IU/kg IV every 8 hours on days 12 to 16 and 26 to 30 (maximum, 28 doses), and tamoxifen 20 mg orally each day. Patients were evaluated for response at day 63 of each cycle, and responding patients were given a second cycle of therapy beginning on day 71 to 85. RESULTS Thirty-eight patients were entered onto this study. Toxicities were as expected for the chemotherapy and immunotherapy components of this regimen. Overlapping toxicity consisted primarily of thrombocytopenia (76% of patients required platelet transfusions), neutropenia, anemia, fatigue, and weight loss. Despite these cytopenias, bleeding and infectious complications were rare. There were no treatment-related deaths. Three patients achieved a complete response (CR; 8%), and 13 achieved a partial response (PR). The overall objective response rate was 42% (95% confidence interval [CI], 26% to 58%). Six additional patients had greater than 50% tumor reduction at day 63, which did not persist until a subsequent evaluation. The median duration of response was 5 months (range, 2 to 20+), and the median survival duration was 11 months. CONCLUSION This intensive treatment regimen appears to possess activity in metastatic melanoma comparable, but not superior, to that of other less intensive cisplatin- and IL-2-based chemoimmunotherapy regimens. Although the toxicity and complexity of this regimen make it unsuitable for phase III testing and impractical for more widespread use, the results of this study support a potential favorable interaction between IL-2 and chemotherapy in this disease and highlight the need for appropriately designed phase III trials.
An autopsy case of portopulmonary hypertension associated with idiopathic portal hypertension
Authors: Megumi Furuta, Takahiro Sato, Ichizo Tsujino, Mishie Tanino, Taku Watanabe, Masaharu Nishimura
Journal: European Respiratory Journal (2013)

Idiopathic portal hypertension (IPH) is a rare cause of portal hypertension. The present autopsy report documents a case of portopulmonary hypertension (PoPH) associated with IPH, focusing on the portal and pulmonary vasculopathy.  In Feb 2011, a 70-year-old woman visited a community hospital, presenting with progressive dyspnea. Right heart catheterization (RHC) indicated pulmonary hypertension, but no further investigations were conducted. In May 2012, she was found to have esophageal varix and referred to our hospital. Second RHC showed marked elevation of mean pulmonary artery pressure (68 mmHg), and comprehensive studies led to the diagnosis of PoPH associated with non-cirrhotic portal hypertension. Medical treatment was started, but to no avail, and she died of right heart failure in Sept 2012. Autopsy showed intact bile ducts and hepatic arteries but obstructed portal veins by fibrosis in the portal tract (A), which was consistent with the pathological features of IPH. In the lungs, pulmonary arterioles showed intimal and medical thickening (B), and plexiform lesions and fibrotic venular obstruction were also noted. Notably, lumens of some arterioles were separated into several compartments (C), suggestive of recanalization.  A case of pathologically-proven PoPH associated with IPH was presented. Varied pulmonary vasculopathy appeared to employ in the development of pulmonary hypertension in the present case.
A holistic approach to child maltreatment
Authors: David Finkelhor, Corinna Jenkins Tucker
Journal: The Lancet Psychiatry (2015)

Children and adolescents experience more violence, abuse, and criminal victimisation than do other segments of the population. Proper public health attention to this vulnerability is hampered by many things, but one of the most remediable is the fragmentation of the response system. Separate institutions, researchers, and advocacy groups lobby and often compete on behalf of victims of child molestation, rape, exposure to domestic violence, corporal punishment, physical abuse, and bullying. Attention is also hampered by the description of abusive behaviours such as peer violence (including that among siblings) as being part of a 'normal childhood' and by viewing efforts to address such abuse as a sign of overwrought protectionism. Language: en
The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential
Authors: Gerald W. Zamponi, Joerg Striessnig, Alexandra Koschak, Annette C. Dolphin
Journal: Pharmacological Reviews (2015)

Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type Ca<sub>V</sub>1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (Ca<sub>V</sub>3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit <i>α</i><sub>2</sub><i>δ</i>-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (Ca<sub>V</sub>2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., Ca<sub>V</sub>1.2 and Ca<sub>V</sub>1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective Ca<sub>V</sub>1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson's disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep, and anxiety. Use-dependent N-type calcium channel blockers are likely to be of therapeutic use in chronic pain conditions. Thus, more selective calcium channel blockers hold promise for therapeutic intervention.
Suppression of Malignancy in Human Lung Cancer (A549/8) X Mouse Fibroblast (3T3-4E) Somatic Cell Hybrids
Authors: Desmond N. Carney, Cora J. Edgell, Adi F. Gazdar, John D. Minna
Journal: JNCI Journal of the National Cancer Institute (1979)

Interspecies hybrid cells were formed by the fusion of two parent cells: 1) the human lung cancer (bronchioloalveolar) line A549/8, which is not contact inhibited, rapidly produces tumors in athymic nude (nu/nu) mice, and forms colonies in agarose, and 2) the mouse fibroblast line 3T3-4E, which is contact inhibited, is nontumorgenic in nuce mice, and does not form colonies in agarose. These hybrid cells were tested 40-50 generations after fusion. The presence of 20 of the 23 different human chromosomes was tested by isoenzyme analysis, and examples of expression of each isoenzyme marker were found in at least some hybrid clones. All 14 independent hybrid clones tested were nontumorigenic in nude mice. Testing of hybrid clones for their ability to form colonies in agarose revealed two distinct phenotypes: agarose (clones forming colonies at 1-4% of the plated cells) and agarose (no colonies formed/10(5) cells tested). These phenotypes were discordant with all human isoenzymes tested. Malignant human lung cancer A549/8 times non-malignant mouse 3T3-4E cell hybrids were nontumorigenic in nude mice; thus malignancy of the bronchioloalveolar lung cancer behaved as a recessive trait. This nontumorigenicity was not accounted for by an absolute loss of the human chromosomes tested, but gene dosage may play a role. In contrast, the ability to clone in agarose was expressed in some hybrids (and thus behaved as a dominant trait); at present, agarose clonability cannot be related to specific human chromosomes.