tbuckley/cabot-search huggingface dataset:
Controlled Mechanical Ventilation Attenuates the Systemic Inflammation of Severe Chronic Obstructive Pulmonary Disease Exacerbations
Authors: Georgios Hillas, Fotis Perlikos, Dimitris Toumpanakis, Eleni Litsiou, Sofia Nikolakopoulou, Kostas Sagris, Theodoros Vassilakopoulos
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Irradiation-Hyperthermia in Canine Hemangiopericytomas: Large-Animal Model for Therapeutic Response&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R C Richardson, V L Anderson, W D Voorhees, W E Blevins, T K Inskeep, W Janas, R E Shupe, C F Babbs
Journal: JNCI Journal of the National Cancer Institute (1984)

Results of irradiation-hyperthermia treatment in 11 dogs with naturally occurring hemangiopericytoma were reported. Similarities of canine and human hemangiopericytomas were described. Orthovoltage X-irradiation followed by microwave-induced hyperthermia resulted in a 91% objective response rate. A statistical procedure was given to evaluate quantitatively the clinical behavior of locally invasive, nonmetastatic tumors in dogs that were undergoing therapy for control of local disease. The procedure used a small sample size and demonstrated distribution of the data on a scaled response as well as transformation of the data through classical parametric and nonparametric statistical methods. These statistical methods set confidence limits on the population mean and placed tolerance limits on a population percentage. Application of the statistical methods to human and animal clinical trials was apparent.
Cancer outcomes at end-of-life in Michigan: 2006 update
Authors: M. Darwish-Yassine, J. Towns, J. W. Finn
Journal: Journal of Clinical Oncology (2008)

9544 Background: End-of-life care (EOLC) is an important focus of comprehensive cancer control. The Michigan Cancer Consortium has identified EOLC as one of its ten key objectives: By 2010, prevent and reduce avoidable suffering up to and during the last phase of life for persons with cancer as measured by specific data markers. 2004 data served as baseline measurements for specific strategies aimed at improving outcomes (2006 ASCO meeting - Abstact #8575). Methods: A population-based sample of caregivers, age 40 and older, including minorities, were contacted by trained, bilingual staff using computer-assisted telephone interviews in 2006. Results: 815 respondents constituted the sample size of caregivers who reported having cared for a family member with cancer in the preceding 5 years, including 199 African-Americans, 127 American Indians, 92 Arab Americans and 70 Hispanic Americans. The average level of pain in the final 3 months was reported as severe to excruciating for 40% (44.7% in 2004). Pain medications had been prescribed for 91.5% (93.5% in 2004); however, not used as directed for 11.1% (down from 30.3%). The most frequent reason given for this was side effects/fear of addiction for 87.9% & 7% respectively. The proportion who died at home was 46.7% (vs. 44.7%). A increasing trend was observed in the percent of African Americans who died at home ( from 40.8% in 2004 to 46.1% in 2006). 79.9% of cancer decedents died with the support of hospice (vs. 68.2% in 2004). The median length of stay on hospice, however, remained quite short, 16.8 days (17.5 days in 2003). The main reason hospice was not chosen was that death occured before hospice enrollment 64.6% (55.2% in 2004). 99.6% of those surveyed were aware of hospice as an available service. Only 1.1% were familiar with the term ‘palliative care.‘ Conclusions: Cancer EOLC is an important part of state-wide comprehensive cancer control. 2006 MI data reveals encouraging trends in regards to the prevelence of severe to excruciating pain in the final 3 months, proportion of those who died at home and the percent of those cancer patients who utilized hospice services. The timeliness of hospice utilization, however, continues to be problematic. Caregiver awareness of end-of-life services, such as hospice, is universal. Awareness of ‘palliative care‘, though, is almost nil. No significant financial relationships to disclose.
Chromosome Studies of Virus-Induced Rabbit Papillomas and Derived Primary Carcinomas
Authors: Harrison McMichael, Joyce E. Wagner, Peter C. Nowell, David A. Hungerford
Journal: JNCI Journal of the National Cancer Institute (1963)

