tbuckley/cabot-search huggingface dataset:
PERITONEAL ABSORPTION
Authors: P. F. Hahn, L. L. Miller, F. S. Robscheit-Robbins, W. F. Bale, G. H. Whipple
Journal: The Journal of Experimental Medicine (1944)

The absorption of red cells from the normal peritoneum of the dog can be demonstrated by means of red cells labeled with radio-iron incorporated in the hemoglobin of these red cells. Absorption in normal dogs runs from 20 to 100 per cent of the amount given within 24 hours. Dogs rendered anemic by bleeding absorb red cells a little less rapidly-ranging from 5 to 80 per cent of the injected red cells. Doubly depleted dogs (anemic and hypoproteinemic) absorb even less in the three experiments recorded. This peritoneal absorption varies widely in different dogs and even in the same dog at different times. We do not know the factors responsible for these variations but there is no question about active peritoneal absorption. The intact red cells pass readily from the peritoneal cavity into lymph spaces in diaphragm and other areas of the peritoneum. The red cells move along the lymphatics and through the lymph glands with little or no phagocytosis and eventually into the large veins through the thoracic ducts.
Prediction of Antidepressant Effects of Sleep Deprivation by Metabolic Rates in the Ventral Anterior Cingulate and Medial Prefrontal Cortex
Authors: Joseph Wu, Monte S. Buchsbaum, J. Christian Gillin, Cheuk Tang, Stephanie Cadwell, Michael Wiegand, Ahmad Najafi, Eric Klein, Kaye Hazen, William E. Bunney
Journal: American Journal of Psychiatry (1999)

Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping.Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale.One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation.High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.
Black-white differences in cholesterol levels of serum high-density lipoprotein subclasses among children: the Bogalusa Heart Study.
Authors: S R Srinivasan, D S Freedman, L S Webber, G S Berenson
Journal: Circulation (1987)

Cholesterol levels of serum high-density lipoprotein (HDL) subclasses, HDL2 and HDL3, were examined in a random subsample (n = 561) of children (7 to 17 years of age) from a total biracial community. Overall, black children in younger (7 to 10 years) and older (11 to 17 years) age groups alike had significantly higher HDL2 cholesterol (HDL2-C) and HDL3-C than their white counterparts. In addition, black children had a relatively higher frequency of joint occurrence of high levels of both HDL2-C and HDL3-C. A significant sex-related difference, with girls showing higher values than boys, was noted among younger age groups for HDL2-C. A male-female crossover trend in HDL2-C levels was apparent only among white children, with girls showing higher values after age 11. Both age and sexual maturation were inversely associated with HDL3-C levels in white children, irrespective of sex (p less than .001). Serum triglycerides were inversely related to both HDL2-C and HDL3-C only in white children (p less than .001). A black-white difference in HDL2-C persisted only among boys and girls in the older age group after adjusting for the covariates (sexual maturation, age, adiposity, oral contraceptive use, cigarette smoking, alcohol use, and serum triglycerides). With respect to HDL3-C, the covariate-adjusted difference remained significant only among boys in the older age group. Metabolic variations between the races in response to both physiologic and environmental factors likely account for the divergence in antiatherogenic HDL pattern.
Assessing periarticular bone mineral density in patients with early psoriatic arthritis or rheumatoid arthritis
Authors: B J Harrison
Journal: Annals of the Rheumatic Diseases (2002)

Periarticular osteoporosis is an early finding in the hands of patients with rheumatoid arthritis (RA), due to release of bone resorbing cytokines from the inflamed synovium. There has been disagreement as to whether periarticular bone loss occurs in psoriatic arthritis (PsA). Bone mineral density (BMD) can now be measured accurately using dual energy x ray absorptiometry (DEXA). Recently, DEXA has been used to measure periarticular BMD at predefined regions of interest (ROIs) around the joints.Firstly, to compare periarticular BMD around the finger joints of patients with early RA or PsA. Secondly, to determine whether periarticular bone loss is related to joint inflammation and radiological erosions in RA and PsA.Seventeen patients with RA and 15 with PsA were recruited, all with disease duration of less than five years. All finger joints were examined by one person for swelling, or tenderness, or both. Hand radiographs were scored for the presence of erosions. Periarticular BMD was measured at 10 predetermined ROIs using a Hologic QDA-4500A fan-beam densitometer.Patients with PsA were less likely to be positive for rheumatoid factor (RF) (13% v 94%) and more likely to be men (60% v 23%) than patients with RA. There were no other clinical differences between patients with RA or PsA. Patients with RA had significantly lower BMD at each of the ROIs than those with PsA (p<0.05). However, these differences disappeared after adjusting for age and sex. Among patients with RA, those with a higher total number of swollen and/or tender hand joints had significantly lower periarticular BMD at the metocarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. No such association was found for patients with PsA.In early disease, periarticular bone loss occurred both in patients with RA and those with PsA. Among patients with RA, periarticular osteoporosis was related to measures of joint inflammation. There was no association between joint inflammation and periarticular bone loss in patients with PsA, which lends support to the hypothesis that the primary site of inflammation in PsA is extrasynovial.
Potent Antiandrogen and Androgen Receptor Activities of an<i>Angelica gigas</i>–Containing Herbal Formulation: Identification of Decursin as a Novel and Active Compound with Implications for Prevention and Treatment of Prostate Cancer
Authors: Cheng Jiang, Hyo-Jeong Lee, Guang-xun Li, Junming Guo, Barbara Malewicz, Yan Zhao, Eun-Ok Lee, Hyo-Jung Lee, Jae-Ho Lee, Min-Seok Kim, Sung-Hoon Kim, Junxuan Lu
Journal: Cancer Research (2006)

