tbuckley/cabot-search huggingface dataset:
Cyst Number but Not the Rate of Cystic Growth Is Associated with the Mutated Gene in Autosomal Dominant Polycystic Kidney Disease
Authors: Peter C. Harris, Kyongtae T. Bae, Sandro Rossetti, Vicente E. Torres, Jared J. Grantham, Arlene B. Chapman, Lisa M. Guay-Woodford, Bernard F. King, Louis H. Wetzel, Deborah A. Baumgarten, Philip J. Kenney, Mark Consugar, Saulo Klahr, William M. Bennett, Catherine M. Meyers, Qin (Jean) Zhang, Paul A. Thompson, Fang Zhu, J. Philip Miller
Journal: Journal of the American Society of Nephrology (2006)

Data from serial renal magnetic resonance imaging of the Consortium of Radiologic Imaging Study of PKD (CRISP) autosomal dominant polycystic kidney disease (PKD) population showed that cystic expansion occurs at a consistent rate per individual, although it is heterogeneous in the population, and that larger kidneys are associated with more rapid disease progression. The significance of gene type to disease progression is analyzed in this study of the CRISP cohort. Gene type was determined in 183 families (219 cases); 156 (85.2%) had PKD1, and 27 (14.8%) had PKD2. PKD1 kidneys were significantly larger, but the rate of cystic growth (PKD1 5.68%/yr; PKD2 4.82%/yr) was not different (P = 0.24). Cyst number increased with age, and more cysts were detected in PKD1 kidneys (P < 0.0001). PKD1 is more severe because more cysts develop earlier, not because they grow faster, implicating the disease gene in cyst initiation but not expansion. These insights will inform the development of targeted therapies in autosomal dominant PKD.
Ambulatory 4-day continuous-infusion schedule of high-dose ifosfamide with mesna uroprotection and granulocyte colony-stimulating factor in advanced solid tumours: A phase I study
Authors: S. Toma, R. Palumbo, A. Comandone, C. Oliva, M. Vincenti, C. Bumma, R. Rosso
Journal: Annals of Oncology (1995)
A 26-Gene Hypoxia Signature Predicts Benefit from Hypoxia-Modifying Therapy in Laryngeal Cancer but Not Bladder Cancer
Authors: Amanda Eustace, Navin Mani, Paul N. Span, Joely J. Irlam, Janet Taylor, Guy N.J. Betts, Helen Denley, Crispin J. Miller, Jarrod J. Homer, Ana M. Rojas, Peter J. Hoskin, Francesca M. Buffa, Adrian L. Harris, Johannes H.A.M. Kaanders, Catharine M.L. West
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Tumor hypoxia is associated with a poor prognosis, hypoxia modification improves outcome, and hypoxic status predicts benefit from treatment. Yet, there is no universal measure of clinical hypoxia. The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types. Experimental Design: Samples were available from 157 T2–T4 laryngeal cancer and 185 T1–T4a bladder cancer patients enrolled on the accelerated radiotherapy with carbogen and nicotinamide (ARCON) and bladder carbogen nicotinamide (BCON) phase III randomized trials of radiotherapy alone or with carbogen and nicotinamide (CON) respectively. Customized TaqMan low density arrays (TLDA) were used to assess expression of the 26-gene signature using quantitative real-time PCR. The median expression of the 26 genes was used to derive a hypoxia score (HS). Patients were categorized as TLDA-HS low (≤median) or TLDA-HS high (&amp;gt;median). The primary outcome measures were regional control (RC; ARCON) and overall survival (BCON). Results: Laryngeal tumors categorized as TLDA-HS high showed greater benefit from ARCON than TLDA-HS low tumors. Five-year RC was 81% (radiotherapy alone) versus 100% (CON) for TLDA-HS high (P = 0.009). For TLDA-HS low, 5-year RC was 91% (radiotherapy alone) versus 90% (CON; P = 0.90). TLDA-HS did not predict benefit from CON in bladder cancer. Conclusion: The 26-gene hypoxia signature predicts benefit from hypoxia-modifying treatment in laryngeal cancer. These findings will be evaluated in a prospective clinical trial. Clin Cancer Res; 19(17); 4879–88. ©2013 AACR.
86 Class III and class I histone deacetylases (HDACS) inhibitors cooperate with DNA damaging chemotherapeutic drugs to induce P73-dependent apoptotic pathways in HCC cells
Authors: S. Vossio, E. Palescandolo, N. Pediconi, L. Belloni, F. Moretti, C. Balsano, M. Levrero
Journal: Journal of Hepatology (2004)
A death photographed: one patient's story
Authors: S. O'Connor
Journal: BMJ (2003)