The chromosomes of 25 primary epidermal rabbit tumors, induced by the Shope virus, were studied in various stages of development from early benign papillomas to invasive carcinomas. Abnormalities of chromosome structure, including the presence of cytogenetically altered stemlines, were observed at all stages. The incidence and extent of such change increased with time and with the conversion to malignancy, usually being well advanced at the time of, or prior to, invasion. No consistent abnormalities were seen at any stage. Hence, the changes observed were probably not causally related to the initiation of the neoplasm, and their significance with respect to the subsequent development of malignancy remains obscure.
Childbirth-related psychosis and familial symbiotic conflict
Authors: R M Ketai, M A Brandwin
Journal: American Journal of Psychiatry (1979)

The authors present 3 cases of childbirth-related psychosis in young women to illustrate an interpersonal psychodynamic pattern that may contribute to such reactions. In each instance, the woman is the submissive partner in a symbiotic relationship with her husband and/or mother. The baby's presence threatens the symbiotic equilibrium of these relationships and leads to the dominant partner's overt or covert aggression against the woman, which precipitates the psychosis. A personal or family history of psychosis may increase the woman's vulnerability to becoming psychotic in this situation.
Thrombotic microangiopathy
Authors: D L Sommerfeld, D C Brennan, J A Gordon
Journal: Journal of the American Society of Nephrology (1992)

Thrombotic microangiopathy most likely represents a spectrum of diseases consisting of multiple etiologies that has a final common pathway of multiorgan microvascular thrombosis. The variable responses to several different modes of therapy would suggest that more than one pathogenetic mechanism is involved. Untreated, it has been associated with very high morbidity and mortality rates. A poor understanding of the basic disease process has prevented specific treatment modalities, although early diagnosis and availability of dialysis and blood product transfusion services remain crucial. Several modes of therapy have been used to date, with plasma exchange being the most effective method studied and shown to improve survival. On the basis of current knowledge, this form of treatment should be instituted promptly in severe cases. Anecdotal reports of recovery with vincristine or IgG alone or with the use of IgG after the apparent failure of plasma therapy appear promising and deserve further investigation as initial therapeutic measures used in thrombotic microangiopathy. Although the majority of patients recover with normal renal function, those with severe thrombotic microangiopathy may heal through sclerosis with residual hypertension and chronic renal impairment requiring continual medical therapy.
Nonmyeloablative allogeneic stem cell transplantation as immunotherapy for pancreatic cancer and other solid tumors
Authors: K. Muta, T. Ito, Y. Abe, K. Nagafuji, E. Baba, T. Matsushima, K. Mitsuki, S. Nakano, H. Nawata, M. Harada
Journal: Journal of Clinical Oncology (2004)

2539 Background: For the treatment of advanced and metastatic disease, conventional anti-tumor therapies such as chemotherapy and radiotherapy have been largely unsuccessful. Particularly in cases of advanced pancreatic cancer, prognosis is extremely poor. Recently, nonmyeloablative allogeneic stem cell transplantation (NST) has been successfully applied for treatment of solid tumors such as renal cell carcinoma. We performed NST in order to establish the role of this immunotherapy in the treatment strategy for Japanese patients with pancreatic cancer and other solid tumors. Methods: Japanese patients under the age of 65 with advanced disease resistant against chemotherapy and/or radiotherapy were enrolled in this pilot study. Fludarabine (Flu) based reduced intensity conditioning was performed prior to the infusion of G-CSF mobilized peripheral blood stem cells obtained from HLA- matched sibling donors. Donor chimerism of both T cells and mononuclear cells (MNC) was determined by PCR-based analysis of polymorphic short tandem repeat markers. In order to investigate the mechanism by which NST elicits an anti-tumor effect, serum levels of TNFα were measured by ELISA in four cases of pancreatic cancer. Results: Outcome of patients is given in the table below. Complete T cell chimerism was achieved within 100 days in all cases. Elevation of TNFα compared to baseline level was noted in patients #5 and #7, who achieved CR and SD, respectively. Serum levels of TNFα were unchanged in patients #6 and #8, who had progressive disease.Conclusions: Successful engraftment and anti-tumor effect of NST were observed. TNFα has a possible immunological role during the clinical course of NST. No significant financial relationships to disclose.
Immune checkpoints expression in MSI versus MSS colorectal cancers and their potential therapeutic implications.
Authors: Nicolas Jose Llosa, Franck Housseau, Elizabeth C. Wick, Lizzy Hechenbleikner, Michael Cruise, Robert Anders, Cynthia Sears, Drew M. Pardoll
Journal: Journal of Clinical Oncology (2014)