Abstract Androgen and androgen receptor (AR)–mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling from Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC50, ∼7 μg/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G1 arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC50 of ∼0.4 μg/mL (1.3 μmol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G1 arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases. (Cancer Res 2006; 66(1): 453-63)
Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis
Authors: Koji Kitamura, Etsuro Hatano, Tatsuya Higashi, Masato Narita, Satoru Seo, Yuji Nakamoto, Kenya Yamanaka, Hiromitsu Nagata, Kojiro Taura, Kentaro Yasuchika, Takashi Nitta, Shinji Uemoto
Journal: Journal of Hepatology (2011)
Blockade of transforming growth factor upregulates T-box transcription factor T-bet, and increases T helper cell type 1 cytokine and matrix metalloproteinase-3 production in the human gut mucosa
Authors: A. Di Sabatino, K. M. Pickard, D. Rampton, L. Kruidenier, L. Rovedatti, N. A. B. Leakey, G. R. Corazza, G. Monteleone, T. T. MacDonald
Journal: Gut (2008)

The role of transforming growth factor beta (TGFbeta) in inhibiting T cell function in the normal gut has been studied in animal models. However, the impact of TGFbeta inhibition on T cells in the normal human gut remains poorly understood. The effect of TGFbeta blockade in normal intestinal biopsies grown ex vivo and lamina propria mononuclear cells (LPMCs) on T-bet, a T-box transcription factor required for T helper cell type (Th)1 differentiation, interferon gamma (IFN gamma) production, T cell apoptosis and matrix metalloproteinase (MMP)-3 production has therefore been tested.TGFbeta transcripts were determined by quantitative reverse transcription-PCR in laser-captured gut epithelium and lamina propria. Biopsies and LPMCs were cultured with anti-TGFbeta neutralising antibody. After 24 h culture, T-bet was determined by immunoblotting, and T cell apoptosis was assessed by flow cytometry. IFN gamma, tumour necrosis factor alpha (TNFalpha), interleukin (IL) 2, IL6, IL8, IL10, IL12p70 and IL17 were measured by ELISA. MMP-3 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were assessed by immunoblotting.A higher number of TGFbeta transcripts was found in the lamina propria than in the epithelium in normal gut. T-bet expression was significantly higher in biopsies and LPMCs cultured with anti-TGFbeta antibody than in those cultured with control antibody. TGFbeta blockade downregulated T cell apoptosis, and induced a significant increase in IFN gamma, TNFalpha, IL2, IL6, IL8 and IL17 production. A higher expression of MMP-3, but not TIMP-1, was observed in the tissue and supernatant of biopsies treated with anti-TGFbeta antibody.The findings support a crucial role for TGFbeta in dampening T cell-mediated tissue-damaging responses in the human gut.
Survivin As a Therapeutic Target for Radiation Sensitization in Lung Cancer
Authors: Bo Lu, Yi Mu, Carolyn Cao, Fenghua Zeng, Sylke Schneider, Jiahui Tan, Jim Price, Jun Chen, Michael Freeman, Dennis E. Hallahan
Journal: Cancer Research (2004)