Michael Willson managed his death in his own way. Having photographs taken was an important part of this management, and the images were pinned up on the walls all around him in his house. More photographs are shown on bmj.com, and below are Michael's own words on the project, as well as comments from his general practitioner and the photographer 

Michael Willson, who was born in 1947, was a self employed psychologist who did consultancy work for the probation service. He was very well respected locally and nationally. He was a free spirit and charismatic and had a wide circle of friends. He liked riding his horse bareback.

In 1994 he presented with anaemia, epigastric pain, and malaise. Gastroscopy showed carcinoma of the gastrooesophageal junction. He underwent oesophago-gastrectomy with splenectomy, but unfortunately tumour was present at the resection margins. He declined the offer of palliative chemotherapy. At this time his prognosis was poor. …
Ethnic differences in prevalence of asthma symptoms and bronchial hyperresponsiveness in New Zealand schoolchildren.
Authors: P K Pattemore, M I Asher, A C Harrison, E A Mitchell, H H Rea, A W Stewart
Journal: Thorax (1989)

Maoris and Pacific Islanders in New Zealand have a higher asthma mortality and hospital admission rates than Europeans. To determine whether difference in asthma prevalence is the major factor underlying these differences in mortality, 2053 Auckland children aged 7-10 years (European 1084, Maori 509, Pacific Islander 460) were randomly sampled from school classes in the Auckland Urban Area, and studied by questionnaire (completed by parents) and histamine inhalation challenge to assess the provocative dose of histamine causing a 20% fall in FEV1 (PD20). Maoris had the highest prevalence rates of respiratory symptoms, and Europeans had rates similar to Pacific Islanders. For "any current wheeze" for example, the prevalence in Maoris was 22.2% compared with 16.1% and 16.3% in the Europeans and Pacific Islanders. The prevalence of diagnosed asthma was similar in the three groups. When bronchial hyperresponsiveness (defined as a PD20 less than or equal to 7.8 mumol histamine) was considered, Europeans had the highest rates (20%), followed by Maoris (13%), and then Pacific Islanders (8.7%). These differences were not accounted for by differences in socioeconomic status, rates of smoking in the home, age, gender, or height. It is concluded that differences in asthma prevalence do not satisfactorily explain the mortality and admission rate differences, although the higher symptom prevalence in the Maoris could be relevant to the higher mortality rate. Maori and Pacific Island children with symptoms of asthma were less likely to be taking prophylactic medication than European children. It is proposed that differences in management are important factors relevant to the increased mortality and morbidity from asthma in Polynesians.
Characterization of Phosphoglycerate Kinase-1 Expression of Stromal Cells Derived from Tumor Microenvironment in Prostate Cancer Progression
Authors: Jianhua Wang, Gigi Ying, Jingchen Wang, Younghun Jung, Jian Lu, Jiang Zhu, Kenneth J. Pienta, Russell S. Taichman
Journal: Cancer Research (2010)

Abstract Tumor and stromal interactions in the tumor microenvironment are critical for oncogenesis and cancer progression. Our understanding of the molecular events by which reactive stromal fibroblasts—myofibroblast or cancer-associated fibroblasts (CAF)—affect the growth and invasion of prostate cancer remains unclear. Laser capture microdissection and cDNA microarray analysis of CAFs in prostate tumors revealed strong upregulation of phosphoglycerate kinase-1 (PGK1), an ATP-generating glycolytic enzyme that forms part of the glycolytic pathway and is directly involved in CXCL12-CXCR4 signaling. Normal fibroblasts overexpressing PGK1 resembled myofibroblasts in their expression of smooth muscle α-actin, vimentin, and high levels of CXCL12. These cells also displayed a higher proliferative index and the capability to contribute to prostate tumor cell invasion in vitro, possibly through expression of MMP-2 and MMP-3 and activation of the AKT and ERK pathways. Coimplantation of PGK1-overexpressing fibroblasts with prostate tumor cells promoted tumor cell growth in vivo. Collectively, these observations suggest that PGK1 helps support the interactions between cancer and its microenvironment. Cancer Res; 70(2); 471–80
Pulmonary resistance measured by impulse oscillometry system (IOS) seems to be related to self-reported COPD and respiratory symptoms
Authors: Sophia Frantz, Ulf Nihlén, Magnus Dencker, Gunnar Engström, Claes-Göran Löfdahl, Per Wollmer
Journal: European Respiratory Journal (2011)

Background: COPD is considered to start with small airway disease, which is not readily detected by spirometry. Measuring pulmonary resistance by IOS may be a more sensitive technique and more closely related to respiratory symptoms.