3620 Background: Colorectal cancer (CRC) is divided into 2 groups based on genomic differences: chromosomal instability (80%), and microsatellite instability (MSI) (20%). MSI CRC is associated with a favorable prognosis independent of classic clinical prognostic factors. MSI CRC has been characterized by an intense immune infiltration which was assumed to be related to a high density of mutations creating numerous neoantigens. We compared the nature of inflammation in MSS and MSI CRC specimens to identify biomarkers which could guide therapeutic interventions. Methods: Pairs of CRC and normal tissues were enzymatically dissociated to isolate leukocytes by density gradient and their phenotypic characterization was done via multi-parameter flow cytometry (MFC). Immune infiltration was scored using immunohistochemistry (IHC) and in situ molecular analysis was performed via laser capture microdissection (LCM) and TaqMan quantitative RT-PCR. Results: IHC analysis of immune infiltrates in 15 CRC specimens delineated 3 distinct areas denominated intraepithelial lymphocytes (TIL), tumor stroma (TS) and invasive margin (IM). Scoring of CD3+, CD4+ and CD8+ cells demonstrated that MSI specimens (n=8) were characterized by a higher infiltration of all three populations compared to MSS samples (n=7). Molecular analysis of the TIL (3 MSI versus 3 MSS) indicated that the tumor microenvironment of MSI CRC was characterized by a high expression of IFNg and genes associated with cytotoxic T cells (CTL) including CD8A, TBX21, PERF, GZM. Strikingly, MSI samples had a greater expression of IFN-g-driven immune checkpoints such as PD-1, PD-L1, IDO-1 and INOS suggesting that the high density of infiltrating CTL and IFNg stimulate mechanisms of adaptive immune resistance in MSI tumors. MFC analysis of TIL performed on fresh tumors confirmed the higher presence of IFNg-producing PD1hi CD8+CTL in MSI samples (n=8). Conclusions: The genetic origin of CRC dictates the nature and intensity of inflammation. A strong IFNg -driven inflammatory response in MSI CRC patients triggered the expression of PD-L1 and IDO-1 which could be targeted to enhance clinical benefit and be predictive of response to immune checkpoint inhibitors.
Parallel Evolution of Copy-Number Variation across Continents in<i>Drosophila melanogaster</i>
Authors: Daniel R. Schrider, Matthew W. Hahn, David J. Begun
Journal: Molecular Biology and Evolution (2016)

Genetic differentiation across populations that is maintained in the presence of gene flow is a hallmark of spatially varying selection. In Drosophila melanogaster, the latitudinal clines across the eastern coasts of Australia and North America appear to be examples of this type of selection, with recent studies showing that a substantial portion of the D. melanogaster genome exhibits allele frequency differentiation with respect to latitude on both continents. As of yet there has been no genome-wide examination of differentiated copy-number variants (CNVs) in these geographic regions, despite their potential importance for phenotypic variation in Drosophila and other taxa. Here, we present an analysis of geographic variation in CNVs in D. melanogaster. We also present the first genomic analysis of geographic variation for copy-number variation in the sister species, D. simulans, in order to investigate patterns of parallel evolution in these close relatives. In D. melanogaster we find hundreds of CNVs, many of which show parallel patterns of geographic variation on both continents, lending support to the idea that they are influenced by spatially varying selection. These findings support the idea that polymorphic CNVs contribute to local adaptation in D. melanogaster. In contrast, we find very few CNVs in D. simulans that are geographically differentiated in parallel on both continents, consistent with earlier work suggesting that clinal patterns are weaker in this species.
Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4)
Authors: R.J. Motzer, A. Alyasova, D. Ye, A. Karpenko, H. Li, B. Alekseev, L. Xie, G. Kurteva, R. Kowalyszyn, O. Karyakin, Y. Neron, T. Cosgriff, L. Collins, T. Brechenmacher, C. Lin, L. Morgan, L. Yang
Journal: Annals of Oncology (2015)
Influence of genetic variants in UGT1A1 and UGT1A9 on the in vivo glucuronidation of SN-38
Authors: A. Singh, L. Paoluzzi, D. Price, R. Danesi, R. H. Mathijssen, J. Verweij, W. D. Figg, A. Sparreboom
Journal: Journal of Clinical Oncology (2004)