Abstract Expression of survivin is elevated in most malignancies, especially in radiation-resistant cell lines. In this study, we investigated how radiation affects survivin expression in primary endothelial cells as well as in malignant cell lines. We found that 3 Gy significantly reduced survivin protein level in human umbilical vein endothelial cells (HUVECs) but not in tumor cell lines. Flow cytometry studies suggest that the down-regulation of survivin is independent of cell cycle. In addition, survivin mRNA level was also down-regulatable by irradiation. However, it was abrogated by actinomycin D-mediated inhibition of gene transcription. Luciferase reporter gene assays suggest that irradiation suppressed the survivin promoter. p53 overexpression reduced survivin expression, but overexpression of a p53 mutant failed to abolish the radiation-induced down-regulation in HUVECs. Alteration of p53 status in Val138 lung cancer cell line also failed to restore the radiation-inducible down-regulation. Overexpression of survivin in 293 cells prevented apoptosis induced by irradiation and increased cell viability after irradiation. The inhibition of survivin using antisense oligonucleotides caused a significant decrease in cell viability of irradiated H460 lung cancer cells. These data suggest that radiation transcriptionally down-regulates survivin in HUVECs. This regulatory mechanism is defective in malignancies and is not mediated by p53. Survivin overexpression may lead to resistance to radiotherapy by inhibiting apoptosis and enhancing cell viability. The inhibition of survivin results in sensitization of H460 lung cancer cells to radiation. These studies suggest that survivin may be a target for cancer therapy.
Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells
Authors: Elizabeth A. Jacobsen, Sergei I. Ochkur, Ralph S. Pero, Anna G. Taranova, Cheryl A. Protheroe, Dana C. Colbert, Nancy A. Lee, James J. Lee
Journal: The Journal of Experimental Medicine (2008)

The current paradigm surrounding allergen-mediated T helper type 2 (Th2) immune responses in the lung suggests an almost hegemonic role for T cells. Our studies propose an alternative hypothesis implicating eosinophils in the regulation of pulmonary T cell responses. In particular, ovalbumin (OVA)-sensitized/challenged mice devoid of eosinophils (the transgenic line PHIL) have reduced airway levels of Th2 cytokines relative to the OVA-treated wild type that correlated with a reduced ability to recruit effector T cells to the lung. Adoptive transfer of Th2-polarized OVA-specific transgenic T cells (OT-II) alone into OVA-challenged PHIL recipient mice failed to restore Th2 cytokines, airway histopathologies, and, most importantly, the recruitment of pulmonary effector T cells. In contrast, the combined transfer of OT-II cells and eosinophils into PHIL mice resulted in the accumulation of effector T cells and a concomitant increase in both airway Th2 immune responses and histopathologies. Moreover, we show that eosinophils elicit the expression of the Th2 chemokines thymus- and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in the lung after allergen challenge, and blockade of these chemokines inhibited the recruitment of effector T cells. In summary, the data suggest that pulmonary eosinophils are required for the localized recruitment of effector T cells.
Clinical symptoms, hormone profiles, treatment, and prognosis in patients with gastric carcinoids
Authors: D Granberg, E Wilander, M Stridsberg, G Granerus, B Skogseid, K Öberg
Journal: Gut (1998)

Background —Type 1 gastric carcinoids are associated with hypergastrinaemia and chronic atrophic gastritis, type 2 occur in patients with multiple endocrine neoplasia type 1 combined with Zollinger-Ellison syndrome, and type 3 lack any relation to hypergastrinaemia. Type 1 tumours are usually benign whereas type 3 are highly malignant. Aims —To identify possible tumour markers in patients with gastric carcinoids. Patients/method —Nine patients with type 1, one with type 2, and five with type 3 were evaluated with regard to symptoms, hormone profile, and prognosis. Results —Plasma chromogranin A was increased in all patients but was higher (p&lt;0.01) in those with type 3 than those with type 1 carcinoids. All patients with type 3 carcinoids died from metastatic disease, but none of the type 1 patients died as a result of their tumours. One type 1 patient with a solitary liver metastasis received interferon α and octreotide treatment. Nine months later, the metastasis was no longer detectable. She is still alive eight years after diagnosis, without recurrent disease. This represents the only reported case of foregut carcinoid with an unresectable liver metastasis that seems to be have been cured by biotherapy. Conclusions —Plasma chromogranin A appears to be a valuable tumour marker for all types of gastric carcinoid. Combination therapy with interferon α and octreotide may be beneficial in patients with metastasising type 1 gastric carcinoids.
Phase 2 Studies of Sunitinib and AG013736 in Patients with Cytokine-Refractory Renal Cell Carcinoma
Authors: Daniel J. George
Journal: Clinical Cancer Research (2007)