Aims and objectives: This study aimed at examining pulmonary resistance measured by IOS in COPD, self-reported and/or diagnosed with spirometry according to GOLD criteria.

Methods: 419 subjects (173 men/246 women), 46-78 years, who participated in a previous population-based study, were examined with spirometry and IOS (resistance at 5 Hz (R5), resistance at 20 Hz (R20) and the difference between them (R5-R20)) and answered a questionnaire on respiratory symptoms and diseases.

Results: 77 subjects had self-reported COPD and of them 34 subjects had COPD according to GOLD criteria. Of the 342 subjects with no-self reported COPD 90 subjects had COPD according to GOLD criteria. Subjects with self-reported COPD had higher pulmonary resistance than subjects with no self-reported COPD (R5 0.40/0.32 kPa/l/s, R20 0.28/0.24 and R5-R20 0.12/0.072, p<0.01 for all), both in subjects with (R5 0.42/0.33, R20 0.28/0.24, R5-R20 0.14/0.085, p<0.05 for all) and without spirometry verified COPD (R5 0.38/0.31, R20 0.28/0.24, R5-R20 0.11/0.068, p<0.05 for all). Respiratory symptoms, e g long-standing cough, were more commonly reported by subjects with self-reported than spirometry verified COPD (p<0.01).

Conclusions: Self-reported COPD is characterized by more respiratory symptoms and higher resistance measured by IOS, compared with spirometry verified COPD. High resistance may reflect early small airway disease better than spirometry.
ELSI practices in genomic research in East Asia: implications for research collaboration and public participation
Authors: Go Yoshizawa, Calvin Wai-Loon Ho, Wei Zhu, Chingli Hu, Yoni Syukriani, Ilhak Lee, Hannah Kim, Daniel Fu Chang Tsai, Jusaku Minari, Kazuto Kato
Journal: Genome Medicine (2014)

Common infrastructures and platforms are required for international collaborations in large-scale human genomic research and policy development, such as the Global Alliance for Genomics and Health and the 'ELSI 2.0' initiative. Such initiatives may require international harmonization of ethical and regulatory requirements. To enable this, however, a greater understanding of issues and practices that relate to the ethical, legal and social implications (ELSI) of genomic research will be needed for the different countries and global regions involved in such research. Here, we review the ELSI practices and regulations for genomic research in six East Asian countries (China, Indonesia, Japan, Singapore, South Korea and Taiwan), highlighting the main similarities and differences between these countries, and more generally, in relation to Western countries. While there are significant differences in ELSI practices among these East Asian countries, there is a consistent emphasis on advancing genomic science and technology. In addition, considerable emphasis is placed on informed consent for participation in research, whether through the contribution of tissue samples or personal information. However, a higher level of engagement with interested stakeholders and the public will be needed in some countries.
Effects of porcine gastric fundic factor, somatostatin, substance P, glucagon, neurotensin, bombesin, VIP, motilin, and pentagastrin on jejunal glucose absorption in the rat.
Authors: N J Andrews, S Rinno-Barmada, K Burdett, J B Elder
Journal: Gut (1983)