2072 Background: The uridine diphosphate-glucuronsyltransferase 1A (UGT1A) family of enzymes is involved in the phase II biotransformation of various drugs, including the irinotecan metabolite, SN-38. The isoforms 1A1 and 1A9 are responsible for most of the glucuronidation of SN-38. Several genetic variants in the UGT1A9 gene have been described recently with altered functionality in vitro. The aim of this study was to evaluate the functional consequence of the UGT1A9 766G>A (D256N) and 98T>C (M33T; UGT1A9*3) variants in Caucasian patients treated with irinotecan given as a 90-minute i.v. infusion, as well as the UGT1A1 (TA)n polymorphism (UGT1A1*28). Methods: Pharmacokinetic studies were performed after the first course of irinotecan (median dose, 600 mg) in a cohort of 94 Caucasian patients (47 males; 47 females) with a mean age of 54 years. Plasma concentrations of irinotecan, SN-38, and SN-38-glucuronide (SN-38G) were determined using HPLC and time profiles were analyzed using NONMEM. Genotyping was performed using direct DNA sequencing. Results: In the entire population, the mean area under the plasma-concentration time curves (AUCs) of irinotecan and SN-38 were 20.3 ± 6.46 μg×h/ml and 629 ± 370 ng×h/ml, respectively, which is in line with earlier findings. For UGT1A9 766G>A, no variant alleles were observed, whereas for UGT1A9*3, the wild-type sequence was observed in all but 1 patient (allele frequency, 0.7%). The genotype distribution of the UGT1A1*28 variant showed 44 patients carrying the wild-type sequence (WT), 37 heterozygous (Het), and 5 homozygous (Var). The extent of SN-38 glucuronidation (ie, the AUC ratio of SN-38G to SN-38) was significantly reduced in carriers of the variant UGT1A1*28 allele [7.82 (WT) vs 7.74 (Het) vs 3.46 (Var); P = .022, Kruskal-Wallis test]. No significant association of UGT1A1*28 with the occurrence of diarrhea was observed. Conclusions: Functional variants in the UGT1A9gene are rare in Caucasian patients, and of unlikely clinical significance in relation to irinotecan treatment. As predicted previously, screening for the UGT1A1*28 polymorphism may identify patients with altered SN-38 pharmacokinetics. No significant financial relationships to disclose.
Experimental Approach to Mechanisms of Weight Loss: II: Comparison of Effects of Thyroxine, Fat-Mobilizing Substance (FMS) and Food Deprivation in Achieving Weight Loss in Mice
Authors: A KEKWICK, G L PAWAN
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cytological Studies of Tumors. XL. Chromosome Studies in Fifty-Two Human Tumors&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: Sajiro Makino, Masao S. Sasaki, Akira Tonomura
Journal: JNCI Journal of the National Cancer Institute (1964)

Chromosomes were investigated in 52 human tumors, effusion and solid, by the water-pretreatment acetic dahlia squash method. The chromosomes studied were from 30 patients with gastric carcinomas, 13 with uterine carcinomas, 4 with rectal carcinomas, 2 with mammary carcinomas, 2 with ovarian carcinomas, and 1 with an ascites hepatoma. Thirty-four tumors were characterized by 1, or rarely 2, marked stemlines with a characteristic number mode (or modes) and a specific karyotype (or karyotypes), while 3 tumors showed karyological heterogeneity, with a wide distribution of chromosome numbers. No detailed analyses of chromosomes were made in the remaining 15 tumors. Tumors characterized by the hyperdiploid-triploid modality were most frequent, the hypotetraploid one ranking next. No definite correlation was detected between the chromosome condition of tumor cells and pathological pattern of the tumor itself. Further, evidence was presented to suggest that the genetic pattern, which is closely correlated with the property of the tumor, may not be identical among tumors, even though they originated from the same organ. Based on the results of detailed karyogram and karyotype analyses, the course of malignant transformation was discussed. It was concluded that heteroploid transformation of cells may be an important factor in malignant transformation, in addition to numerical alteration and/or structural reorganization of chromosomes.
P52 Neutrophil dysfunction: a potential biomarker of poor prognosis in acute liver failure?
Authors: N Taylor, A Nishtala, F Lin, R D Abeles, W Bernal, J Wendon, Y Ma, D Shawcross
Journal: Gut (2010)