Abstract Frequent loss of the von Hippel-Lindau (VHL) gene product in conventional-type renal cell carcinoma results in constitutive expression of proangiogenic growth factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). VEGF and PDGF function in a paracrine manner to stimulate tumor angiogenesis that results in a hypervascular phenotype. Dependency on this hypervascularity is underscored by the recent clinical efficacy shown by inhibition of the VEGF pathway. Most strategies that primarily target the VEGF pathway (neutralizing antibodies or receptor tyrosine kinase inhibitors) result in objective tumor responses in ≤10% of cases but show a significant delay in time to disease progression. In contrast, two multitargeted receptor tyrosine kinase inhibitors that target both VEGF and PDGF receptors (sunitinib and AG013736) have shown ≥40% objective responses with clinically important duration. Several hypotheses may explain the discrepancy of these response rates from other strategies in the class, including the synergistic effects of dual inhibition of VEGF and PDGF receptors, supported by preclinical studies. Ultimately, further clinical investigations with pharmacodynamic and correlative science end points are needed to clarify the mechanisms of action and resistance to build on the biological and clinical effects of these multitargeted agents.
Clinical Outcome Prediction by MicroRNAs in Human Cancer: A Systematic Review
Authors: Viswam S. Nair, Lauren S. Maeda, John P.A. Ioannidis
Journal: JNCI Journal of the National Cancer Institute (2012)

MicroRNA (miR) expression may have prognostic value for many types of cancers. However, the miR literature comprises many small studies. We systematically reviewed and synthesized the evidence.Using MEDLINE (last update December 2010), we identified English language studies that examined associations between miRs and cancer prognosis using tumor specimens for more than 10 patients during classifier development. We included studies that assessed a major clinical outcome (nodal disease, disease progression, response to therapy, metastasis, recurrence, or overall survival) in an agnostic fashion using either polymerase chain reaction or hybridized oligonucleotide microarrays.Forty-six articles presenting results on 43 studies pertaining to 20 different types of malignancy were eligible for inclusion in this review. The median study size was 65 patients (interquartile range [IQR] = 34-129), the median number of miRs assayed was 328 (IQR = 250-470), and overall survival or recurrence were the most commonly measured outcomes (30 and 19 studies, respectively). External validation was performed in 21 studies, 20 of which reported at least one nominally statistically significant result for a miR classifier. The median hazard ratio for poor outcome in externally validated studies was 2.52 (IQR = 2.26-5.40). For all classifier miRs in studies that evaluated overall survival across diverse malignancies, the miRs most frequently associated with poor outcome after accounting for differences in miR assessment due to platform type were let-7 (decreased expression in patients with cancer) and miR 21 (increased expression).MiR classifiers show promising prognostic associations with major cancer outcomes and specific miRs are consistently identified across diverse studies and platforms. These types of classifiers require careful external validation in large groups of cancer patients that have adequate protection from bias. -
The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells
Authors: Zhen Lu, Robert Z. Luo, Yiling Lu, Xuhui Zhang, Qinghua Yu, Shilpi Khare, Seiji Kondo, Yasuko Kondo, Yinhua Yu, Gordon B. Mills, Warren S.-L. Liao, Robert C. Bast
Journal: Journal of Clinical Investigation (2008)

The role of autophagy in oncogenesis remains ambiguous, and mechanisms that induce autophagy and regulate its outcome in human cancers are poorly understood. The maternally imprinted Ras-related tumor suppressor gene aplasia Ras homolog member I (ARHI; also known as DIRAS3) is downregulated in more than 60% of ovarian cancers, and here we show that re-expression of ARHI in multiple human ovarian cancer cell lines induces autophagy by blocking PI3K signaling and inhibiting mammalian target of rapamycin (mTOR), upregulating ATG4, and colocalizing with cleaved microtubule-associated protein light chain 3 (LC3) in autophagosomes. Furthermore, ARHI is required for spontaneous and rapamycin-induced autophagy in normal and malignant cells. Although ARHI re-expression led to autophagic cell death when SKOv3 ovarian cancer cells were grown in culture, it enabled the cells to remain dormant when they were grown in mice as xenografts. When ARHI levels were reduced in dormant cells, xenografts grew rapidly. However, inhibition of ARHI-induced autophagy with chloroquine dramatically reduced regrowth of xenografted tumors upon reduction of ARHI levels, suggesting that autophagy contributed to the survival of dormant cells. Further analysis revealed that autophagic cell death was reduced when cultured human ovarian cancer cells in which ARHI had been re-expressed were treated with growth factors (IGF-1, M-CSF), angiogenic factors (VEGF, IL-8), and matrix proteins found in xenografts. Thus, ARHI can induce autophagic cell death, but can also promote tumor dormancy in the presence of factors that promote survival in the cancer microenvironment.