The effects of a porcine gastric fundic mucosal extract (molecular weight less than 10 000) has been compared with the effects of eight candidate gastrointestinal peptides on glucose absorption from the jejunum in a rat model. Bolus injection of the extract produced immediate and marked depression of glucose absorption. None of the candidate peptides tested produced this response, although somatostatin and substance P depressed absorption as a late phenomenon after 30 minutes. We conclude that the effects of the fundic extract are not reproduced by any of these candidate peptides. This strengthens the evidence for a novel gastrointestinal peptide, resident in fundic mucosa, which affects absorption from upper small bowel.
Clinical Relevance of Dominant-Negative p73 Isoforms for Responsiveness to Chemotherapy and Survival in Ovarian Cancer: Evidence for a Crucial p53-p73 Cross-talk <i>In vivo</i>
Authors: Nicole Concin, Gerda Hofstetter, Astrid Berger, Adriana Gehmacher, Daniel Reimer, Rafal Watrowski, Dan Tong, Eva Schuster, Lukas Hefler, Kurt Heim, Elisabeth Mueller-Holzner, Christian Marth, Ute M. Moll, Alain G. Zeimet, Robert Zeillinger
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We aimed to determine the clinical role of the p53 family members p53 and p73 in the responsiveness to platinum-based chemotherapy and survival in ovarian cancer, considering their cross-talk and the p53 polymorphism at codon 72. Experimental Design: A detailed analysis of p53 and p73 in a series of 122 ovarian cancers was done. We used a functional yeast-based assay to determine the p53 mutational status. Red yeast colonies, indicating mutant p53, were subsequently sequenced to determine the specific p53 alteration. p53 mutations were divided into two groups according to their previous characterization in the literature: those that efficiently inhibit transcriptionally active TAp73 function and those that do not. A p53 polymorphism at codon 72 was determined in corresponding normal tissue or blood of ovarian cancer patients. Isoform-specific p73 expression analysis using real-time reverse transcription-PCR has previously been done in the majority of ovarian cancers included in this study. In a retrospective chart review, responsiveness to chemotherapy was assessed, and survival data with long follow-up times were collected. Results: Eighty of 122 (65.6%) of ovarian cancers harbored p53 mutations. p53 mutational status was an important determinant of responsiveness to platinum-based chemotherapy in all patients with a residual tumor of &amp;lt;2 cm in diameter after initial surgery (wild-type versus mutant, P = 0.029). In addition, p53 mutational status was a strong prognosticator for recurrence-free and overall survival (P &amp;lt; 0.0001 and P = 0.003, respectively) in univariate analyses. High expression levels of dominant-negative p73 isoforms (ΔNp73 and ΔN′p73) significantly correlated with chemotherapeutic failure (P = 0.048) and with worse recurrence-free and overall survival in patients with p53 mutant cancers (P = 0.048 and P = 0.005, respectively). Eight p53 mutations, present in 19 cases, were found that efficiently inhibit TAp73 (i.e., 175H, 220C, 245S, 245D, 248W, 248Q, 266E, and 273H). Patients with p53 mutations that efficiently inhibit TAp73 function had a significantly shorter overall survival than patients with p53 mutations of unknown effect on TAp73 (P = 0.044). The p53 polymorphism at codon 72 had no influence on responsiveness to chemotherapy or survival. Conclusion: We provide the first clinical evidence that dominant-negative p73 isoforms contribute to drug resistance in vivo, underscoring the importance of a p53-p73 cross-talk. NH2-terminally truncated p73 isoforms were of significant clinical effect by providing an additional unfavorable factor for response to platinum-based chemotherapy and survival in p53 mutant ovarian cancers.
Reduced Metabotropic Glutamate Receptor 5 Density in Major Depression Determined by [<sup>11</sup>C]ABP688 PET and Postmortem Study
Authors: Alexandra Deschwanden, Beata Karolewicz, Anteneh M. Feyissa, Valerie Treyer, Simon M. Ametamey, Anass Johayem, Cyrill Burger, Yves P. Auberson, Judit Sovago, Craig A. Stockmeier, Alfred Buck, Gregor Hasler
Journal: American Journal of Psychiatry (2011)