Introduction  In acute liver failure (ALF) an exaggerated systemic inflammatory response can result in neutrophil activation with subsequent tissue damage from release of proteolytic enzymes and reactive oxygen species, contributing to ongoing organ failure. Neutrophil function in ALF has not been previously interrogated.  Aim  This ongoing longitudinal study aims to characterise neutrophil function in patients with ALF admitted to King9s College Hospital.  Method  Neutrophils were isolated from a cohort of age/sex matched patients with ALF (n=22), healthy volunteers (n=9) and septic controls (n=5). Serial samples were taken on admission and every 3–4 days following ITU admission until death/discharge. Phagocytosis was analysed by flow cytometry using FITC-labelled  E coli  and oxidative burst (OB) was determined by the percentage of CD16-Phycoerytherin labelled neutrophils producing reactive oxygen species at rest and after stimulation with opsonised  E coli . Physiological variables, biochemistry, arterial ammonia and microbial culture results were collected prospectively.  Results  Within the ALF cohort 14 patients fulfilled poor prognostic criteria, of whom 8 underwent successful liver transplantation (LT) and 6 died without LT, 8 survived with medical management. Aetiology of ALF was acetaminophen n=5; acute viral hepatitis n=4; seronegative liver failure n=10; drug/other n=3. APACHE II and SOFA scores on admission were higher in patients with ALF compared to septic controls 21 (17–25) vs 12 (9–15) (p=0.08) and 16 (15–17) vs 5 (1–6) (p=0.01) respectively. Impaired neutrophil phagocytosis (p E coli  which was also observed in septic controls (p=0.045). The defects in neutrophil function showed a trend towards improvement (phagocytosis, spontaneous and stimulated OB all p=ns) during the first 72 h following successful LT.  Conclusion  In conclusion, in patients with ALF fulfilling “poor prognostic criteria” neutrophils demonstrate early impairment of phagocytosis, increased baseline OB but decreased OB in response to bacterial stimulation. These observed defects are likely to contribute to ongoing cellular/organ dysfunction and the increased susceptibility to nosocomial sepsis seen in ALF.
Micronucleus Assay in Lymphocytes as a Tool to Biomonitor Human Exposure to Aneuploidogens and Clastogens
Authors: Hannu Norppa, Sirpa Luomahaara, Hannele Heikanen, Stina Roth, Marja Sorsa, Luigina Renzi, Carita Lindholm
Journal: Environmental Health Perspectives (1993)

The analysis of micronuclei (MN) in cultured human lymphocytes is, in principle, able to detect exposure to clastogens and aneuploidogens alike.There is, however, no clear evidence from human biomonitoring studies or animal experiments showing that in vivo exposure of resting lymphocytes to an aneuploidogen could actually be expressed as MN in cultured lymphocytes.In vitro, a pulse treatment of human lymphocytes with vinblastine, an aneuploidogen, did result in MN induction even if performed before mitogen stimulation, although a much more pronounced effect was obtained in actively dividing lymphocyte cultures.On the other hand, it is probable that a considerable portion of "spontaneous" MN contain whole chromosomes, their contribution increasing with age.It also seems that cytochalasin B, used for the identification of second cell cycle interphase cells in the MN assay, is able to slightly increase the level of MN with whole chromosomes.If MN harboring chromosome fragments represent a minority of the total MN frequency, there may be difficulties in detecting a weak effect in this fraction of MN against the background of MN with whole chromosomes.This would reduce the sensitivity of the assay in detecting clastogens, unless MN with whole chromosomes and chromosome fragments are distinguished from each other.That a problem may exist in sensitivity is suggested by the difficulty in demonstrating MN induction by smoking, an exposure capable of inducing chromosome aberrations.The sensitivity ofthe lymphocyte MN assay could be increased by detecting kinetochore or centromere in MN, or by automation, allowing more cells to be analyzed.