Objective: Clinical and preclinical evidence suggests a hyperactive glutamatergic system in clinical depression. Recently, the metabotropic glutamate receptor 5 (mGluR5) has been proposed as an attractive target for novel therapeutic approaches to depression. The goal of this study was to compare mGluR5 binding (in a positron emission tomography [PET] study) and mGluR5 protein expression (in a postmortem study) between individuals with major depressive disorder and psychiatrically healthy comparison subjects. Method: Images of mGluR5 receptor binding were acquired using PET with [11C]ABP688, which binds to an allosteric site with high specificity, in 11 unmedicated individuals with major depression and 11 matched healthy comparison subjects. The amount of mGluR5 protein was investigated using Western blot in postmortem brain samples of 15 depressed individuals and 15 matched comparison subjects. Results: The PET study revealed lower levels of regional mGluR5 binding in the prefrontal cortex, the cingulate cortex, the insula, the thalamus, and the hippocampus in the depression group relative to the comparison group. Severity of depression was negatively correlated with mGluR5 binding in the hippocampus. The postmortem study showed lower levels of mGluR5 protein expression in the prefrontal cortex (Brodmann's area 10) in the depression group relative to the comparison group, while prefrontal mGluR1 protein expression did not differ between groups. Conclusions: The lower levels of mGluR5 binding observed in the depression group are consonant with the lower levels of protein expression in brain tissue in the postmortem depression group. Thus, both studies suggest that basal or compensatory changes in excitatory neurotransmission play roles in the pathophysiology of major depression.
Induction of IFN-αβ enables <i>Listeria monocytogenes</i> to suppress macrophage activation by IFN-γ
Authors: Manira Rayamajhi, Jessica Humann, Kristi Penheiter, Karl Andreasen, Laurel L. Lenz
Journal: The Journal of Experimental Medicine (2010)

Production of type I interferon (IFN; IFN-alphabeta) increases host susceptibility to Listeria monocytogenes, whereas type II IFN (IFN-gamma) activates macrophages to resist infection. We show that these opposing immunological effects of IFN-alphabeta and IFN-gamma occur because of cross talk between the respective signaling pathways. We found that cultured macrophages infected with L. monocytogenes were refractory to IFN-gamma treatment as a result of down-regulation of the IFN-gamma receptor (IFNGR). The soluble factor responsible for these effects was identified as host IFN-alphabeta. Accordingly, macrophages and dendritic cells (DCs) showed reduced IFNGR1 expression and reduced responsiveness to IFN-gamma during systemic infection of IFN-alphabeta-responsive mice. Furthermore, the increased resistance of mice lacking the IFN-alphabeta receptor (IFNAR(-/-)) to L. monocytogenes correlated with increased expression of IFN-gamma-dependent activation markers by macrophages and DCs and was reversed by depletion of IFN-gamma. Thus, IFN-alphabeta produced in response to bacterial infection and other stimuli antagonizes the host response to IFN-gamma by down-regulating the IFNGR. Such cross talk permits prioritization of IFN-alphabeta-type immune responses and may contribute to the beneficial effects of IFN-beta in treatment of inflammatory diseases such as multiple sclerosis.
The Implication of Brown Adipose Tissue for Humans
Authors: Eric Ravussin, José E. Galgani
Journal: Annual Review of Nutrition (2011)

We here discuss the role of brown adipose tissue on energy homeostasis and assess its potential as a target for body weight management. Because of their high number of mitochondria and the presence of uncoupling protein 1, brown fat adipocytes can be termed as energy inefficient for adenosine-5'-triphosphate (ATP) production but energy efficient for heat production. Thus, the energy inefficiency of ATP production, despite high energy substrate oxidation, allows brown adipose tissue to generate heat for body temperature regulation. Whether such thermogenic property also plays a role in body weight regulation is still debated. The recent (re)discovery of brown adipose tissue in human adults and a better understanding of brown adipose tissue development have encouraged the quest for new alternatives to treat obesity since obese individuals seem to have less brown adipose tissue mass/activity than do their lean counterparts. In this review, we discuss the physiological relevance of brown adipose tissue on thermogenesis and its potential usefulness on body weight control in humans.
Cerebellum-Like Structures and Their Implications for Cerebellar Function
Authors: Curtis C. Bell, Victor Han, Nathaniel B. Sawtell
Journal: Annual Review of Neuroscience (2008)

The nervous systems of most vertebrates include both the cerebellum and structures that are architecturally similar to the cerebellum. The cerebellum-like structures are sensory structures that receive input from the periphery in their deep layers and parallel fiber input in their molecular layers. This review describes these cerebellum-like structures and compares them with the cerebellum itself. The cerebellum-like structures in three groups of fish act as adaptive sensory processors in which the signals conveyed by parallel fibers in the molecular layer predict the patterns of sensory input to the deep layers through a process of associative synaptic plasticity. Similarities between the cerebellum-like structures and the cerebellum suggest that the cerebellum may also generate predictions about expected sensory inputs or states of the system, as suggested also by clinical, experimental, and theoretical studies of the cerebellum. Understanding the process of predicting sensory patterns in cerebellum-like structures may therefore be a source of insight into cerebellar function.